New Models for MPNST: Establishment and Comprehensive Characterization of Two Tumor Cell Lines

New Models for MPNST: Establishment and Comprehensive Characterization of Two Tumor Cell Lines | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article New Models for MPNST: Establishment and Comprehensive Characterization of Two Tumor Cell Lines Sara Ortega-Bertran, Edgar Creus-Bachiller, Miriam Magallón-Lorenz, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6219394/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Jul, 2025 Read the published version in Cancer Cell International → Version 1 posted 10 You are reading this latest preprint version Abstract Background Malignant peripheral nerve sheath tumors (MPNSTs) are rare, invasive, and aggressive soft tissue sarcomas arising from peripheral nerves. They may occur sporadically or in association with Neurofibromatosis type 1 (NF1), in which they are the leading cause of mortality. Currently, there are no effective therapies other than surgery. Therefore, tumor-derived cell lines are essential for testing new therapeutic strategies, especially when used in parallel with in vivo models. In this study, we present two new MPNST cell lines and two patient-derived orthotopic xenograft (PDOX) models from a sporadic (SP-10) and an NF1-related (NF1-18B) MPNST patient to increase the number of available preclinical models for in vitro and in vivo drug testing. Methods The cell lines were isolated and extensively characterized genetically (tumor suppressor gene mutation status, DNA content), phenotypically (cell morphology, marker expression), and functionally (proliferation rate, colony formation capacity, migration rate, tumorigenic ability). We validated the models by comparing the genomic (copy number variation profile) and histological characteristics of the cell lines and PDOX tumors with their corresponding patient tumors. Results The new cell lines and PDOXs tumors exhibited similar genomic copy number variation profiles, histological patterns, and marker expressions as the patient tumors, validating them as faithful models. Interestingly, the NF1-18B cell model presented two cell subpopulations with different ploidy states (one < 3n and the other 4n) and functional features in vitro . NF1-18B 4n, along with SP-10 cell lines, exhibited in vitro functional hallmarks of MPNSTs, including high proliferation and migration rates and colony forming ability. However, only the SP-10 model exhibited aggressive tumorigenicity in athymic mice. In contrast, the NF1-18B < 3n showed a low migration rate and did not form colonies or aggregates in vitro . Conclusions The newly established MPNST cell lines, along with their corresponding PDOX models, serve as valuable tools for both in vitro and in vivo testing of novel therapeutic agents. Notably, the SP-10 cell line model represents one of the few documented cases isolated from a genuine "classic" MPNST. Cellular model malignant peripheral nerve sheath tumors neurofibromatosis type 1 NF1 sporadic and patient-derived xenograft Figures Figure 1 Figure 2 Figure 3 Figure 4 BACKGROUND Malignant peripheral nerve sheath tumors (MPNSTs) are a rare and heterogeneous group of soft tissue sarcomas (STSs), accounting for 3–10% of all STSs, with an incidence of approximately 0.001% in the general population [ 1 , 2 ]. About half (40–50%) of MPNSTs occur in patients with Neurofibromatosis type 1 (NF1), an autosomal dominant genetic disorder caused by mutations in the NF1 gene [ 3 , 4 ]. The remaining MPNSTs occur sporadically (40–47%) or at sites of prior radiation therapy (10–13%) [ 3 , 5 ]. Despite these different clinical settings, the histology of MPNSTs is consistent across cases: fibrosarcoma-like fascicular spindle cell histological pattern, high hypercellularity and mitotic activity, cytologic atypia, and sites of tumor necrosis [ 6 ]. In the clinical context of NF1, MPNST arise from a plexiform neurofibroma (pNF), a benign tumor caused by the bi-allelic inactivation of the NF1 gene in the Schwann cell lineage [ 7 , 8 ], which is a tumor suppressor gene (TSG) that regulates cell proliferation and survival through the mTOR and MAPK pathways [ 9 ]. In some cases, pNFs first develop into atypical neurofibromas (ANNUBPs), premalignant lesions characterized by the recurrent deletion of the CDKN2A gene, which plays a critical role in cell cycle regulation [ 10 ]. Mutations in other TSGs, most commonly SUZ12 or EED , which encode Polycomb Repressive Complex 2 (PRC2), further drive MPNST development [ 11 ]. Less frequently, the TP53 gene is also inactivated [ 12 , 13 ]. This core pattern of inactivated TSGs is the primary genetic hallmark of "classic" MPNSTs [ 14 , 15 ], along with histologic features such as loss of expression of the neural crest-Schwann cell differentiation axis markers S100B and SOX10, and tri-methylation of lysine 27 on histone H3 (H3K27me3), a marker of PRC2 inactivation [ 16 ]. The clinical outcome of MPNST patients is poor, with an overall five-year survival rate of 50% [ 4 ], which is critically worsened in the event of recurrence or metastasis. Currently, the most effective treatment for MPNSTs is complete surgical resection with wide negative margins [ 17 ]. However, this strategy is often complicated by tumor size, location, and the presence of metastases [ 18 , 19 ]. Chemotherapy and radiotherapy have shown limited efficacy, highlighting the need for better therapeutic approaches [ 20 ]. As such, preclinical models are critical for studying MPNST biology and testing new treatments [ 21 , 22 ]. Cell lines provide a simple, cost-effective platform for in vitro preclinical research. However, due to the rarity of MPNSTs, especially in sporadic cases, there is a significant lack of established human cell lines, with only 44 currently listed in Cellosaurus (version 51, updated in December 2024) [ 22 , 23 ]. In addition to in vitro models, patient-derived orthotopic xenograft (PDOX) in vivo models are of particular interest for drug testing, as the engraftment of a piece of the patient’s tumor into the mouse allows a better recapitulation of the tumor’s genomic complexity and the cell heterogeneity compared to genetically modified mouse models or mice engrafted with tumor cell lines [ 24 ]. For this reason, our group has collected tumors from MPNST patients over the years and developed a preclinical platform comprising 30 PDOX models [ 25 , 26 ]. However, only three patient-derived cell lines have been successfully established, highlighting the challenges of generating MPNST cell lines from primary tumors [ 26 ]. In this study, we establish and comprehensively characterize two new cell lines derived from MPNST patients: one from a NF1-related tumor (NF1-18B) and other from a sporadic one (SP-10). These cell lines are currently being used in preclinical studies alongside patient-derived PDOX models. METHODS Patients and primary tumors Primary MPNSTs were obtained from the Hospital Infantil La Paz (NF1-18B) and the Hospital Universitari Germans Trias i Pujol (SP-10). The tumors were analyzed by the pathology department according to the standard protocols and a piece of each tumor was placed in Dulbecco’s modified Eagle’s medium (DMEM, Gibco), 10% fetal bovine serum (FBS, Gibco), and 1% penicillin/streptomycin (P/S, Gibco) at room temperature (RT). In the laboratory, samples were divided into portions and stored as follows: one portion was processed directly for cell line establishment, a second portion was used for mouse engraftment, a third portion was frozen for DNA, RNA, and/or protein extraction, and a fourth portion was cryopreserved using FBS and 10% dimethyl sulfoxide (DMSO). This study was approved by the IDIBELL Ethics Committee (#PR213/13) and all subjects gave written informed consent. Cell lines establishment and culture Tumor samples were minced into small fragments and digested with 100 U/mL collagenase (Sigma-Aldrich) and 1 U/mL dispase (Worthington Corporations) in DMEM medium (10% FBS and 1% P/S). After 18-24h, the enzymes were removed and the digested tissue was filtered through a 40 µM filter to seed single cells into 6-well Corning® plates, which were initially incubated at 37ºC in 10% CO 2 . After a few passages, the MPNST cell lines were then expanded and maintained at 37ºC and 5% CO 2 . All cell lines were tested for mycoplasma prior to experimental procedures by a PCR amplification of the 16S RNA of eight different mycoplasma species (results not shown). The SP-01 and NF1-09 cell lines used as controls in this work were previously established and described [ 26 ], and the human foreskin fibroblast (HFF) cell line was obtained from the American Type Culture Collection (ATCC, BCRJ Cat#0275). Animal care conditions Five-week-old male Athymic Nude- Foxn1 nu (Envigo) mice were housed in sterile cages with autoclaved bedding, food, and water and maintained on a 12-h light/12-h dark cycle daily. PDOX establishment Fresh tumor samples of 2–3 mm 3 were implanted into 5-week-old athymic nude mice. Briefly, mice were anesthetized with isoflurane (continuous flow of 1–3% isoflurane/oxygen mixture, 2 L/min), and a subcutaneous pocket was made in the upper thigh with surgical scissors. A small incision was then made in the muscle to expose the sciatic nerve, where the piece of tumor was engrafted using Prolene 7.0 suture to grow around the epineurium. After implantation, tumor growth was monitored weekly by palpation and volume was measured with a caliper. When the tumor reached 1,000 to 1,500 mm 3 , the mice were sacrificed and the tumors were passed to other animals. After each passage, tumor samples were cryopreserved to provide a source of viable tissue. Mouse experiments were approved by the campus animal ethics committee and followed the procedures of the Association for Assessment and Accreditation of Laboratory Animal Care International. DNA isolation and quantification Puregene Core Kit A (Qiagen) was used to isolate DNA from frozen tumors and cell lines, according to the manufacturer’s recommendations. For tumor DNA extraction, TissueLyser (Qiagen) was first used to homogenize the tissue. DNA quantity of each sample was assessed using Qubit (Qubit™ dsDNA BR Assay Kit, Invitrogen) and quality was assessed using NanoDrop 1000 spectrophotometer (ThermoFisher Scientific). Visual inspection of the DNA integrity was also performed on 1% agarose gels. Short tandem repeat (STR) authentication DNA fingerprints were obtained using the AmpFISTR Identifiler Plus PCR Amplification Kit (Applied Biosystems) according to the manufacturer’s protocol. The kit amplifies 15 tetranucleotide STR loci and the sex-determining marker amelogenin in a single PCR amplification using 33 primers. Allele calls were made from peak plots by comparing peaks to known fragment sizes using GeneMapper 4.0 (Applied Biosystems). Cell cycle analysis A total of 5 x 10 5 cells from an 80% confluence plate were fixed with frozen 70% ethanol and stained with a mixture of phosphate-buffered saline 1X (PBS 1X, Gibco) + 1% FBS, propidium iodide (0.0625 mg/mL; Sigma-Aldrich), and RNAse A (10 µg/mL; Sigma-Aldrich) for 30–45 min at 37ºC. Each cell line was tested in triplicate. The HFF cell line was used as a diploid control. 20,000 events per sample were analyzed using a FACS Canto II cytometer (Becton Dickinson) and ModFit LT V.3.3.11 software. Goodness of fit to the model is expressed by the reduced chi-square (RCS). Whole genome sequencing (WGS) WGS was performed at BGI (Shenzhen, China). Briefly, libraries were prepared according to standard DNBseq protocols, sequenced on a BGISEQ-500 to a median of 881 million 150-bp paired-end reads per sample, and mapped to the GRCh38 genome using BWA-MEM [ 27 ]. WGS data were processed as described in [ 14 ]. Immunofluorescence Cells seeded in 12-well Corning® plates with coverslips (12 mm Ø) were fixed in 4% paraformaldehyde for 15 min. Cells were then permeabilized with PBS 1X + 0.1% Triton X-100 (Sigma-Aldrich) for 15 min and blocked with 10% goat serum (Gibco) for 30 min at RT. Antibodies anti-SOX9 (1:100; ab76997, Abcam), smooth muscle actin (SMA, 1:100, RB-9010-R7, ThermoFisher Scientific), S100B (1:1000, Z031129, Dako), H3K27me3 (1:1500, 9733, Cell Signaling), and SOX10 (1:50, 383R-14, Cell Marque) were diluted in PBS 1X-1% goat serum and incubated overnight (ON) at 4 o C; then the cells were washed 3 times for 5 min with PBS 1X. Secondary antibodies Alexa Fluor 488 goat anti-mouse (1:1000, A11029; Invitrogen) and Alexa Fluor 568 goat anti-rabbit (1:1000, A11036; Invitrogen) were diluted in PBS 1X-10% goat serum and incubated for 1h at RT. After three 5-minutes washes with PBS 1X, the nuclei were stained with DAPI (1:1000, ThermoFisher Scientific) for 10 min at RT. Finally, coverslips were mounted with Immu-Mount (ThermoFisher Scientific). Images were captured using a Nikon Eclipse 80i microscope and NIS-Elements Microscope Imaging software. Population Doubling Time Population doubling times (PDTs) were calculated using the MTT (3-(4,5-dimetrhylthiaziol-2-yl)-2,5-diphenyl-tetrazolium bromide, Sigma-Aldrich, #M2128-1) colorimetric cell viability assay [ 28 ]. Different numbers of cells for each cell line were seeded in six replicates in Corning® 96-well plates to reach 100% confluence after 8–9 days of culture: 1,100 cells/well for NF1-18B and 1,300 cells/well for SP-10. Every 24h 0.5 mg/mL of MTT was added to each well. After 3h of incubation, the formazan precipitate was diluted by adding 100 µL of a 1:3 solution of glycine buffer (0.1 M NaCl and 0.1 M glycine) and DMSO to each well. Absorbance was measured at 540 nm with VictorTM X5 2030 Multilabel Reader (PerkinElmer). PDT was calculated using an exponential growth equation with GraphPad Prism 6. 2- Dimension (2-D) colony formation assay Cells were seeded in triplicate at a density of 300 cells/well in 12-well Corning® plates. After 10 days, cells were fixed with ice-cold methanol for 10 min and stained with 0.1% crystal violet (80% H 2 Od + 20% methanol) for 15 min. Hanging drop assay 200 cells in a 20 µL drop of DMEM were seeded on the top of the inverted lid of a 60 mm plate. 20 drops were placed in each plate and three plates were used for each cell line. 5 mL of PBS 1X was added to the bottom of the plate. The lid was inverted onto the PBS 1X filled bottom chamber and incubated at 37ºC in 5% CO 2 . Droplets were monitored at 24 and 48h and images were captured with a Leica DM IL LED light microscope using the contrast phase mode from Leica Microsystems’s. Wound healing assay 7 x 10 5 cells/mL were seeded (70 µL/well) into culture inserts (2 wells; Ibidi #80209) to reach confluence after 24h, then the culture inserts were removed and the cells were cultured under standard conditions. Images were captured at 0, 4, 8, 12, and 24h after removal of the inserts using a Leica DM IL LED light microscope at 10X magnification using the contrast phase mode from Leica Microsystems’s. Each cell line was seeded in triplicate. In vivo tumorigenicity 3 x 10 6 tumor cells in 100 µL of PBS 1X were injected intramuscularly near both sciatic nerves of five-week-old female athymic nude mice (N = 2 for the SP-10; N = 3 for each of the two NF1-18B subpopulations). Animals were monitored weekly. When tumors reached 1 cm in diameter, they were excised, cut into small fragments, and engrafted into mice (N = 4) both subcutaneously and orthotopically to assess tumor growth rate for each engraftment procedure. Tumors were measured twice weekly with a caliper, and tumor volume was calculated using the formula v = (pi/6 x L x W x W) [L: length; W: width]. All experiments with mice were approved by the IDIBELL Animal Care and Use Committee (#9111). Immunohistochemistry analysis Clinically relevant MPNST markers were analyzed in patient tumors, PDOX tumors, and cell lines. For the latter, cells were trypsinized and washed with PBS 1X, then equal volumes of human plasma and thrombospondin (Grifols) were added until a uniform pellet was obtained, which was embedded in paraffin. Paraffin-embedded tumor and cell line sections (3 µm) were deparaffinized in xylene and gradually rehydrated through graded ethanol solutions. Antigen retrieval was performed by heating the tissue sections at 110ºC for 15 min in citrate buffer (pH = 6). Endogenous peroxidases were then blocked by incubation with hydrogen peroxide (3% H 2 O 2 + 30% methanol + H 2 Od) for 15 min at 4ºC. Blocking was performed by incubation with 5% goat serum for 1h. Primary antibodies anti-vimentin (1:200, 180052, Life Technologies), Ki67 (1:10 M7240, DAKO), SOX10 (1:50, EP268 Cell Marque), H3K27me3 (1:200, 9733, Cell Signaling), and S100B (1:300, Z031129, Dako) were incubated ON at 4ºC followed by 30 min at RT. Secondary antibodies EnVision + System HRP-conjugated polymer anti-rabbit or anti-mouse (DAKO) were incubated for 1h at RT. Finally, detection was performed by incubation with diaminobenzidine (DAB) (DAKO) for 10 min and nuclei were counterstained with hematoxylin. Images were captured using a Nikon Eclipse 80i vertical microscope. RESULTS Patient Tumor Clinical and Genetic Information Two MPNST patients underwent surgical tumor resection at Hospital Infantil La Paz (NF1-related tumor, NF1-18B) and Hospital Universitari Germans Trias i Pujol (sporadic tumor, SP-10). The NF1-18B tumor was removed from the leg of an 18-year-old male patient with NF1, and the SP-10 tumor was located on the ribs of a female patient without NF1 (sporadic MPNST case) (Table 1 ). After resection of MPNSTs, a piece of tumor was digested to establish a cell line, and another was engrafted close the sciatic nerve of athymic mice to generate a PDOX model. We also performed genomic characterization of the patients’ tumors using WGS to analyze the mutational status of the most frequently inactivated TSGs in MPNSTs ( NF1 , CDKN2A , SUZ12 , EED , and TP53 ) (Table 1 ). Both tumors had mutations that inactivated NF1, CDKN2A , and PRC2, as described in “classic” MPNSTs. In addition, the NF1-18B tumor harbors inactivation of TP53 . After isolating the cell lines, we obtained their methylome profiles and compared them to those of other tumor types using a methylome classifier [ 14 , 29 ]. The analysis confirmed that both patient-derived cell lines matched the MPNST profile (Table 1 ). This tool could serve as a diagnostic aid to validate MPNST diagnoses and prevent misidentification with similar tumor entities. Moreover, STR authentication analysis was performed on the cell lines and PDOX models to confirm their patient-specific origin and rule out cross-contamination, verifying that their microsatellite patterns match those of the corresponding patient tumors (Table 2 ). Phenotypic and Functional Diversity Among MPNST Cell Lines We performed a comprehensive phenotypic and functional characterization to analyze the in vitro behavior of the newly generated MPNST cell lines. Flow cytometry-based cell cycle analysis confirmed that both cell lines exhibited an aneuploid state slightly above 2n, without reaching triploidy. Interestingly, the ploidy of the NF1-18B cell line evolved over successive passages, progressively increasing to approximately 4n at passage numbers greater than 16 (Fig. 1 A). This shift may be attributed to the presence of two distinct subpopulations in the primary tumor. Indeed, early-passage analysis of NF1-18B revealed a predominant subpopulation with a ploidy state between 2n and 3n (< 3n), alongside a minor tetraploid subpopulation. With continued in vitro passaging, the tetraploid subpopulation became progressively enriched, eventually leading to the complete loss of the < 3n cells (Supplementary Figure S1 ). Given this finding, we characterized both NF1-18B different ploidy cell lines as two independent lines: NF1-18B < 3n and NF1-18B 4n. Phenotypic characterization of the cell lines aimed to describe their cell morphology and MPNST markers expression by immunofluorescence. The three cell lines (NF1-18B < 3n, NF1-18B 4n and SP-10) exhibited small, spindle-shaped to polygonal morphology, consistent with the characteristics of MPNST cells (Fig. 1 B). In addition, the cell lines overexpressed SOX9 compared to non-tumoral fibroblasts, as previously described for MPNSTs [ 30 ]. They did not exhibit expression of S100B or H3K27me3 (Fig. 1 C), which are commonly lost in MPNSTs compared to their benign precursor [ 14 ]. The functional characterization focused on analyzing cell growth rate, colony formation ability, and tumorigenic capacity in mice. First, cell proliferation was assessed by calculating the PDTs: 44h for NF1-18B < 3n, 34h for NF1-18B 4n, and 29h for SP-10 (Fig. 2 A). Notably, the proliferation rate of the NF1-18B 4n cell line was higher than that of NF1-18B < 3n. The evaluation of colony formation and migration capabilities revealed functional differences between the cell lines. The NF1-18B 4n and SP-10 cell lines formed 2-D colonies, aggregated in the hanging drop assay to assess cell-cell cohesion, and achieved 100% wound closure at 12h and 24h, respectively. In contrast, the NF1-18B < 3n cell line did not form colonies or aggregates, with cells remaining loosely attached, and exhibited low migration capacity in the wound healing assay (Fig. 2 B, 2 C, 2 D). Finally, we evaluated the tumorigenic capacity of the cell lines in vivo by injecting them close the sciatic nerve of athymic mice. The SP-10 cell line formed large tumors within six weeks after engraftment and the NF1-18B < 3n cell line formed small tumors after four months, which were only detected at the time of sacrifice (Fig. 2 E). Notably, the NF1-18B 4n cell line did not generate tumors, despite having a higher proliferation and migration rate in vitro compared to NF1-18B < 3n. After tumor resection, hematoxylin and eosin (H&E) staining revealed that the histologic features of the tumors generated by the cell lines were consistent with MPNSTs (Fig. 2 E). Additionally, the proliferation marker Ki67 was more highly expressed in the SP-10 tumors than in the NF1-18B tumors, as expected from its higher proliferation rate in vitro (Fig. 2 E). To further investigate tumor growth dynamics, we compared the in vivo growth rates of SP-10-derived tumors using subcutaneous and orthotopic (sciatic nerve) engraftment procedures. This comparison aimed to assess how the tumor microenvironment influences growth, as orthotopic models more closely mimic the native tumor niche. Remarkable differences in growth rates were observed, with orthotopic tumors growing, on average, 7-fold faster than subcutaneously implanted tumors, confirming that orthotopic engraftments better recapitulate the aggressive tumor growth observed in the patient (Fig. 2 F). Newly Established Models Recapitulate Genetic Features of the Patients Tumors To validate our models, we performed WGS and compared the genetic characteristics of patient tumors with the generated models (PDOX and cell lines). The same mutations in NF1 , CDKN2A , and PRC2 found in patient tumors were also found in the models (Table 1 ). Copy number (CN) variation profiles showed that the models recapitulated the major genomic features of the patient tumors, with minor differences. For example, the SP-10 tumor, showed few structural alterations, mostly CN-gain (CNG) regions, and large loss of heterozygosity (LOH) areas, which were observed in both the patient tumor and the models (Fig. 3 A). In contrast, NF1-18B showed a higher proportion of genomic alterations and CNG regions (Fig. 3 B), consistent with high-grade “classic” MPNSTs [ 14 , 15 ]. In addition, histologic analyses were performed to compare patient tumor and model characteristics. H&E showed that PDOX tumors highly recapitulated the histology of patient MPNSTs (Fig. 4 A). In addition, IHC of SOX10, S100B, H3K27me3, Ki67 and Vimentin markers in primary, PDOX tumors and cell lines were also performed to compare their expression with the primary tumors (Fig. 4 B). Both NF1-18B and SP-10 PDOXs and cell models did not express SOX10, S100B, and H3K27me3 markers which is consistent with the primary tumors, although the SP-10 cell line presented focal expression of H3K27me3 (Fig. 4 B). This phenomenon could be related to the intrinsic heterogeneity of the tumor, allowing the cell line to be isolated from a piece of the tumor where some cells retained the activity of the PCR2. Additionally, as expected, the Ki67 marker was more highly expressed in both cell lines compared to the tumors, probably due to the cell culture conditions In conclusion, these results confirm that the newly established PDOXs and cell models accurately recapitulate the major genomic and histological features of the primary tumors. DISCUSSION MPNSTs are aggressive tumors that are the leading cause of mortality in patients with NF1, although they also occur sporadically in the general population [ 3 ]. The development of in vitro and in vivo models is critical for testing new therapeutic strategies [ 18 , 19 ]. However, the generation of genuine MPNST models presents several challenges: (1) the low success rate (25%) in isolating cell lines from solid tumors [ 31 ]; (2) the low incidence of MPNSTs [ 2 ]; and (3) clinical misidentification with other tumor entities, such as soft tissue sarcomas or melanoma, due to overlapping histologic features [ 16 ]. Moreover, recent studies suggest that some of the commonly used sporadic MPNST cell lines (STS-26T, HS-Sch-2 and HS-PSS) may actually represent other tumor identities, including melanoma, desmoplastic melanoma, or epithelioid sarcoma [ 14 , 16 ]. In this study, we established two new patient-derived MPNST cell lines and two PDOXs models derived from a sporadic (SP-10) and an NF1-related (NF1-18B) patient, thus expanding the available models in our preclinical MPNST platform [ 25 , 26 ]. The primary MPNSTs exhibited genomic and histologic features consistent with "classic" MPNSTs, including the inactivation of NF1 , CDKN2A , and PRC2 [ 9 – 11 , 14 ]. Genomic analysis revealed chromosomal aneuploidy, multiple CNGs, and large areas of LOH, as expected for MPNSTs [ 14 , 15 ]. Furthermore, methylome profiling confirmed that the tumor-derived cell lines closely matched with the “classic” MPNST methylation signature. This diagnostic validation is particularly important for the SP-10, given the high rate of misdiagnosis of sporadic MPNSTs [ 14 , 26 ]. Thus, our SP-10 cell line model represents one of the few documented cases isolated from a genuine "classic" MPNST. Histological and genomic analyses showed that the established cell models and PDOXs faithfully recapitulated key features of the primary tumors. Both models retained the same NF1 , CDKN2A , and PRC2 inactivating mutations, displayed similar CN variation profiles to patient tumors, and lacked expression of markers related to MPNSTs such as S100B, SOX10, and H3K27me3 [ 16 , 32 , 33 ]. Interestingly, the NF1-18B cell line also could be recapitulating the intra-heterogeneity of the patient tumor [ 14 ], as two subpopulations with different ploidy states were detected in culture: one slightly higher than 2n (< 3n) and the other tetraploid (4n). We have previously reported this phenomenon in another cell line derived from our group [ 26 ]. Nevertheless, the shift in subpopulation predominance in the NF1-18B cell line through passages may not fully reflect in vivo tumor dynamics. In this study, we extensively characterized the phenotypic and functional properties of the new MPNST cell lines. In terms of proliferation rate, both lines exhibited PDTs values between 29h and 44h, similar to other widely used MPNST cell lines such as sNF96.2 (33h), NMS-3 (50h), and ST88-14 (24h), as reported in Cellosaurus . The SP-10 and NF1-18B 4n cell lines exhibited colony formation capacity, aggregate formation, and high migration rates, similar to other MPNST cell lines described in the literature [ 21 , 26 , 34 ]. Remarkably, the NF1-18B < 3n cell line exhibited distinct functional characteristics compared to NF1-18B 4n, such as an inability to form colonies or aggregates and a lower proliferation rate (Table 3 ). The underlying cause of these functional differences remains unclear, although a higher ploidy state may contribute to the more aggressive in vitro behavior observed in NF1-18B 4n cells. Consistent with the in vitro functional characteristics of the SP-10 cell line, it formed large tumors in mice six weeks after engraftment, whereas the NF1-18B 4n cell line failed to generate tumors in vivo. In contrast, NF1-18B < 3n cells generated small tumors that were detected only at post-mortem, despite not exhibiting aggressive behavior in vitro (Table 3 ). Finally, we emphasize the value of generating matched in vitro and in vivo models from the same primary tumor, as we did with the two patient tumors. This approach enhances the translational relevance of experimental findings. Indeed, the cell lines and PDOXs established in this study have already been used in preclinical drug screens targeting pathways disrupted by NF1 , CDKN2A , and PRC2 inactivation [ 35 ]. CONCLUSIONS This study introduces two novel patient-derived MPNST cell models, one NF1-associated and the other sporadic, along with their corresponding PDOXs. These models serve as valuable resources for advancing research and drug testing in these aggressive tumors, further expanding our MPNST preclinical model platform, which now includes 30 PDOXs and five patient-derived cell lines. In particular, the SP-10 cell model stands out as one of the few well-characterized models of a genuine "classic" sporadic MPNST. Abbreviations BAF B allele frequency CN Copy number CNG Copy number gain DMEM Dulbecco’s modified Eagle’s medium DMSO Dimethyl sulfoxide FBS Fetal Bovine Serum h Hours H3K27me3 Trimethylation of the histone H3 at lysine 27 H&E Hematoxylin and Eosin LOH Loss of Heterozygosity LRR Log R ratio min Minute MPNST Malignant peripheral nerve sheath tumor MTT 3-(4,5-dimetrhylthiaziol-2-yl)-2,5-diphenyl-tetrazolium bromide NF1 Neurofibromatosis type 1 ON Overnight PBS Phosphate Buffered Saline PDOX Patient-derived orthothopic xenograft PDT Population doubling time pNF Plexiform neurofibroma PRC2 Polycomb Repressive Complex 2 P/S Penicillin/Streptomycin RT Room temperature SMA Smooth muscle actin STR Short tandem repeat STS Soft tissue sarcomas TSG Tumor suppressor gene WGS Whole genome sequencing Declarations Ethics approval and consent to participate: This study was approved by the IDIBELL Ethics Committee (#PR213/13) and all subjects provided written informed consent. Consent for publication: Not applicable. Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests: The authors declare no conflict of interest. Funding: This work is supported by the Carlos III National Health Institute funded by FEDER funds – a way to build Europe – [PI23/00017, PI19/00553 and CIBERONC] as well as by project CPP2022-009550, funded by MCIU/AEI/10.13039/501100011033 and by the European Union “NextGenerationEU”/PRTR. With the institutional support of CERCA Programme / Generalitat of Catalunya and Department of Research and Universities of the Generalitat de Catalunya and AGAUR (2021SGR01112). We thank the finantial support of Fundación PROYECTO NEUROFIBROMATOSIS (FPNF) and Fundació La Marató de TV3. Authors' contributions: Conceptualization: S.O-B., J.F-R., C.L.; Molecular and cellular experimental work: S.O-B.; Mouse experimental work: S.O-B., J.F-R.; Bioinformatic analysis: M.M-L., B.G.; Scientific input: J.F-R., E.C-B., A.V.; Manuscript Figures: S.O-B.; M.M-L.; Writing manuscript: S.O-B.; E.C-B., C.L., E.S; Manuscript revision and editing: all authors; Funding acquisition: C.L., E.S. Acknowledgements: We would like to thank the patients and families that participated in this project, and all Spanish NF patients and NF associations for their continuing support and effort, in particular the Spanish Asociación de Afectados de Neurofibromatosis (AANF) and the Associació Catalana de les Neurofibromatosis (ACNefi). We thank CERCA Program/Generalitat de Catalunya for institutional support. References Ducatman BS, et al. Malignant peripheral nerve sheath tumors. A clinicopathologic study of 120 cases. Cancer. 1986;57(10):2006–21. Ferner RE, Gutmann DH. International consensus statement on malignant peripheral nerve sheath tumors in neurofibromatosis. Cancer Res. 2002;62(5):1573–7. LaFemina J, et al. Oncologic outcomes of sporadic, neurofibromatosis-associated, and radiation-induced malignant peripheral nerve sheath tumors. Ann Surg Oncol. 2013;20(1):66–72. Evans DG, et al. Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J Med Genet. 2002;39(5):311–4. Uusitalo E, et al. Distinctive Cancer Associations in Patients With Neurofibromatosis Type 1. J Clin Oncol. 2016;34(17):1978–86. Belakhoua SM, Rodriguez FJ. Diagnostic Pathology of Tumors of Peripheral Nerve. Neurosurgery. 2021;88(3):443–56. Miettinen MM, et al. Histopathologic evaluation of atypical neurofibromatous tumors and their transformation into malignant peripheral nerve sheath tumor in patients with neurofibromatosis 1-a consensus overview. Hum Pathol. 2017;67:1–10. Higham CS, et al. The characteristics of 76 atypical neurofibromas as precursors to neurofibromatosis 1 associated malignant peripheral nerve sheath tumors. Neuro Oncol. 2018;20(6):818–25. Ratner N, Miller SJ. A RASopathy gene commonly mutated in cancer: the neurofibromatosis type 1 tumour suppressor. Nat Rev Cancer. 2015;15(5):290–301. Serrano M. The INK4a/ARF locus in murine tumorigenesis. Carcinogenesis. 2000;21(5):865–9. De Raedt T, et al. PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature. 2014;514(7521):247–51. Brohl AS, et al. The genomic landscape of malignant peripheral nerve sheath tumors: diverse drivers of Ras pathway activation. Sci Rep. 2017;7(1):14992. Lee W, et al. PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumors. Nat Genet. 2014;46(11):1227–32. Magallón-Lorenz M, et al. Deep genomic analysis of malignant peripheral nerve sheath tumor cell lines challenges current malignant peripheral nerve sheath tumor diagnosis. iScience. 2023;26(2):106096. Cortes-Ciriano I, et al. Genomic Patterns of Malignant Peripheral Nerve Sheath Tumor (MPNST) Evolution Correlate with Clinical Outcome and Are Detectable in Cell-Free DNA. Cancer Discov. 2023;13(3):654–71. Le Guellec S, et al. Malignant Peripheral Nerve Sheath Tumor Is a Challenging Diagnosis: A Systematic Pathology Review, Immunohistochemistry, and Molecular Analysis in 160 Patients From the French Sarcoma Group Database. Am J Surg Pathol. 2016;40(7):896–908. Porter DE et al. Survival in Malignant Peripheral Nerve Sheath Tumours: A Comparison between Sporadic and Neurofibromatosis Type 1-Associated Tumours. Sarcoma, 2009. 2009: p. 756395. Kim A et al. Targeting Refractory Sarcomas and Malignant Peripheral Nerve Sheath Tumors in a Phase I/II Study of Sirolimus in Combination with Ganetespib (SARC023). Sarcoma, 2020. 2020: p. 5784876. Higham CS et al. SARC006: Phase II Trial of Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated Chemotherapy-Naive Malignant Peripheral Nerve Sheath Tumors. Sarcoma, 2017. 2017: p. 8685638. Zehou O, et al. Chemotherapy for the treatment of malignant peripheral nerve sheath tumors in neurofibromatosis 1: a 10-year institutional review. Orphanet J Rare Dis. 2013;8:127. Longo JF, et al. Establishment and genomic characterization of a sporadic malignant peripheral nerve sheath tumor cell line. Sci Rep. 2021;11(1):5690. Kim A et al. Malignant Peripheral Nerve Sheath Tumors State of the Science: Leveraging Clinical and Biological Insights into Effective Therapies. Sarcoma, 2017. 2017: p. 7429697. Bairoch A. The Cellosaurus, a Cell-Line Knowledge Resource. J Biomol Tech. 2018;29(2):25–38. Richmond A, Su Y. Mouse xenograft models vs GEM models for human cancer therapeutics. Dis Model Mech. 2008;1(2–3):78–82. Castellsagué J, et al. Comprehensive establishment and characterization of orthoxenograft mouse models of malignant peripheral nerve sheath tumors for personalized medicine. EMBO Mol Med. 2015;7(5):608–27. Creus-Bachiller E et al. Expanding a precision medicine platform for malignant peripheral nerve sheath tumors: New patient-derived orthotopic xenografts, cell lines and tumor entities. Mol Oncol, 2023. Li H. Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM . 2013. Kumar P, Nagarajan A, Uchil PD. Analysis of Cell Viability by the MTT Assay. Cold Spring Harb Protoc; 2018. 2018(6). Koelsche C, et al. Sarcoma classification by DNA methylation profiling. Nat Commun. 2021;12(1):498. Miller SJ, et al. Integrative genomic analyses of neurofibromatosis tumours identify SOX9 as a biomarker and survival gene. EMBO Mol Med. 2009;1(4):236–48. Kodack DP, et al. Primary Patient-Derived Cancer Cells and Their Potential for Personalized Cancer Patient Care. Cell Rep. 2017;21(11):3298–309. Magro G et al. Practical Approach to Histological Diagnosis of Peripheral Nerve Sheath Tumors: An Update. Diagnostics (Basel), 2022. 12(6). Miettinen M, et al. Sox10–a marker for not only schwannian and melanocytic neoplasms but also myoepithelial cell tumors of soft tissue: a systematic analysis of 5134 tumors. Am J Surg Pathol. 2015;39(6):826–35. Oyama R, et al. Establishment and characterization of patient-derived cancer models of malignant peripheral nerve sheath tumors. Cancer Cell Int. 2020;20:58. Ortega-Bertran S et al. Triple Combination of MEK, BET, and CDK Inhibitors Significantly Reduces Human Malignant Peripheral Nerve Sheath Tumors in Mouse Models. Clin Cancer Res, 2024. Additional Declarations No competing interests reported. Supplementary Files SupplementaryFigureS1OrtegaBertranetal.pdf Cite Share Download PDF Status: Published Journal Publication published 18 Jul, 2025 Read the published version in Cancer Cell International → Version 1 posted Editorial decision: Revision requested 23 Apr, 2025 Reviews received at journal 22 Apr, 2025 Reviews received at journal 17 Apr, 2025 Reviewers agreed at journal 11 Apr, 2025 Reviewers agreed at journal 10 Apr, 2025 Reviewers agreed at journal 04 Apr, 2025 Reviewers invited by journal 01 Apr, 2025 Editor assigned by journal 13 Mar, 2025 Submission checks completed at journal 13 Mar, 2025 First submitted to journal 13 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6219394","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":445067075,"identity":"e14ca9a7-14ad-4687-a1c4-57f24186f911","order_by":0,"name":"Sara Ortega-Bertran","email":"","orcid":"","institution":"Hereditary Cancer Program, Catalan Institute of Oncology (ICO-IDIBELL)","correspondingAuthor":false,"prefix":"","firstName":"Sara","middleName":"","lastName":"Ortega-Bertran","suffix":""},{"id":445067076,"identity":"eea58f60-7e62-47d8-aff5-9741922a12b1","order_by":1,"name":"Edgar Creus-Bachiller","email":"","orcid":"","institution":"Hereditary Cancer Program, Catalan Institute of Oncology (ICO-IDIBELL)","correspondingAuthor":false,"prefix":"","firstName":"Edgar","middleName":"","lastName":"Creus-Bachiller","suffix":""},{"id":445067077,"identity":"e07d42ed-4b2f-42c8-a213-9dd688843ee1","order_by":2,"name":"Miriam Magallón-Lorenz","email":"","orcid":"","institution":"Hereditary Cancer Group, CARE Translational Program, Germans Trias i Pujol Research Institute (IGTP)","correspondingAuthor":false,"prefix":"","firstName":"Miriam","middleName":"","lastName":"Magallón-Lorenz","suffix":""},{"id":445067078,"identity":"ffe5384e-83fb-45c9-9fb1-b712d294508a","order_by":3,"name":"Meritxell Carrió","email":"","orcid":"","institution":"Hereditary Cancer Group, CARE Translational Program, Germans Trias i Pujol Research Institute (IGTP)","correspondingAuthor":false,"prefix":"","firstName":"Meritxell","middleName":"","lastName":"Carrió","suffix":""},{"id":445067079,"identity":"dd731ce3-c85f-4181-b0a3-c6a0e9e0d4a4","order_by":4,"name":"Bernat Gel","email":"","orcid":"","institution":"Hereditary Cancer Group, CARE Translational Program, Germans Trias i Pujol Research Institute (IGTP)","correspondingAuthor":false,"prefix":"","firstName":"Bernat","middleName":"","lastName":"Gel","suffix":""},{"id":445067080,"identity":"fb0c0809-c265-41b1-9a99-040182ab3717","order_by":5,"name":"Alberto Villanueva","email":"","orcid":"","institution":"Procure Program, Catalan Institute of Oncology","correspondingAuthor":false,"prefix":"","firstName":"Alberto","middleName":"","lastName":"Villanueva","suffix":""},{"id":445067081,"identity":"272702ed-0795-4e8e-9908-7d3ee3b53b67","order_by":6,"name":"Eduard Serra","email":"","orcid":"","institution":"Hereditary Cancer Group, CARE Translational Program, Germans Trias i Pujol Research Institute (IGTP)","correspondingAuthor":false,"prefix":"","firstName":"Eduard","middleName":"","lastName":"Serra","suffix":""},{"id":445067082,"identity":"c6529184-0c62-4156-a71e-754cdd16a1df","order_by":7,"name":"Juana Fernández-Rodríguez","email":"","orcid":"","institution":"Mouse Lab, SCT-IDIBELL","correspondingAuthor":false,"prefix":"","firstName":"Juana","middleName":"","lastName":"Fernández-Rodríguez","suffix":""},{"id":445067083,"identity":"ccdef694-be74-4a22-beb0-140f882518e2","order_by":8,"name":"Conxi Lázaro","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8klEQVRIiWNgGAWjYDACdgglxwahLRgYmAlpgSowhmqRgIkYENSS2ADXwkBAC38z8+MPP/fYpPexHz724EeFhJy8O/MD5oKKPzi1SBxmMzDseZaW28aTlm7Yc0bC2BAowjzjDG5bDJgZDBJ4DhzObZPgMZNmbJNI3NgMFORtw6eF/cPBPwcOp7MhtLB/YOb9h08Lj2Ez0JYEuJb5zDxAWxpwa5E4zFPMLHMgzRDolzRJkF+AhhQc5jlmjFMLf3v75o9vDtjIy7cfPibxo8JGTr7/+MbHPDVyOLVgceoBBoYDJKgHAvkG0tSPglEwCkbB8AcA0IpF9ZTYZKwAAAAASUVORK5CYII=","orcid":"","institution":"Hereditary Cancer Program, Catalan Institute of Oncology (ICO-IDIBELL)","correspondingAuthor":true,"prefix":"","firstName":"Conxi","middleName":"","lastName":"Lázaro","suffix":""}],"badges":[],"createdAt":"2025-03-13 11:08:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6219394/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6219394/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12935-025-03845-4","type":"published","date":"2025-07-18T16:05:18+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":81699849,"identity":"6f6d2c84-a942-4bd0-941b-d3d86b6b442d","added_by":"auto","created_at":"2025-04-30 13:03:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1338426,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePhenotypic characterization of newly established MPNST cell lines.\u003c/strong\u003e \u003cstrong\u003eA.\u003c/strong\u003e DNA content analysis of the tumor cell lines, plotted as number of cells versus amount of DNA, and performed at low and high passages. The NF1-18B cell line shows aneuploidy below 3n at low passages and it is tetraploid (4n) at high passages. \u003cstrong\u003eB. \u003c/strong\u003eRepresentative morphological images of NF1-18B (“\u0026lt;3n” and “4n”) and SP-10 cell lines at low and high confluence. \u003cstrong\u003eC.\u003c/strong\u003eRepresentative immunofluorescence images of SOX9, S100B, and H3K27me3 markers. DAPI nuclear staining is shown in blue. Fibroblasts were used as positive control for expression of SOX9, SP-01 melanoma cell line was used as positive control for S100B, and NF1-09 MPNST cell line was used as positive control for H3K27me3 marker (Creus-Bachiller et al., 2023). C+: Positive control. The magnification of the images in B and C is 20X. The scale bar is 150 μm.\u003c/p\u003e","description":"","filename":"Picture1.png","url":"https://assets-eu.researchsquare.com/files/rs-6219394/v1/e90e5929cebe47d99c5c2d9c.png"},{"id":81699584,"identity":"e8ee7941-a235-4339-8219-f98fb1098c5f","added_by":"auto","created_at":"2025-04-30 13:03:46","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1410231,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFunctional characterization of the newly established MPNST cell lines. A. \u003c/strong\u003eCell growth curves of the three cell lines (NF1-18B “\u0026lt; 3n”, NF1-18B “4n\", and SP-10) plotted as MTT absorbance values every 24h. Growth curves were generated using the mean values (N=6) \u003cu\u003e+\u003c/u\u003e standard deviation (SD, error bars). Population doubling time values are calculated in hours. \u003cstrong\u003eB.\u003c/strong\u003e Representative images of the 2-D colonies generated by the cell lines in a single well of a 12-well plate. Images were taken without amplification. \u003cstrong\u003eC.\u003c/strong\u003eRepresentative images of cell aggregates obtained in the hanging drop assay. Images were taken at 24 and 48 hours at 4X magnification. The scale bar is 50 μm. \u003cstrong\u003eD.\u003c/strong\u003e Representative images of the wound healing assay. Images of wound closure were taken at 0, 12, and 24 hours at 100X magnification. Scale bar is 200 μm. \u003cstrong\u003eE. \u003c/strong\u003eRepresentative images of Hematoxilin \u0026amp; Eosin (H\u0026amp;E) and immunostaining for Ki67 and vimentin in orthotopic cell line-derived tumors. NF1-18B \"4n\" did not generate tumors in mice. Images were taken at 4X magnification. The scale bar is 50 μm. \u003cstrong\u003eF. \u003c/strong\u003eRelative tumor volume growth over two weeks in mice orthotopically and subcutaneously engrafted with a cell line derived SP-10 tumor. Growth curves were generated using the mean values (N=3) \u003cu\u003e+\u003c/u\u003estandard deviation (SD, error bars).\u003c/p\u003e","description":"","filename":"Picture2.png","url":"https://assets-eu.researchsquare.com/files/rs-6219394/v1/f21bf6d85ab4a50c686e70c1.png"},{"id":81699952,"identity":"adfbbfec-72d9-4481-ac71-c0a7f31d5e0a","added_by":"auto","created_at":"2025-04-30 13:04:05","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":623131,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePatient-derived cell lines and PDOX recapitulate the major genomic features of primary SP-10 (A) and NF1-18B (B) tumors.\u003c/strong\u003e Copy number (CN) variation profile represented by BAF and LRR of patient tumors, PDOX tumors, and cell lines. In the case of the NF1-18B cell line, the CN profile of the two NF1-18B cell line subpopulations (“\u0026lt; 3n” and “4n\") is shown. CN variation is represented by a colored line below the LRR: gray for 2n region; yellow to red for chromosomal gain regions (\u0026gt;2n); and green to dark green for chromosomal loss regions (\u0026lt;2). LOH regions are shown in blue. Major genomic differences between the primary tumors and the models are highlighted in purple. A calculation of the mean ploidy of the sample is shown on the right side. BAF: B-allele frequency; LRR: Log-R ratio; LOH: loss of heterozygosity.\u003c/p\u003e","description":"","filename":"Picture3.png","url":"https://assets-eu.researchsquare.com/files/rs-6219394/v1/6950e1045383896b81c7ed2a.png"},{"id":81699973,"identity":"93f91753-218b-4c64-bbdb-7c7ea562a05b","added_by":"auto","created_at":"2025-04-30 13:04:11","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":893977,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCell lines and PDOX tumors recapitulate the main histological features of primary tumors. A. \u003c/strong\u003eRepresentative images of Hematoxilin \u0026amp; Eosin (H\u0026amp;E) staining of primary and PDOX tumors.\u003cstrong\u003e B. \u003c/strong\u003eRepresentative images of immunostaining of SOX10, S100B, H3K27me3, Ki67, and Vimentin in patient primary tumors, PDOX tumors, and cell lines. SP-01 melanoma cell line was used as positive control for S100B and SOX10, and NF1-09 MPNST cell line was used as positive control for H3K27me3 marker (Creus-Bachiller et al., 2023). Images were taken at 4X magnification. The scale bar is 50 μm. C+: Positive control.\u003c/p\u003e","description":"","filename":"Picture4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6219394/v1/081f222058ac4cb517b8b84d.jpg"},{"id":88505949,"identity":"5466a3c3-2793-434b-be7c-aaad09f9d8d5","added_by":"auto","created_at":"2025-08-07 07:29:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5201702,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6219394/v1/15a95379-535c-46f1-b6aa-814946eb6c66.pdf"},{"id":81699908,"identity":"d94a0ea3-f203-4d62-9b98-f6cfa0a8b7be","added_by":"auto","created_at":"2025-04-30 13:04:02","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":251174,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigureS1OrtegaBertranetal.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6219394/v1/1caf1312b71470e9629d7e9b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"New Models for MPNST: Establishment and Comprehensive Characterization of Two Tumor Cell Lines","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eMalignant peripheral nerve sheath tumors (MPNSTs) are a rare and heterogeneous group of soft tissue sarcomas (STSs), accounting for 3\u0026ndash;10% of all STSs, with an incidence of approximately 0.001% in the general population [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. About half (40\u0026ndash;50%) of MPNSTs occur in patients with Neurofibromatosis type 1 (NF1), an autosomal dominant genetic disorder caused by mutations in the \u003cem\u003eNF1\u003c/em\u003e gene [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The remaining MPNSTs occur sporadically (40\u0026ndash;47%) or at sites of prior radiation therapy (10\u0026ndash;13%) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Despite these different clinical settings, the histology of MPNSTs is consistent across cases: fibrosarcoma-like fascicular spindle cell histological pattern, high hypercellularity and mitotic activity, cytologic atypia, and sites of tumor necrosis [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the clinical context of NF1, MPNST arise from a plexiform neurofibroma (pNF), a benign tumor caused by the bi-allelic inactivation of the \u003cem\u003eNF1\u003c/em\u003e gene in the Schwann cell lineage [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], which is a tumor suppressor gene (TSG) that regulates cell proliferation and survival through the mTOR and MAPK pathways [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In some cases, pNFs first develop into atypical neurofibromas (ANNUBPs), premalignant lesions characterized by the recurrent deletion of the \u003cem\u003eCDKN2A\u003c/em\u003e gene, which plays a critical role in cell cycle regulation [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Mutations in other TSGs, most commonly \u003cem\u003eSUZ12\u003c/em\u003e or \u003cem\u003eEED\u003c/em\u003e, which encode Polycomb Repressive Complex 2 (PRC2), further drive MPNST development [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Less frequently, the \u003cem\u003eTP53\u003c/em\u003e gene is also inactivated [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. This core pattern of inactivated TSGs is the primary genetic hallmark of \"classic\" MPNSTs [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], along with histologic features such as loss of expression of the neural crest-Schwann cell differentiation axis markers S100B and SOX10, and tri-methylation of lysine 27 on histone H3 (H3K27me3), a marker of PRC2 inactivation [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe clinical outcome of MPNST patients is poor, with an overall five-year survival rate of 50% [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], which is critically worsened in the event of recurrence or metastasis. Currently, the most effective treatment for MPNSTs is complete surgical resection with wide negative margins [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. However, this strategy is often complicated by tumor size, location, and the presence of metastases [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Chemotherapy and radiotherapy have shown limited efficacy, highlighting the need for better therapeutic approaches [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. As such, preclinical models are critical for studying MPNST biology and testing new treatments [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Cell lines provide a simple, cost-effective platform for \u003cem\u003ein vitro\u003c/em\u003e preclinical research. However, due to the rarity of MPNSTs, especially in sporadic cases, there is a significant lack of established human cell lines, with only 44 currently listed in \u003cem\u003eCellosaurus\u003c/em\u003e (version 51, updated in December 2024) [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In addition to \u003cem\u003ein vitro\u003c/em\u003e models, patient-derived orthotopic xenograft (PDOX) \u003cem\u003ein vivo\u003c/em\u003e models are of particular interest for drug testing, as the engraftment of a piece of the patient\u0026rsquo;s tumor into the mouse allows a better recapitulation of the tumor\u0026rsquo;s genomic complexity and the cell heterogeneity compared to genetically modified mouse models or mice engrafted with tumor cell lines [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. For this reason, our group has collected tumors from MPNST patients over the years and developed a preclinical platform comprising 30 PDOX models [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. However, only three patient-derived cell lines have been successfully established, highlighting the challenges of generating MPNST cell lines from primary tumors [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this study, we establish and comprehensively characterize two new cell lines derived from MPNST patients: one from a NF1-related tumor (NF1-18B) and other from a sporadic one (SP-10). These cell lines are currently being used in preclinical studies alongside patient-derived PDOX models.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients and primary tumors\u003c/h2\u003e \u003cp\u003ePrimary MPNSTs were obtained from the \u003cem\u003eHospital Infantil La Paz\u003c/em\u003e (NF1-18B) and the \u003cem\u003eHospital Universitari Germans Trias i Pujol\u003c/em\u003e (SP-10). The tumors were analyzed by the pathology department according to the standard protocols and a piece of each tumor was placed in Dulbecco\u0026rsquo;s modified Eagle\u0026rsquo;s medium (DMEM, Gibco), 10% fetal bovine serum (FBS, Gibco), and 1% penicillin/streptomycin (P/S, Gibco) at room temperature (RT). In the laboratory, samples were divided into portions and stored as follows: one portion was processed directly for cell line establishment, a second portion was used for mouse engraftment, a third portion was frozen for DNA, RNA, and/or protein extraction, and a fourth portion was cryopreserved using FBS and 10% dimethyl sulfoxide (DMSO). This study was approved by the IDIBELL Ethics Committee (#PR213/13) and all subjects gave written informed consent.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCell lines establishment and culture\u003c/h3\u003e\n\u003cp\u003eTumor samples were minced into small fragments and digested with 100 U/mL collagenase (Sigma-Aldrich) and 1 U/mL dispase (Worthington Corporations) in DMEM medium (10% FBS and 1% P/S). After 18-24h, the enzymes were removed and the digested tissue was filtered through a 40 \u0026micro;M filter to seed single cells into 6-well Corning\u0026reg; plates, which were initially incubated at 37\u0026ordm;C in 10% CO\u003csub\u003e2\u003c/sub\u003e. After a few passages, the MPNST cell lines were then expanded and maintained at 37\u0026ordm;C and 5% CO\u003csub\u003e2\u003c/sub\u003e. All cell lines were tested for mycoplasma prior to experimental procedures by a PCR amplification of the 16S RNA of eight different mycoplasma species (results not shown).\u003c/p\u003e \u003cp\u003eThe SP-01 and NF1-09 cell lines used as controls in this work were previously established and described [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], and the human foreskin fibroblast (HFF) cell line was obtained from the American Type Culture Collection (ATCC, BCRJ Cat#0275).\u003c/p\u003e\n\u003ch3\u003eAnimal care conditions\u003c/h3\u003e\n\u003cp\u003eFive-week-old male Athymic Nude-\u003cem\u003eFoxn1\u003c/em\u003e\u003csup\u003enu\u003c/sup\u003e (Envigo) mice were housed in sterile cages with autoclaved bedding, food, and water and maintained on a 12-h light/12-h dark cycle daily.\u003c/p\u003e\n\u003ch3\u003ePDOX establishment\u003c/h3\u003e\n\u003cp\u003eFresh tumor samples of 2\u0026ndash;3 mm\u003csup\u003e3\u003c/sup\u003e were implanted into 5-week-old athymic nude mice. Briefly, mice were anesthetized with isoflurane (continuous flow of 1\u0026ndash;3% isoflurane/oxygen mixture, 2 L/min), and a subcutaneous pocket was made in the upper thigh with surgical scissors. A small incision was then made in the muscle to expose the sciatic nerve, where the piece of tumor was engrafted using Prolene 7.0 suture to grow around the epineurium. After implantation, tumor growth was monitored weekly by palpation and volume was measured with a caliper. When the tumor reached 1,000 to 1,500 mm\u003csup\u003e3\u003c/sup\u003e, the mice were sacrificed and the tumors were passed to other animals. After each passage, tumor samples were cryopreserved to provide a source of viable tissue. Mouse experiments were approved by the campus animal ethics committee and followed the procedures of the Association for Assessment and Accreditation of Laboratory Animal Care International.\u003c/p\u003e\n\u003ch3\u003eDNA isolation and quantification\u003c/h3\u003e\n\u003cp\u003e Puregene Core Kit A (Qiagen) was used to isolate DNA from frozen tumors and cell lines, according to the manufacturer\u0026rsquo;s recommendations. For tumor DNA extraction, TissueLyser (Qiagen) was first used to homogenize the tissue. DNA quantity of each sample was assessed using Qubit (Qubit\u0026trade; dsDNA BR Assay Kit, Invitrogen) and quality was assessed using NanoDrop 1000 spectrophotometer (ThermoFisher Scientific). Visual inspection of the DNA integrity was also performed on 1% agarose gels.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eShort tandem repeat (STR) authentication\u003c/h2\u003e \u003cp\u003eDNA fingerprints were obtained using the AmpFISTR Identifiler Plus PCR Amplification Kit (Applied Biosystems) according to the manufacturer\u0026rsquo;s protocol. The kit amplifies 15 tetranucleotide STR loci and the sex-determining marker amelogenin in a single PCR amplification using 33 primers. Allele calls were made from peak plots by comparing peaks to known fragment sizes using GeneMapper 4.0 (Applied Biosystems).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCell cycle analysis\u003c/h3\u003e\n\u003cp\u003eA total of 5 x 10\u003csup\u003e5\u003c/sup\u003e cells from an 80% confluence plate were fixed with frozen 70% ethanol and stained with a mixture of phosphate-buffered saline 1X (PBS 1X, Gibco)\u0026thinsp;+\u0026thinsp;1% FBS, propidium iodide (0.0625 mg/mL; Sigma-Aldrich), and RNAse A (10 \u0026micro;g/mL; Sigma-Aldrich) for 30\u0026ndash;45 min at 37\u0026ordm;C. Each cell line was tested in triplicate. The HFF cell line was used as a diploid control. 20,000 events per sample were analyzed using a FACS Canto II cytometer (Becton Dickinson) and ModFit LT V.3.3.11 software. Goodness of fit to the model is expressed by the reduced chi-square (RCS).\u003c/p\u003e\n\u003ch3\u003eWhole genome sequencing (WGS)\u003c/h3\u003e\n\u003cp\u003eWGS was performed at BGI (Shenzhen, China). Briefly, libraries were prepared according to standard DNBseq protocols, sequenced on a BGISEQ-500 to a median of 881\u0026nbsp;million 150-bp paired-end reads per sample, and mapped to the GRCh38 genome using BWA-MEM [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. WGS data were processed as described in [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eImmunofluorescence\u003c/h2\u003e \u003cp\u003eCells seeded in 12-well Corning\u0026reg; plates with coverslips (12 mm \u0026Oslash;) were fixed in 4% paraformaldehyde for 15 min. Cells were then permeabilized with PBS 1X\u0026thinsp;+\u0026thinsp;0.1% Triton X-100 (Sigma-Aldrich) for 15 min and blocked with 10% goat serum (Gibco) for 30 min at RT. Antibodies anti-SOX9 (1:100; ab76997, Abcam), smooth muscle actin (SMA, 1:100, RB-9010-R7, ThermoFisher Scientific), S100B (1:1000, Z031129, Dako), H3K27me3 (1:1500, 9733, Cell Signaling), and SOX10 (1:50, 383R-14, Cell Marque) were diluted in PBS 1X-1% goat serum and incubated overnight (ON) at 4\u003csup\u003eo\u003c/sup\u003eC; then the cells were washed 3 times for 5 min with PBS 1X. Secondary antibodies Alexa Fluor 488 goat anti-mouse (1:1000, A11029; Invitrogen) and Alexa Fluor 568 goat anti-rabbit (1:1000, A11036; Invitrogen) were diluted in PBS 1X-10% goat serum and incubated for 1h at RT. After three 5-minutes washes with PBS 1X, the nuclei were stained with DAPI (1:1000, ThermoFisher Scientific) for 10 min at RT. Finally, coverslips were mounted with Immu-Mount (ThermoFisher Scientific). Images were captured using a Nikon Eclipse 80i microscope and NIS-Elements Microscope Imaging software.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003ePopulation Doubling Time\u003c/h2\u003e \u003cp\u003ePopulation doubling times (PDTs) were calculated using the MTT (3-(4,5-dimetrhylthiaziol-2-yl)-2,5-diphenyl-tetrazolium bromide, Sigma-Aldrich, #M2128-1) colorimetric cell viability assay [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDifferent numbers of cells for each cell line were seeded in six replicates in Corning\u0026reg; 96-well plates to reach 100% confluence after 8\u0026ndash;9 days of culture: 1,100 cells/well for NF1-18B and 1,300 cells/well for SP-10. Every 24h 0.5 mg/mL of MTT was added to each well. After 3h of incubation, the formazan precipitate was diluted by adding 100 \u0026micro;L of a 1:3 solution of glycine buffer (0.1 M NaCl and 0.1 M glycine) and DMSO to each well. Absorbance was measured at 540 nm with VictorTM X5 2030 Multilabel Reader (PerkinElmer). PDT was calculated using an exponential growth equation with GraphPad Prism 6.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e2- Dimension (2-D) colony formation assay\u003c/h2\u003e \u003cp\u003eCells were seeded in triplicate at a density of 300 cells/well in 12-well Corning\u0026reg; plates. After 10 days, cells were fixed with ice-cold methanol for 10 min and stained with 0.1% crystal violet (80% H\u003csub\u003e2\u003c/sub\u003eOd\u0026thinsp;+\u0026thinsp;20% methanol) for 15 min.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eHanging drop assay\u003c/h2\u003e \u003cp\u003e200 cells in a 20 \u0026micro;L drop of DMEM were seeded on the top of the inverted lid of a 60 mm plate. 20 drops were placed in each plate and three plates were used for each cell line. 5 mL of PBS 1X was added to the bottom of the plate. The lid was inverted onto the PBS 1X filled bottom chamber and incubated at 37\u0026ordm;C in 5% CO\u003csub\u003e2\u003c/sub\u003e. Droplets were monitored at 24 and 48h and images were captured with a Leica DM IL LED light microscope using the contrast phase mode from Leica Microsystems\u0026rsquo;s.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eWound healing assay\u003c/h2\u003e \u003cp\u003e7 x 10\u003csup\u003e5\u003c/sup\u003e cells/mL were seeded (70 \u0026micro;L/well) into culture inserts (2 wells; Ibidi #80209) to reach confluence after 24h, then the culture inserts were removed and the cells were cultured under standard conditions. Images were captured at 0, 4, 8, 12, and 24h after removal of the inserts using a Leica DM IL LED light microscope at 10X magnification using the contrast phase mode from Leica Microsystems\u0026rsquo;s. Each cell line was seeded in triplicate.\u003c/p\u003e \u003cp\u003e \u003cb\u003eIn vivo\u003c/b\u003e \u003cb\u003etumorigenicity\u003c/b\u003e\u003c/p\u003e \u003cp\u003e3 x 10\u003csup\u003e6\u003c/sup\u003e tumor cells in 100 \u0026micro;L of PBS 1X were injected intramuscularly near both sciatic nerves of five-week-old female athymic nude mice (N\u0026thinsp;=\u0026thinsp;2 for the SP-10; N\u0026thinsp;=\u0026thinsp;3 for each of the two NF1-18B subpopulations). Animals were monitored weekly.\u003c/p\u003e \u003cp\u003eWhen tumors reached 1 cm in diameter, they were excised, cut into small fragments, and engrafted into mice (N\u0026thinsp;=\u0026thinsp;4) both subcutaneously and orthotopically to assess tumor growth rate for each engraftment procedure. Tumors were measured twice weekly with a caliper, and tumor volume was calculated using the formula v = (pi/6 x L x W x W) [L: length; W: width]. All experiments with mice were approved by the IDIBELL Animal Care and Use Committee (#9111).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eImmunohistochemistry analysis\u003c/h2\u003e \u003cp\u003eClinically relevant MPNST markers were analyzed in patient tumors, PDOX tumors, and cell lines. For the latter, cells were trypsinized and washed with PBS 1X, then equal volumes of human plasma and thrombospondin (Grifols) were added until a uniform pellet was obtained, which was embedded in paraffin.\u003c/p\u003e \u003cp\u003eParaffin-embedded tumor and cell line sections (3 \u0026micro;m) were deparaffinized in xylene and gradually rehydrated through graded ethanol solutions. Antigen retrieval was performed by heating the tissue sections at 110\u0026ordm;C for 15 min in citrate buffer (pH\u0026thinsp;=\u0026thinsp;6). Endogenous peroxidases were then blocked by incubation with hydrogen peroxide (3% H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;+\u0026thinsp;30% methanol\u0026thinsp;+\u0026thinsp;H\u003csub\u003e2\u003c/sub\u003eOd) for 15 min at 4\u0026ordm;C. Blocking was performed by incubation with 5% goat serum for 1h. Primary antibodies anti-vimentin (1:200, 180052, Life Technologies), Ki67 (1:10 M7240, DAKO), SOX10 (1:50, EP268 Cell Marque), H3K27me3 (1:200, 9733, Cell Signaling), and S100B (1:300, Z031129, Dako) were incubated ON at 4\u0026ordm;C followed by 30 min at RT. Secondary antibodies EnVision\u0026thinsp;+\u0026thinsp;System HRP-conjugated polymer anti-rabbit or anti-mouse (DAKO) were incubated for 1h at RT. Finally, detection was performed by incubation with diaminobenzidine (DAB) (DAKO) for 10 min and nuclei were counterstained with hematoxylin. Images were captured using a Nikon Eclipse 80i vertical microscope.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\n \u003ch2\u003ePatient Tumor Clinical and Genetic Information\u003c/h2\u003e\n \u003cp\u003eTwo MPNST patients underwent surgical tumor resection at \u003cem\u003eHospital Infantil La Paz\u003c/em\u003e (NF1-related tumor, NF1-18B) and \u003cem\u003eHospital Universitari Germans Trias i Pujol\u003c/em\u003e (sporadic tumor, SP-10). The NF1-18B tumor was removed from the leg of an 18-year-old male patient with NF1, and the SP-10 tumor was located on the ribs of a female patient without NF1 (sporadic MPNST case) (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). After resection of MPNSTs, a piece of tumor was digested to establish a cell line, and another was engrafted close the sciatic nerve of athymic mice to generate a PDOX model.\u003c/p\u003e\n \u003cp\u003e\u003cimg 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\" width=\"584\" height=\"279\"\u003e\u003c/p\u003e\n \u003cp\u003eWe also performed genomic characterization of the patients\u0026rsquo; tumors using WGS to analyze the mutational status of the most frequently inactivated TSGs in MPNSTs (\u003cem\u003eNF1\u003c/em\u003e, \u003cem\u003eCDKN2A\u003c/em\u003e, \u003cem\u003eSUZ12\u003c/em\u003e, \u003cem\u003eEED\u003c/em\u003e, and \u003cem\u003eTP53\u003c/em\u003e) (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Both tumors had mutations that inactivated \u003cem\u003eNF1, CDKN2A\u003c/em\u003e, and PRC2, as described in \u0026ldquo;classic\u0026rdquo; MPNSTs. In addition, the NF1-18B tumor harbors inactivation of \u003cem\u003eTP53\u003c/em\u003e.\u003c/p\u003e\n \u003cp\u003eAfter isolating the cell lines, we obtained their methylome profiles and compared them to those of other tumor types using a methylome classifier [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e]. The analysis confirmed that both patient-derived cell lines matched the MPNST profile (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). This tool could serve as a diagnostic aid to validate MPNST diagnoses and prevent misidentification with similar tumor entities. Moreover, STR authentication analysis was performed on the cell lines and PDOX models to confirm their patient-specific origin and rule out cross-contamination, verifying that their microsatellite patterns match those of the corresponding patient tumors (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003e\u003cimg 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\" width=\"584\" height=\"523\"\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\n \u003ch2\u003ePhenotypic and Functional Diversity Among MPNST Cell Lines\u003c/h2\u003e\n \u003cp\u003eWe performed a comprehensive phenotypic and functional characterization to analyze the \u003cem\u003ein vitro\u003c/em\u003e behavior of the newly generated MPNST cell lines. Flow cytometry-based cell cycle analysis confirmed that both cell lines exhibited an aneuploid state slightly above 2n, without reaching triploidy. Interestingly, the ploidy of the NF1-18B cell line evolved over successive passages, progressively increasing to approximately 4n at passage numbers greater than 16 (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eA). This shift may be attributed to the presence of two distinct subpopulations in the primary tumor. Indeed, early-passage analysis of NF1-18B revealed a predominant subpopulation with a ploidy state between 2n and 3n (\u0026lt;\u0026thinsp;3n), alongside a minor tetraploid subpopulation. With continued \u003cem\u003ein vitro\u003c/em\u003e passaging, the tetraploid subpopulation became progressively enriched, eventually leading to the complete loss of the \u0026lt;\u0026thinsp;3n cells (Supplementary Figure \u003cspan class=\"InternalRef\"\u003eS1\u003c/span\u003e). Given this finding, we characterized both NF1-18B different ploidy cell lines as two independent lines: NF1-18B\u0026thinsp;\u0026lt;\u0026thinsp;3n and NF1-18B 4n.\u003c/p\u003e\n \u003cp\u003ePhenotypic characterization of the cell lines aimed to describe their cell morphology and MPNST markers expression by immunofluorescence. The three cell lines (NF1-18B\u0026thinsp;\u0026lt;\u0026thinsp;3n, NF1-18B 4n and SP-10) exhibited small, spindle-shaped to polygonal morphology, consistent with the characteristics of MPNST cells (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eB). In addition, the cell lines overexpressed SOX9 compared to non-tumoral fibroblasts, as previously described for MPNSTs [\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e]. They did not exhibit expression of S100B or H3K27me3 (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eC), which are commonly lost in MPNSTs compared to their benign precursor [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\n \u003cp\u003eThe functional characterization focused on analyzing cell growth rate, colony formation ability, and tumorigenic capacity in mice. First, cell proliferation was assessed by calculating the PDTs: 44h for NF1-18B\u0026thinsp;\u0026lt;\u0026thinsp;3n, 34h for NF1-18B 4n, and 29h for SP-10 (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eA). Notably, the proliferation rate of the NF1-18B 4n cell line was higher than that of NF1-18B\u0026thinsp;\u0026lt;\u0026thinsp;3n.\u003c/p\u003e\n \u003cp\u003eThe evaluation of colony formation and migration capabilities revealed functional differences between the cell lines. The NF1-18B 4n and SP-10 cell lines formed 2-D colonies, aggregated in the hanging drop assay to assess cell-cell cohesion, and achieved 100% wound closure at 12h and 24h, respectively. In contrast, the NF1-18B\u0026thinsp;\u0026lt;\u0026thinsp;3n cell line did not form colonies or aggregates, with cells remaining loosely attached, and exhibited low migration capacity in the wound healing assay (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eB, \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eC, \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eD).\u003c/p\u003e\n \u003cp\u003eFinally, we evaluated the tumorigenic capacity of the cell lines \u003cem\u003ein vivo\u003c/em\u003e by injecting them close the sciatic nerve of athymic mice. The SP-10 cell line formed large tumors within six weeks after engraftment and the NF1-18B\u0026thinsp;\u0026lt;\u0026thinsp;3n cell line formed small tumors after four months, which were only detected at the time of sacrifice (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eE). Notably, the NF1-18B 4n cell line did not generate tumors, despite having a higher proliferation and migration rate \u003cem\u003ein vitro\u003c/em\u003e compared to NF1-18B\u0026thinsp;\u0026lt;\u0026thinsp;3n. After tumor resection, hematoxylin and eosin (H\u0026amp;E) staining revealed that the histologic features of the tumors generated by the cell lines were consistent with MPNSTs (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eE). Additionally, the proliferation marker Ki67 was more highly expressed in the SP-10 tumors than in the NF1-18B tumors, as expected from its higher proliferation rate \u003cem\u003ein vitro\u003c/em\u003e (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eE). To further investigate tumor growth dynamics, we compared the \u003cem\u003ein vivo\u003c/em\u003e growth rates of SP-10-derived tumors using subcutaneous and orthotopic (sciatic nerve) engraftment procedures. This comparison aimed to assess how the tumor microenvironment influences growth, as orthotopic models more closely mimic the native tumor niche. Remarkable differences in growth rates were observed, with orthotopic tumors growing, on average, 7-fold faster than subcutaneously implanted tumors, confirming that orthotopic engraftments better recapitulate the aggressive tumor growth observed in the patient (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eF).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec20\" class=\"Section2\"\u003e\n \u003ch2\u003eNewly Established Models Recapitulate Genetic Features of the Patients Tumors\u003c/h2\u003e\n \u003cp\u003eTo validate our models, we performed WGS and compared the genetic characteristics of patient tumors with the generated models (PDOX and cell lines). The same mutations in \u003cem\u003eNF1\u003c/em\u003e, \u003cem\u003eCDKN2A\u003c/em\u003e, and PRC2 found in patient tumors were also found in the models (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Copy number (CN) variation profiles showed that the models recapitulated the major genomic features of the patient tumors, with minor differences. For example, the SP-10 tumor, showed few structural alterations, mostly CN-gain (CNG) regions, and large loss of heterozygosity (LOH) areas, which were observed in both the patient tumor and the models (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eA). In contrast, NF1-18B showed a higher proportion of genomic alterations and CNG regions (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eB), consistent with high-grade \u0026ldquo;classic\u0026rdquo; MPNSTs [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\n \u003cp\u003eIn addition, histologic analyses were performed to compare patient tumor and model characteristics. H\u0026amp;E showed that PDOX tumors highly recapitulated the histology of patient MPNSTs (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003eA). In addition, IHC of SOX10, S100B, H3K27me3, Ki67 and Vimentin markers in primary, PDOX tumors and cell lines were also performed to compare their expression with the primary tumors (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003eB). Both NF1-18B and SP-10 PDOXs and cell models did not express SOX10, S100B, and H3K27me3 markers which is consistent with the primary tumors, although the SP-10 cell line presented focal expression of H3K27me3 (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003eB). This phenomenon could be related to the intrinsic heterogeneity of the tumor, allowing the cell line to be isolated from a piece of the tumor where some cells retained the activity of the PCR2. Additionally, as expected, the Ki67 marker was more highly expressed in both cell lines compared to the tumors, probably due to the cell culture conditions\u003c/p\u003e\n \u003cp\u003eIn conclusion, these results confirm that the newly established PDOXs and cell models accurately recapitulate the major genomic and histological features of the primary tumors.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eMPNSTs are aggressive tumors that are the leading cause of mortality in patients with NF1, although they also occur sporadically in the general population [\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]. The development of \u003cem\u003ein vitro\u003c/em\u003e and \u003cem\u003ein vivo\u003c/em\u003e models is critical for testing new therapeutic strategies [\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e]. However, the generation of genuine MPNST models presents several challenges: (1) the low success rate (25%) in isolating cell lines from solid tumors [\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e]; (2) the low incidence of MPNSTs [\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e]; and (3) clinical misidentification with other tumor entities, such as soft tissue sarcomas or melanoma, due to overlapping histologic features [\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e]. Moreover, recent studies suggest that some of the commonly used sporadic MPNST cell lines (STS-26T, HS-Sch-2 and HS-PSS) may actually represent other tumor identities, including melanoma, desmoplastic melanoma, or epithelioid sarcoma [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eIn this study, we established two new patient-derived MPNST cell lines and two PDOXs models derived from a sporadic (SP-10) and an NF1-related (NF1-18B) patient, thus expanding the available models in our preclinical MPNST platform [\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e]. The primary MPNSTs exhibited genomic and histologic features consistent with \u0026quot;classic\u0026quot; MPNSTs, including the inactivation of \u003cem\u003eNF1\u003c/em\u003e, \u003cem\u003eCDKN2A\u003c/em\u003e, and PRC2 [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]. Genomic analysis revealed chromosomal aneuploidy, multiple CNGs, and large areas of LOH, as expected for MPNSTs [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e]. Furthermore, methylome profiling confirmed that the tumor-derived cell lines closely matched with the \u0026ldquo;classic\u0026rdquo; MPNST methylation signature. This diagnostic validation is particularly important for the SP-10, given the high rate of misdiagnosis of sporadic MPNSTs [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e]. Thus, our SP-10 cell line model represents one of the few documented cases isolated from a genuine \u0026quot;classic\u0026quot; MPNST.\u003c/p\u003e\n\u003cp\u003eHistological and genomic analyses showed that the established cell models and PDOXs faithfully recapitulated key features of the primary tumors. Both models retained the same \u003cem\u003eNF1\u003c/em\u003e, \u003cem\u003eCDKN2A\u003c/em\u003e, and PRC2 inactivating mutations, displayed similar CN variation profiles to patient tumors, and lacked expression of markers related to MPNSTs such as S100B, SOX10, and H3K27me3 [\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e]. Interestingly, the NF1-18B cell line also could be recapitulating the intra-heterogeneity of the patient tumor [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e], as two subpopulations with different ploidy states were detected in culture: one slightly higher than 2n (\u0026lt;\u0026thinsp;3n) and the other tetraploid (4n). We have previously reported this phenomenon in another cell line derived from our group [\u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e]. Nevertheless, the shift in subpopulation predominance in the NF1-18B cell line through passages may not fully reflect \u003cem\u003ein vivo\u003c/em\u003e tumor dynamics.\u003c/p\u003e\n\u003cp\u003eIn this study, we extensively characterized the phenotypic and functional properties of the new MPNST cell lines. In terms of proliferation rate, both lines exhibited PDTs values between 29h and 44h, similar to other widely used MPNST cell lines such as sNF96.2 (33h), NMS-3 (50h), and ST88-14 (24h), as reported in \u003cem\u003eCellosaurus\u003c/em\u003e. The SP-10 and NF1-18B 4n cell lines exhibited colony formation capacity, aggregate formation, and high migration rates, similar to other MPNST cell lines described in the literature [\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e]. Remarkably, the NF1-18B\u0026thinsp;\u0026lt;\u0026thinsp;3n cell line exhibited distinct functional characteristics compared to NF1-18B 4n, such as an inability to form colonies or aggregates and a lower proliferation rate (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). The underlying cause of these functional differences remains unclear, although a higher ploidy state may contribute to the more aggressive \u003cem\u003ein vitro\u003c/em\u003e behavior observed in NF1-18B 4n cells.\u003c/p\u003e\n\u003cp\u003e\u003cimg 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4YsRdEQs6ohKnjHjJGcg4CTk/XTy5ECnz1UjxdTQoUNVzo4ZNYo/9onOnAGXDp5Bl4U/sx10gvycKzvlSAEDMOuiw6Hj4QTjs+kQOCEZcBlQyInBn86MQoSOIu7k4yqbQVN5LseCWV3lXB2fQQfNA9lsA4Uwx41ilM6HzDh2PPLAAKqcqeRz2SY6DDpECiu2gQKDQj924TOV/tJBM8iwfopUOngGKXJVArCSbVXqYIClvbBtyjY+7YBOjEKRNscxYZ84TlxsUNCx3fyMwYCOikKPdkqxHrtQmNFOmXXgGJBDYqKSmQ1F7HP8yZjtYT8oSCgOGKwYtDhPuLhiMGSA5/85hiwUFPwb5wyfzSBPccigS4fMYE57oJDg57Qj8uL9zFDwHBNFE22IgoyBVMmQkC3HhEE5IVHJIEx2FLsUA3TynFO0Y9oHX9zhnGP2hUGRQoY/0355LdvK//g3bsHx+XzhhTxZWH9iopLznEGHwoiBjkKFfaPdcMuZ40txzYUdAy3HnTZB5uw7g6ayEOEzGUg5NzkWXLyxzVwEUQzyOdyKpI2w3xQP8RXOJwrs2MeA2Bb6HQZPjjm3PGk7rIM+i8GZdkzRxaDKPtCe6Pfiikr6BtoixQznBK9lEKWd8plcoFHEcsw5hmw3/0Z7IU+KfraB8/nkyZMqX0wfQXvkIp5jyQWWkqmkAGT7OV8pAH18fFR+mkGbPjh2YT/oU1kfRSu50bdxPFgvRSfti4sm1kfGZMF2UlRSfFHQcFzYfi4u2BdyIFMufui7afeMG2w/F59kQhFFEUYfw8JxoE3xdy7M2HcmLth32ifnIcdbKZz/ij/iPRQrfAGR85H2QM4UxFxAsW7aAudtQqKSooe+g/44Z86cKpvjWHDhSR4U/fGJSvpD2gfPVFKkkzX9NvvLZ3IBoXCJvf3NecD4Rz/EMVLmtNLHxEQlfSbjDxe97Bdtgr6GPoX+hfOH/pFjwwUOx4A+i+L+Z4hKjjcXK/TzzO7Sf9BG+B99BBen9NWMbRxvMuJcYCyiL3Bzc1MtjBhzyF5EZepWsEkWlZxANFAGHjoXOk8aJh0PgwvFAicCAzodIQUgnT+FAFf5zA4oopIBlitIBicaDo2fKyyKS55nins4ms/kZFQKHR8nOo00sUIBxODOlTAdKgM4HQNFcmKZSj6Tk5zOmpOSzo994mRkZpOOixOYjp5ZQAYGBh4GOj6XzpiCiNlXOjw6XWY7lW3p2G2nk2FQ5WqafaMTpFigM2OhSGFAp3MmH05ICkA6uLjbu3FFZVxGFIusg1kFjgF/ZpuUs4scV4oXOjyKPUVUMgDQGVN0MsixMNhSNHL8YpcTJ06oHD8DirJIYH94rcLoR0QlhTsDKutkexjEGJzZJjpvjovCl8z4DL6YwWCUVFFJ+6Y9MEPIDAoDLp0jHTMdKh1h7OMiyvMSEpUMgFzo0BHHfqmCQVQRCUqAZpaNhcKPtku7jvv2OAMnHTPH43tEJecgRQUDHnlRGHDRR/vl4iTuW7L8jHOBiwkK+B8RlbQ72joXnixceHIO0Z8wCHF8GXC4QGEWirajLGbjCzgU2JzfDGica0rhIo5+iOLkR0UlBa6S6addsX1ctHD8OW9o20rGk6KFIkc5IqK0g/OKPoR+Q3mzlv1iBof30HboRylOGeTpQ2nftAP2gYtYJbuq7EAw00d/RoHLcaeA4mJaEZVcCLF9zKpRYFEEUXBwURL3TClFEO1YedGSv/M5tAvaKceG/WLhPKMgYLsp7tgfMla2bjlP2X4+k36QYpL3s/B6ZhPp6+lnyITjzPgQX+H1FN4UtPRFcUUlx51cyE/ZtWEWjWKJCQXOLWZLleNSnLvcxaH9JSQqq1atqhLk9Cu0bwpMJdtGRnFFJRdVjGHsN30Dd0i4aFNEJRfxbAMFKW2R/jW2qKS90I7o+/nNFBy72Iv1xEQlM8Aca2a2Y78QRKbMwHMLnr5DOXLD+ctYwSz+zxKV7C850d4owrmA42KYMYqCks+nsGfhwoT2yoWgcsSE/kBepE1M1aSOz5MsKumo6BxomEpqnqtx/i22qFRe1KHopAPiaoUTnIJUEZV0JMzAKOcolTNN3Bqhw+Bkjq/QedAxcbXFAE5xROeubqFgo5NgRoDBODFRyclJR8WASqdER8LJyslIp8ozcsrWJQMMhQ0FE7N+FJW8jgKbGQGKSjoaTmgKQToQBm8GOfafn9MhKqKS2QKKcW5fsPB6OmoGGIpUOgM67Pjego8rKulEucpncODzlfNasUVl7Le/KVYYMLi6ZqBURCWdJSc/sz9xhSw/i13oPMiHbVTOP9IO2AY6HTqWHxGVcd/+ZkBl/7iYYX10wnFf+mEbfoaoZJBQMpt8JlfWdJ4MGhw7ZoIYMOKWhEQlgyXnBcV57Mw7+8JxYr8oKsmdAoNFeXucgYfBgG3iZ2wL20Vb4b3fIyppF1zsUSzGzhozQ0ohQkfPucDncOwp+JgRS4qoZNBn25UXpShQaB/0L8oZQ/aXC0JmXznXKBopnDkvmNGIPdZc4DELQp4UKkphppWChPb3o6Iy9tvfDN60aW6Pct5yrJQzkrHHPu6cUEQl/QTHlIX+jhk1zjXajnLuNvYZZf6Nvoh+lv6XLJihZH28n/OTWT76NYqWuG9/M5tMcUifRHHBBTXvizuH+RnFKUUvs20U5mwXbYxjTRtRzsey7fTX5KqISiYblLN+zDCzLsYDzg366thHUHg/xQSTCxwr+h9lcaGcI+YYK/fQ/9JW4hOV9JMUs+yPIphYP9vMRS0X7My8MzmhlMRe1OEChr6egov1Mu7wGWRCG2Xs+FamMu78V0QlM7rsB4U74w9FI0Wv8qJO7Pso+tkG+kr6HZbERCX9Nu2EcSXu1wGxL5zHsRcSnOfsD2PNzxKVXHwoQp39pajk/FMy5MqZeqWvFJoUnXw+FzE8LsBFO312cn7dmrqaQa77NoEki0pmPijg6JzoDOhYKZY40WKLSk4gGiozCnQWFCBc3XFLTxGVDCIMUnQiXJkw60DRymwAM3OxD1jTGOm4lYwmRRcDC50bHSyNlJONW10JHV4mGq7q6RDoNCkUmXmiI+WZKz6DW7sMBMqZyuQUlRScFMZkyewls13K+ScyiSsqGcQZMCjW2Hau8ikK4/t+MIobZnGV7W9OUApSZhIo5pg15uexRSWdp/LWPp00hRCzJlwcKKKSwYjCmo6Oz0iosG7yo8imA2dhYFH+xsxCQqKS40HnS8cbe/v7W6KSQYmCR8kExxWWcdsa3/Y3nRo5UIBSnDHIM3usnKlMSFQqZz55bdzCPjBzFN/2N4MdFwl0vLG3I7l44Bgxg5OQqOQY0YbpjBmEme2jAOW8+V5RyXaQAYNS3MLgx+fQlpjlYcDg/FFEJReXzNLE3v5mv2nHrJcBmPOOgkc5UxlXVHLhQ5HC4J/Q1hf7xjnLgMRMn1LoQ2gfbB+FhFK4uKVYpr9ITFTSv1DE0acoJe7b37FFJcUfx579SuxN/sREJbdKOTdpQ8z4xC1cmFPc0E4oOji3uN1JO6Hd0oeQSVxRSTFJJhR69MXMZjE7HvflOtZL0cMAz8J5xzHk/dwV4QInvm/2UM5UxicqaQ8UNLTn+L4ZQDlTGVtUkhMXxkweKFlTslUylRSq9GfK9jcXG1wEc+zi+1osjh8XWrRhFp7t5k4H53lCmUo+m9v7bBvjHgU2jyBxnv2oqOTz+dVUnC/0qxSC8YlKXqccD1HO7iYmKjnfuaji/KeQjz2+rIOLqrhvsys2ltyikjt9jL3su/L2e3zxg/6WYpq7DUr8EmGXOgkkWVTSkVJAUsQwyFFk0kDonBRRyYnH1SudHJ0Tz4TRoShn6RRRSafGrQc6PwYH5fA2JztX8bGNjtkRrjYpNikU6BTpeBmQKLI46en8KFy44lcKRRjPsDCjyGew0OmwLRRyfCadBttKB8WAw1UVz03+G6JSeSOYGQNF7FK0fytTyfaz3+wrM1R0Esp2aFyTo5inKFOcKB0nBQGfQ8FOoaKIUmX7m46SXOjMudXGAMHx5TMVUcmVI7dmKLiUVT8dFccx7ndcMnND26BzI1c6OG5LK5ldtiMhUclxY18ZXCn2uaqO7yuFlEwlBRszMhxf5QwUHRkDHs/Bxl31xhWVtD32k8GPz2W/6dwo4NURlWRFEUrRxeMPDIxkw8BF0UGHz60elthnKineGQg4nzheXGhQXHHRQVunnSYkKnkP+65kQfgzgyDn3/eIStoBbVE580p7YOaP23Hkx4BKrsoZSgYIfqaISooaZrc4H5lp5PxjMOcihsJSefGNi8lviUr2gQtS3qd8XRgXURTeXDBSZJAVC3/nXGVdSqFd0obZJmZllPOpnA8UJOSYmKhkFpTClMc3FHGVkKhkOzhWtBMlCNJ2eLYs7suBiYlKLsRo61yYs2+cw8xKUxDS/3E8uNvBhR6zymTFfnGxxn5xMUg7j+97KnkUhUw4vyleuZsStygZMeXlJ2apyY6Ckgs2inn6EuUfSeBCiL6Tz2dmLD5Rye1djhtjBH2bcgaW/aDNMJEQN1PJBARfZFPOUPI+zk3aH//PuUa/woSF0hbGGS4o2Tf6DC4wKGg5l5kB5/8ZD7hYoZ3z2fRLiYlK+loubrl1TbvgLhNLUkQl72edFKjclSMb2gsTMcoRAGaeyYjslPiVmKikD6MPolBVzv0zJnL+UFRzV4ssOZ9ZyJfClWOS3KKS9sbnkxvjC/055wltmj6XLOhT6Lfod+n3aF9SUi+B7xKVnIQ8v8MVPp0WC4M8V8Z0eNzWYLDk9jeDjyIquRKmI+W2ECchz4hx1U/HS4fGiaQ4BgYQrlwpPJkd5MqEwYcrzdhZJj6LE4SrUwpbOjjWw+BCh8JJQoFFh8jrlMLMiPKGKp0hC9tKUcSJzO01Oie2gROOhk1n9G9lKhkAlC+9ZRCmyKQISUhUMmPAvvJIAX/+1r9iQKfMDAPFOZlyHDiWzIRye4hBkhmO2JlK5eUPTnJOeIoIBrK4b39zDHgtBSoLx4PilvxiF0XUky+dJQsdOp0knRztKSFRyfHj+LBujhWFEoPGtzKVzFjRHmknZEgHS+HKzAoFStytt7iiks+joKD4piCmzVLkq5up5HYzAxoXQRSGzKJw0cMgzvNTDJIUWMwCUoAoL+pwnMicjpZzghl4suFCitcxOCYkKnk9gzKPhnCbju3mixDfe6aSc44OnfOV3Mmcb95TjPD5FOhsOwUxr6UdMiAropLzlH3kWTkuWugHKMz4M+ulMKI9kvu3RCWZUaAw4CvbyQyotDe2hQGdwZaFbeA8UI5WKLbHdrIPFFkcc+Xsq7Idnpio5HO56KUA5EKVC0wuXL61/U02FB5cOChfmcMxZ3CPm21NTFSy/+wf+SjfyUuRQdtQ3njnwozBlplp2gcz05xH9J/KmcH4RCUDOOcoxSEX7rG3sRV2FGq8Rsn2MRtKn8QMJX2UMt7K8ScuYChuKdYSEpVkSnFJn6N8DRSPjvA5CpPYmUrlm0aUb02gDXDxxL5TVLI+3st5w7OOtBfOX543p+1z3Dn/uQBiBpPXM44xPpAj/R9FDMcpMVHJec3FArPAtF0l4ZFUUcmvQ6J9cfFAn6i8sKR8rQ6FIf0RxZjiuxITlRxH1ktxxvnIOcxncN5QpNG2uGhRxp6+kTy5w5DcopJ2RRtkPKBPZdvoD2lbXLzQd9JGOAf4d87hxF7ETb1y67/Rsu8Slf8NJL9eL+l4uPXPIE3hL0UICAEhoA4BBmsukrjDEPetb97PXQAuPCkklWBOwcpsKBc4CW1ZqvN8uUYICIG0RUBEZRoYT2Y3mZVg9k7df6YyDXRbuiAEhEASCTBbxaME3DGK798DZ9aPGVpm0JVvduBRDma+mSmNfc49iU2R24WAEEgDBERUpoFB5BkibonwkDe3DKQIASEgBNQhwK9v4Zu5CS1GefyCx5GUwuNCPMaQ2Etv6jxfrhECQiBtERBRmbbGU3ojBISAEBACQkAICIEUISAWb/skAAAgAElEQVSiMkWwy0OFgBAQAkJACAgBIZC2CIioTFvjKb0RAkJACAgBISAEhECKEBBRmSLY5aFCQAgIASEgBISAEEhbBERUpq3xlN4IASEgBISAEBACQiBFCIioTBHs8lAhIASEgBAQAkJACKQtAiIq09Z4Sm+EgBAQAkJACAgBIZAiBERUpgh2eagQEAJCQAgIASEgBNIWARGVaWs8pTdCQAgIASEgBISAEEgRAiIqUwS7PFQICAEhIASEgBAQAmmLgIjKtDWe0hshIASEgBAQAkJACKQIARGVKYJdHioEhIAQEAJCQAgIgbRFQERl2hpP6Y0QEAJCQAgIASEgBFKEgIjKFMEuDxUCQkAICAEhIASEQNoiIKIybY2n9EYICAEhIASEgBAQAilCQERlimCXhwoBISAEhIAQEAJCIG0REFGZtsZTeiMEhIAQEAJCQAgIgRQhIKIyRbDLQ4WAEBACQkAICAEhkLYIiKhMW+MpvRECQkAICAEhIASEQIoQEFGZItjloUJACAgBISAEhIAQSFsERFSmrfGU3ggBISAEhIAQEAJCIEUIiKhMEezyUCEgBISAEBACQkAIpC0CIirT1nhKb4SAEBACQkAICAEhkCIERFSmCHZ5qBAQAkJACAgBISAE0hYBEZVpazylN0JACAgBISAEhIAQSBECIipTBLs8VAgIASEgBISAEBACaYuAiMq0NZ7SGyEgBISAEBACQkAIpAgBEZUpgl0eKgSEgBAQAkJACAiBtEVARGXaGk/pjRAQAkJACAgBISAEUoSAiMoUwS4PFQJCQAgIASEgBIRA2iIgojJtjaf0RggIASEgBISAEBACKUJARGWKYJeHCgEhIASEgBAQAkIgbREQUZm2xvO7e/P+/Xu0aNHiu++TG4SAEBACQkAIJDeBgwcPQktLK7kfI/X/JAIiKn8SyF+5mqioqF+5+dL2VEjA3d0dEydOREREBDQ0NFJhC1OuSTo6OnB1dcXo0aOFTcoNQ4o9+erVqyhbtiw2bdqEZs2apVg7UvuDbW1tsXHjRpUP0dbWTu3NlfZ9ISCiUkxBCAiBn05gxIgRmDBhAqKjo0U4xaHLrIubmxvGjBkjbH665aX+Cq9cuYLSpUtjy5YtIioTGK727dtjw4YNIipTv0n/o4UiKn+xAZPmCoFfgYCIym+PkojKX8GCk6+NIirVYyuiUj1Oqe0qEZWpbUSkPUIgDRAQUSmiMg2YcbJ0QUSlelhFVKrHKbVdJaIytY2ItEcIpAECIipFVKYBM06WLoioVA+riEr1OKW2q0RUprYRkfYIgTRAQESliMo0YMbJ0gURlephFVGpHqfUdpWIytQ2ItIeIZAGCIioFFGZBsw4WbogolI9rCIq1eOU2q4SUZnaRkTaIwTSAAERlSIq04AZJ0sXRFSqh1VEpXqcUttVIipT24hIe4RAGiAgolJEZRow42TpgohK9bCKqFSPU2q7SkRlahsRaY8QSAMERFSKqEwDZpwsXRBRqR5WEZXqcUptV4moTG0jIu0RAmmAgIhKEZVpwIyTpQsiKtXDKqJSPU6p7SoRlaltRKQ9yUfgzXEM6DITBi3d4NatHNIlx5NionD7wAJMmLMPb3O2wPKFPZH1pz/nPU4vX4B5F80wY0EvWKbCfwUxuURlTPR5jGnjgay9BqNrSX8M7zQR0Y1dMda+Moz9T2JQxwnwNrRE094u6FanAHR/FvugO1joPg27NBph9YxmMEvCPz2ZKr/8/NVFjJg0B2btl8GpvC6S0L2fRfyb9Tw99QfcFz1CO1cn1C2UBanQ/BNkkOyiMuIDTm6ch3knDDF2Vl/kM9L7eYx898HRfi2y2Q5GvxbFYZiM8EVUJvtUSpYHiKhMFqz/9Up94TW4P5wW7MY7BUX5Hji/ZiKKWhmnHJxn61E+ZzekG7QJXlMawyQZWhIVHoJJLUywy3wsPKcORj5znZ/n0L+29w22DeuHPvuscerqTORJRsf+o4jiF5Xn0c+wOlbExCDmS8Valabj3qG+sFRTxURH7UFTM2fkmemJibWfoXb2tojqvwl75rbEg9m1UGnQMYw/HgLnirrQ0dL80eYDCMB252bosKgIjofOR9mA83Bo0BHztfri6UknZFOzvfE1IPWJykAcmDIYvVyX44VWL5z8tAjlNDWSwW5/bDh8b29H/xaTUGLWMgypVwT3tw5GQ8ercN34B7pXyplq2qlu735cVF7FUOu6mP/2AzJXtsWqRbNQNY8xEO6PrVMc4DhpB97GdMChtxPxako/9N2UHnvOzEcZE4MkMHoC94pV4V1uGubNaIOsT5ei9G9jUHCUJxY410D6JMyDxHiJqEyMUOr8XERl6hyXX7xVvtg4oDf6zdHGhhgv1PrSm/C3D3HlUQAy5iiInPpB8H74DBlylYZ59As89/8IreBg+IeHA3rpkCNXHmRJH47HF+7go7Exwt5/QqZ8BWAV8xIX77/5UmNGFCiXFxkQjaDXT/Dg+RuER2nAMENW5MqbFZ98vPHgzUcA2jC1tEFOK108u3gH4VnzIG82U2iFv8WtKw8Q/KU2w6z5UDS7CUIDX+K5Xwi0QkJU7dE2SA+b3HmRyUj773GJDMKj2w/wJjRc9Tc9U0vkz2mOt7fOYWzfJriTZzCGD+2J+oWzfLnnI17euofAjJmh9fQpAgEYZs0BsyAfPGUD0pmjcJ4cMNL5gHsX7qk+Z9HUtEChMlYIf+YD34/RiAoIRFR6LVxbNgWDD1nj1JUZyOBzA49C06nuT6enifcv7uHO8881aGhaoHAZGxjh0+fnG6RD5JsA6GW1QoYIf/j4h6j4mGTNgVzWZtBJig6LZbXxi8qz6KVZGRd/n4ZNh7vhwbCmaDj9FCYcD0Rvm1fwDf3cv0hjC+TOlQn+Dx/CN/jTZ74mWZAvZzboa+37W1R2LYzX570RapELVobB2DOpJTrNicKEvathVy4vrLUDcP7W0y8C1gjZC+ZB1vT6+PThJZ4+fYfIiAgEheshW24TvHv4DCTBYpjeGlnN3mGNYwc4b8iNpedHo6aNNXT8X+FZjDlKFMoC3chgPLn7d/t0M1ggX67sMNINwsNrTxClr4+QwEDQOizyloBNxr9zpqlNVEa+uYOxDp1w3F8f14+fRsNF17GyRyHoaADvn1zAXd/or4sApMuOormN8frhLbxRJo6WHjJny40cFpp4esEboRkyIDwgBBly5YWNrj8u3PVFjGoVYYJ8ZfLBVFMDYe9f4cHjpwgO+wJdNz1y5bVAyJ2H8I2K/vJHE+QrnR1P9szFAPvlyD94FLrUqY6iOTTx9H4gzPPkRGZjPXx89xR3H7xC2JeVinme4siVCfC99wBv05lC+/lzBMTEwCBzThSxyQzNFF6E/biovAxn8xpYkaMYrN6Go9PCZRhYrzCCfU5iYIcu8A4NwTXvOjj0cSmK+b/AE99o5C5sA4OoT3j24CZ8g74A0tSFWTZrGAa9QaCmHiLfBkArkznSRYbANzAIn+kbwDJvdui+OYmhzTrhUZEBGOpmi2pFMuL11SfQsMoNm6zpoRXmh5vXniDk8wDDyLowClsZIMj3GV6FREPn3Tv4R0VB29gMuXPZIIO+ltqxTUSl2qhS1YUiKlPVcKSVxiii8hGaT7ZFHmRA8Vr1UUJrC2qWcYOZwzy45PKG/ZwLmLD3KIrcGgenEVsRbFgA1Qr5w3Pna3SesQLjOkXDQa8ajuTOjYB7unA5thCFlrvA+Z41mpXVw5F1j1Ft4zrMr6CNZe69sOS2BX4vbA49g2xo1qkSPPu0xF8Z26JW5jCkL1UfPdobYahRLTxTZSor4vZcd9gO3osSvRoh6sJB3NBvDK8dk6F1cjwch21GULgVfiv8GpvOaGPkorUY2Lwg9FRDFIq7e5agV49F0GvSDNZvT+PUbTOMXT0VFieXYOSchXhtXhv1eg/F3K6VvmQJ7mBSuabwMM+PPD6BeBNxF36Zy6L0ixf4mC8GZ70zYf7GlWiX/Qhsq66BWcuSCDm3GpvO5cWmR5sRNac/xuz2RuCtOzCpaY9WhX0x/7g1/jzYCnPa9sTlgn2wfkIP2Bg/xeRW3bEjOjeqZAvE5mXv4HRqE5xLf8CUis2xKDIdPl7wQbW+vWD0YCOuZ2iOWlkikP63muhm1xBZ9X+ODSYuKgciYllrFOm9HW777qLUiREYvfUaAm7fQboqzhgz0AaLHeYjpkET5PxwDn9dMYLbSg/YlrkaS1TGYIBmJdzovxYL7QywarQj5uyPRtOhg9CvU0Ok3zkRFeY/Q582+fDo+E3otxuCrS6NcO/4FPTrOB8PPnzA06DqmO5ZHqeXXIJVxdx4eXAarup1w4SxtXFojDOWnjZHR/cOaNWoNG4PHYjhYV3hc7I3wo+sRN/ucxFZpwlyh57HXxf1MHT5H+hc6RbamneEt01pFMvoj/WHLqHR0ANYObE2Mn4RM6lNVL667oVe3Rej2bieON+vE04WHodtG1yQ78Nl9GldEecydcZvkdew52oEmg2ZBft8V+AycRWsC5fF673LcT2LLWbMHo3WFfzhbFgZu3PmxgfvCHTfOAs1j05B17OmaF3NBGe3PUCheUuxvG5WHFgyGK7bX6Jm6Ww4sWEjwss5YeGYYphXbjK0+9aAkc957Nz/CgNPHUb2jY4YOe8ULGo3RIXqndGhzFXYt9yF7huYqdTAH517YtE1DZT7PSsuLlgHkz6eWDGpHHa264BZkRmR7VEoPurdx2P99jhybBKKGOr8HCP/wVqSKip3lnZCDT0vPPttLLxGtMCrw66wnXIblTO/gceOvNj7cQ4iF7qi18IwrDszH1mveqL7qAUwK1Ae7w6vxsUMzTFtdg8EzxuF+Y9CEXzlIQrZdkd+/+fwy2sJq6gP+HPnXhQftgid9E/AdcQSvLGsibrt7DCkX3q4ZO0BPXdPzHcujEvjndF3znUUb18JAYf34l72Xti+0RHv1rli+IpziPQ3gU2+5zh4PxtmrvJAlyo2UFdWiqj8QQNL4dtEVKbwAKTNxyuicgfeqjpog96zl2GaUwnccG2Len/cRma9CGS3W4Hdk2vh3vZx6NTnCFosXQS3CloY2aEJ9lv0wvY55TDGvC6utRiO4V3qomzGs6ha3R0NPC5gbjt9LGpbF273O+PKkYZY2Kcj1t+vj703JiF/gD8iX/yJGi36IsR6PHYf6IiMHyORzvgGeut+EZX9dWBbpxte11mMfVPrIXDXJDSyX4hyCy/CxWAZOvY4gCazZ8G5kgYcmjdGeIOFWDiyFcwYj97fxYT+XbE6tBkOrHaB4cNd6NuxH961Xo6DgytiQrPsuPTbPHiM6QCLryLts6gcE14HW1f2QdCusXCc+AxOWz3Q0uwOhvUYCMM+27HaNiNu3tVAntI2CNs9EOYtF2PYjisoedwd9psiMXF+TxQwN8eTLVPhvM8fTTP44WJEPczwGolqVhkQcdoNhToewaBlXuhTPgBDS5XCqVJLscWzHDwrNsfIkGpYNqk1imk8RI9BI/HW1B37jnWF+cdwGBpngF6yZyorYlOmAiheNiciHp3BOZ22OHtiHF7McIT9mhCMXdAbBXT1cGzjWKz1q41969yQ4dlBONr1xPOGC3BkpCaamX/Z/u6qiMpN2D23Je7PqI6KQ6OwyecEWmocQ5vG3eBdex0uTiiMk3Od0X1uJLwerkT6E1Nh19YLNUY4oHqekijymwE+hhojV97MCFjZEIUmB2LW2nUwXNkWref/htNRS1Be8wFm/t4Kgykq9zXFliHdsPhlDexdNxKmr45ggG13PKkzG8fG6aN5+h6I6TcJs+3LYF3folj9bgDWHpiG0uk/q8rUJiovLu+GPtszYMmiMYhYXA2NN5li9sbtsI1YCYPKzhiyNxA9NT3RasB5jDu3FEaLWqPXX7mxduEYfFxQBT3Pd8GO/Q7IpXEJ/Q0rY3+1ARjv0AilTa6jYc0BKDb9Ilb3zIR1/Vqj98FquHqlJ3a52GJ/liHYP6YuVveug2PZhmHusDJ4+Ocb5K1TBHq3vNDMrh+ie57C6urXYN94PErO84Rrw6J4fmEuOrTYiW4UlYbrkKf+KnSY5YXhbXLgjHNNtN1riJkb5yBotD0G3iuE9WtdYXZrCXq7HEW/v/5C/3yGSdgOTrrHTqqoPFBnHAYUOoepSzSx5JoHfIeXxMqYzmiS7hiGzsvyf6JSb30XtNuTCSsXT4XmirqwO9QMu463wvG2nTHgug0WzLRDUesc0AuPgXmxPDALeY7pTo2xycgBR2bWxNQqFeBdfjYWz22PrJpH0S5DZ+hSVDZ9gxrleiBzPy94ulbBq9UuqDFgIzpuOIOmz+ag1+S7sPeYhZYWD+DQaSAs+6/EzB7VYKimqhRRmXRbS4kaRFSmBPU0/0xFVGpgVcha1IAGtHV1oaOthY/+G9DEvD2O2DTBtv1L0Sy/Ca5SVDrfxIQDS9AwuwE8+pXB1HctcWDJ75ho2QjPB2/C5kmNELy+G7J1WAkdPX3oaAGR4WHQMXLAiYCZ0NkwEE0dFuDlR2OUbzgFqzZ0x+NxZVBjzA3oG+RB98kLMdFBF07an0XlkkY+aGY7HFmGX8Mh+1yIub0ZZZr0hanzSczIth4dHa5izH4PNMphgAnNbXCl2HwsGd1eJRJDH5+GU482OF9iHq5Nbw74XcdgezscyjkGlyfUSVBUjkvnhAeHO+PRooGwHeoPjw9bUcXnDAZ0bw3/xluwyT4dBlYsh+V3YoDoCHyK0sKAzWdR6cwE2H89Q/nlTOW0LfCP1kTJejOwYZ8jcgO4PbMyCrucgY6uHrQ1gYhP4fit9kxs3F8XXhWbY5SePR4edYBVTBROTK6M6m4XoWeYE53GzMeUwXV+2jnTb2cqK2LplzOVDSYcwibn6jDUf49dIx3QZ4c5TlybDavnlzCkV0sczzsZ1+e0h8a7OxjpYIvtZoNxdWZ6tURljefLUd9uEC4+DYe+tgaiI8MRFlEPuyN3IjdFZec/MXC7BzqUsMaLqxvQv213HHwOICocOtlKYYbnapis6xivqLy7sRoW9G6GIzkn4No8O2gG3MNYJ1tszuCIa/PM0DyjI7JP88SUHhVwwl4bDpd7w3PvfFTIlDpF5eyWuhi8E9DR0YFGVBg+6WdHn6lrML2HFpzTVcUKaEMLkQir7oYPO93w+txs2NZwxXUdbSAqDMXcj+Gka2VofRGVp+1W4eCSNojY5YLcrWcjQkMXulpEG4awyC44GTkNH6YNQt9RG+CnrYkokxxwmO2FKa1MsbRRUTj/+REx0VEICwtH6UlXsa3h/W+Kyho3eqPkFF9M8DyMflXMgQMOMOlzAhM8PaAxzQkD/Zrj/ukhiD4yE+17LkPz7RcxpPgvLiobzMdyO3849x6C/H0m4MZMD1SYsQK1b01A++kW/5+pfLIMHcoOwiXtz+OVd+ghXBqdE8vbdsIAnzq4ddYVNprBODimMzrPOoig8BhERoQhp91snF5QH9OqVoxXVLoXPI4K7aeg7rw78OxoA40rHrCs5YzfZ51B92AP9J4fAs+T81Ek7AmGt6+LkJYrMb9vLcQ+RZRQKBRR+WsKBRGVv+a4pfJWK6IyCKPPTULZr2cO0+PogMro4PUe6aICYFx/Ls552uIRRWW/v9B56Rz0LqmF8b2a4kw2Z6ybXAwjTGt/FZUmF6YhQ5UxsFt4HjO7FYJe+Fvcfa2DvBYaeBscgQwmGXGwvzE6nyyHOQsWoEbRHLAwiMCUNhZYqjUAB5bUwiTLhp+3v3tGoUnD3ghvsR77R1WC774paGy/BOUXnMZgvRUJikq8vYURfTvBS6crTiztB427O9G3x0AENF+EA4MqJ0lUjokYiGordTHPczPqvZgKi9bz4bTpG6JynzVWDX6Nzu5X0WX8KoxtWwYxRxyQo88FuC/djN41s0Hrky+evU+H7BbPVdvfiqi0CPGDb4QxshprYnqbjFgYYY9dHuNR9Cftf6uz/Z3nqxW/xc5YojJP4H2Md+qE1WFt8OdKZ+g+3g/H7v3wou4sHB6hpZaobBm+H/Wb98KrmutwcnoVpIsKho9fBHJYmuLu8SmxRKUV1jr8BteHv2O7x1hk3d8VBae8xHTP9ci8xQ5NZ2TGttdrUTfDIyxsYPs5U7m7IdY6d8KKkBY4vsoF+j6HMKB7H/j8Pg1Hxxr8UqIy7NI4FK88BZ9y5kdm489nht89fYQs9YZjSetwlGq+AU2bZ8CVt0Ww7I/pqGRjgBNTWmHI1jfw87uL3/oex5rBBWCs0ssXVZlKRVSaXfeARfn+qDH5PFY4loBBZADuvNRAPuO3mDywPy4Fx2DnzsNw9PTB+HZWCNjpgrxtZqH9yoeYXfgCmnd0QJDtAexo7IN+zQbD2n0lRjQshOD7q/7OVEYthkW7HXBYsAMu9TPj1Jj6aOdliBmbpiNoVN80KioX4OjEPBjVozuWHvBGptzV4bF/K7SWtUe7eESlxqqusPd8iQ9BD5G38y6scy2BDBpP4dG641dRaXpjGzp07QP/Frvxl70pZjq1hadud5ya3xRz6xTHyXzjMHuqHQpnOo/2Jl0+ZyrrPEXJav1QaMh+eDqVxNONw1Gj/2Z02nAcTZ7OQ695IipTeaBOluaJqEwWrP/1SuNufwMZ6zpjY29tjOiwCKXm7EXdDyvRe8wVOPx1AA2ezEWnLnPha1IG7asGYsn+EAycvhJuHSLQ3yCWqAy8gumdu2Lew1yw7VwBpu+vYnVwF1wclB4zl25AsI4lQs4uxn6tlljQLQeWH3uD37Lo4vy+tQitOATL3Www3KTeZ1HpXgQH3R1hO/8u7Aa2ROCxg3hj2RHLt/bHpz3jExaV4e9wesUEtB++A6V69oTlo30486wwJm0Yj5pZdZMkKucVWY+6drvxW7tW0PQ/g5ubzqPmtzKV+6zx10UXHOxZH4tulcLMDTNQy+gKnFoPxjnjEmhSIz90/M/gttVwrHJM/w9RaXp1Nfqtvo+CWYxwad8qBJRyxnL3LrBOH+tlpCSYcZJEZeR7nF8zBbZDvFCoW0/YPN2Pv+7nwdj1E9Eg17l4zlTGs/1t+gzbxjmj1dQX6De5BbJ9fIrtvsVxcn533Pvzn6LyyLx26L/wJeq1rITHN/bjmbc++nruQe2nw2DTfimKtR+LYT0Kw2fcGAyjqDzWBa/XT4XdkM3I37kncr84gD/v2GD02kloXOAympk6/CKZymAcdiwJuyN5scBrE1oWNFKN+NHpTdB1vRGm9M+J4X2m4kl4FABL1O3RHra9hsHyeDe0HLob71UvZ5TBgMX90LlRGxS3uvVPURnkjSV9umDUaXN06lcD5h+84fGmBW5NLIQ5g9rDfeUF8DUs8+z10X+qE1pne4yutRwR03wgyps9wfmN+6Hh/BcOd9TE6F714OlfAfVrNsHAJu/QWzlTWeA1hrXtjW3BudGymgm2zD6CyiNXYLJbTmxu2iHtisoVLfFsUR/UHLwGxew2YtOSWrg0sh3aTvv/TGXkGjs0ctqGgGiOVyk4LOiDTo0q4vKgPl9FZRbfMxhm2x27dOugY/konNy2EyElh2DvAnucGlUMHbfqo0rD7lg4MQdcrHp/FpU9s2LLgF5w3hOKNl2q4uHOw4gs5Yxlq1rimYcres4VUZkEF/rL3iqi8pcdutTc8DC88r6Bm499VW+/qoppdhQx9of3ywgUKl8HWaMe48yVuzDIWxG6l6ejk/NpdB7RCwUsjKBrbIYixUsia/pgXNt7Dp9ylUTJApnB44yRr67hwGXuU34uOjnLoU5uXXjfvIrHr4MADS2Y5SqBktbROHfxJt6HhAM6xshTpDjyWkbh5t5z+MjPC1hAJ+AB9py++6UmQ+QqVUYlsoL8HuDqrQ/IW6YoLAw18eDiMbxPXxhF81n+feYw+BVOXbyJQNYPHVjkLqL6XBdReHDxCN6n//z732cUg/Hg1CU80LZB9XLWCPXxxtU74ShatxQyfgyA9/XLCM9cCiWyh+HS/ovwY6uyZEF2vzfQLlkRpgEPcPONPipWKQRDhOP1nZuff69cEOHPb+LS9Q/IVbEEcpoY4M3Dizh/V1UDX/+GeaEKKGujg4enL+KeZg7UKG8D/RBfnL54AwF8/VYnHXIVLob8Vib4SUcqEb+oDMSNvafxPlNBlCiXE58lDEs4fO/dws3XuihftfDnv4f44sylm3gXRNmhg8w5C6Fofmvoafrh0iFvGBYqjvzWgPfe0wjKURJlCmdByKOzOH0nBiV/r4AsPMsa+Ah7T99BzJc3U2FRAA1K50Yov4Xg2jvkKl0Ulun1EcLfz93Be8bc7Nlh9fYDMhUri2waz7H39G3EaBvCpmBe6L14hHvR1vi9Yk7oh/jh7OUbePuB7dOGuU0hFC2QDQZab3Dx4C0YFCyGAtlM8e7mXtx6nx3FyhSB6ZcXwFPPmcpPeHL2GB5HWqN42aJf2xf0yhsXb7+C/+kl6DfmA4Zsc0DBkPtYOm4mTtQaD9enc3BQuz46d66ADK/3YKD7Cdh57MTIhpngvf80AqyKoWxRzgUA/rew97zP32OQrRQqGHvD1XYEwuvaoXnpHHh+aimmHDaAx8rxsHp2Dz6RUYhJnx7mERGIylEGFbJr4dHtq7jzLAAxJgVQobAm7lzyQ7aSRZHN1BCBTy7htPfrr2+Yl/i9EiwNQuFz8Qq8w7KgeqXciPF/hCvXnyFL6crInV7NQ33J5GJ//Ezle9w+dBZvMhdBuWJWgN9d/HnlESyKVEMxKx343b2CK4/0UKZeIcT43MV1n2iUqGiGdZ0aY0toLXTtWRWmfvvh7LofzRd6wT5HKG5/MkfVinlgqPERTy9fhferd4jS1YWxkRH001miROEc+PT8Kv669QoxRlaoVDELHh+9CY28xVEkVyZo+9/G3vOPv4xvOuSrWAF5TTXx1ucubgq2BZwAACAASURBVDyJRLEKRWAcHYq7V84jMmsxFMlhBi01376X7e9kMsBkrlZEZTIDluoTIxDxjzOVjfOaJ3aDfP4LEEiuLz//BbqeaBNTj6hMqKkxOD+7PqoMPgotAz1oxUQh7FMY2m8MRFFPU7ju14GurjY0oiOQLlsJzNt6Eq0KqSfWAh+fhXP7Klh3/fN3iUZHhiFPAyd4LpyCYhY/a1mT6DCk2AU/Lip/pMnRWNhaDwN2an8dL/3M+TFrxyXY/qadoi8sJdYbEZWJEUqdn4uoTJ3j8h9qVSTuHV8K99XvMHaiE/JZ/J2/+g9BSHNdFVH57SH9NUTll/afnYqyjpsRY1YWI6eOQOMiWaER9AKrZrlh/q5bQBEn7Fpuiyzf+yXYL85igOsEnPJ+jXxNJ2CBWx2YqJnB+tUny78rKpn198PGeW6YsfUqYgraY8eKrrBM6S/rVGMQRVSqASkVXiKiMhUOijRJCPzqBERUphFR+asbYips/78uKlMhA3WaJKJSHUqp7xoRlalvTKRFQuCXJyCiUkTlL2/EydQBEZXqgRVRqR6n1HaViMrUNiLSHiGQBgiIqBRRmQbMOFm6IKJSPawiKtXjlNquElGZ2kZE2iME0gABEZUiKtOAGSdLF0RUqodVRKV6nFLbVSIqU9uISHuEQBogIKJSRGUaMONk6YKISvWwiqhUj1Nqu0pEZWobEWmPEEgDBERUiqhMA2acLF0QUakeVhGV6nFKbVeJqExtIyLtEQJpgICIShGVacCMk6ULIirVwyqiUj1Oqe2qREVleHg4vL29U1u7pT1CQAikYgILFizA0qVLcfnyZWh873cYpuJ+/YymlSxZEj169EDfvn1/RnVSxy9G4M6dO7C1tcX06dNRo0aNX6z1/15zhw8fjv379+PixYvgd7tKSR4CxYoV+6k+OlFR6ePjAxsbm+TpjdQqBISAEBACQkAICAEhkCIEwsLCoKv75d+Q/QktSFRUhoaGYu/evWDGUooQEAJCQB0Cmzdvxvbt27F27Vp1Lv9PXWNnZ4dmzZqhVatW/6l+S2c/E2CihsdDnJycULp0acHyDQLz58/HmTNnsHr1amhqpv1/vjOlDKFdu3Y/lW+iopIdjYiIwKdPn1Kqz/JcISAEfjEC48aNw7Rp0/D+/fufurXyi2GIt7kmJiYYPHgw3NzchE1aGNDv7MP169dRtWpVlVhq3Ljxd97937m8W7du8PLywrt376Ctrf3f6fi/3FNjY+Of+kQRlT8Vp1QmBIQACYio/LYdiKj8b88REZXqjb+ISvU4JfUqEZVJJSj3CwEhkOwERFSKqEx2I/tFHyCiUr2BE1GpHqekXiWiMqkE5X4hIASSnUBKicqYmKuY1WcNzDv0QdtqwJpOY/GsVn8M6lQW6ZK71+8uYOyAudBsOwpuDfNA4xvPUydTGfzwL8xcvBr30jXHHPd6yJSMb9D73d+HBfOu43fH7qiax+yb7U5ufOrU73t4EnYb9US3Cko7b2DT6CeoPKoRLH8GI9/DcBuxGzat+6BjnQLQV6dR33lNUkTlzbX2mHogBsVrd0E3u/Iw0QCCfK9gxbo/UaF5F5SxMUm8NZFBOL9jBVZsv4DgnK0wY3QTZNb8lrUmXl1yXSGiMrnI/rNeEZX/Dmd5ihAQAkkgkLCoDMChGaPgNm8n/JRnWFbH3KWT0Sj/LfTM0wNHYmK+Pt04Z0m4z5wBoy1O6LfmOv7+BNDQ0ITr1ofoWeJzUIw+6oLf3LwxaeV2NMp/FQNMauNWj5XYNL0ZMiahP2rdGh2OXf0sMOnlBKzZbo9c3xA5iYnK2zvHoFu/JbgbHIJIDQPkLV0FkxZPwzP3fphw8haiYzWmhNshbO2RF0nRU4/PzUe3LofRzXMu7MpkT8Wi8jrc89THgTzDsHZvf+TR1IDP6jaoMc0PI5ZuQdeymZLe9sdLUanyLBQfuQRTe1eGUTJorR8VlX5Hp6J6twdw21wL+2btRQfXqWhQJDMOTWyDFQHNMXViW1jrJP5CS/Arb4ztWR3eRWdi4aCWsDYzQOJ3qTUDfupFIip/Ks5vViai8t/hLE8RAkIgCQQSFpVvsXe8CwZMDcX89+tR9MZWDOjUCxF227B5QAjaZxoIE9fZmDK0HjL4rEezmoPhW6kPPGe4In8mDfw5sz0a78qA/UunoGIe01it/AivzpaYHTwJa7z6wEbjApxMauNyh2mY1b8SDAEYZskDm4y6QNRHvH76Au8+fv5WC510GZEta2boxwTioU8g0mexhrmxLoJf3cbrT6awyp4Roc+fI0jXAFGBH6BjaoZ00UHwDQxFDLSQLqMFsmY2gc5fQ1HI5SrGr9iJFoX14iWYmKi8f3k7boWURLMq+ljetAAG3cmHoXPGw3jRaLgdK4GDgXNRJvg2Zvd3xJgd5zFoxyuMqGb0T2EZHoynL14h+GMEoK0Hs6zWyGwQDp/7zxHyRbDrmVoiVxYTPDn/T1EZ/sEXz168RfgX9W5qnRdZ08fg3dMX+GCUHlp+fgiKicHn+w3h9/gxPhlkhqWFKXQ0g/H87mtoZbaEhanhTxYrVzDUsh4O53PBuqODkF9TA4/+aIwqc97CfckWtM7+Cb5BH78sOvRhns0SZsZRePXgJaL09PEpOBgRMTEwscoLyww6+BTwDE9eByFaWaXomSJXTmP4338FTXMrZMmoiTd3n+CTiSli3r1DaEwMDDLnQk4zfUSEvMOLV74IVSBpGyGrdVaYGib+1Sw/KipveXZH3eW5sWt1I3i6j8BvPaeg7qN5qL8qANMXr0Wt3Jr/FNWRwXj68DlCoqJVTPRMssAmSzo8vXAAYwYPQHit0XDp1gTFs2X4+76IADx68BphMTGqewwy50ROMz2EBvjB/2M0tIOC8D4qCjF6xrC2zIr0BtoIC3iBR68/IEZlVxlgU9AKhhoRCHzxEoF6RtB+80ZlL7qq55tCS82sqIjKJDjg77hVROV3wJJLhYAQSBkC3yMqK/icw3D7Nrhbfgn2u+EfotI0JgZnlvRAyxURWLlqBurkz/RtURlyHB2tmsFvoBe2jqoFI1BU1sIGq7womckI95/ehWGVhTjk2QCfTm6As/08BFeogWwhV3H5QUYMWzgHrU22oXzD1Wg6azWGN8iDQwNMMOR6d3h42eN8p07wCDPCx3P3UbpzN2T23YOzqIwqFtEwLVIDnTs1gXXIetQuNxMVpq6Ae8siiO+d1cRE5d8j9gbLGuTHuNfFMXnFHLx1t/9bVGpqQOOOJwpVdELWAVuwe2QNGHxNV4bh2eEVsHNcCL0KtWANf+St2xv1oo6ge981yNG2LnTvn8Fd7RpYvm4yTB4sQvevmUpNrO7ngCWXwlC0vDmurdqJrA6rsNC1KLZ16ILF+lbI7u2HAO0neJ2pI/bvssfuDlWx1bgrPKY7o8DH1ahebSF+n7Yaw1oUROIS63vs87Oo3GJaHZ0df4eFhgb8Ty/B/At6GDV/GoLnzsf57Flg8ekdzh49h4ruKzHVNhT2ubrBO3dJ5Nbxw77zN1Gt31Ysc8mHLeO6YsZ1K9TIFoyTf95EtkYuWDIlO4bnHID0qkylEcZlq49DZaohp58vbvneh2bpKTi0qinurxmNEZvuoGQhS1zaswdhxbtjxmQnVMmV+PGBHxWVHy4txu9NdqCyY0UEPAtE84Y54Ol6APX/8ESPUpniZKuDcHvrQnTvuxLmTWvD0Oc87kSUxQLPofBdMQpTPfcgMlcNVOrkgpntS+CzzvPH2dkj0H/WBeRrVBrvTx3Ds3x9sfmPbvDbOAZjNl4FPpohl/Ur7L2qDZc5C9Cvbnps7NMDs31MUSF3JI56BcJu9woMKRON1d16YV5wOljcDUSooQ+eGrbA1q2jUcxEvUMFIiq/Z278+LUiKn+cndwpBITAv0RAPVF5EjZNy8E0+A1uPA5Br5kr4FD1/j9FJWJwZf1gdBjng7Eb5qJ10SzfFpUvtqN24S7QG3cIuxzKQEMlKmvjr7pDsMC9GW6vssdAj0zYdH0WHs3oiz+eV8CmVSOQ8eUhuHRzxOsGM7CrzRNUSEBUur0shlnuTVFM5zWGT5iEV+mGYNuuDsgU+hH66TPCQOsQ2mVzgfV4D4zrXBYG8fBWV1Q+OjAMLdstglG32dg8phq22XaCq5KppKh8uQv1i3ZCSMdl2Dar+d/nLkOe449RfbHoYSmsXzkSWT89hq/PbUx1HYHLuYdgx6xWCD+xGJ2d5iPH2CMYm2M7unc98nn7W38jSjRfj5aTVmJQ82w45dwAvU6aYYrneLwd6QjXJwWwdMkgmN7+AwNHn4fj8UMoeWUk+k14BpdlM5H7YGO08SqAORuWoq5N/JnaHzfBz6JycbCSjfxck5F1YYxeuBqVtD8hU/lCMAt8iKmD2uGAxWAcmGCOXtl6IdDWDdP6lsN2t9pY+8wOyxfVx/QBjtDtfhgLq73EGKeJsLQfB6dar9DFyuEfonJXqT5YOL4tnnsNwoB52lh+YR585vTA7gx9sNW9LrycmuKY5SBMd6uv1tnXHxWV+OSLM0cvwC8CMIj+gD0b1uFTw/bIdfggblkVh0Pvrn+fqfS/hEHd+uKYWW9sm2sHXFyFXg7TkXHQDiyuFYnR3VsirIUHZnSvBgNl5fNkO6pXs4dpt+VYMrQqXq12RSO3Xei45hDqPVkIxxl3YPfHXPSwfAZX+/64X2o4vFq/QY22K9F8hheG1Y3CjMZ1sTGdK3Z41cPRHr0x7HIWzFw0DNmfrYfziMPotG0X+hU2Veu4hojKH58p33OniMrvoSXXCgEhkCIE1BOVXngNwKJQJUxctAFNihpDBwfQLtb2t+lPEJXKmcqH8xqi9shwLD40HVcmd8DxnO44O60t8O4+Jrl0w46MDjjT5w0qNFzzzUyl2ydb3DrUF9bRETgxuymajL0E40w50dJhAkYNrAVT/BxRGXhtC7r2HYwj2r1xbu8gFDR6hoVN4xeV7+q4oJLBXmw//hJACUzzGoPLU9rjkOUwnJreATpaGnh/ZQPa9hqCiI4HcMihIDQeHUDzLk740Hob/ih7GD2+iMoq1/qj8pwAjP5jO7qXz4TogwOQY/AljPaYiYgpg+D6vhWuH3ZA5NHZ6OK4Di02n0RHg0sY3q0njHtNRd71XeFpPQdb57eDhdbPPpD4WVQeyNUPi7fZI4+GBnzW2KHJ0g9wX7Iauf4cCccVZxEWGYWPIUGwajsDJ2ZYo3fOAcgw0gNTelfCuWFWcDjRFB7bB+Fq/+6YcNoHejrRCLWujD8WzECTYt7oGEdUHm88F7sWtsaLZR1Qf9grzL64DZl2jMDgyTvwXl8XEfomsB2zGhNbF4Y6Xf5hUanM5PB32D3HBV4f6qB5zDhMedQJrXJdw/GPdbB2gh2M9bXw4eYOdO0zEG+bbsLRQaWg8exPdOzpiOe1l2NHez2M7t7q/0Tlm0MTULbzTNSccQke7XIAV5cjbxNX1Jh6BJ2CVsBxSSg8Ds9AsRhfzBzYDF6G9lhe7AhquB6BnlF6GOgAnz4EwjT3EGw6bYsLPfpg2KPqOHvUBZpnlqN3/0WovuQQXMpm/JIZTdg1iaj8d1y3iMp/h7M8RQgIgSQQUE9Ufj5TWSfWWybRkfvQLpMDNHoNg3O3SkgfE41Vg6vicCYnrJ4xFAXNdb6dqfTbg0b5bBHjvg87nCtA+0umMq6oXHlqEe7P7YUNka1wcGFfaD/9E0P798ejihOwv6svqpWfjcKuM+HWLC8OjiiJeU//3v5WRGXWT+8REKkPM2N9LOiYGfODO2H9vHEonvkoWuYdgTwTlmKMXal43x5OLFMZcPcYhg3ojfUvK2Hj2sGw0dWHaeZP8OrcGyOO5YTHWVcU1QC8Nziix5y7cNx8HqNrZ/n7XNz7J5jt2gOeofWwY/YgZAh/gdCX1+DoNATPK8/DvpFV8eHMMnR0mAnzoXsxOc/er6LS7uNi5Op9BI6zN6B/DTOcn9IEtlsNMXHleLwfPQCu71v+n6h0zO6HRSN7YdmdGOifu44qay9jUoNY7UmCHf3z1m+fqXS0t8MJzykIbbcbBzvpYYZLV3gZ9fimqFw0uxnmDZ2FPBUyYf2uRxizdB9sy2eANo4mKipnHV0J38UuuBgUg/37j6GXx22MbJYZ+mpq6KSKyrt/Tsagyc8wcNb/2DvvgBz394+/2qVhNIRIGdmhsvfeZM+kQqgQQhkRQoqWkhHh2Htz7C1k7z0aGpra9fuVcTiH832inp6j+/mvuu7P9bne13XfvZ7Pusfw0rELaxoG4ql3lmU3yuEz04LiSjLw9jyWVjbcre3CobmdSL7+B1Z2rihabyGwk/T3RyrvbqBm50kYTtlPwKjavNk1iw4TttF/9WF6vA3AzjsMp42LaasWyvyJVrw0nkdg0xvUttqJ9bJdTOqqh1xGLKFx8pTViGbdiFFMFaAy36q/oBoSoLKglBXaFRQQFMg3BX4NKgdy+MvubynKNhzKzCnjMO1Qg2LZWf+yUeces6s24XQLHzatHEqZTxt1/gGVN7ahfWoJo533U2f0OCq9OsDRG9pMXzuX7lWjcGzahQ0ZFTGSlSNJ5TnvMnp+WVP5GSpL3dmO047n1ChXipAD/jzTt8R/liUVn7tTa+gBRnpvYnyb8t/V839B5UWvQXSaefDTxgdAUYdhM6dQ/thqFp669dfu7/LGWHQYzQSPAVT8GmjS4wne7M7o2QGo95hN1ai9qLa2pv6rrYz2vMVgh+FkXDrIw6y2eO+ehvK15X+tqdR7hcPgiZyUrkX/lmpscjtEg8l+zJ2uz84+5jjGfgcqa2Zxa4s7o6Z4cl+uBweurqJ5SREJK08V92OonDLTnscr53BWqy/mRkmc2LKTxIZOHPzBSKXnsp5smDqBXdffko0ytVv2wXLKOMyahTKivN03099/H6lcciKQmBUjcNlwnZRs0NDpjM3isQxq0YQyanL/M6JfgcqEB4eZPsMN/ZH+jO1QmpA5vbG8X4duCmHE1hjI0kndUc7ZAZ4cysGls7D0CKbnRHNkQw5xO7ExS7Y5Ui3hMbNGfGf6O/4+KyeMw+VMNoMsWvF49yHiq47GP6gPYavnYOuyjfjiTehpFMrmC9JMdvfFtlE8LuZTOJ5dh76m9VCLucyhbHO2OlRgg+VoASr/ZzUUvoEAlf+Wg6hzzJ4UhFLjoYyybvEvR4jEciFwNeuf6zJ3bk8SLu5k5c5ohkwbTi115U8e3rBzmjsnS/dk3phqnAtcxe6waiyY2xfNwq+Dwu1B3Es2BAZwLKQMDutsqPlVb57vm8/GF02wtm2NRs7vs9J5cDIIv6AweriMpW2FTwe7JDwgYIE/V2Mb4Og3mIoFFVFmOiF7PVm2O5mhc8fSXlf9L0/Rl5hj70dEueqYjbKlUUVlyM7g0ekdXIzUxbRXI9Tksol8fJrVh58xYNAg9ErJcmOvF8t2fWCw8xg66OVG+VOfmEtrCEjsxrR2Wp+uf0zQqEs0DxiGHpDzd/sV56jawYbxg+qTU5lvj7pyRsOaQfVzdj3HcHjBVN53WvzpZ3hzyIUZ+z7Qacgo+jTV43//i/uprudeFHNlLfZ+p6ncbhwThxjn9u/z59+hMo2weze58TCD+qaNKf3VddnZ4VzafTF3WvzzR7N2S5pV/nwgUDaRDy9xLlSO5iZ10FD5eitIMuecmjH2Qj2Wb1pJM+33hOw+TbxeAxobliPxyVlO386iQaeWlMsM5+zlEKLic14/K0vpSrWpV7MiOYM8r28e5+qzeECb2rXTePamBMZNKhFz5TK3M3Xp1LIySonhnLscQmTO9bLK6Nc2plbFUtxdXI+Be+rh9Ycf7XR/bvd39ONLnLkT9pUCCugYVEE55jUPI+P++n3pGvRsXBXp750nlBTB+SshvItNBgVVqtZtSE2ld+w5fZusXGBXRK9+Qwx1S/Eh+gnBwRHoNaiHbqlixDy5xOnbn/2XxKRjS3SKfeDp+SvcTtehQ8sqZL97xJWQV+g0aUMVNWnSHh2gn8VEXjZdwfmFrQvkKB54z619Z4lQNaBRSwNUpSDp2TlOPE6lhlE9pB7f4lb4e7Ll5SmurIxCcV0aGRbj6oEbyNUwok4lDWJu7SMkUgv1rJu4TNpNrWnDMZJN4fLuQHZJ9eDa6oHcO3YLuRrG1Kkky719Z4gsW49mRuVJfnaJM7dTqFRDnnXjZxNt1I3O9Svw7tpmfM8psczPnfbVv3q+/ODW+hWoTHp+gbNP5TFqboSmghS8u83uC0/IzlbDoKER1cqW+GvHfexzDpy9TVpGZs7ebyrUMaGuvibZKXHcCb5AVjljDPU1v52yf3eH3Rce8/E7nQo1WraiaqlUzq+cjY3/G8bZ90G9mByK6uUxqV8XTRVZ4p8Hc+LGmy9HfalWa07basV4efUqtxK1aNvKAKno51y9/hQt45YYlJIX6egniZz+jjqDs9N2tLqPwrxrLYoVxHenr+sm6ixznLai3nUUFt1z/P3NYe7ft6He1QqL7rX/+XcRHu8CVH5XpAh2O01nzh9HeRmdgJSiCrUGObHZZeQPvjmGscXOhknXDTl/bipR2+Zj7fKKhQeW0bb858Nj7zHfqDerK03j4pqmbLIdy4LHzbhybnbBAZAIBVDYJqmJt5ndszuBt+JJTpWhTKVu+B0JpI3WE3y6WuF2/SFV285j9QZLKgAHHSphvTGB+IRMlEup0X7BaZbUfcAMeyt2Xo4nNUuRik07smCJN11rqOVzeKGs6N2ceRfjiEvKRqVkA9zOHmJIhWgOLZjBrJX7eBYdT4asPKqqahha+3PAoSVH3IZhtiyZhcdWMLxaSTY7dWTR65Zs9bTgtHV7XC7GfmpPDesNz5jV/GeeLM/w7TqY+Q86cPjJXOpIQdj+KRiZb8V6zU70Ly9j4bojvIpPQa5YeUwnzMd1YgUW63cmpNVC1mzsxS3HIVivCWbYqpu4Ng3DafgkNl69TUxSFsVU1eg1ZzfLKmyj1pitX+kqQ83m0/EKNEf3Z9VODmWTqyMLAg/xMi4ZOSUdetq54DqpD6U/bewsrMPPM5J2MsDEgyaeG5jUvsC+qvxAuZtMLduSGxP2sm9yc+R/cHTK/xqp/Nm0FN51qdzesQiryXvps/MMU+oVEwkaCq+/2Tw/7oWF3TyepKihQDYpSQnUG7OarY7dUZL79/s5/vV1HM07sOORCsUUZMlMTUS76XD8ly2grrbM/wzrV6DyfzZeIAaJnMuFyo9rKk1Kiie/30JlMqc9JzHB/wQJ6d8GabP+AXaNZEVap/nL8rwMomVjF/QmrcDTvjXFf+WAWFE682oDrRvNpvzEFXhPakvxvz9TPv1dZ4I/PpPr8qddb5be68GKY5OoIfO3I6Z+4E+Ayr8Lk53OvUOeWI91I7zfch659YHIu6y9FEHnVi1Qz47kaVjOqEPOR5XyBmUpRh6hcutQlCLCeZeiiK6uOpkJUUQnpCOTnExcRgYyiipoa5dBRUGajPiw7/gTpXr+Gzbvd1qjO/Mxrj6rGNta79M/j2iOLVnAwutQMzSI+zoLc6GyzKNAWjR1wmDJUdb2+MDE7sPZqmSOS5eHLDpSkp2Bc6j4fgMdu62i1Xx/nAYao/QzfPYj6S65odZ1CZ1c9rNprAkfH/eZPDm1gjGj56FouZ59Dm1zN2osdhrD4s0xzLl0nUFSJ5hqPZgQA3f2O6X9/3Ed3tR29WNqlRPo9/Zk/MbbzG7wjAldLNikPJarx8bx/YnOf8vpIzzaDML1bhuOhLtRXwrebLeh9uitjFlxiP4GxSivV52SCim4DSxNkKwt273a41vVlNtt5uBsncFUO1/SLYO47tAEqdibzN8ag+PIVry9vhlbs9GcM17Mu7XWX3ZaJp9yQdt0Ge0nb8FzVA2ysmWRe/+enLEvOZXiqJFMdGIayCmiWbospZTlyE6M4NHb2E+BqKBjUA7llHBuPY6hTMUaqBdLw2OQJoFZY9niPZtaZT5SZWFBZc4Qy0G/KdzXGY5Nj9rk9/7jf71L353AqvtGBu5dRbvSPy7k3w4qU6M46L+AJec0CdjoQGX5/w1WEvG0u7+NVqM8SJJSp/vYuUwZUF/050/oFSbPmJc7oqvfdS5+sztRSkTA+O9B5QeubfNm3mkVVi8alftcEMfnRyOVDwMtaLQigQBfT/oZlYXsTBJjIoj4IIduWQ2ks9OJCntNloo2WiWkePcsjEwlJdISEsg5lVZZozTS8e9IyDljVK0MVcuoIZWVSnRYONGJKbkjrrJKqmhra6Msn0L4k1DS5OVJS86kRHl10t9Gkq2ujXYpZVIin/Hmffqnkd2cCQB19MuX4ENUGBHvc86wBVl5dXQqaqAglUrUszckqxWHT+ee5oz4VtAohlRGMuHh4cQl5fRQGuXiWmhr56zx/UDY4zCyS2mjra6M9IcoHr2J+bg0plhJ9MsqE/UsnOxSWqjygtUj++DzoCMeuyZQV0ma1BRptCpWoLh8JvHh4bxLVaRCBQ3kv3o8CVD592pOT+DAUmtGrYI1x33oWP7rw5DD2WszHMfbqrSsLs25vXH02RPILBOpvI1Ubu3EqfHjmHytDmfPTSNmxwIcPU+S8V4ZrYoRnHyqwRyfACzaKHLYdjhTb6rSqoYM5/fFYrorkNkNyorjHhSLj/hL82nYaz01+w+hQ6++jGpT/Su/r1nSqj5HPkGl1JbR1B1/kGlb7zKlRRpbRndi3I4SNGv2nlD1gWxbMhFtuTvYt+zJ+55L8ZraG438pIDnGzCqZwetzBlh1ZtBrRqgrpTNKb8xDA2C9ZuX0Fr/47TqyyOu9B7nhtGSFwR0SWefuz3jlz6lcYcEnmb2IMDHhVInx2I4ZhdOu55g3yyKFaZ9mHmpDUdCF/PphS55yMFHqJx3Sxu7RX2oIAXvr29m3qYbjAm6wYJmaez78wIRIB48CwAAIABJREFUMQkcC5pPUlNn/B2rsrB8D85X60a1si8Jy+6B365JVP+GX7J5c3ULtsNGkTR4O0dmdvgI/ikRbHAwZfyxkmw4vI7MtZNZdDUa5YcpyJR9y52UsphIQXZVCD4ZzUAXP5yH6hPsMByrC4q0q6vEtcPRtN64ikVNykPcS/Yf/9i/P4NciGs4C/8Z5lQo/vEfTqFBZR4yUFimvx1UFpaQ/1G//z2oLByhRYbKtPfsXzYRu3MVOBfkSPHUV8wZ0Z24rstxHy3HpEpDuWVggm5mOCdv36dCqwFUib7D44i3PNEczMXdMynx/CAzxrnxvEIdKiu+4mpIFqOW+GDRJhTbCgO5qKFF5DMVpp+1J6TLNLLs/fE018HHtgvb45tRR/4l527HYWLmjNvosqy0ncnFrNJULx7J2QvqTNvlQf+q4bjU6cWeag2o8OotT2KfkVlnNkc3mSF3fSdjpgciX7kyqrFPeJ7VDFfviZhohzCy3AhSJ/jjPakeTxaNp7vvHZq2NyQyywA/t/p41B1H6gRPbAxf4u44nzPh+rQz70yd9Jv4bbiP5dYzTK8byTIbG1al9edkkAWlZf96h5IAlX+r76wPMaye1o1Jj5sREuRMJc2c92Z8+jwMoG4rVzosO8z8XjJ49+uOT7INp4715mJepr+/A5WjHc7RbcECrOsmMH74WNQG+uDW4SUt28yj3bKjuJrK4jOwB55x1pw5YZs7Ffw7fDLSXrHHbSGu/ht4pFKXIW3HMs1n4Kep1H9CZb0Jh1h06BWWdaO+gcokXSvWzhuDhtSNgoNKorn8xzpc5jhzJlWPtg1HMG+jNS8XD2LgCR3OBM6nbvmPU+7RF/zpajkHLfvz7B2pT+gJD3pau/IwSop2s3azeUITMl5vpn+dMYQ37EjtMjK8vnaGW5GDfgkqna8+/qYspOUUGRt0g+lljtPF3JGbL+JArjT9py1j8QQNZml0ZJOsMrKymfRwPcRKi3rfXJ+dmcYfTi2ZfrgkC3xXMLTpxzHU8IsrMB/pzHvT7ZxyqcbxOZOYsCWByctdMUnaic3YzdQaO4c5o6viP7w/VyqOIcBcjR5txtPA/TQ+Q1VZYzUAp3t9CA6egtaNP+hmMY3rT2NBTos+U5biZt8djU9LHAWo/PHdLkDl7/Ak/PkYBKgUTbv8gko7nWG86e2Am10dNtqase1VSxastaf0rVVYzD7A+O0X0Tk1Adfz2ixfOY9asveZY2ZOiOEktszRxUHfnFddLDHr0ooWXdKYW2UsmTlQ2f4tTUyn0s3nLhPUjzBu2lHM1ntQ99Yi+sx7hqO3F6YGrxnfagDvu3rhOasCvoamrNPuje/C4cQfdWbS0g8sC16L1B8TmH/NgM0BDpSK3M+oIT40mOXFhO5x2Oh8gsoBqQzuMJasXl6scWxF7MtItKq8Zpq+1UfonFyH/eatcbnZny3XZmEQfQLb1lY86OLL2mHpzLRzoaTNRrz6VvtmHa0AlX+vx5RYNrsMZtRBbfbvX0qLcsW/WLzdbEmN0TtQLqGOioIUybHRSJe0Zf/DMdz7Vaic8yJ3DWaz4mksGNqIF029cSi3h8bjtqHylT/UxnHgyTzqiHYf/SesMtM+EBf3gu32g5lyJIGBnntZMShnu46kQSVkZ6eTEP2G02vmMsnjAHLWf+Am7/s/oLI4B10mY+dxF+1aD0lQ7c3yFYE0LZ9OXHgUMcmRpKfLccbVDKcwC64dHoNOnjP3caRywZ1GbLo1k9pA2AEn2jjsyx2pnNe+BO/jEkhLS2XHHFPmXqtF4KZ+HDIx47qxGQ3077P7YAWC3qykxVcjlY9W9aO162P6O/rgYt4EFZmcb6QxHJo/GTu3ONzebqGXchz7c6DyUGmOXFyI/LWN2AxdQ7t1q7Ex1mHj5KasSRnA/EZv6WS3CqXimqgpSpES/57EjOEcjXSnfkYy72MTSU9PY5dLL2Zdrsbqje70qP5x240AlQJU5vmWKCIXCFApWqLzDSp1R8Jkf5ZNqMGuwc1Y/NiMzZed0Dq5iOYW7gzyuYrqnj78IWPOEQ9rNKRiCHQejm9cFw551GK6gfVHiMxdQ3kOy3KWH3+2LcGCun3ZkCSDkkwqcdUHczFoFmEru9PL/Q4qqqooyGaTGJ1Gw0GL8PGqxWrD3myrN4ujgUOJ3jyWXlPu4XhgA7HL+zB/byglVIshlZ1G/HsNrLyXM2NwGuM/QeVsoxt0t1yMkfNF1g7T//S6y7OMKmtOynegso5sFiec6mN9sB6T7euybd0NHNYso32Fkt+seRag8u/1mJnMucDpjJp2lI7LArBtXRM1mZwz5JSp+HIVuv0CsPQ5zuze+simxxMaJ0tZjbhfnv4e/R2oXNb0PjX7+WLhcwLnPvrIZsQTGpvj76vRU9HuJ4m1Sol5TfgHWUprlCD+sAtVR61jwNLjBAyp9g+orBDsQZmuSxjqdYJZneNZ1H44a+JNmTT8EWsu6bPBdzblU4IY0nAFdRYvx9myyTc7iH9VhIyECF68S0SzbAWyb26kk8Us4vpvZH3VA1iMP0e/1a5Yt21GsZS7BM1ywnVXKu6XD9E24RiTbCYS1mEpO4xPUW3kQQY5L2f2oNrExslQTl2O2MeHsRs0nZC+K7nl2PgnNib8y5rKwCvYm8iDqgbqMnFsdjZjdGA2S49YEdJqFLfbLcB5XBIuY12509yDR95mlJBO5Oq68bSdsou6AxfiMak1agolqFhBkw9PTjN1zGgO6jvw0t8CKalokaByVT9FmvSdRX/PiywZVhX5jETevJdGp5Qs0ZHRZCmXQkM+kW3OZlitTmfJgZWMMvm4/UeASgEqf/X+/V2vF6BStMyKDJXpsRz0msT4tR9w37WMugm3mG8/Dvr65U5/2/0PqBy24hYVzliz9EUDtvlMQSf9Ca62wzhVbgw751dmatXR34VKjzYvaNZnPe26leLMo5J4eHvRqkoxXmwaQ5flsSzy9qJ7XU2yUuJISFekpOpj5tbu9Q+onHVsK9KbrFnypAE7/CZRqYQcSUmJIFsMZcWLf01/d42iXc/JVBiziQDLeqQlJ1NC4x52FSw+jVTW5/DIFsy80olVp11orCaP3E1PqvZailYlA1Sq9yZw0ah/bF4WoPI79Rj38hrL547Gc88jpHS70bD4TZ7rj+TgDGNW20xid5IhQ80aUzLmChvjBvLn3KoFA5XmpfGxsmFngiHDhn/0F/R+ACfntRLtLvoPWD0J6EV73ygG9m7J5fVBRNbsib/vUirFXeTU9WD2LprP3RK9GTZ+MAMayLPBbiLrQsvT1jCdgxdi6DovgAmqJxk7cTXFOg6iwm1XjiqMwNt9Bu2rfj42Jn+EeH9wKvpmgZiOnkLWlU1cSNJl4ZpdtFe7w0qXkXjsuEvd4UsweLmaldcy6TF+IUFjm7FrXk+ctmvitnMZXXQ/sHRoJ4IyTVnnWI3pzncY0E2TMzs3cTu7Dcv+cKPZT50x9S9Q6bmN4qe8uKJsRCeteyxedgbN/pNZP7cOS/V750Ll2h29eTrdjr4Bx7H2v8qcurfoOmgCVx5F/iVeGTNO319GwlobrOc/YXzgaka3yIE+EaFyaht22Y9m9ZsamFu3QDP2Br5vuxM8Ux+PqdM4L1+XzmUf4uZ+EvV+kwiaO4oqn5afCFApQGX+3MW/XysCVIqWU5GhklTu71/O2PELeWfUG8OnwdxNz6ThqCV4WIsAlWuf0TPWn3GOmynT15wG6efZcVQGa98FDG7yCutyVt+FynmtnjGg3wxuR33IeS8YrYcMZthIa9ooXGTiqGXEGbams7EuSeE3SNAfxcwB2cyrY/pPqDx9gHp3V2Az/SDVLU1pUEKGe2+iadHFgu4NnjHq85rKUeXY4TARx0OP6dS9J09iFPBa1gK/ejafoLIdkYG9aTo7hHq9p+A4sgvNamfi3qYzC+4Ww8LVlzlmzVD5/FrOT2kQoPIH9Rj38ipnQ56TnHvcgALlaxljZFCWjNdX2H/l5ZerlAxa0q2OKi+vXSUkpiTt21cn9dVdgu98oG6r+pQu9vncuzjuHj7LU5UadGhWhnfXrnI9pgTt29ck9fVdgm8nYtjKCC25LO5eOEKipjFG1cqR9eYK+y7/5U/RoCXd63w+h1C0m0mSrdJeB7Pn0osvXdSu34XmlRSIfHSdy3dekpxzJFrOR7kcTVsYofH+1l/2xQ3o0qEOyimx3Lh2hcehcSAlQ2mDRjSuXTb/z1SMus+2k3e+9LV41SZ0MCyX+3P8m5ucv/6IxNRPf1bXo10jQ0ooSHHvwi5eSFejhXENVOUh7N4Fzr2QpomxFg/O3CDm0yXl6ralSZWfBeEEHhw/z9240rTuXS/3TNUPr69y8Morqpi0QDnyLrefvSMjx5ecGgb1GlBTN4uQbSeJ1a5Lo+aVUYl+wLaTd9Gs0ogm+nDu/DWiEz4HlHNhOZr1aURKyDGuxpaiTaO6qOfu3Ezl7e0Qrocp0rpDXaRjXnD1wlO0GzekaqlivAg5xtNMXRoaVqNY1DV2nH/2RUPpSs3pU0eNZ7eucvNpxKf+5ZyD2CD3nMbP+37/u1AZwYGAdej0nILhv+zg/pV7VFhTmTf1ji234aZyb8wHtsnfjXx560a+WUsaVKa8f8P2gKWkG1sxpHV15L/s4XjF1olu3KoxiClWjb8cn3N7xxJOpTZn2KAGlJCSIiMxkoPrPdj7pgrTpg+hkko2j07uYO2fqVhNH4K+isJfMzlRZ5g77yD6A20Y0lDn08kUGby5foiLkdp0a2vy5V3kP4LK+GeXOPokgwbGRlQopZSbl/S4t1wJvkbo+1QUFHTR1ExERr0m9StLcW3PFbKrm2BUrThvzh/jXoIeTTvWRDHiPscu3UevSW9qqkRzJTiYV+8S/3+eRQb18jUwNqqGmtw7Lu++THa1BhhVK40cn3+ujcKtVVhNvEFP92FUSwtj/5pAztedw4PFHXlz7zLXHkd+PLtTTgm9us0w0oW7h87yqmQtWjeqSGous8RRq30bKkrHcPXqVV5EJHysM9XSmJgYU1E9iSu7LpFZzQTjatrIRd1hx+kHH8+a1axKl8Za3D0YTGa1Bt/+Xb4ktU2MqVqmOPcDBtElMJ3FXt70Mynz1zmmAlTm2z0tNCQoIChQwAoUHFRm8+xiAJPNPbib86ZrxyNsMqv48Z9T+BEGtrQjBC162NpjFLWR2ZtuixRpze7dqfXwIVsfyVOpYihRidFodHRj/8yeX45kEqkhEYwEqBRBpK9Mlg/V4XCpWXi7jkRXOT/PHMtbP/LLWtKgMjH0LrMsepNiGoC7ZcsvUMe9jdTqNIneq54wq70KslL3WNxkOH4vYjAZ7IqXWz+0326lV7uZBMdEkpAhj7p6cSZuvEK9my7Y+iex4pgHDUp9da5l5gd8zOpwvvxili0wpbT0JexrjOG8UlnUy7zlxfMUOrn8yRJTHawsLdm+fTsxMTHIyv5teC2/kvHT7WRzc90oTKftJUu1OPLZGSTGxdF64WWCzCuTu5RdIj5vWda1OXuKW+HlM5Xapf553JcwUikRiRI6ISggKPBvChQkVD467YHVmPVIZ8RwQ9uG68enoC+XwdmF3enuq4BhmQdU7e3J4mmdKJmdzZmlA+m+R439qxbTvMqnI8eeHqLr0Amca+BF7LKOSEmlExsaTtSZJbSef5Xh0xYyrosxZUp+HAnJz09+Q2V6SiwRb6P5PEYtr6iOdjlV0qLCCY/LeWOQNEpq6mhpFCMp7BVRybmn56GmVRpN1SzCn4aR9CVANUqXVyIhLBrZUqVz322ekRLLu4gPqJXWQlWx4P+555xgEBMZRmxSzji9AtsdG3G+dA5UmqH8LpRUpWJkJKVSTLM0GkqpvHkVlXv+YM5HQV0HnRJyfIiNJi4dZBMSiM8Z1ZFXRru0JspfztDM2XT3juikj+cSgjwltUtTUlmKmNeviM1tUI5SOjqoSScTGRZO0qdZMC3dssgmRvMu58UJudfKoFyiFMVIJCouC80KOqjKZhAfHkFURjEq6JTka9X+DpVZGalER4SDihYaxZVIi4vgTXw22lqaKCukEfH8HVIltdBQySbidQQfsrJyvcqpaqCjWZzM5GjCotNRz7WXIT7iOYlSJdHUUCL+VSipqmpkx8aSUwkKpcqhU1KRrNREIiKj+JCaSXLUK3ycrJHu9zVUZnBl+XB6u5Zk+wsvGspEsMthBm5vNan+YgtJjRfhmQOVobuYebAic6yqcHKRJcOXHEbPYSfzShxi/IoY5q+cjEFxRWQVVSitpYmSnDQPg0ZhtlsRT093GpXPIOLuHTb6z2Hpm5rsmDOCylUMKKUkhUS+UefvD4KrXphYryWjeC0mzHVmSFP9b3Kdn8+Nn2ordC/D+ntSevhcZls2QfU7L2QQoPKnlBUuEhQQFBCnAgUPlRfpZprCAt+3LDp1jtH6D3EwteRkp9m02DaV+DxDZSQnvFazO0MWqSPHyG7QgJothjGqfdWf2IT170rnN1Q+Ou7JbOeTqNYtT/Tl9TwtZsnK9aM4PdOCLXF1aaQFGrXbYdFDm7m9u/G08mBqKmZQYYAN9k0fMtzIB5lONUm//ycHgyuw7JAD5xxsSerjSdD49jw5NJMRLs9xWuVBt1pa+a7H39WKur0Pe+up3Fetg07MQ+7HR1ClgzM+rsYsr9KZw/pViLuVwMCVi+ketpPxy65SqUMdYs6d5l39qez0H8jLNU7MP/gE2ffKlNYO5c9Hajgv98WqVeWPb15Je8TSQbM4p1kKzbRYrp4JofnsQBa1jmF4H1uSDLqgm5FGVadldIsMYLzzFtSqGFHyfQrNlyxCbcci1px7i5ZOSR6e2olSqykM072J3cJrOBw6z4RqL3ExG80GVRsurB2Ixlf/zP8OlSnvHuFqM5j7Rs6ste/KhYWt6btLnRUBnvQ3uE7vmo6Ud/bCstQ1xlqvpkTnlii9vs5T6eb4r1uAxo0FmM59zDz/pfQw1GbV8HLsVJqOl1sz1hh241j9FpR/85r7Uc+QabCIY+v6EHvEH2uHFWDYEpXHZ7kXnU6nqavwsPo0Upn2BB/z0cxJ6se9XaPR/NL/lzg3b82DhgtZlgOVXw58T+SEqwVm7ofpt/ompu98sFu8l4xsHaroRxMcWZnF/l4MaKhD6IUlDBh3jrHLvRjcOIWgKQGExMeDvCLZsjJ0GruEzlVksLSwkOCRSnE+TQvWlwCVBauv0LqggKBAPiggDqi09e1MUK9JSI9Yx7y+odiM2cXwQz7c7dOdeNO8jlR+DjqMq0ceULZJa8qq5oMQ32kiv6Ey9tV9XsapUa12Od4H9aLRsjgWONmyZZkTL1Ud2L5rIKUSk1B8ug3dzo60HvEHXrMbkpGpSDmZt1y6kkmtttVIPzoLg0FeWKw8R63g2bjdrMuBPY6cm2xCQNJgVrhNoGrJgh+pvLl2NIP8opnl7UkL2Us429sRVmf2F6jcZzgE++EdaaT7llGmDpQdu4HlDs14uXISXZ2PMW77nzS75cH45c8ZvtoXi1L3mTJmMmGt5rJrZm8UZaUg7T03L7xEo2lttOKf42bfnyOlJ3Oo7Q30LA9h4RzI9N5leCdXhoSNw+nlncjc1V4MrZjKW2UdeP6EFHUdKpcrwYl5bbC/VgfvqU1Z3mcc8Vab8O0Wht1Yd6rMPYB7p7LfvELwH9PfyRH8MX8cc65WZ/92a3b0q4XrdT1svVcypthaOk4NxnbRfB4FOHKipBU7fYcjdTmQkXYeaE3bh7P6Bvq4/BgqdxoMw2veYCL2TGeyrzQrr/kTs2IM7jeqELhmHoohfjjN9KPcyJW4f4bKuNvMtRiDp8Z43vn1/XR8TU4xfx8qox8ewMl6PFvlenByvTPx++Zgu/gu/RctYGD5Z9hbz0FvnB8LzJoR92gNI3ptobu/N6NaV0WWDCKf3OLlBw0Ma1VA7tPU8X9ipLJgHhFibVWASrHKLTgTFBAU+BkFxAKVm5cg723I9JDaNK5WjmMfjHiwzZRZTboR99NQ+TPR5u2a/IbKdw8PMmvMJE6HZpOdGkeCahVc/Dahd3EUfeZdo4R2ZXqOdmbmuEb8aVeRsTsUKaFuwqTVboxuKseinp0JepRFdloSYVFxmK25g63SZiym7GXYrrW8tO1FgqkfrqOaoyKGtWL7Z7Zg8o26rPNxpaGuMn+tqfw4Unm2lw97ffuSdcSZOsO86L38Fr59y5N1zY/yXWfQy+c0fUL9Gb9eio1n3KmW+BzX8X3Zr2HPGffhFMvdiRLPCTc7Jq69TGpGBklx79Hqu4gzrr3xsaiEx3k1iqu1xzvYG+PwYBysTDnyqgQqCv3ZcG8WSof9mD43gMdx2aQlvkemdh8CfeYTv6wOU0K6MX54WQL/eI3HDi8allT8ZnT3H1CZncL1ba6MmXYXx90dCBrsjlTV2qgZj6B//ASmnhuCr1ddPOzsiem1jRP29eHVKYaNtONtx7WsrLHnX6HyWFs39q8YSPhaM7pOe82Cw6t469mP7cqjOe5uhez7h/9cU5kHqEyPfc1yx4HMv1SZwB0edNFT4Pyq2dj4fVxTWSPtJc4jepHUwx+Pka2Jf/x3qPz+/SNAZd6eKz9rLUDlzyonXCcoICggNgXEA5Ve9In1R7e3J3Fp8pgu2kugtQYOjYoWVO6Y2pgZDxuxwXsuVS7bU8PlEc5eQfQ11qaEsgJ+Zpp4xQ0hcNEkqlTQQfZdMI5WnblS25MNVTbQ1v8DcwK2MzBtPRVN5zEw4BZeDZ4y1MyGFxWMkL/xlhFrtjHM6NtDkwuqmK4HmDNkmyze3gsxKZ6I99imXCk/G+9P09+foVLjdiB67afQet5JfM0NeLl9Oi1tt2EedIwOj30YvyYRt51LaCT9hDkTrAht6k6QfUdyloXG3tjGMOvJJPbfy1FzZTynjmCz4giOz+5EtkpZEi77McLWkUzzkxy00iFLSYNnG83oMHkPnZx3onthAvtLTeCUxzBueg3C4mRp1ni70TTCncqDVqOto4dqAwu2uQ5BReHbzRHf26iTcG8fVqMnIq/biDthBtgNjMNrzx1qXLpK9MzDHOydjOVIWx4aLebwrDZ8CNmMha0LclbbcdfbRf+xpxjs7YFF3ZKstG3CafXpeC35NP39N6h0O7GBxLWjWP6uNXu8xyH97BzOE22RH/TVmsqEuyywsMZdZSyhqwei8KPp75T3rHfsjO1eRSbPd2ZAw4ooqSjxdI8b438AlXH3Axjefxd9/L2xbFn5h2sQBagsqDvs23YFqBSPzoIXQQFBgV9QQFxQ2be2DIt6muD5uAHLNnvRv04SU4oYVJ5aPhT7de8xHdyGFxe2cPe+IkPthvIyPIGa5TW5sc+Lu2XNWNg8kjnXK9GzbDj79+yheC8XFtY8QjfLQ9Q3M0f13WnObDpD41V38OytxKHpYxjmf5SKLaeyfuN0aqiIZ+f124trGG3lRlbzTpS+eoH7sglomkzAZ+G3I5Ua8bfxGj2GpTdVGGbZnNub9xJXdRwrN/bkpfcM7Nz28KFka3oZPeeP87JM8/LHtqNB7ivqPrw+xZQRtpwrM4iRJkkc2bCZ+IZOBDU4wYxnHWgqe43Ve67T1nkDpm/nsyW2GXrv9uCy9z0zly9Ffv8U/O9XZGx/A05sXcsrmeYszoFK/dfMbtKZZc/UGe8dwIw+9b86oufjDfXd3d/JD3AzG8XCIzcwsd+Nf7dw7MZN4dR9eVzPPGFs1TD2LZnJKM8Q+k4biWzwXq69N2HJzplUfvcnE01Hc7FMYxpHveGxfCwl6ozD+0dQeWEvehfdsJm5CwOLQUjt3cHNlGya2XjiYdXi0+7vcLbYWDH+TD2Oh8yhhkwGoTfOcebOTXa4uhGm15eBlgMYqLyfqv39yPy0eSgnPr12s3Ho+Ba3gA/fHakM2z+FXh5huPospVudHx/yK0DlLzyA83CpAJV5EEswFRQQFCgcBQoOKiE+4h4XL0VSrYUJuiWVeHHtEDcTtGnRwJCSSh+4dug4aRVMMKpVjpxTZyPuneHEaznaNjFCK+fg0ZxPwltOnAsmQqMBA03KFvjmk6+zkN/T34mRD7hwPITonG3MlSpRMeI9mrWq8vrhLcLffwA5FSrXbUS9kjHs/DOEzKxsKKZNw2YN0FeP5+zm07zJ2SFdtiyVwsKgSXcaVFAm+dwSKvScTweXE6weUw9F8TAlmSlx3L5ymvtvc/ak62NgEE9sRkUa1lfn4e4/iSjfkDYNdVHIETX8OptPPSSn+6CGYadO1CiZyAkvJ+yCophg1x1lOWmUSuvTtIERml9Ofk7k8ZkLXH8bTZaCAiVUVVEqrkcznTi2n3n0sT21SnTqaEz2swscvf764+/UDenRvgoJj0K4cv1p7q55BR0dtNLkMWj4sf0LS00ZtEuV5cs96FJL4x+19f0jhZJ4cu4C119HUaFxDxpqJHL+4hVeR8nTuEcHKuYcpfT+CTuPXyc1PecwYCX0jZtgXFkLqbQE7gaf4s7rnDMW9ahWLYGY1PI0MNLiyb4ThJYxom0jPZKfnuP49SSMunSgXPobLl4Ozj3XUUmpIhoaichp1cG4SulP74VO5/5GBzran2b2mWAsDLIIu3WBC/dDSf+4+RxU9WhfR5Y/Lzwh+2MCcj/KxatRrXImDx9n0LidMcWzkrh54SQZOo0wrqrNoWkmLHzVFV9PR+pqfT4X+p/PKQEqxfPsFqBSPDoLXgQFBAV+QYGChMpf6JZEXJrfUFkwQcVx3MWc/h6ReF89yaBKcmIF71+LKe4TVH5cU2n45YUWv9aqaFe/xrVjK07p2uGzxJYqav9chCpp51T+KK7MlEtMrtGXWza7ODbBGOnvHEcjmiZfW13CuoYlclODcB9m9I9R3K8tBajMu7o/c4UAlT+jmnCNoICggFgVEKDyx3L/J6Ay/i55j2SuAAAgAElEQVRudo5sTDfl0IbhlPlydIxYy+gnnSVwca07c66UZsfSkSgrFPyO9S8dfb2V/v1XYzBuHtOHGFPsO7r9V6AyJ6a328dhE9KZlfO6opEfNfB2BzZjrzFs9TwaaEj/6xcVASp/svzzeJnYoTIxMZHNmzeTnp578qvwERQQFBAU+J8K7Nu3j0OHDrF8+fL/aVvUDMaNG0enTp3o3r17UQtdiBd4/fo1CxcuZNSoURgaGgqa/ECBNWvW5L660MfHB2lpMRw7UEQzMXr06HzVVyr768UQ3xH15cuXVKxYsYjKLYQtKCAoICggKCAoICggKPB7KpCamoq8/I/XtuY16v8JlRkZGbx58yav7Qr2/xEF9PT0ckdN/Pz8/iM9Frr5X1DA3d09d4Th2bNnSOXHtNl/IWgR+6ivr4+NjQ329vYiXiGY/U4K3L17lx49euQ+czt06PA7hZavsdjZ2ZEz4/H48WMJfPd3voZaqI3p6urm6zP6f0JloUYrOC9wBXL+4ffp0yf3dVjCR1AgvxSYMWMG8+fPJysrK18fWPnVv8JsR0ZGBicnJ+bMmSNoU5iJKCTfISEhGBsbs2PHDnr16lVIvZB8t4MGDfqy9E5WVozrYiVfGonuoQCVEp2egu+cAJUFr3FR9CBA5Y+zLkBlUbwj/opZgErR8i9ApWg6SZqVAJWSlhEx90eASjELXkTcCVApQGURKfU8hylApWiSCVApmk6SZiVApaRlRMz9EaBSzIIXEXcCVApQWURKPc9hClApmmQCVIqmk6RZCVApaRkRc38EqBSz4EXEnQCVAlQWkVLPc5gCVIommQCVoukkaVYCVEpaRsTcHwEqxSx4EXEnQKUAlUWk1PMcpgCVokkmQKVoOkmalQCVkpYRMfdHgEoxC15E3AlQKUBlESn1PIcpQKVokglQKZpOkmYlQKWkZUTM/RGgUsyCFxF3AlQKUFlESj3PYQpQKZpkAlSKppOkWQlQKWkZEXN/BKgUs+BFxJ0AlQJUFpFSz3OYAlSKJpkAlaLpJGlWAlRKWkbE3B8BKsUseBFxJ0ClAJVFpNTzHKYAlaJJJkClaDpJmpUAlZKWETH3R4BKMQteRNwJUClAZREp9TyHKUClaJIJUCmaTpJmJUClhGUkMyWejc79mBdswKp1c2mhU6JAeyhAZYHKW2QblxSoPD2rOs/63GOEodSXXMQ+v8yu08G06mWDXsHeXt/Nv/BGnSJ7W+QGLmlQ+eq0OxYzrjPcbT6DG1VE5u/pSYpg45KJzH1uzHkfGzRU5MWSQAEqxSJzvjsRoDLfJc1Dg2kJhKfIo62m8PGiV+tpVX8ajxUgIzmO6Dg9lt69gW21f9zmeXDy76YCVH6tTyZJ0ZGgpo2yXL5JXCQbKnSozErjwXp7mk1eS5VB6zjg1YdSOZnISGT1uJbYnS5HwKblDKmnI/b8CFApdsklyqH4oTKNm9vnM3qKL69SFZCSKkEHi/ksmtuFqzZ6ON23Z/PaRiwcaUXS4GNsMtNB5st3sHOMMXRA3dkFg4Pu2K0pyY4PQbRWkOGvr2kFI+9/Dyqz+BATSaayFqoKBa1OwWieH60KUJkfKua1jeQYgq9c5PGJNdh/GEe4W5uPLUSd40REM9rUhLt/jKOLzXJqL3pCUMdEbr9KQCEykmfJySiULEuDxk0pX+LXyUeAyq+T95qlrWshvySWcUZF96GQ13L+nn1hQ2XCw13YO95ljMUbbI60Z/8nqAzdZ45TUFUUKn+gRX9rBgtQmR/pFtrIgwKFBZUbXxsyc1xvVL8MNIYwpbQVWvtOMdlEkYue/Rn62oJHbt2Qlf7O8y/8IN1ru9P/ylGGVpRBqoAfkf89qIwgsI8Rz22e49xKju9JmIcy+c+aClAp5tTFBwfi4L2fs6dfU8+iHx07DmZYo3JfepEQHMiU1ZeJeXKWQy8r4Ld3PdVve2AzfQsxsob0bhHGsl2pzAwIYlLvWnwa4/zpKASoFKDyp4vnXy4sVKhMimDDSl/eVOqBg8wqmh9uz74cqHz+J93Gr2LMLAeCd+yiav/RAlQWRPKFNv9VgcKCSqeAS2jpVkSzbCMsJpljoBbNJUdzRoRo0r2+Bs9fxNPbdjYDG5b9JzAmv2Gvtwue12rhu3Ic1dSkCzzLAlQWuMQF4kCAygKR9fuNhu6ZTAu7P9DpNgd3u45U0itLCXnZb4yvL26G0dTzH3+n0JQNT05Q7YIzZpNDmLjJmwGV0pjSpxWxnQNYPrUXpX5xsFKASkh+c535ThPYfvkt71+/QEqzCiUUDXHavpRhtcqKsUJ+H1eFCZXht7bju/ku/cY7Uuua7SeobMtVx36sqbGZ9Z2jWLBkA1UEqPx9Cu4/FIn4oTKb1IRowiKiSc2E894j2JTehaXznKilfIPRjRoS+BCyWkwhdMdstNS+XTP5+rQHlqN9uP4mjA8N5vPw2ATKywhQ+bnk0uPDCJw7gqUHnhL79gXpJfRRL1YJy0ULsOtRF8UCHtGVtNIXoFKcGbm8hLK9lpAkU4bRc92x6VwP7TIl+d6y5+jTS2k8cAYxdRawxjKC6dMf4358BW3UM5nTuzqPmgbg79gb9V9cM10QUPnhxUUc7cey9VIEysVHsvP+HGqLU+ef9vV7TX+H7XXAeMwGsrPLMsDRDWeb1hT/aW3ydmGhQWV2Fuvm9uOO/iTs2+mRdXwqvU61wqdPPOP2pLJnlhnSsU9x99uBfo8RDG9dB+Vvv9flLdCfsC7MNZUvAvvQdMYlsrNrMnWTD7Ytq1LwePATIhXgJYfmtsdqxV2ys1ux8tEauqgoFvj6wK/DET9UfitmwptbTJ0/m7bDzTnRx4aK218wqVESJ+eb0/t+T8KCzCj216LKry6+wwz9FjydeYWN5pWQLuD5b2GksgBvggJsWoDKAhT3e01npSZydM0sVmw7yZ8XlZl2cQdOdUt/NI28w45zMTRpX4+4Q0vpNHYxCfpOBExKYNZ/CCrFLGk+uvu9oDIfhclzU4UHldnsWTKEzdezc/ucHXqV4+F6mLavQsaHGJKTgdR47jx4iWqFVsxc601nbfEOJRQmVOY5kcIF+a5AYUNl5J19OLhvZkC7Oph5RLD/1BJMVKVJvbCMCkNfs+emE2rPH6OpVx8t6Ve8TNZHV0MKUsLwG1qHzY0OcsLeGJkCXjQoQGW+l55YGhSgUiwy/9NJ8tub7D4eTHqVzpg1/rSm8q4vVY0XU8W0Ce+vniI4xZBFW/xo+XolZgJUiiFTidzatxWZRhbU1BSDu9/YRaFB5d80zTpo/deays9/i37IHGH6+zeuPskOTexQmZHI9cN/8MeBEJKA5LgXaDayw6GXLh5jTQku0ZrKKlIkv3pJSucZLO6Wjuvc5XSb6Es3vbNMNT9KfM7zMPlV7jr/lf6LaFdNrcBHd/97UJnMw6Pbia81BOOy0gWuj6RWuQCVkpSZ9DhePAklZzAl96OoTmU9TTLjowiNTEOrgjbKMhD15ilpxcqgra761dEPPxdIQUx//1xPhKt+JwUkBSpJDOdFkjLlS6v+df5eZhpR0XHIq5VETVHMc9+AMFL5O1V63mMRO1RmZ5IQFU5YVDyZgLSsPJrldClVTJakd495HZ3Bx3F9eTQrVqSkTDLh72JR09BGVTGVtw9eE5/90YLi5ahWtuCBMsfVfw8q814Lv+MVAlT+jlnNQ0wCVOZBLMFUZAUkBipF7rH4DAWoFJ/WkuhJ7FApiSKI0CcBKkUQSQJNBKiUwKSIs0sCVIpT7aLjS4DKH+dagMqicx98L1IBKkXLvwCVoukkaVYCVEpaRsTcHwEqxSx4EXEnQKUAlUWk1PMcpgCVokkmQKVoOkmalQCVkpYRMfdHgEoxC15E3AlQKUBlESn1PIcpQKVokglQKZpOkmYlQKWkZUTM/RGgUsyCFxF3AlQKUFlESj3PYQpQKZpkAlSKppOkWQlQKWkZEXN/BKgUs+BFxJ0AlQJUFpFSz3OYAlSKJpkAlaLpJGlWEgeVOYeDn9qynveVO9C9SaXvvm0mR8SEh8dYsjaCIa5DqfpZ1Sf7sfX8k/K1OzLMrDNlFCVNbsnrjwCVkpeT36FHAlQKUPk71HFBxCBApWiqClApmk6SZlUAUJnKzb3ezHBaxwuqM/fIVkzLJnFp1SymnNZjy/qRRO3zwclxLS8+qaHbsDsu8xdQr/RVptYcRlCoDAPc/Flg1Yxi/1AslVv7fZhm68afb9pwJP0PWpPEpdWzcVgSxNkHUSipalKu10T+XNYM/5Zj2P9VG6VaObPTuw/qkpaJQuqPAJWFJPxv7laASgEqf/MS/+nwBKgUTToBKkXTSdKsCgAqk7kUNBNzKx9ekYaGzQGeLmnG6UWWDNpvQPB5J8LXz8TcLBiHJ9uwqPT51SX3WWDcFz+Nxhg8O0MthzXfhcq40K0Mb+1GStkULl2qya7kzbQOC8bacjgByhPI2GbGlQ0zMJ8bit+JgawpP4g3g70I2mjJ81kGdPZNxOvEWywNJS0VhdMfASoLR/ff3asAlQJU/u41/rPxCVApmnICVIqmk6RZFRxU+oYyouIVXE6WY9mxjVQ8aP8/oPKjNInvzjGmmQXqP4DKj1YJHF9kxSBnKbbkQGXyW9ZNt8TukAqL5pkSeuAPDma2YrePIdNL9CCkuQV249sSsdkO9+cm7Ni+m7YVJS0VhdMfASoLR/ff3asAlQJU/u41/rPxCVApmnICVIqmk6RZFRxUuoSyyK8ZK0ZPI7PXYoaqnMD+z69HKjdRfngXahRXoXztDgwd2gltxZ+ESiD6qh+m3R04G54IVMYuIJAFI7OwlmrJhq9UL9ncnAObAvn8uu3/lZD4+Hhmzpz5v8z+s3/38vKicuXKdOnS5T8bg9BxyVPg4sWLBAcHY2trS84XF+HzlwLe3t6YmJjQsGFDQZsiWBiRkZFs3rw595mrr68v1MAPauDw4cM8evQIGxsbpKWli2CliCdkDw+P3FfH5tenQKHS77QXpTab02RtEgOrZrI3rOVX098nGXzAnV46pSimpoVO+dIoyvwTKh/6D8Lc7x5QnpEBq7FpWPqfI5UfXrBmxkSmHy/DutVDuOE7Dfc/y+J/fiC7dQfzoMs05ruaon3Nl3pjtzFowT78JzZFRQQVMzIyuHcvx//v+TE0NKRdu3a4u7v/ngEKURWKAj4+PqxcuZIbN24I/zT/loG6desycuRIxo0bVyi5EZwWrgIPHjzIfa91zjO3TZs2hdsZCfY+depUcsDy+vXr+Qo9EhxyoXStdu3a+fqMLmCo9MNE9g62rVux9l4G1J/B82s/WlP5Uc+fmf42fngUqxFmpA89zvaxBjw8tJQRw1fSYfNsnrcd9XFNZdAwit9fQyujaejO3EbQjPaoFkoKJcupMP0tWfn4XXojTH//OJPCaxp/lyr/uTiE6W/RdBOmv0XTSdKsChwqW2vIcNjXhuGz1vGu6r9BZSqvrpzi/P1rrJjug6qpDUP69qJH6xrf7ADPSI3mxpkjHFi/HI8tUkzeOpVmKlLsXz4V39vV8XTtTej+tey4ooPb0Z78odOfG80tsesjh/PclchU74ab9woG1CshabkolP4IUFkosv/2TgWoFKDyty/ynwxQgErRhBOgUjSdJM2qAKAyg7D7Fzl2OZE2/dqioyxPYth9jh07wkvZhlgMNuHD/YscPRKB0Yiu1Cyu9EmTD9w7uJmjj+L/0kgrx74xal+plp4cyomtW7n//tMvZRTQN2lHDdnHnLj0iA8ZOb9XwqBJe9oYK3DKaxv3v7q+UjsLutf6ukVJS4l4+yNApXj1LireBKgUoLKo1Hpe4xSgUjTFBKgUTSdJsyoAqJS0EIX+/JsCAlQK9VEQCghQKUBlQdTV79CmAJWiZVGAStF0kjQrASolLSNi7o8AlWIWvIi4E6BSgMoiUup5DlOAStEkE6BSNJ0kzUqASknLiJj7I0ClmAUvIu4EqBSgsoiUep7DFKBSNMkEqBRNJ0mzEqBS0jIi5v4IUClmwYuIOwEqBagsIqWe5zAFqBRNMgEqRdNJ0qwEqJS0jIi5PwJUilnwIuJOgEoBKotIqec5TAEqRZNMgErRdJI0KwEqJS0jYu6PAJViFryIuBOgUoDKIlLqeQ5TgErRJBOgUjSdJM1KgEpJy4iY+yNApZgFLyLuBKgUoLKIlHqewxSgUjTJBKgUTSdJsxKgUtIyIub+CFApZsGLiDsBKgWoLCKlnucwBagUTTIBKkXTSdKsBKiUiIxEcWTRfHar9MdvXGOx9kiASrHKXWScFTpUvjrD6KmuhNSeweXpTZGS+kv6uJfXOHD+Os26jqRCcfGnRHhNo/g1lySPhQ6VSe/Y4u2E+5t6HFk0kpLKct+X5+EuOlq7o9p8Oiucu6Au/dVNJAZBBagUg8gF4EKAygIQNW9NpnL5j5lYDFvCvSxDAp6FMFIvby38irUAlV+rl0168gdQUEZO+ldUFa4tPKjM5vGZpVjOvM+C1f3YWq8n50xc2PLnZKrk5DQrjXW2DRh5uByB21cwpJ6O2JNV2FCZnZVBekYWsnLyiJkTxK71jxxmZaSRni2Ngpys2PtUuFB5iuH64ym9aDHVdi9m/Kay7EtdR0s5aT4jY3Z2PMd9pmK3JpugE0tJ3jKOmzUWMq651jdfzgpaOAEqC1rhgmlfgMqC0VXkVlMjQpg9diIXI6K5eVMWt1vX6K/4mMdhScjFxPAmNRV5NS1q162Htmr+PwAFqPw6Va9Z2roW8ktiGWck3m/lIhfMf8Sw8KDyW4GyHnnS1/wpDvu9aFQK3h2xxmG5NvI1MmjV35rBRRAqw25vZfmGWwya7EINzaJY56lc3+TMH5FNmTe2G4r5/1j917u0cKHyq66FH6RbLXcGBB9jaEXpL8D4/sV5nBesoau9Gx2qlSq0J44AlYUm/S85FqDyl+T79YsverTB4bAJll2jmT3nGjOuXaZ+sDN2s3YSl1WFNiZhrPpTCueVQYzvUR2FX3f5TQsCVApQmc8llducREBl3G18J0/kqvpY5s/uTdnIM/Qfv5SBDk7c2ruHqv1HC1ApQGXRhMqUUA4HLMTtZAU8A+2pWeKvkcqXZ5fj6/uG4o1UiQt9j2a9AVgPrI/q12tICuKh8bc2BagUg8gF4EKAygIQVeQmb6ykpqkjw3zv0THWmV42F75ApZn9FUYFemJWLYWJfbqS1isA3yk9KPmD5S8i+/yboQCVkBx6E495juy9Fkr4g9tIlTeitHItJq2dT//q2j8rbZG+rlChMvUde7wX4LnxAME3n9Jw+kF2zm/MNedB+JRfzaZe8bgu2UCVIgaVkaeXYTp9M0kJ0byL/oC6tg5Kcj1YecmROmIGhsK6Od7usKWv22USot4QnaGKjlYJdKtb47bWHD0xaVDYI5VvzvtiN2HF/7V3JuA2VW0c/3MvmTJHJEKZoklpMDVpkHyKUJkaVCJJSpIicxFKSVFRkYRGmm4oKqRIQjJklsyE3OF7fru2jtuVfXLOPufe/Z7n8Vzu2Xutd/3fd633t961z6E5y1do1/kDtHRaB50U8hzEiqk91PyxpWrdrZ1qlNqtl3o9pTIdX9JDV5S34+9YBW4m6tegMobO+qJnFdXpteQwCwoUa6cnhhXUsO7LNThppC4tkqye11fR8lovaGS361U4Z2QNjgZU7l35he5r10avz9qkfAU76KP1A3VWZM2OUmtZ6/ibBFqx9UtKSyulFo8P18D766lglJRL32xMoTLEmLTUD9W66uOq2rahJq3Ko6T+tyv79uXqN3S8yjduq5YXlFeizyfAsX6m0o6/7fj7zymyUF1LXqwN/edrTKuyyv4XVK+cNkjDp52kB4Y2V4ns2bTo+XbqsbiORgz7899+vTJTpXL3kqlqe2d7vTf/V5Uo/6CmfNdDVRP+rv76pVk89GNQGUMv/PD6Xeo6bq1jwe4Ni/XN4u2qckU9NapVQeNfzLxQGUNJj7HrrAWVxyjGMd0eS6jcv3uT9iecqIJ5pLQ9K3X/LU2VesZ1OvjTl1q9TdIfe7V81XrlLVFbPSeMVsOS2Q59SOGYBu3xZoNKj0JF7bIAQ+W+tdqw/2SVLCTpwBaNalNZY8+Zqmm3FNPKHdlUqWxp/bZsggb2XayWg7ur+om59PkTTfXcnlZ6rtc1KuxTNRfXZyaojFqoZsKGDSrjxGmLx7VX/dDj724Glf67ZrfmjR+thEs66Rw79T4m+WMHlWla+fWLGvXySqUWktK2zdfX+y/VMwPu0xklc/05pq3L1CuAx9+uQ/dsWarvFv+qyjXqqGieY3JzJr05RZuXzNKPv5dS7bPLK9Hnb3qI6fH3zkl65J55Si4hae8KvbUgr4aMGKzT1ozSfR+m6rX+XZTnwFIN7tFTS34voVLF82n9bzvUuHNvNTr9BF83XwaVmXN6GVTGid/2bV2tZav3qGTV05V37zqtWLtfZSqVVf7ENK1b/r32H19WZUsWjvhRXTSOv+NEUjMjhgrEDiql/bs26Ocla7XXGX825S9dRZVL5PtbjeT9Wr/xN+UqXExF8kb4eRIPmse6UunBRLskigrEFCq1Sz/PXaqtaWl/jrDoqapRrpD2bd+oldvSVLHsScqRPUXbNqzS6nXbdFBS7qLlVbl8UUX4cf6jKmxQeVSJ4vICg8q4dIt/RhlU+qd1kHqKJVTGu84GlfHuoejaF1uojO7YItm6QWUk1fSvLYNK/7SOy54MKuPSLZneKIPKI7vQoDLTh/cxDcCg0pt8BpXedIq3qwwq480jPttjUOmz4AHpzqDSoDIgoR72MA0qvUlmUOlNp3i7yqAy3jzisz0GlT4LHpDuDCoNKgMS6mEP06DSm2QGld50irerDCrjzSM+22NQ6bPgAenOoNKgMiChHvYwDSq9SWZQ6U2neLvKoDLePOKzPQaVPgsekO4MKg0qAxLqYQ/ToNKbZAaV3nSKt6sMKuPNIz7bY1Dps+AB6c6g0qAyIKEe9jANKr1JZlDpTad4u8qgMt484rM9BpU+Cx6Q7gwqDSoDEuphD9Og0ptkBpXedIq3qwwq480jPttjUOmz4AHpzqDSoDIgoR72MA0qvUlmUOlNp3i7yqAy3jzisz0GlT4LHpDuDCoNKgMS6mEP06DSm2QGld50irerjgqVO3bs0ODBg+PNbrMnQgr06dNHlSpVUpMmTSLUojVjCkgzZszQrFmz1L17d7FxsdffCvTt21c1a9ZU3bp1TZsABsamTZs0evRoZ82tUKGCxcARYmDKlClavHixunXrJv7DAHtFR4GePXtGVN+jQuWBAwc0d+7c6IzGWo25AnXq1HGSW+/evWNuixmQdRQYNWqUxo4dq5kzZ1rSTOdW5lurVq102223ZR2H20g8K7B8+XK1bdvWWXNr167t+b6gXdirVy8lJSVp+vTpEYWeoOl4tPHWqlUromv0UaHyaAbZ+5lbATv+ztz+i1fr7fj7yJ6x/6YxXqPWH7vs+Nubznb87U2neLvKoDLePOKzPQaVPgsekO4MKg0qAxLqYQ/ToNKbZAaV3nSKt6sMKuPNIz7bY1Dps+AB6c6g0qAyIKEe9jANKr1JZlDpTad4u8qgMt484rM9BpU+Cx6Q7gwqDSoDEuphD9Og0ptkBpXedIq3qwwq480jPttjUOmz4AHpzqDSoDIgoR72MA0qvUlmUOlNp3i7yqAy3jzisz0GlT4LHpDuDCoNKgMS6mEP06DSm2QGld50irerDCrjzSM+22NQ6bPgAenOoNKgMiChHvYwDSq9SWZQ6U2neLvKoDLePOKzPQaVPgsekO4MKg0qAxLqYQ/ToNKbZAaV3nSKt6sMKuPNIz7bY1Dps+AB6c6g0qAyIKEe9jANKr1JZlDpTad4u8qgMt484rM9BpU+Cx6Q7gwqDSoDEuphD9Og0ptkBpXedIq3q7I+VCbv1w8zJ2ry7FRd276Jzi6SN2wf/LF1pd5/91ud0vBqnePev3e1Jr80WSsOnqGWnS/XiWG3Gh83GFTGhx+ymhUGlQaVWS2mIzUeg0pvShpUetMp3q7K4lC5Wa/e1VQDpy3S4jVpqnTBdRo85XmVW/yKBvaboDWuNwqcplu7dFWzi8oqMZ2H9m5L0iPXdNH4JUXUe87raluxuLYum67Bve/XS5MXa2vKibq4TQv1fOhh1SwbPrDGOiAMKmPtgazZf8yhct1X6txziFLqD9HQ605Stmx/6py2frJuv2+a6tzXU60vPCkm4tt/0xgT2eOm05hC5bfP687FNTWiRTVl/2tOIMzmBW/ro42F1eTyOsqTI51UB3fqi/HDNOSzXOr7dEdVyp9LIbdGTVeDyqhJG9WGszZUfv6oEuo/q2ZDPtGrt54pKZuyJxzUvHGPqs3NX6nTkglqXuhnta9dV2uuHqk3+7VV8cO48Au1zl1fX55dQzlWHtR9Myeq7an5lDS8vVq8lU9Jb/TTCauHqlajd9TyxVf0YKNqyhlVd0W+cYPKyGtqLUqxg8o0LZvxpFrVe1jzUlKkbAk665In9eYnrfT9vdeq+YhqmrKwqca3uV1F7pusoTee7UuCDI0Jg8pgz5DYQOVOTe1xk2588kOVbDpGM165WcX/okpO4vrffZV6L6ql2bOHq0ahPIfNiZE3ltS0ok9qeOs9Ov+qLrpj8nb1qJ14GJRGw6MGldFQNfptZm2oXDBYxc97TKe17KlHOl2nupVPUe4cyZr7F1R2XjZRrUtm11O3V9eYHB308TOdVapg+lplspZ9Oly3tpisNjMn6pZSiXr27os0MuUWfTS8i4qkzlO7CxtqX4sXNbJrIxXKZFRpUBk6ydZqyCVVlXPQDrWv7sdePPoTPFY9xA4qDx9x6k/DdHXTd3VP/3s1+PEkPTp7qC7Jnk2rP+yvzp+foNf63q48Prs61lC5cdGbeu6173Vjl96qcjjiBs4AACAASURBVILPg49VQB7W7wF9O76nxm2pqT53N1Cu9Et+lG2MBVRu+naSpm0sqhq/PKFmc25U0st/Q+V347poQlKC5iqf+g+6Px1UJumeys/pig/GqUG5bJraobT6nfy2Pn/gfCWEljqjoFnmg8rNerlxda3qsEo9L84RdeiOguQRaTJrQ6VWa9z9PTXglTFalP8CdWreSff2b6RfHah8UxU7NddZeVOV9M6rKnfrKA1rX18F/gGFGUPlpPz36c0Bdyn/ga8MKiMSivHQiEFlpLwQN1A5p4fqdPpVTw65Rg/3+FIDPu6v87Nl07Y5o1V/wEq9OrmPTnPPxiM1+KO0Y1Dpk9BH7CZ4UOlKseqFa3Tt7BCoXP2p7howQY2bNdQLry9Ulyc7p4PKFRp54216t1g9XVM6WUlfL1fzh59Rk7MKHXqkJFreNKiMlrLRbTeLQ6WUcnCnls77XFNffkr9xi7RecPfVp+8U9Tm5ie0RFKu/EV099Cp6tCginIvGKaWT8yQVEB123RWp2YXKV+iQWV0QzD2re/f+IOeHdxHHy5crzXzv1a20y7Wyfkrq/2zj6hRhWKxNzATWhAfULlEQ6tfqfmt3tbItgX1wh13aOwmqUi2bDq4c70W6ErNm/NUYKBy6+wRatF7ivbu3KR1G/foxDLllTfnVRr6cWed7jNYxyqkN77XVa2f+UY7N67U5oMFVa5UUZWucIsef/ZGlfZJg1hUKjOGyh2aenddfVBnmp664Ce16DM7A6iUNswbrZuaddA361L0e/Mx+uOV5kqMcpUSezMLVCbv2aKJzzyol6ev1PqFc7SvVE2VK1RGN3Ttojb1qui4WAV7jPrN8lDp6pq2aKwqXd1Re24erylnzlCbm7/UvYvf0K2nFVdC4p/Ph6Slpig5JdW5JXtCghKyZ5d0OFS2PSWX3njsej2y6mIlPd9VhQ5M0vUle6jyc6PV/666yhcjR/7XbqNx/L13xefqeEdLvfrFRuUr1FFJmwfp7P9qoB/3paUpJSVFqWlrNazeWco5cIvanZNdCYkJyu5ToonGMNdNvFvlW4xSWlopteozQoMevFIFo9FRBm3GHiq3aXLHBmq+v5t+f76BkwRTU5KVkprmWLtt7stqODFFXw5ppwSfT4BjVal017eNP7ylkeO+V7POvVS5aIIScyT4/lypT2H4j27SUpOVnLJf303orTe2XKRed9VX7hwJSkjM7psG8QKVaR89pjPfq6q1T9+gnOtn6obeszKAys/UofIDuvCN2bqhym96qfG5evG8NzW3e207/j4UXWlKTUlRSupmjWlWQ6vbLVePujmVmAhD+Ly4xGpihfSbpaFy04Q2KnvHB+o04GntnNRPE5alqfc783Xu0j8/qMMzlbdXKP4vbjigtQvnavaMt9Tv8ZmqP7y3rq92hpIXjlDbeyapeo+BKvdxUz29o5leHPGUGp/1b23FgbczMCEaUBmfI/VilR1/e1HJyzWxhMrkfb/qveHdNfy3i/TJgFv+8WxT6h97NWtML716oJZeaN8w6sd46fWKFVS6dtgzlXb8zTOVO99/VB2HTdeeA5IO7NTStbt00imXqd8bw1Qt2yYVKFZOBb58SJWfK6Op49qr7HHZdOCDDqrW92S998UDqphA0SV6r8xSqfxbAXumEi2yNFRq9ad6ZBTH2X++StRto/b1TtG6hUmaNHGNana6UecW/bfa4g5NHzFISev/Dpu8lRrpnv+VUNKUtzTvpy1S9uNUsW4z3XBZBeWK3vyKWssGlaHS7tTs0U8r4aoeuiA23zYTNT/73XAsoXLl9BFq02GoSlzSSGeUyC/lKqwaNavrj6XztWD9NiXv2q31W3OpycMddEW5on5Lo1hD5e7NizRnwSadUaueimW+b0GLgL+SteH7z7RwbxnVO7+iEqPLRv+wNxaVyp2/fKN3PvhYiz4Zo7G/nKlbWzVQ4+sa6JwyheUM/5cZhyqVFXZ9p0f7DtfVHYerfu65uvG2Hsp7USOVzZtNO75J0vZrBmnIbWfr+Cif4mQ+qNyjb8c9q20XdNFlZRN836xGYGJEpImsDZURkShrN2JQmbX9G6vRxRIqd21cqgWL1mi/O/jEPCpTrrSSN6/R+p2/SzpOJcpXUaXyJyj9V/L5oVesodKPMVofR1YgFlC5b9sa/fDjMm3//c/HP3RcIVWqdrpOLvzX1wft36aFK3bolApllDt5u5YsW6cTy1VW8fzHae33n2jp5jSlObcWUNXaNVQyd/SPdTMfVFrUo4BBZcDjwKAy4AEQpeHHEiqjNKSINWtQGTEpM2VDsYDKzCiUQWVm9JpBZeb0WgStNqiMoJjW1CEFDCqPHAwGlcGeKAaV3vxvUOlNp3i7yiqV8eYRn+0xqPRZ8IB0Z1BpUBmQUA97mAaV3iQzqPSmU7xdZVAZbx7x2R6DSp8FD0h3BpUGlQEJ9bCHaVDpTTKDSm86xdtVBpXx5hGf7TGo9FnwgHRnUGlQGZBQD3uYBpXeJDOo9KZTvF1lUBlvHvHZHoNKnwUPSHcGlQaVAQn1sIdpUOlNMoNKbzrF21UGlfHmEZ/tMaj0WfCAdGdQaVAZkFAPe5gGld4kM6j0plO8XWVQGW8e8dkeg0qfBQ9IdwaVBpUBCfWwh2lQ6U0yg0pvOsXbVQaV8eYRn+0xqPRZ8IB0Z1BpUBmQUA97mAaV3iQzqPSmU7xddVSoPHDggBYuXBhvdps9EVLg/PPP1yWXXKIBAwZEqEVrxhSQnn/+eb388sv6+uuvxcbFXn8rcMEFF+iWW27RnXfeabIEUIGffvpJrVu3dtbcunXrBlABb0NmY/rJJ5/oyy+/dP5rU3tFR4Hzzjsvomv0UaHyl19+0SmnnBKd0VirpoApYAqYAqaAKWAKmAIxUYDCYc6cOSPW91Ghct++ffrss88i1qE1ZAqYAqaAKWAKmAKmgCkQewWuvvpqZc+ePWKGHBUqI9aTNWQKmAKmgClgCpgCpoApkGUVMKjMsq61gZkCpoApYAqYAqaAKeCfAgaV/mltPZkCpoApYAqYAqaAKZBlFQgkVKakpOidd95RoUKFnE8+e3n9/vvv6tOnj5o2baqzzjrLyy2er1m/fr0mTZqk6667TieffLLn+7gwLS1NCxYs0PLly3Xttdcqd+7ch+7nAdwnnnhCfDVDyZIl1b9/f11//fU6++yzw+rj3y7G9jFjxui2225T8eLFI9au2xC+mj17tk466SSVL1/e+fWyZcu0bds21ahRw/lU4N69e51rqlevriJFikTMhl27dqlbt27q1KmT82G1F198UXxann5CX5s2bdJbb72la665RmXLlo1Y/8fSUHJyssaNG6fatWtHxaYff/xR7777ru69914tWrTIicGbbrpJ+fLlOxazPd2bmprqfCqU2L/qqqs83fNfLtqwYYMefPBB53mjdu3a6cILLzysGeKQ9xs0aKA2bdooR44c/6Wbf9zD+HiO/Y8//hDPO/EVNHPmzHH0LVCgQET6sEZMAVPAFIiGAmFDZcuWLZ1k4r6GDRvmLKhjx451EvCePXuct/LmzatXXnlFFStWdEBs6dKlh+7hk0YPPfSQ7rnnnn986mj79u0OBH311VfO9fnz59fo0aN1xRVXRGz8JNynnnpKJUqUEOM50uuxxx7T/v37NXDgQO3cuVONGjXSww8/rHr16kXMFheS6OOBBx5Q5cqVw2qbxEqCnTdvnjp27Kjjjz/+0P2AcLNmzdSzZ0+ddtppaty4sdPHsWgJwN1///1OuwA5iRVfomc0gOrgwYMaPHiwAyt8BQtfT9O3b18HZEaMGKETTjhBK1euFHHINxVMnz79MP1KlSqlDz744D99g8Fvv/2mOnXqONB8xhlnOABFDKQHGfoH2Nu3b/+PDQdgz33A/LHoHk5Q8BUc+ISx8+fnn392vuKH+cjXmBAPxIr7Yq7dcccdzrjYhHj5CqBZs2Y5mr/00kuO5p9++qnTbuHChcMx9T9dy0aDNYHYj+bX8rDRmzx5sqMdm7XExETHXmDv6aef1ocffujExvjx41WrVi3xVUGReDE+1lM+JHnXXXc585tNcK9evZx49/rCP0uWLHHmiRefem3XrjMFTAFT4EgKhA2Vbdu2deCEBPTqq686C9bUqVOdStuvv/7qgCUv/s0i+N5776lMmTIOlFFJA9Quu+wy55qtW7eKahBVIHfRowL1+OOPO5WvatWqOUkQWAAsgFHglEWd6gEQw8599+7dDswCpCTxggULHqr4kVBLly6tPHnyHOqPqtfQoUMPQSWgRB8AJJUv7OHvjIWFHZtpY8uWLU7SBNxY+IEJ+sZ2ALVYsWLO7zdv3uzYwdiwGaBL/5F9xsD9tE+li8REf0AlGqxdu9Zp67jjjnPuxy6upxoIaNMv9qBtUlKS811eVMq4jvFjL324UHnOOedozZo1TnUW+9Geigh908+JJ554qNJI37zPC53Ri2TG9cAc3x9Wv359NWzY0Bnzxo0bnftJuvTBT4CMn1QXV69e7eiBrthGO9xDvPBiTOiHjmiHPe6/AYcpU6Y4lcgePXo4Ot5999369ttvHbA499xzneT+zTffOPDG2Kga8v2Ijz76qBMf9E27jMGt5BIv6IxObDKoSrna7Nixw4kn7CIuqPKiayhUArv4g9hhrFQFqWiGVrEZJ0kdwAMoqUQzNmxAN96nDaqr/J33XH/wPhqgP/ZgB+/j+3Llyjm/x37+uP92Jzm2z50714kn/M4mgDhhLlHRJrYHDRrkjJ1+R40a5WjM95UxZ4lbfJa+P3RkE8Hv+a69CRMmOFCF34hHbMauFStWOG3wAmrRnbmJzhmNj+sYI2sEduJz4o/4RYP07aFXKFRyH/1xLTGHL5k3zFX6ZM3AX6wB7lwKXRC5H325lvvZCDMvXWBmw4fGuXLlcm77/vvvNXz4cHXt2vVQ9Ty0PTZzjAdNaLNChQrOeBg7eqMHujBO+sVW5gI6Yh//DoVK/EV76It9+Jx5RlvMTebUqlWrRL+8mGe03a9fP8dPbHj4Hfbzb9pjHvE7Nmv41b2f+cOcjeSnQS39mgKmQHAUOCaoJBGxiwcgSTChUElio0J5++23O1WajKDyySef1Pz5850Kirtgp4fK5557zlnwqIJMmzbN6YcjYqCE6hEJk0rJa6+95iRnEh6LK5UYkgzwSwLiyJckAYDwk3Z5v0WLFvrhhx+cdrmPvvhC2ipVqjgJlt9xDWPABv4OFANxL7zwgooWLeokNBZ2jsJIhNjkJgDGRzuhx+wkGkCchExiJwkCPQA6yYYqCHYAEEAHIH/RRRepSZMmTiIDUADJZ555xhk3tjAe9+gcbbp37+4ks+bNmzt2V61a1TnC49+XXnqp4zeO1eiDhId2QBh+AqIBH8CCP1x78cUXO2N79tlnnWNg4Jcv8OUImvaxCwjjiA4II/kBflT6uA+YAXCo9AKtfDE2upHsATZ+jz+opJLwaNM9TqQKi8/og3Z5j5/YhCbYg9+ptnFPeqgE7Hh0gfuJGV4c1w4ZMsTRnGRP1ZyKOxsmYoHNCHq1atXK8V9opZJK9ccff+zYhL+4Hx9SGQqFSsZG++gHqKAXQEJM9e7d2wEt4oq/0x8VQyAYUAWAunTp4viFNgArEj3XURVGf3z+/vvvO/Mv9LEHYobjU2DqzDPPdPrDL2yk0JpYI8b/97//OeCDLsAJUIP+9Ec/9AeEoNOpp57qbCLpi78DQ9xLBY0xffTRRw5Uc0IBsBJTaIJdxOnEiRP1xRdfOOMjxvg9mwQ2I7xmzpzpXMdagG+BNmxlAxHaHusE7wHxbqWSSjTz2q2UsukBApmrXMcGg/uYUwA+c8l9uVVHjvOxDWjmi8mBO6q2xAlxwR/mNC82ylRqgS98xdrCYwbuFzSzwUEz1gYA8oYbbnBiis0HIOhuVHkPv6AB9jEvaIfqJHa7lUraQ2f0JS6IR+Y47TNOjsjxDf5gjPj88ssvd2KeNpnznP7gU/yHj4gB7kMj9EFT2qtUqZKzZkfye+uCk05tpKaAKRA2VLI4ARoABItk586dnSNBICEUKtn93nrrrU7yItlnBJWLFy92Fk5gw90ZA5UkXxZrgIefQA6JjCRP4mDRJAkAjiNHjnSSJ0kFkKLaRPLkXippVEf/DSo5/sYGEioLO+AKlJDIqFDwHrDAeBgHizDHXFR9SE5UB4EK7GLxJtGQuKhqUfnBJnb/AKebdIApqrEAF/aRbOmDJAAAACuMmSQGuAMwVJ1IdkeCSpIOYEZiIBkCuYyNPxlBJeCK1iR2gIXxYjfJhqop46M6CDjzbxf68QeJHh2AK3fsLlQCZfjdfVQA35Dw8BcwxNgAaqqs6Al4YR/PpQGJgCjAAYS5MUFc4Qs2KSROjlqpUgM8HIVzPwkSPXmlh0piD1ggYRIXvNw4Q1f6wR/4DhtdiLryyisdIEgPlRx1Uv0BJhgvz7uhHzCT/nlbN26oGFPdBVLoC/35n6qYN2jC5gAAwO9syIgFNg9U7oAtxolPsZexMxcYE2BKnKX/HyeAF94H8N3n8IBXKlPMXUCQeAHIgG42IAAJ42H+UOViLnENGx90ALwBXcbNsTDVNGIjFCrRlxjmJ5s1fAb4coQL7KIlsIl+xJH7fC/xwOkE8wQ/8D6VXSArtD3soD02VUeDSjZ/xD/asuEilolD5pp7MkIMMVb0BayZa2z28A99oA+gG3p8TDy//vrrDqgxLwA1gM+FVeKBNQdAB06BUNY69KMKiQ+JdTZ3gD1zibbQkTlBe2yUM4JKt/LIRoUNDRVL5jwvgBNAZO4yVuymX34SJ+4jR2ww2XRgF3EL8LOhwTf43F6mgClgCvxXBcKGSnaxJHB2wiy07HpJaCyi4UJlRkaT7Ems7OCpFpLw6YPFkQUXeAK2OA4CPkm+LKwcy7rPaLLguke/gOXRoJKFmgRHRYBkTHWTKhALbkZQefrppzuJgXv44AbXkJhIKizYJEQgCyB44403HOgFLt3KG1UG7qciAaCS/N1nKkksJDMSO0mCJAhUkMwZ/5Gg0n2mEiCjcge4UuFEoyNBJVUw3scexgoMAi4kH4Ad3fAxlSv3dTSoBCLoj2NpgJWKFVriP3xFWzzK4D7OQLskRa450jOHHNcBYsAUwAXkkKwBd7ThjwsjgEZ6qMwozrgO+4g3kjtAB1wDAviSnwAZldD0UMkmCIAEBKhAhz5TSbLGVpIzcEJ84DcXKoFMdAAEAS3AnI0JmyOAA7DCdwAgVWCqdvTDe/iCKjf2UA0P90WbwB42A8/EFL4mFokB4JKKLLa6/bnQzzxifjEmKsqhz1SGQiXxg23AMnOJuQsgUYnEfrQAIAF3Nh6MkRf+wL5169Y5VUE2HoAaMUp7gDftEd+09fnnnx8VKtmYMFbmEX0zFvwZCon0w7+JdTZ/fPCMOcYpCpu9jKCSOc2agx5AJVq6JxRU+IBKgA37iW3aYk1zq3/4gPGzyQAqeY+1g/hDZ6ASOMwIKpnnPK6Aze4GCd8xX4knKvZ8kIxKJzDtQiUxShyxFrGmch19Mj7mFFCNz/jDBs+ewQx3dtn1poApgAJhQ2XoM5WhEoZCJQsWyZXjVBY2Kg8ZVSpZzPg9FQL3lf742/09iyGVOqojAAWwxQcjAEiOdUgygAWVGBZskhkJhEWbRZ9PbvJ7njULPf6musiunsRDVQO7qUIAPcAK8Jq+UkniJRFzLyBEtY6xUkWhGhYKlW+++aZjayhUMmYSKPAKnHMMTeIBcgBMqpNAJWBCRYjqKRADhAIdHJnyYSk0p1LE8TcJhfFTlcJeYITkzPGtF6hkvOhLwgccADmSPoAR+gIqSZbAY0aVyqNBJfDE+PAz1Ta3Aur2gd4kU44EQxMb91Ah4j0AHMDkQxoc//E7QA3gyAgqATHgFj1Dj/VI0FTiAA98CowCImhAkqWtjKCyZs2ah1WqSdz4HEjLqFLZoUMHp+oGRABGxATxSsUOQMAudCEuaIOfgCmxQTWKo0mqz25FKhTwqSzzbJyXZ+BcqCSG0NB91pU5RfUPqAQoiB82GaH90Q8QT5xz9M5xN3MPn4RCJfFLXBK/gBex+vbbbx8GlZxwMBeZmy5UMibmAXMQ+OF5SDawPD7C/MQmgJN7iP1QqOSUgj7cShunJ1RAqVyzOaUSd6T/apb5zjynD46jqVRiP7+bMWNGhlDJpo9qORsP7KQyyHxDHzaO6aGSuEJb7GJdcl/ELeNhc8qJBePHN0AlQJsRVFL9RTvihs0184j1AW2Yl/gCHRgP46byD4CiObGFDZz0ZPQiHpjzHNUzD+xlCpgCpkC4CkQUKtn1spBzXMXOmF03f3hlBJXAHTtyqlfu8d2RoJIFlsTKbp5KEZVJKlZUWljggSKqQkAVCykLKIsnCyzPf5G8WLTd42X3mUrAkCQCbFJlZPGlWkF7QAcLOHDGMT4AwlEVR1csvCQzKnLAARUoQJNqyNGgkmtI5FRJON7jfpIBfVHpcZ8N45gSWATkqQ6TSEieJH6OKklUblWDpIv9AApjoboDKB3pmUqO90IrlS5UAsgAMEmOBAiEAVbu82RUZLgWmwFIAD/0mcqjQSVVVBIjSY9HGoB599lXfIcviJ3QZyqJHwCFhAtous8QAn4kdCCYft2KV/pKJe0BOcAdx7yhUAbsAaOAG0BBjAF0wDSxkhFUAnvAPFVzjsLRjGNtbEkPle43DRCD2EgcEZ8APBsdwIxNGFCJ3cQWsQ7EscmgGoU/+Ol+YIjNC9ANTAA/6Z+pPNIi4EIlFTZij+oWcEl7LviwUXMf2aA/YBW7iSu0wXZilo2c+4xeKFQSl9wPqDMufINOoZXKI0El84KNBhtI5hD90B/zimoyQM6aQRUwFCrdxyA44gYMeQ+AZ1xoiJ6cevBiPWIj4r5Yl1hDiHUAHl2Y74yZDV1GlUqeDyb2uB7wZtOI3e5RfnqoRB/mG/YR48w75jAbKqCSOUAssN4wh7GH+MoIKqkg4z/WCTZWVLWZR2jCWsQ9HGUzz7CTeQSo4w+u4T3WSV70ybqIxlSe2TDyEwh153u4CcWuNwVMgWArEDZUAmYkm/TfSUjSZPEkifKiOskxsQuLJAwAkkqe+7UYwAWLIMc1bqUFaCGpUFlwj3dcF/E8HQmDa1hcWRRZXEkELIa0Q8UA+0juABFH8izy2AEA8WwRUEryY1FnoSeBMy5swTaOwajGAIr0x6JPe8AJ17Pgci3jobJGnyQD91PjJDn64j4AlYU/9BlBxsPvqDBSESRhU2EFePhJP1S/SMqMD3ChAuKOn+SKHdjHmLGBIzCOcN1PzJLgGDOAyVjQEvBxP40LnKMPYI4N7qfkAQD0cj+hD+wAqO7XKFG9Qzt8R3ImoeEvbMcnbn/YTbLFHrRjvFSxsIs2uJ+Y4e9Ue0iI6AhAA3Ik3dDqG3FF2/zOfYaQ8TIm9Al9FgzN8TOaoxv6YCM6pP+ePx55IDaJCSrnPEcKzNAe+qOFex/xDQAT+/gC/5OIGSv6EvPp22d8VIDYBBEfgD5AzqaHcVLJc6GSNtGRMaIrc4W/u3OL6/g3GzdilA0TtgA06Z+pzGhZQwP0wE76AibwDTajGb9Ds/T9oQc+otpLBQ2wp19+En+AGfOMdvkdcxHN0ZB/oy0gyd/RgJgg3tAy/TN8gBBVN3zMXMDv9Jm+PWxBW8CKa9hgMW/YIPDYCXOb2MY27MHHLki5Hw5yNWLDQhyhL3AJ2DM30IQNQ/rvJQ3tj7nIuJn/brwSe8xHfEg77ifQmXNcT6y4jzYAle73T+IbquDEk/vpbvRy5zf9MMfQiPnDi3WA3xPHxC/rF9fwzRmMh/ULu5hfaMK/me+8iGv8jS9Yb9CT9rjWXqaAKWAK/BcFwobK/9JJNO9hIQQq3WcqQ4+XotlvVm2bCgxQQWXP/eQr+pIgo/0Csqmc8TxYVvYjcMojFlQKefTDhUr3mUovOrNxofJIBcw+XOFFsfi7xj3+dp+ptOcY489HZpEpYAqEp0CWgEoqESRZdvyhX60SnhR2NQoAOBztcxRPJRhosVfkFGATRLWIqhXxSvUIzTl+plJF5dJewVDA/WJ8npWO9P/SFQwFbZSmgCkQbwpkeqiMN0HNHlPAFDAFTAFTwBQwBYKogEFlEL1uYzYFTAFTwBQwBUwBUyDCChhURlhQa84UMAVMAVPAFDAFTIEgKmBQGUSv25hNAVPAFDAFTAFTwBSIsAIGlREW1JozBUwBU8AUMAVMAVMgiAoYVAbR6zZmU8AUMAVMAVPAFDAFIqyAQWWEBbXmTAFTwBQwBUwBU8AUCKICBpVB9LqN2RQwBUwBU8AUMAVMgQgrYFAZYUGtOVPAFDAFTAFTwBQwBYKogEFlEL1uYzYFTAFTwBQwBUwBUyDCChhURlhQa84UMAVMAVPAFDAFTIEgKmBQGUSv25hNAVPAFDAFTAFTwBSIsAIGlREW1JozBUwBU8AUMAVMAVMgiAoYVAbR6zZmU8AUMAVMAVPAFDAFIqyAQWWEBbXmTAFTwBQwBUwBU8AUCKICBpVB9LqN2RQwBUwBU8AUMAVMgQgrYFAZYUGtOVPAFDAFTAFTwBQwBYKogEFlEL1uYzYFTAFTwBQwBUwBUyDCChhURlhQa84UMAVMAVPAFDAFTIEgKmBQGUSv25hNAVPAFDAFTAFTwBSIsAIGlREW1JozBUwBU8AUMAVMAVMgiAoYVAbR6zZmU8AUMAVMAVPAFDAFIqyAQWWEBbXmTAFTwBQwBUwBU8AUCKICBpVB9LqN2RQwBUwBU8AUMAVMgQgrYFAZYUGtOVPAFDAFTAFTwBQwBYKogEFlEL1uYzYFTAFTwBQwBUwBUyDCChhURlhQa84UMAVMAVPAFDAFTIEgKmBQGUSv25hNAVPAFDAFTAFTwBSIsAIGlREW1JozBUwBU8AUFIJ7dQAAADlJREFUMAVMAVMgiAoYVAbR6zZmU8AUMAVMAVPAFDAFIqyAQWWEBbXmTAFTwBQwBUwBU8AUCKIC/we0jnnprxK8qAAAAABJRU5ErkJggg==\" width=\"661\" height=\"282\"\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eConsistent with the \u003cem\u003ein vitro\u003c/em\u003e functional characteristics of the SP-10 cell line, it formed large tumors in mice six weeks after engraftment, whereas the NF1-18B 4n cell line failed to generate tumors \u003cem\u003ein vivo.\u003c/em\u003e In contrast, NF1-18B\u0026thinsp;\u0026lt;\u0026thinsp;3n cells generated small tumors that were detected only at post-mortem, despite not exhibiting aggressive behavior \u003cem\u003ein vitro\u003c/em\u003e (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eFinally, we emphasize the value of generating matched \u003cem\u003ein vitro\u003c/em\u003e and \u003cem\u003ein vivo\u003c/em\u003e models from the same primary tumor, as we did with the two patient tumors. This approach enhances the translational relevance of experimental findings. Indeed, the cell lines and PDOXs established in this study have already been used in preclinical drug screens targeting pathways disrupted by \u003cem\u003eNF1\u003c/em\u003e, \u003cem\u003eCDKN2A\u003c/em\u003e, and PRC2 inactivation [\u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e].\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eThis study introduces two novel patient-derived MPNST cell models, one NF1-associated and the other sporadic, along with their corresponding PDOXs. These models serve as valuable resources for advancing research and drug testing in these aggressive tumors, further expanding our MPNST preclinical model platform, which now includes 30 PDOXs and five patient-derived cell lines. In particular, the SP-10 cell model stands out as one of the few well-characterized models of a genuine \"classic\" sporadic MPNST.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eBAF B allele frequency\u003c/p\u003e \u003cp\u003eCN Copy number\u003c/p\u003e \u003cp\u003eCNG Copy number gain\u003c/p\u003e \u003cp\u003eDMEM Dulbecco\u0026rsquo;s modified Eagle\u0026rsquo;s medium\u003c/p\u003e \u003cp\u003eDMSO Dimethyl sulfoxide\u003c/p\u003e \u003cp\u003eFBS Fetal Bovine Serum\u003c/p\u003e \u003cp\u003eh Hours\u003c/p\u003e \u003cp\u003eH3K27me3 Trimethylation of the histone H3 at lysine 27\u003c/p\u003e \u003cp\u003eH\u0026amp;E Hematoxylin and Eosin\u003c/p\u003e \u003cp\u003eLOH Loss of Heterozygosity\u003c/p\u003e \u003cp\u003eLRR Log R ratio\u003c/p\u003e \u003cp\u003emin Minute\u003c/p\u003e \u003cp\u003eMPNST Malignant peripheral nerve sheath tumor\u003c/p\u003e \u003cp\u003eMTT 3-(4,5-dimetrhylthiaziol-2-yl)-2,5-diphenyl-tetrazolium bromide\u003c/p\u003e \u003cp\u003eNF1 Neurofibromatosis type 1\u003c/p\u003e \u003cp\u003eON Overnight\u003c/p\u003e \u003cp\u003ePBS Phosphate Buffered Saline\u003c/p\u003e \u003cp\u003ePDOX Patient-derived orthothopic xenograft\u003c/p\u003e \u003cp\u003ePDT Population doubling time\u003c/p\u003e \u003cp\u003epNF Plexiform neurofibroma\u003c/p\u003e \u003cp\u003ePRC2 Polycomb Repressive Complex 2\u003c/p\u003e \u003cp\u003eP/S Penicillin/Streptomycin\u003c/p\u003e \u003cp\u003eRT Room temperature\u003c/p\u003e \u003cp\u003eSMA Smooth muscle actin\u003c/p\u003e \u003cp\u003eSTR Short tandem repeat\u003c/p\u003e \u003cp\u003eSTS Soft tissue sarcomas\u003c/p\u003e \u003cp\u003eTSG Tumor suppressor gene\u003c/p\u003e \u003cp\u003eWGS Whole genome sequencing\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eThis study was approved by the IDIBELL Ethics Committee (#PR213/13) and all subjects provided written informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThe authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis work is supported by the Carlos III National Health Institute funded by FEDER funds \u0026ndash; a way to build Europe \u0026ndash; [PI23/00017, PI19/00553 and CIBERONC] as well as by project CPP2022-009550, funded by MCIU/AEI/10.13039/501100011033 and by the European Union \u0026ldquo;NextGenerationEU\u0026rdquo;/PRTR. With the institutional support of CERCA Programme / Generalitat of Catalunya and Department of Research and Universities of the Generalitat de Catalunya and AGAUR (2021SGR01112). We thank the finantial support of Fundaci\u0026oacute;n PROYECTO NEUROFIBROMATOSIS (FPNF) and Fundaci\u0026oacute; La Marat\u0026oacute; de TV3.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u0026nbsp;\u003c/strong\u003eConceptualization: S.O-B., J.F-R., C.L.; Molecular and cellular experimental work: S.O-B.; Mouse experimental work: S.O-B., J.F-R.; Bioinformatic analysis: M.M-L., B.G.; Scientific input: J.F-R., E.C-B., A.V.; Manuscript Figures: S.O-B.; M.M-L.; Writing manuscript: S.O-B.; E.C-B., C.L., E.S; Manuscript revision and editing: all authors; Funding acquisition: C.L., E.S.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eWe would like to thank the patients and families that participated in this project, and all Spanish NF patients and NF associations for their continuing support and effort, in particular the Spanish Asociaci\u0026oacute;n de Afectados de Neurofibromatosis (AANF) and the Associaci\u0026oacute; Catalana de les Neurofibromatosis (ACNefi). We thank CERCA Program/Generalitat de Catalunya for institutional support.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDucatman BS, et al. Malignant peripheral nerve sheath tumors. A clinicopathologic study of 120 cases. Cancer. 1986;57(10):2006\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFerner RE, Gutmann DH. International consensus statement on malignant peripheral nerve sheath tumors in neurofibromatosis. Cancer Res. 2002;62(5):1573\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLaFemina J, et al. Oncologic outcomes of sporadic, neurofibromatosis-associated, and radiation-induced malignant peripheral nerve sheath tumors. Ann Surg Oncol. 2013;20(1):66\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEvans DG, et al. Malignant peripheral nerve sheath tumours in neurofibromatosis 1. 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Chemotherapy for the treatment of malignant peripheral nerve sheath tumors in neurofibromatosis 1: a 10-year institutional review. Orphanet J Rare Dis. 2013;8:127.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLongo JF, et al. Establishment and genomic characterization of a sporadic malignant peripheral nerve sheath tumor cell line. Sci Rep. 2021;11(1):5690.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim A et al. \u003cem\u003eMalignant Peripheral Nerve Sheath Tumors State of the Science: Leveraging Clinical and Biological Insights into Effective Therapies.\u003c/em\u003e Sarcoma, 2017. 2017: p. 7429697.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBairoch A. The Cellosaurus, a Cell-Line Knowledge Resource. J Biomol Tech. 2018;29(2):25\u0026ndash;38.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRichmond A, Su Y. Mouse xenograft models vs GEM models for human cancer therapeutics. 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Sox10\u0026ndash;a marker for not only schwannian and melanocytic neoplasms but also myoepithelial cell tumors of soft tissue: a systematic analysis of 5134 tumors. Am J Surg Pathol. 2015;39(6):826\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOyama R, et al. Establishment and characterization of patient-derived cancer models of malignant peripheral nerve sheath tumors. Cancer Cell Int. 2020;20:58.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOrtega-Bertran S et al. Triple Combination of MEK, BET, and CDK Inhibitors Significantly Reduces Human Malignant Peripheral Nerve Sheath Tumors in Mouse Models. Clin Cancer Res, 2024.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"cancer-cell-international","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ccin","sideBox":"Learn more about [Cancer Cell International](http://cancerci.biomedcentral.com/)","snPcode":"12935","submissionUrl":"https://submission.nature.com/new-submission/12935/3","title":"Cancer Cell International","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Cellular model, malignant peripheral nerve sheath tumors, neurofibromatosis type 1, NF1, sporadic, and patient-derived xenograft","lastPublishedDoi":"10.21203/rs.3.rs-6219394/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6219394/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eMalignant peripheral nerve sheath tumors (MPNSTs) are rare, invasive, and aggressive soft tissue sarcomas arising from peripheral nerves. They may occur sporadically or in association with Neurofibromatosis type 1 (NF1), in which they are the leading cause of mortality. Currently, there are no effective therapies other than surgery. Therefore, tumor-derived cell lines are essential for testing new therapeutic strategies, especially when used in parallel with \u003cem\u003ein vivo\u003c/em\u003e models. In this study, we present two new MPNST cell lines and two patient-derived orthotopic xenograft (PDOX) models from a sporadic (SP-10) and an NF1-related (NF1-18B) MPNST patient to increase the number of available preclinical models for \u003cem\u003ein vitro\u003c/em\u003e and \u003cem\u003ein vivo\u003c/em\u003e drug testing.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe cell lines were isolated and extensively characterized genetically (tumor suppressor gene mutation status, DNA content), phenotypically (cell morphology, marker expression), and functionally (proliferation rate, colony formation capacity, migration rate, tumorigenic ability). We validated the models by comparing the genomic (copy number variation profile) and histological characteristics of the cell lines and PDOX tumors with their corresponding patient tumors.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe new cell lines and PDOXs tumors exhibited similar genomic copy number variation profiles, histological patterns, and marker expressions as the patient tumors, validating them as faithful models. Interestingly, the NF1-18B cell model presented two cell subpopulations with different ploidy states (one\u0026thinsp;\u0026lt;\u0026thinsp;3n and the other 4n) and functional features \u003cem\u003ein vitro\u003c/em\u003e. NF1-18B 4n, along with SP-10 cell lines, exhibited \u003cem\u003ein vitro\u003c/em\u003e functional hallmarks of MPNSTs, including high proliferation and migration rates and colony forming ability. However, only the SP-10 model exhibited aggressive tumorigenicity in athymic mice. In contrast, the NF1-18B\u0026thinsp;\u0026lt;\u0026thinsp;3n showed a low migration rate and did not form colonies or aggregates \u003cem\u003ein vitro\u003c/em\u003e.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe newly established MPNST cell lines, along with their corresponding PDOX models, serve as valuable tools for both \u003cem\u003ein vitro\u003c/em\u003e and \u003cem\u003ein vivo\u003c/em\u003e testing of novel therapeutic agents. Notably, the SP-10 cell line model represents one of the few documented cases isolated from a genuine \"classic\" MPNST.\u003c/p\u003e","manuscriptTitle":"New Models for MPNST: Establishment and Comprehensive Characterization of Two Tumor Cell Lines","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-30 12:12:46","doi":"10.21203/rs.3.rs-6219394/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-23T09:56:09+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-22T17:22:19+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-17T07:11:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"338358538872912145395047708653527245695","date":"2025-04-11T12:27:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"328496030306840856642955391809937721838","date":"2025-04-10T12:51:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"319277170068696459276503511977034916235","date":"2025-04-04T13:04:06+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-01T09:01:41+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-13T14:19:56+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-13T14:16:18+00:00","index":"","fulltext":""},{"type":"submitted","content":"Cancer Cell International","date":"2025-03-13T10:56:22+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"cancer-cell-international","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ccin","sideBox":"Learn more about [Cancer Cell International](http://cancerci.biomedcentral.com/)","snPcode":"12935","submissionUrl":"https://submission.nature.com/new-submission/12935/3","title":"Cancer Cell International","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"14826017-fe16-49d6-a25f-5d3fd77bea79","owner":[],"postedDate":"April 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-08-07T07:10:47+00:00","versionOfRecord":{"articleIdentity":"rs-6219394","link":"https://doi.org/10.1186/s12935-025-03845-4","journal":{"identity":"cancer-cell-international","isVorOnly":false,"title":"Cancer Cell International"},"publishedOn":"2025-07-18 16:05:18","publishedOnDateReadable":"July 18th, 2025"},"versionCreatedAt":"2025-04-30 12:12:46","video":"","vorDoi":"10.1186/s12935-025-03845-4","vorDoiUrl":"https://doi.org/10.1186/s12935-025-03845-4","workflowStages":[]},"version":"v1","identity":"rs-6219394","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6219394","identity":"rs-6219394","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}