Atypical femoral fracture in a multiple myeloma patient undergoing treatment with denosumab: A case report and literature review.

INTRODUCTION AND IMPORTANCE: Denosumab is a new standard treatment for bone disease caused by multiple myeloma. There are a few reports of atypical femoral fracture in patients with multiple myeloma, all of which were associated with long-term use of bisphosphonate. Here, we report the first case of denosumab-induced atypical femoral fracture in a patient with multiple myeloma. CASE PRESENTATION: A 71-year-old woman with multiple myeloma developed dull pain in her right thigh 8 months after restarting high-dose denosumab following its initial administration for 4 months and subsequent withdrawal for 2 years. Fourteen months later, complete atypical femoral fracture occurred. Osteosynthesis was achieved using an intramedullary nail and she was switched to oral bisphosphonate 7 months after cessation of denosumab. There was no exacerbation of the multiple myeloma. Bone union was achieved and she recovered to her pre-injury level of activities. The oncological outcome was alive with disease at 2 years after surgery. CLINICAL DISCUSSION: Prodromal symptoms such as thigh pain and radiographical finding of thickening of the lateral cortex in the subtrochanteric region of the femur were attributed to denosumab-induced atypical femoral fracture in the case. A unique aspect of this case worth highlighting is that the fracture occurred after short-term denosumab use. This may be associated with multiple myeloma or other medication including dexamethasone and cyclophosphamide. CONCLUSION: Atypical femoral fracture may occur in patients with multiple myeloma who receive denosumab, even for a short period. Attending physicians should be cognizant of the early symptoms and signs of this fracture.

Blue light induces apoptosis and autophagy by promoting ROS-mediated mitochondrial dysfunction in synovial sarcoma.

BACKGROUND: Synovial sarcoma (SS) has limited treatment options and there is an urgent need to develop a novel therapeutic strategy to treat SS. Blue light (BL) has been shown to inhibit the growth of several cancer cells. However, the efficacy of BL in soft tissue sarcomas such as SS has not been demonstrated, and the detailed mechanism underlying the antitumor activity of BL is not fully understood. In this study, we investigated the antitumor effect of BL on SS. METHODS: Human SS cell lines were continuously irradiated with BL using light-emitting diodes (LEDs) in an incubator for in vitro analysis. The chicken chorioallantoic membrane (CAM) tumors and xenograft tumors in mice were subjected to daily BL irradiation with LEDs. RESULTS: BL caused growth inhibition of SS cells and histological changes in CAM tumors. BL also suppressed the migration and invasion abilities of SS cells. The type of cell death in SS cells was revealed to be apoptosis. Furthermore, BL induced excessive production of reactive oxygen species (ROS) in mitochondria, resulting in oxidative stress and malfunctioned mitochondria. Reducing the production of ROS using N-acetylcysteine (NAC), a ROS scavenger, attenuated the inhibitory effect of BL on SS cells and mitochondrial dysfunction. In addition, BL induced autophagy, which was suppressed by the administration of NAC. The autophagy inhibitor of 3-methyladenine and small interfering RNA against the autophagy marker light chain 3B facilitated apoptotic cell death. Moreover, BL suppressed tumor growth in a mouse xenograft model. CONCLUSION: Taken together, our results revealed that BL induced apoptosis via the ROS-mitochondrial signaling pathway, and autophagy was activated in response to the production of ROS, which protected SS cells from apoptosis. Therefore, BL is a promising candidate for the development of an antitumor therapeutic strategy targeting SS.

Dedifferentiated liposarcoma in the extremity and trunk wall: A multi-institutional study of 132 cases by the Japanese Musculoskeletal Oncology Group (JMOG).

BACKGROUND: Dedifferentiated liposarcoma occurs predominantly in the retroperitoneum. Given the paucity of cases, information on the clinical characteristics of this entity in the extremities and trunk wall is quite limited. In particular, the significance of preoperative evaluation and principles of intraoperative management of the different components, i.e., well-differentiated and dedifferentiated areas, are still to be defined. METHODS: Clinical characteristics, treatment outcomes, and risk factors for poor oncological outcomes in cases of dedifferentiated liposarcoma in the extremity or trunk wall were analyzed by a retrospective, multicentric study. RESULTS: A total of 132 patients were included. The mean duration from the initial presentation to dedifferentiation was 101 months in dedifferentiation-type cases. The 5-year local recurrence-free survival, metastasis-free survival, and disease-specific survival rates were 71.6%, 75.7%, and 84.7%, respectively. Among 32 patients with metastasis, 15 presented with extrapulmonary metastasis. A percentage of dedifferentiated area over 87.5%, marginal/intralesional margin, and R1/2 resection in the dedifferentiated area were independent risk factors for local recurrence. Dedifferentiated areas over 36 cm2, French Federation of Cancer Centers Sarcoma Group grade III, and intralesional or marginal resection were independent risk factors for metastasis. A dedifferentiated area over 77 cm2 and lung metastasis were independent risk factors for disease-specific mortality. CONCLUSIONS: The typical clinical characteristics of dedifferentiated liposarcoma in the extremity and trunk wall were reconfirmed in the largest cohort ever. The evaluation of the dedifferentiated area in terms of grade, extension, and pathological margin, together with securing adequate surgical margins, was critical in the management of this entity.

ZFTA::RELA fusion in a distinct liposarcoma morphologically overlapping with chondroid lipoma.

Chondroid lipoma is a rare benign adipose tumor characterized by a recurrent ZFTA::MRTFB fusion. Herein, we report an unusual liposarcoma that partly exhibited overlapping features with those of chondroid lipoma and harbored a ZFTA::RELA fusion. A 59-year-old man presented with a shoulder mass that had existed for approximately 8 years and with increasing pain due to a pelvic mass. The 5.8-cm resected shoulder tumor partly consisted of nests and strands of variably lipogenic epithelioid cells within a hyalinized or focally chondromyxoid stroma, indistinguishable from chondroid lipoma. The histological pattern gradually transitioned to highly cellular, stroma-poor, diffuse sheets of cells with greater nuclear atypia and mitotic activity. Vascular invasion and necrosis were present. The metastatic pelvic tumor revealed a similar histology. Despite multimodal treatment, the patient developed multiple bone metastases and succumbed to the disease 14 months after presentation. Targeted RNA sequencing identified an in-frame ZFTA (exon 3)::RELA (exon 2) fusion, which was confirmed by reverse transcription-polymerase chain reaction, Sanger sequencing, and break-apart fluorescent in situ hybridization assays. The tumor showed a different histology from that of ependymoma, no brain involvement, and no match with any sarcoma types or ZFTA::RELA-positive ependymomas according to DNA methylation analysis. p65 and L1CAM were diffusely expressed, and a CDKN2A/B deletion was present. This is the first report of an extra-central nervous system tumor with a ZFTA::RELA fusion. The tumor partly displayed an overlapping histology with that of chondroid lipoma, suggesting that it may represent a hitherto undescribed malignant chondroid lipoma with an alternative ZFTA fusion.

Combination chemotherapy of doxorubicin and ifosfamide with proton beam therapy for myoepithelial carcinoma originating in the paraspinal region: A case report and literature review.

Soft tissue myoepithelial carcinoma (MEC) is an extremely rare mesenchymal tumor that has a poor prognosis unless complete surgical resection is achieved. The present study reported a case of a 38-year-old woman with a tumor in the left paraspinal region at L2 to L3 with vertebral destruction. MEC was diagnosed based on molecular pathological examination of a biopsy specimen. Because curative surgery was expected to be difficult, a combination of chemotherapy with doxorubicin and ifosfamide and proton beam therapy as local therapy was performed, resulting in long-term survival for at least 7.8 years. To the best of our knowledge, this is the first case of soft tissue MEC for which classical cytotoxic chemotherapy and proton beam therapy were effective. Although surgical resection with negative margins is the mainstay of treatment for MEC, adequate doxorubicin-based systemic therapy and high-dose radiation therapy may be a feasible alternative in patients with unresectable or advanced MEC. Future studies on the relationship between molecular pathological features, including biomarkers, and the selection of therapeutic agents are warranted.

Hemangioblastoma of the Cauda Equina†:†A Case Report and Review of the Literature.

Introduction : Hemangioblastoma in the spine mainly occurs at the cervical and thoracic levels and is often associated with von Hippel-Lindau (VHL) syndrome. Here, we reported a quite rare case of spinal sporadic hemangioblastoma arising from the cauda equina. Case presentation : A 66-year-old woman presented with a 5-year history of low back and leg pain. Imaging revealed a hypervascular intradural extramedullary tumor in the lumbar region. Preoperative angiography helped to identify the feeding arteries and draining vein, and so facilitated subsequent tumor resection. The pain was dramatically improved but weakness of the left tibialis anterior and left extensor hallucis longus muscles persisted. Discussion : We reported a rare case of spinal hemangioblastoma arising from the cauda equina. Preoperative angiography may be useful for diagnosis and understanding of the anatomy of feeding veins. J. Med. Invest. 69 : 312-315, August, 2022.

Clinical Outcome of Patients with Pelvic and Retroperitoneal Bone and Soft Tissue Sarcoma: A Retrospective Multicenter Study in Japan.

This study aimed to retrospectively analyze the clinical outcomes of patients with pelvic and retroperitoneal bone and soft tissue sarcoma (BSTS). Overall, 187 patients with BSTS in the pelvis and retroperitoneal region treated at 19 specialized sarcoma centers in Japan were included. The prognostic factors related to overall survival (OS), local control (LC), and progression-free survival (PFS) were evaluated. The 3-year OS and LC rates in the 187 patients were 71.7% and 79.1%, respectively. The 3-year PFS in 166 patients without any distant metastases at the time of primary tumor diagnosis was 48.6%. Osteosarcoma showed significantly worse OS and PFS than other sarcomas of the pelvis and retroperitoneum. In the univariate analyses, larger primary tumor size, soft tissue tumor, distant metastasis at the time of primary tumor diagnosis, P2 location, chemotherapy, and osteosarcoma were poor prognostic factors correlated with OS. Larger primary tumor size, higher age, soft tissue tumor, chemotherapy, and osteosarcoma were poor prognostic factors correlated with PFS in patients without any metastasis at the initial presentation. Larger primary tumor size was the only poor prognostic factor correlation with LC. This study has clarified the epidemiology and prognosis of patients with pelvic and retroperitoneal BSTS in Japan.

Image-guided core needle biopsy for musculoskeletal lesions.

BACKGROUND: Image-guided percutaneous core needle biopsy (CNB) has been an important diagnostic procedure for musculoskeletal lesions. Here we surveyed the variety of diagnostic strategies available and assessed the clinical usefulness and limitations of image-guided CNB carried out by a multidisciplinary team comprising specialists in various fields. METHODS: We conducted a retrospective study of 284 image-guided CNBs among 1899 consecutive biopsy procedures carried out at our institution for musculoskeletal tumorous conditions, focusing on their effectiveness including diagnostic accuracy and utility for classification of specimens according to malignant potential and histological subtype as well as their correlation with biopsy routes. RESULTS: Among the 284 studied biopsies, 252 (88.7%) were considered clinically "effective". The sensitivity for detection of malignancy was 94.0% (110/117) and the specificity was 95.3% (41/43). The diagnostic accuracy for detection of malignancy was 94.4% (151/160) and that for histological subtype was 92.3% (48/52). The clinical effectiveness of the procedure was correlated with the complexity of the biopsy route (P = 0.015); the trans-pedicular, trans-retroperitoneal and trans-sciatic foramen approaches tended to yield ineffective results. Repeat biopsy did not have a significant impact on the effectiveness of image-guided CNB (P = 0.536). CONCLUSIONS: The diagnostic accuracy rates of image-guided CNB performed at multidisciplinary sarcoma units were usable even for patients who have variety of diagnostic biopsy procedures. It is important to establish and implement diagnostic strategies based on an understanding that complicated routes, especially for spine and pelvic lesions, may be associated with ineffectiveness and/or complications.

The survival and proliferation of osteosarcoma cells are dependent on the mitochondrial BIG3-PHB2 complex formation.

Previous studies reported the critical role of the brefeldin A-inhibited guanine nucleotide exchange protein 3-prohibitin 2 (BIG3-PHB2) complex in modulating estrogen signaling activation in breast cancer cells, yet its pathophysiological roles in osteosarcoma (OS) cells remain elusive. Here, we report a novel function of BIG3-PHB2 in OS malignancy. BIG3-PHB2 complexes were localized mainly in mitochondria in OS cells, unlike in estrogen-dependent breast cancer cells. Depletion of endogenous BIG3 expression by small interfering RNA (siRNA) treatment led to significant inhibition of OS cell growth. Disruption of BIG3-PHB2 complex formation by treatment with specific peptide inhibitor also resulted in significant dose-dependent suppression of OS cell growth, migration, and invasion resulting from G2/M-phase arrest and in PARP cleavage, ultimately leading to PARP-1/apoptosis-inducing factor (AIF) pathway activation-dependent apoptosis in OS cells. Subsequent proteomic and bioinformatic pathway analyses revealed that disruption of the BIG3-PHB2 complex might lead to downregulation of inner mitochondrial membrane protein complex activity. Our findings indicate that the mitochondrial BIG3-PHB2 complex might regulate PARP-1/AIF pathway-dependent apoptosis during OS cell proliferation and progression and that disruption of this complex may be a promising therapeutic strategy for OS.

Morphometric Analysis of Subaxial Cervical Spine with Myelopathy: A Comparison with the Normal Population.

INTRODUCTION: The specific morphology and differences between patients with cervical spondylotic myelopathy (CSM) and those with normal spines remain unclear. This study aimed to evaluate and determine the features of cervical spine morphology on reconstructive CT. METHODS: We investigated that axial reconstructive CT scans of the cervical spine at C3 to C7 were obtained from 309 individuals (97 CSM patients and 212 controls). Those of the optimal pedicle diameter were selected, and the following parameters were measured: (a) sagittal diameter of the spinal canal (b) transverse diameter of the spinal canal, (c) pedicle width, (d) lateral mass thickness, (e) transverse diameter of the foramen, (f) sagittal diameter of the vertebral body, and (g) transverse diameter of the vertebral body. The following ratios were calculated using these values: the sagittal-transverse ratio and the canal-body ratio. RESULTS: Most parameters differed significantly between the sexes in both groups. The parameters without the mean sagittal diameter of the spinal canal were significantly larger in men than in women. However, the mean sagittal diameter of the spinal canal did not differ significantly between the sexes in CSM patients. The sagittal-transverse ratio and canal-body ratio were significantly smaller in the CSM patients at all levels. According to relative operating characteristic curves of the sagittal diameter of the spinal canal, sagittal-transverse ratio, and canal-body ratio, the sensitivity from C3 to C7 in both sexes was > 60% at the threshold. In men, the specificity from C3 to C7 was also >60% at the threshold. CONCLUSIONS: The morphometry of the sagittal diameter of the spinal canal, sagittal-transverse ratio, and canal-body ratio on axial reconstructive CT images appears useful for distinguishing cervical spinal canal stenosis involving myelopathy.

Establishment and characterization of a novel alveolar rhabdomyosarcoma cell line, NCC-aRMS1-C1.

Alveolar rhabdomyosarcoma (aRMS) is a histological subtype of RMS, which is the most common pediatric and adolescent soft-tissue sarcoma, accounting for 3-4% of all pediatric malignancies. Patient-derived cells are essential tools for understanding the molecular mechanisms of poor prognosis and developing novel anti-cancer drugs. However, only a limited number of well-characterized cell lines for rhabdomyosarcoma from public cell banks is available. Therefore, we aimed to establish a novel cell line of aRMS from the tumor tissue of a patient with aRMS. The cell line was established from surgically resected tumor tissue from a 4-year-old male patient diagnosed with stage III, T2bN1M0 aRMS and was named as NCC-aRMS1-C1. The cells were maintained for more than 3 months under tissue culture conditions and passaged more than 20 times. We confirmed the presence of identical fusion gene such as PAX7-FOXO1 in both the original tumor and NCC-aRMS1-C1. The cells exhibited spheroid formation and invasion. We found that docetaxel, vincristine, ifosfamide, dacarbazine, and romidepsin showed remarkable growth-suppressive effects on the NCC-aRMS1-C1 cells. In conclusion, the NCC-aRMS1-C1 cell line exhibited characteristics that may correspond to the lymph node metastasis in aRMS and mirror its less aggressive features. Thus, it may be useful for innovative seeds for novel therapeutic strategies.

Intra- and inter-rater reliability of a three-dimensional classification system for intertrochanteric fracture using computed tomography.

INTRODUCTION: Intertrochanteric fractures are common fragility fractures in elderly patients. The importance of a reliable classification system for these fractures has been increasingly recognized. The aim of this study was to test the hypothesis that three-dimensional classification by CT has better intra- and inter-observer reliability than conventional two-dimensional classification. MATERIAL AND METHODS: Two hundred and three consecutive patients (39 male, 164 female; mean age 84.5 years) with intertrochanteric fracture were included in the study. In each case, the fracture was classified using the two-dimensional Evans-Jensen and AO/OTA systems that rely on plain radiographs and using a three-dimensional fragment-based CT system. The second evaluation was performed 1 month after the first evaluation by the same examiner to determine intra-observer reliability. Another blinded examiner also classified each case to assess inter-observer reliability. The kappa coefficient was used for determination of intra- and inter-observer reliability. RESULTS: The kappa values for the two-dimensional Evans-Jensen and AO/OTA classification systems showed moderate intra-observer reliability (κ=0.65 and κ=0.61, respectively) and slight inter-observer reliability (κ=0.20 and κ=0.19). The intra-observer kappa value for the three-dimensional classification system was 0.88, indicating almost perfect reliability; the inter-observer kappa value was 0.70, indicating substantial reliability. CONCLUSION: The findings of this study confirm that the fragment-based classification system has high reliability. Surgeons should be aware that the three-dimensional fragment-based CT system for classification of intertrochanteric fractures has better intra-observer and inter-observer reliability than the conventional two-dimensional systems.

Establishment and characterization of patient-derived cancer models of malignant peripheral nerve sheath tumors.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are a rare subtype of soft-tissue sarcoma, derived from a peripheral branch or the sheath of the sciatic nerve, brachial plexus, or sacral plexus. The clinical outcomes for MPNST patients with unresectable or metastatic tumors are dismal, and novel therapeutic strategies are required. Although patient-derived cancer cell lines are vital for basic research and preclinical studies, few MPNST cell lines are available from public cell banks. Therefore, the aim of this study was to establish cancer cell lines derived from MPNST patients. METHODS: We used tumor tissues from five patients with MPNSTs, including one derived from a rare bone tissue MPNST. The tumor tissues were obtained at the time of surgery and were immediately processed to establish cell lines. A patient-derived xenograft was also established when a sufficient amount of tumor tissue was available. The characterization of established cells was performed with respect to cell proliferation, spheroid formation, and invasion. The mutation status of actionable genes was monitored by NCC Oncopanel, by which the mutation of 114 genes was assessed by next-generation sequencing. The response to anti-cancer agents, including anti-cancer drugs approved for the treatment of other malignancies was investigated in the established cell lines. RESULTS: We established five cell lines (NCC-MPNST1-C1, NCC-MPNST2-C1, NCC-MPNST3-C1, NCC-MPNST4-C1, and NCC-MPNST5-C1) from the original tumors, and also established patient-derived xenografts (PDXs) from which one cell line (NCC-MPNST3-X2-C1) was produced. The established MPNST cell lines proliferated continuously and formed spheroids while exhibiting distinct invasion abilities. The cell lines had typical mutations in the actionable genes, and the mutation profiles differed among the cell lines. The responsiveness to examined anti-cancer agents differed among cell lines; while the presence of an actionable gene mutation did not correspond with the response to the anticipated anti-cancer agents. CONCLUSION: The established cell lines exhibit various characteristics, including proliferation and invasion potential. In addition, they had different mutation profiles and response to the anti-cancer agents. These observations suggest that the established cell lines will be useful for future research on MPNSTs.

Intracanalicular Osteochondroma in the Lumbar Spine.

Osteochondroma is a common benign bone tumor that is relatively rare in the spine. Here, we report two cases of symptomatic solitary osteochondroma of the lumbar spine. The first case was a 61-year-old man who presented with a 2-year history of right leg numbness. Imaging findings showed that the cause of the radiculopathy was osteochondroma of the right inferior articular process at L4. The tumor was removed en bloc, and the numbness resolved. The second case was a 62-year-old man with osteochondroma of the right superior articular process at L5 that caused pain and numbness in the right leg. En bloc resection of the osteochondroma with the ligamentum flavum relieved the symptoms. Spinal osteochondroma occurs relatively frequently in elderly individuals compared with peripheral lesions and mimics a degenerative spinal disorder. Careful physical examination and imaging evaluation can reveal this tumor and surgery is effective for relieving the symptoms.

A novel three-dimensional classification system for intertrochanteric fractures based on computed tomography findings.

A novel three-dimensional fragment-based classification system based on computed tomography findings was established to characterize femoral intertrochanteric fractures. The intertrochanteric bone fragments were defined as follows : neck, posterior portion of the greater trochanter, anterior portion of the greater trochanter, lesser trochanter, and shaft. Each type of fracture was classified as 2-, 3-, 4-, or 5-fragment according to the number of floating bone fragments. Following the description of the fracture type, each floating bone fragment was appended, with the exception of a fragment involving the shaft. Ninety-five intertrochanteric fractures were classified by the same surgeon. The fractures occurred in 14 men and 81 women with a mean age of 84.7 years. The frequency of each type of fracture was investigated. Thirty-one fractures (32.6%) were 2-fragment and 64 (67.4%) were ≥ 3-fragment. A fragment of the anterior portion of the greater trochanter, which cannot be classified using conventional systems, was included in 29 cases (30.5%). A 5-fragment fracture was detected in two cases (2.1%). Using this fragment-based classification system, intertrochanteric fractures can be evaluated in more detail than is possible using conventional classification systems. J. Med. Invest. 66 : 362-366, August, 2019.

A Rare Case of Acute-Onset Spastic Quadriparesis Caused by a Chondroma of the Cervical Spine.

Chondromas are benign cartilaginous tumors that occur very rarely in the spine. Moreover, chondromas of the extraskeletal origin are also very rare. In this case report, we describe an extremely rare case of chondroma arising from the ligamentum flavum in the cervical spine. A 67-year-old man presented to our clinic with acute-onset spastic quadriparesis. We performed emergent magnetic resonance imaging and found an epidural mass in the right ligamentum flavum at C4-C5. The acute-onset presentation was suspicious for intraligamentous hematoma in the ligamentum flavum at this level. We performed emergency decompression surgery and en bloc removal of the epidural mass with the right C4 and C5 lamina. The lesion had the appearance of cartilaginous tissue rather than hematoma. Based on the histological investigation, the final diagnosis was intraligamentous chondroma of the cervical spine. The quadriparesis improved postoperatively, as did the results of manual muscle testing in the affected area, and he was able to resume walking independently with a cane. At the one-year follow-up, the manual muscle testing results were almost normal. Surgeons should keep in mind the possibility of benign tumors including chondroma of the cervical spine when a patient presents with acute-onset quadriparesis.

Intimal sarcoma arising from the common iliac artery presenting with artery occlusion : a case report and literature review.

We present a rare case of intimal sarcoma arising from the common iliac artery in an 82-year-old man who presented with intermittent claudication. He had undergone endovascular therapy with self-expanding stents to both iliac arteries that had occluded soon after placement. After salvage bypass grafting, a diagnosis of intimal sarcoma with angiosarcoma phenotype from the iliac artery was made. Further bypass graft surgery relieved symptoms temporarily. However, the tumor progressed and the left limb became ischemic. The chemotherapy of eribulin did not prevent tumor progression. The patient died of the disease 20 months after the first surgery. J. Med. Invest. 66 : 205-208, February, 2019.

Establishment and characterization of a novel cell line, NCC-MFS1-C1, derived from a patient with myxofibrosarcoma.

Myxofibrosarcoma (MFS) is an aggressive sarcoma that requires novel therapeutic approaches to improve its clinical outcome. Cell lines are a valuable tool for pre-clinical research; however, there is a lack of patient-derived cell lines of MFS available from public cell banks. This study aimed to develop a patient-derived cell line of MFS. A cell line designated NCC-MFS1-C1 was established from the primary tumor tissue of an 82-year-old male patient with MFS. The short tandem repeat pattern of NCC-MFS1-C1 cells was identical to that of the original tumor, but distinct from that of any other cell lines in public cell banks. NCC-MFS1-C1 cells were maintained as a monolayer culture for over 20 passages in 19 months; the cells exhibited spindle-like morphology, continuous growth, and ability for spheroid formation and invasion. Genomic assay showed that NCC-MFS1-C1 cells had gain and loss of genetic loci. Proteomic profiling revealed that the original tumor and the derived NCC-MFS1-C1 cells had similar, but distinct protein expression patterns. Screening of anti-cancer drugs in NCC-MFS1-C1 cells identified five candidate drugs for MFS. In conclusion, we established a novel MFS cell line, NCC-MFS1-C1, which could be used to study tumor development and effects of anti-cancer drugs.

Establishment and characterization of a novel dedifferentiated chondrosarcoma cell line, NCC-dCS1-C1.

Dedifferentiated chondrosarcoma is an aggressive mesenchymal tumor of the bone, and novel therapies are needed to improve its clinical outcomes. Patient-derived cell lines are essential tools for elucidating disease mechanisms associated with poor prognosis and for developing therapies. However, few lines and xenografts have been previously reported in dedifferentiated chondrosarcoma. We established a novel patient-derived dedifferentiated chondrosarcoma cell line, NCC-dCS1-C1. Primary dedifferentiated chondrosarcoma tissues were obtained at the time of surgery and subjected to primary tissue culture. The cell line was established and authenticated by assessing DNA microsatellite short tandem repeats. The cells maintained in monolayer cultures exhibited constant growth, spheroid formation capacity, and invasion ability. When the cells were implanted into mice, they exhibited histological features similar to those of the original tumor. Genomic analysis of single nucleotide polymorphisms showed aberrant genomic contents. The DNA sequencing revealed the absence of IDH1/2 mutations. The global targeted sequencing revealed that the cell line preserved homozygous deletion of CDKN2A and CREBBP. A proteomic study by mass spectrometry unveiled similar but distinct molecular backgrounds in the original tumor and the established cell line, suggesting that tumor cell functions might be altered during the establishment of the cell line. Using a screening approach, four anti-cancer drugs with anti-proliferative effects at a low concentration were identified. In conclusion, a novel dedifferentiated chondrosarcoma cell line, NCC-dCS1-C1, was successfully established from primary tumor tissues. The NCC-dCS1-C1 cell line will be a useful tool for investigations of the mechanisms underlying dedifferentiated chondrosarcomas.

Establishment of novel patient-derived models of dermatofibrosarcoma protuberans: two cell lines, NCC-DFSP1-C1 and NCC-DFSP2-C1.

Dermatofibrosarcoma protuberans (DFSP) is a common type of dermal sarcoma, characterized by the presence of the unique collagen type I alpha 1 chain (COL1A1)-PDGFB translocation, which causes constitutive activation of the platelet-derived growth factor ß (PDGFB) signaling pathway. Patients with DFSP exhibit frequent local recurrence, and novel therapeutic approaches are required to achieve better clinical outcomes. Patient-derived cancer cell lines are essential in the preclinical research. Here, we established novel patient-derived DFSP cell lines from two patients with DFSP and designated these cell lines NCC-DFSP1-C1 and NCC-DFSP2-C1. Tumors of the two patients with DFSP had COL1A1-PDGFB translocations with distinct COL1A1 breakpoints, e.g., in exons 33 and 15, and the translocations were preserved in the established cell lines. NCC-DFSP1-C1 and NCC-DFSP2-C1 cells exhibited similar morphology and limited capability of proliferation in vitro, forming spheroids when seeded on low-attachment tissue culture plates. In contrast, NCC-DFSP1-C1 cells had considerably higher invasive capability than NCC-DFSP2-C1 cells. Overall proteome contents were similar between NCC-DFSP1-C1 and NCC-DFSP2-C1 cells. Notably, in vitro screening studies identified anticancer drugs that showed antiproliferative effects at considerably low concentrations in the DFSP cell lines. Bortezomib, mitoxantrone, ponatinib, and romidepsin were more cytotoxic to NCC-DFSP1-C1 cells than to NCC-DFSP2-C1 cells. These cell lines will be useful tools for developing novel therapeutic strategies to treat DFSP.