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Myxofibrosarcoma (MFS) is a rare and aggressive mesenchymal malignancy characterized by complex karyotypes with heterogeneous clinical features. The standard treatment for primary MFS is curative resection; however, the utility of systemic chemotherapy and radiotherapy has not been established. Although patient-derived cancer cell lines are a key bioresource for developing novel therapies, the number of MFS cell lines available from public cell banks is limited by the rarity of the disease, and large-scale drug screening has not yet been performed. To address this issue, we aimed to establish and characterize a novel MFS cell line. We successfully established a cell line, NCC-MFS6-C1, which harbors genetic abnormalities common in MFS and exhibits aggressive phenotypes such as continuous growth, spheroid formation, and invasion in tissue culture conditions. We performed drug screening using NCC-MFS6-C1 along with five MFS cell lines established in our laboratory and clarified the response spectrum of 214 existing anticancer agents. We found that two anticancer agents, gemcitabine and romidepsin, showed considerable antiproliferative effects, and these observations were concordant with the findings of our previous report, in which these agents attenuated the proliferation of five previously reported MFS cell lines. We conclude that NCC-MFS6-C1 is a useful resource for studying MFS.

Synovial sarcoma (SS) is a rare and aggressive mesenchymal malignancy driven by a unique chromosomal translocation that generates the expression of the SS18:SSX fusion protein. It occurs at almost any anatomical site and most commonly in young adults. The standard curative treatment for primary SS is a wide surgical resection combined with radiotherapy and/or neoadjuvant chemotherapy. The prognosis of SS varies among patients, with the 5 years survival rate ranging from 50 to 60% in adults and 90% in children. Although patient-derived cell lines are a useful resource for the development of new therapies, only a few are available from public cell banks. Therefore, this study aimed to establish and characterize a novel SS cell line. We successfully established a novel cell line, NCC-SS5-C1, harboring an SS18-SSX1 fusion gene. NCC-SS5-C1 cells demonstrated constant growth and invasion ability. We performed integrative drug screening using eight SS cell lines, including NCC-SS5-C1 cells, and examined the response spectrum of existing anticancer agents. We conclude that NCC-SS5-C1 is a useful resource for studying SS.

Dedifferentiated liposarcoma (DDLPS) is morphologically characterized by well-differentiated liposarcomas associated with high-grade non-lipogenic sarcoma and molecularly characterized by the coamplification of MDM2 and CDK4(12q14-15). DDLPS is highly aggressive, and effective systemic chemotherapy has not been developed yet. In this study, we established a novel DDLPS cell line, NCC-DDLPS6-C1, as a potential tool for the development of novel therapies. NCC-DDLPS6-C1 cells were established from surgically resected tumor tissues of a patient with DDLPS. Amplification and overexpression of MDM2 and CDK4 were observed in NCC-DDLPS6-C1 cells. NCC-DDLPS6-C1 cells proliferated rapidly, invaded aggressively, and formed spheroids. Moreover, NCC-DDLPS6-C1 cells formed tumors in mice. These observations suggested that the malignant potentials that may reflect the original features of DDLPS were retained in the NCC-DDLPS6-C1. Anticancer drugs that significantly reduced the proliferation of NCC-DDLPS6-C1 cells were identified by drug library screening. Thus, NCC-DDLPS6-C1 may recapitulate the original genotypes and phenotypes, and we conclude that the NCC-DDLPS6-C1 cell line is a useful resource for the study of DDLPS.

Ewing sarcoma (ES) is a small round cell sarcoma that is characterized by the unique gene translocation EWSR1-FLI1. It is the second most common primary bone and soft tissue malignancy in children and adolescents. It constitutes 10-15% of all bone sarcomas and is highly aggressive and rapidly recurring. Although intensive treatments have improved the clinical outcome of ES patients, 20-25% of them exhibit metastases during diagnosis. Thus, the prognoses of these patients remain poor. Cell lines are pivotal resources to investigate the molecular background of disease progression and to develop novel therapeutic modalities. In this study, we established and characterized a novel ES cell line, NCC-ES2-C1. The presence of the EWSR1-FLI1 fusion gene in these cells was confirmed in the NCC-ES2-C1 cells. Furthermore, these cells exhibited constant proliferation, and invasion, but did not form tumors in mice. We screened the anti-tumor effects of 214 anti-cancer drugs in NCC-ES2-C1 cells and found that the drugs which effectively reduced the proliferation of NCC-ES2-C1 cells. We concluded that NCC-ES2-C1 cells are a useful resource to study functions of the EWSR1-FLI1 fusion gene, investigate phenotypic changes caused by genes and proteins, and evaluate the anti-tumor effects of novel drugs.

Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft-tissue sarcoma genetically characterized by the presence of the FUS-CREB3L2 gene fusion. While LGFMS exhibits indolent features during its early stages, the rates of recurrence, metastasis, and death from the disease are high. Presently, the role of FUS-CREB3L2 gene fusions in the unique features of LGFMS is not clear, and there is no modality to improve the clinical outcomes of patients with LGFMS; thus, extensive studies on LGFMS are required. Patient-derived cancer cell lines are critical tools for cancer research. However, no cell line has been established for LGFMS. Here, we aimed to develop a novel cell line for LGFMS and successfully established it using surgically resected tumor tissues. The cells, named NCC-LGFMS1-C1, possessed the same fusion genes as their original tumor and visible copy number variations. The cells had a fibroblastic appearance, formed spheroids when they were seeded in a low-attachment dish, and exhibited constant growth and invasion. Additionally, we demonstrated the feasibility of high-throughput drug screening using these cells. In conclusion, the NCC-LGFMS1-C1 cell line is a useful tool for studying LGFMS.

Giant cell tumor of bone (GCTB) is a locally aggressive and rarely metastasizing tumor. GCTB is characterized by the presence of unique giant cells and a recurrent mutation in the histone tail of the histone variant H3.3, which is encoded by H3F3A on chromosome 1. GCTB accounts for ~ 5% of primary bone tumors. Although GCTB exhibits an indolent course, it has the potential to develop aggressive behaviors associated with local recurrence and distant metastasis. Currently, complete surgical resection is the only curative treatment, and novel therapeutic strategies are required. Patient-derived cancer cell lines are critical tools for basic and pre-clinical research. However, only a few GCTB cell lines have been reported, and none of them are available from public cell banks. Therefore, we aimed to establish novel GCTB cell lines in the present study. Using curetted tumor tissues of GCTB, we established two cell lines and named them NCC-GCTB2-C1 and NCC-GCTB3-C1. These cells harbored a typical mutation in histones and exhibited slow but constant growth, formed spheroids, and had invasive capabilities. We demonstrated the utility of these cell lines for high-throughput drug screening using 214 anticancer agents. We concluded that NCC-GCTB2-C1 and NCC-GCTB3-C1 cell lines were useful for the in vitro study of GCTB.

Background Spontaneous pneumomediastinum is characterized by the presence of interstitial air in the mediastinum without any underlying disease. Some cases of spontaneous pneumomediastinum have been reported in the past, although only few reports are available, and its management remains uncertain. This study reviewed our experience in the diagnosis and treatment of spontaneous pneumomediastinum. Methods A retrospective study of 71 cases treated for spontaneous pneumomediastinum at the Yodogawa Christian Hospital between April 2005 and March 2020 was conducted. Results The patients’ mean age was 19.3 years (range, 7–48 years). A triggering event was noted in 69% of the cases. Seventy-six percent of the patients were admitted to the hospital, and 24% were outpatients. Treatment included analgesia, rest, antibiotics, and/or oxygen therapy. Thirty-six patients (51%) were treated with antibiotics. None of the cases presented any complications, including mediastinitis or worsening respiratory condition. Two patients (3%) had a recurrence of spontaneous pneumomediastinum. Conclusions All the patients, with or without antimicrobial treatment and hospitalization, had favorable outcomes. We should therefore reconsider the need for hospitalization and antimicrobial therapy for patients with mediastinitis prophylaxis.

Spindle cell/sclerosing rhabdomyosarcoma (ssRMS) is a rare subtype of rhabdomyosarcoma (RMS) that has fascicular spindle cell and/or sclerosing morphology. SsRMS has a diverse molecular background and is categorized into three groups: congenital/infantile ssRMS with a gene fusion involving the NCOA2 and VGLL2, ssRMS with the MYOD1 mutation, and ssRMS with no recurrent identifiable genetic alterations. Because ssRMS is a newly defined disease concept of RMS, the optimal treatment methods have not been determined. This results in unfavorable prognosis and consequently signals the urgent need for continuous research. Patient-derived cell lines are essential tools in basic and translational research. However, only two ssRMS cell lines with the MYOD1 mutation have been reported to date. Thus, we established a novel ssRMS cell line named NCC-ssRMS2-C1 using a surgically resected tumor tissue from an adult ssRMS patient. NCC-ssRMS2-C1 cells retained the copy number alterations corresponding to the original tumor and are categorized into the group with no recurrent identifiable genetic alterations. NCC-ssRMS2-C1 cells demonstrated constant proliferation, spheroid formation, and capability for invasion in vitro, reflecting the malignant features of the original tumor tissue. In a drug screening test, ssRMS demonstrated remarkable sensitivity to romidepsin, trabectedin, actinomycin D, and bortezomib. Hence, we conclude that the NCC-ssRMS2-C1 cell line is the first ssRMS cell line which belongs to the group with no recurrent identifiable genetic alterations, and it will be a useful resource in both basic and translational studies for ssRMS.

Myxofibrosarcoma (MFS) is one of the most aggressive sarcomas with highly complex karyotypes and genomic profiles. Although a complete resection is required in the treatment of MFS, it is often not achieved due to its strong invasive nature. Additionally, MFS is refractory to conventional chemotherapy, leading to poor prognosis. Therefore, it is necessary to develop novel treatment modalities for MFS. Patient-derived cell lines are important tools in basic research and preclinical studies. However, only 10 MFS cell lines have been reported to date. Furthermore, among these cell lines, merely two MFS cell lines are publicly available. Hence, we established a novel MFS cell line named NCC-MFS3-C1, using a surgically resected tumor specimen from a patient with MFS. NCC-MFS3-C1 cells had copy number alterations corresponding to the original tumor. NCC-MFS3-C1 cells demonstrate constant proliferation, spheroid formation, and aggressive invasion. In drug screening tests, the proteasome inhibitor bortezomib and the histone deacetylase inhibitor romidepsin demonstrated significant antiproliferative effects on NCC-MFS3-C1 cells. Thus, the NCC-MFS3-C1 cell line is a useful tool in both basic and preclinical studies for MFS.

Background Histone deacetylase inhibitors (HDACi) are used to treat patients with cutaneous T-cell lymphoma (CTCL), but they show limited efficacy. Hence, combination therapies should be explored to enhance the effectiveness of HDACis. Objective This study was conducted to identify novel therapeutic targets that can be combined with HDACis for treating CTCL. Methods We performed a global kinome profiling assay of three CTCL cell lines (HH, MJ, and Hut78) with three HDACis (romidepsin, vorinostat, and belinostat) using the PamChip® microarray. The three cell lines were co-treated with romidepsin and an inhibitor against the tyrosine kinase pathway. Results Principal component analysis revealed that kinome expression patterns were mainly related to the cell origin and were not affected by the drugs. Few kinases were commonly activated by the HDACis. Most identified kinases were Src-associated molecules, such as annexin A2, embryonal Fyn-associated substrate, and progesterone receptor. Phosphorylated Src was not observed in any untreated cell lines, whereas Src phosphorylation was detected in two of the three cell lines after HDACi treatment. Ponatinib, a Src inhibitor, significantly enhanced romidepsin-induced apoptosis not only in HH, MJ, and Hut78 cells, but also in Myla and SeAx CTCL cell lines. Conclusion The Src pathway is a possible target for combination therapy involving HDACis for CTCL.

Dedifferentiated liposarcoma (DDLPS) is a highly aggressive subtype of liposarcoma that is histologically a transition form between an atypical lipomatous tumor/well-differentiated liposarcoma and a non-lipogenic sarcoma. DDLPS is genetically characterized by a complex karyotype with copy number variations and genomic complexity. DDLPS has a poor prognosis, a high local recurrence rate, and refractory behaviors for chemotherapy and radiation, which indicate a requirement for a novel therapeutic strategy for better clinical outcomes. We report here, a novel DDLPS cell line (NCC-DDLPS2-C1) developed from a tumor tissue. NCC-DDLPS2-C1 cells showed an amplified 12q13-15 region and exhibited constant growth, spheroid formation, and invasion. High-throughput drug screening revealed distinct sensitivity between monolayer- and three-dimensional cells. Romidepsin and trabectedin especially showed high anti-proliferative effects in both culture methods of NCC-DDLPS2-C1. Thus, the NCC-DDLPS2-C1 cell line may serve as a useful resource for DDLPS studies.

Pleomorphic sarcoma (PS) is a heterogeneous group of malignant mesenchymal tumors without a specific histological lineage of differentiation. PS is genetically characterized by genetic instability and diversity and histologically characterized by morphological pleomorphism. PS is one of the most common soft tissue sarcomas. The only curative treatment for PS is complete surgical resection, in which neoadjuvant radiotherapy is frequently combined. PS demonstrates both local recurrence and metastasis after surgical treatment, and effective systemic chemotherapy has not yet been established. Patient-derived cancer cell lines are critical tools for basic and preclinical studies in the development of chemotherapy. However, only six PS cell lines are available from the public cell bank, and none of them are derived from PS after neoadjuvant radiotherapy, despite the fact that radiotherapy causes changes in the posttreatment cancer genome. Here, we reported a novel cell line of PS from a primary tumor specimen resected after neoadjuvant radiotherapy and named it NCC-PS1-C1. NCC-PS1-C1 cells showed a variety of copy number alterations and pathological mutations in TP53. NCC-PS1-C1 cells demonstrated constant proliferation, spheroid formation, and invasion capability in vitro. The screening of antitumor agents in NCC-PS1-C1 cells showed that bortezomib and romidepsin were effective against PS. In conclusion, we report a novel PS cell line from a primary tumor resected after neoadjuvant radiotherapy. We believe that NCC-PS1-C1 will be a useful tool for the development of novel chemotherapies for PS, especially for recurrent cases after neoadjuvant radiotherapy.

Purpose Community-acquired pneumonia (CAP) is highly common across the world. It is reported that over 90% of CAP in older adults may be due to aspiration. However, the diagnostic criteria for aspiration pneumonia (AP) have not been widely agreed. Is there a consensus on how to diagnose AP? What are the clinical features of patients being diagnosed with AP? We conducted a systematic review to answer these questions. Methods We performed a literature search in MEDLINE®, EMBASE, CINHAL, and Cochrane to review the steps taken toward diagnosing AP. Search terms for “aspiration pneumonia” and “aged” were used. Inclusion criteria were: original research, community-acquired AP, age ≥ 75 years old, acute hospital admission. Results A total of 10,716 reports were found. Following the removal of duplicates, 7601 were screened, 95 underwent full-text review, and 9 reports were included in the final analysis. Pneumonia was diagnosed using a combination of symptoms, inflammatory markers, and chest imaging findings in most studies. AP was defined as pneumonia with some relation to aspiration or dysphagia. Aspiration was inferred if there was witnessed or prior presumed aspiration, episodes of coughing on food or liquids, relevant underlying conditions, abnormalities on videofluoroscopy or water swallow test, and gravity-dependent distribution of shadows on chest imaging. Patients with AP were older, more frailer, and had more comorbidities than in non-AP. Conclusion There is a broad consensus on the clinical criteria to diagnose AP. It is a presumptive diagnosis with regards to patients’ general frailty rather than in relation to swallowing function itself.

Giant cell tumor of bone (GCTB), is a rare intermediate malignant bone tumor with high local infiltrative ability, and is genetically characterized by mutation in the H3-3A gene. Standard treatment is curative surgical tumor resection. GCTB demonstrates both local recurrence and pulmonary metastasis after surgical treatment, and effective systematic chemotherapy is yet to be established. Therefore, development of novel chemotherapies for GCTB is necessary. Although patient-derived tumor cell lines are potent tools for preclinical research, 15 GCTB cell lines have been reported to date, and only four are publicly available. Thus, this study aimed to establish and characterize a novel GCTB cell line for preclinical studies on GCTB. Herein, we described the establishment of a cell line, NCC-GCTB5-C1, from the primary tumor tissue of a patient with GCTB. NCC-GCTB5-C1 was shown to harbor a mutation in the H3-3A gene, which is typical of GCTB; thus, it has useful properties for in vitro studies. We conducted the largest integrated screening analysis of 214 antitumor agents using NCC-GCTB5-C1 along with four GCTB cell lines. Romidepsin (a histone deacetylase inhibitor), camptothecin, and actinomycin D (topoisomerase inhibitors) demonstrated remarkable antitumor effects, suggesting that these antitumor agents are potential therapeutic candidates for GCTB treatment. Therefore, the NCC-GCTB5-C1 cell line could potentially contribute to the elucidation of GCTB pathogenesis and the development of novel GCTB treatments.

Pleomorphic liposarcoma (PLPS) is a rare subtype of liposarcoma, characterized by the presence of pleomorphic lipoblasts without definitive molecular aberrations; it accounts for less than 5% of all liposarcomas. PLPS is an aggressive cancer that exhibits frequent local recurrence and metastasis, with an overall 5-year survival rate of ~ 60%. Owing to the lack of effective treatment options in inoperable conditions and resistance to chemotherapeutics, novel therapies are required to treat PLPS. Although patient-derived cell lines are a critical tool for basic and pre-clinical research, only one PLPS cell line is reportedly available for analysis. A paucity of adequate cell line hinders the progress of research and treatments of PLPS. Thus, we aimed to establish and characterize a novel patient-derived cell line for PLPS. Using surgically resected tumor tissue from a 71-year-old male patient, we established the NCC-PLPS1-C1 cell line. The cells were maintained for more than 8 months and passaged ~ 40 times in the tissue culture condition. NCC-PLPS1-C1 cells were characterized by multiple genetic deletions and showed rapid growth, spheroid formation, and invasive potential. The NCC-PLPS1-C1 cells and the original tumor tissue shared similar kinase activity profiles for FES and PDGFR-β. NCC-PLPS1-C1 constantly proliferated, being suitable for the screening of anti-cancer drugs. A screen for the anti-proliferative effects of anti-cancer drugs on NCC-PLPS1-C1 cells showed a significant response for bortezomib, gemcitabine, romidepsin, topotecan, and vinblastine. In conclusion, NCC-PLPS1-C1 cells represent a useful tool for basic and pre-clinical studies related to PLPS, especially high-throughput drug screening.

Myxoid liposarcoma is a rare mesenchymal malignancy, which is characterized by a FUS-DDIT3 fusion known as chromosomal translocation t(12;16)(q13;p11) and arises in the fat tissue. Although surgery with radiation has been established as a standard treatment, myxoid liposarcoma shows frequent recurrence and poor prognosis, thus requiring new therapeutic approaches. Patient-derived cell lines represent a critical tool for basic and preclinical research. However, only two such myxoid liposarcoma cell lines have been reported, and they are not available in cell banks. The aim of this study was to establish and characterize a novel myxoid liposarcoma cell line. Using surgically resected tumor tissue from a 47-year-old male patient, we established the NCC-MLPS1-C1 cell line. NCC-MLPS1-C1 cells were characterized by FUS-DDIT3 fusion, slow growth, spheroid formation, and invasive capability. We screened the effect of anti-cancer agents on the proliferation of NCC-MLPS1-C1 cells. The cells displayed a remarkable response to multitarget kinase inhibitors of RET, PDGFR-β, VEGFR, or FGFR. NCC-MLPS1-C1 cells and the tumor tissue shared common profiles of kinase activity including identified drug targets, such as RET and PDGFR-β. We believe that NCC-MLPS1-C1 cells will represent a useful tool for basic and preclinical studies of myxoid liposarcoma.

The efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in lung squamous cell carcinoma is said to be low. Thus far, only four cases of osimertinib in lung squamous cell carcinoma have been published. We experienced a case of EGFR mutant lung squamous cell carcinoma in which fifth-line treatment with osimertinib was effective after T790M EGFR mutation turned positive. Osimertinib was resumed after sixth-line chemotherapy was ineffective, showing efficacy again. Osimertinib may be a promising treatment option for EGFR mutant lung squamous cell carcinoma. This is the first report to show its effect in a case of rechallenge after intervening chemotherapy. It may therefore be important to evaluate EGFR in never-smoker lung squamous cell carcinoma patients.

Tenosynovial giant cell tumor (TGCT) is a mesenchymal tumor arising from the synovium of tendon sheath and joints, characterized by translocation t(1;2)(p13;q37). Clinical behaviors of TGCT range from favorable to locally aggressive and further research is required to lead the identification of novel therapeutic avenues for TGCT. Patient-derived cell lines are an indispensable tool for interrogating molecular mechanisms underlying the progression of disease. However, only one TGCT cell line is currently available from cell banks, and a paucity of adequate patient-derived cells hinders basic and translational research. This study aimed to establish a novel cell line of TGCT. To this end, a novel cell line, NCC-TGCT1-C1 was established from the primary tumor tissue of a 40-year-old female patient with TGCT. The cells exhibited translocation t(1;2)(p13;q37), generating COL6A3-CSF1 fusion gene. The cells were maintained as a monolayer culture through more than 30 passages over 12 months. The cells exhibited continuous growth and the ability for spheroid formation and invasion. When used in a high-throughput assay to evaluate the anti-proliferative effects of 164 anticancer drugs, the cells responded strongly to a kinase inhibitor such as gefitinib, and mitoxantrone. Our results indicate that the novel TGCT cell line, designated NCC-TGCT1-C1, was successfully established and could be used to study TGCT development and the effects of anticancer agents.

Giant cell tumor of bone (GCTB) is a rare osteolytic bone tumor, accounting for approximately 5% of all primary bone tumors. GCTB is characterized by unique giant cells. It is also characterized by recurrent mutations in the histone tail of the histone variant H3.3, H3F3A, on chromosome 1, therapeutic implications of which have not been established yet. There are few effective standardized treatments for GCTB, and a novel therapy has long been required. Patient-derived cancer cells have facilitated the understanding of mechanisms underlying the etiology and progression of multiple cancers. Thus far, only 10 GCTB cell lines have been reported, and none of them are publicly available. The aim of this study was to develop an accessible patient-derived cell line of GCTB, which could be used as a screening tool for drug development. Here, we describe the establishment of a cell line, designated NCC-GCTB1-C1, from the primary tumor tissue of a male patient with GCTB on the right distal radius. NCC-GCTB1-C1 cells were maintained as a monolayer culture for over 23 passages for 7 months. These cells exhibited continuous growth, as well as spheroid formation and invasive ability. Using an oncology agent screen, we tested the effect of anticancer drugs on the proliferation of NCC-GCTB1-C1 cells. The cells displayed a remarkable response to romidepsin and vincristine. Thus, we established a novel GCTB cell line, NCC-GCTB1-C1, which could be a useful tool for studying GCTB tumorigenesis and the efficacy of anticancer drugs.

Myxoid liposarcoma (MLPS) is a lipogenic sarcoma, characterized by myxoid appearance histology and the presence of the FUS-DDIT3 fusion gene. MLPS shows frequent recurrence and poor prognosis after standard treatments, such as surgery. Therefore, novel therapeutic approaches for MLPS are needed. Development of novel treatments requires patient-derived cell lines to study the drug responses and their molecular backgrounds. Presently, only three cell lines of MLPS have been reported, and no line is available from public cell banks. Thus, this study aimed to establish and characterize novel MLPS cell lines. Using surgically resected tumor tissue from two patients with MLPS, two novel lines NCC-MLPS2-C1 and NCC-MLPS3-C1 were established. The presence of FUS-DDIT3 fusion, slow growth, spheroid formation, and invasive capability in these cell lines was confirmed. Growth retardation was monitored for 213 anti-cancer agents using NCC-MLPS2-C1 and NCC-MLPS3-C1 cells, and the results were integrated with the response to treatments in an MLPS cell line, NCC-MLPS1-C1, which was previously established in our laboratory. We found that romidepsin suppressed cell proliferation at considerably low concentrations in all three examined cell lines. NCC-MLPS2-C1 and NCC-MLPS3-C1 cell lines developed here represent a useful tool for basic and preclinical studies of MLPS.

Dedifferentiated liposarcoma (DDLPS) is a highly aggressive subtype of liposarcoma that is morphologically defined as a transition from a well-differentiated lipomatous component to a non-lipogenic one. Curative therapy for DDLPS is complete resection, and the benefits of current systemic chemotherapy remain marginal. Although DDLPS is molecularly characterized by co-amplification of MDM2 and CDK4 (12q14-15) and detailed genomic analyses have been conducted by multiple research groups, the effects of molecular targeted drugs are marginal, and novel therapeutic modalities are required. Although patient-derived cell lines are pivotal for cancer research, no DDLPS cell lines are currently available from public cell repositories. Accordingly, in this study, we established a novel DDLPS cell line, NCC-DDLPS5-C1, using surgically resected tumor tissues from a patient with DDLPS. NCC-DDLPS5-C1 cells exhibited typical gene amplification, overexpression of MDM2 and CDK4, and other DNA copy number alterations. The NCC-DDLPS5-C1 cells were capable of rapid cell proliferation, aggressive invasion, and spheroid formation, but not tumor formation in mice. We reported the utility of NCC-DDLPS5-C1 cells for a drug-response assay to detect anticancer drugs that significantly attenuated cell proliferation. Thus, we concluded that the NCC-DDLPS5-C1 cell line could be a useful resource for the study of DDLPS. Considering the diversity of disease in terms of clinical outcomes, continuous efforts are required to develop more patient-derived cancer models with different clinical and pathological backgrounds.

Myxofibrosarcoma (MFS) is a highly aggressive malignancy with complex karyotypes and a postoperative recurrence tendency, owing to its strong invasiveness. Although systemic chemotherapy is considered in patients with unresectable MFS, the efficacy of conventional chemotherapy is hitherto unclear. Recently, drug screening analysis using a large number of tumor cell lines has been attempted to discover novel therapeutic candidate drugs for common cancers. However, the number of MFS cell lines is extremely small because of its low incidence—this hinders the conduction of screening studies and slows down the development of therapeutic drugs. To overcome this problem, we established a novel MFS cell line, NCC-MFS5-C1, which was shown to harbor typical MFS genetic abnormalities and thus had useful properties for in vitro studies. We conducted the largest integrated screening analysis of 210 drugs using NCC-MFS5-C1 cells along with four MFS cell lines, which we previously reported. Bortezomib (a proteasome inhibitor) and romidepsin (a histone deacetylase inhibitor) showed stronger antitumor effects than the standard drug, doxorubicin. Therefore, the NCC-MFS5-C1 cell line can potentially contribute to elucidating MFS pathogenesis and developing a novel MFS treatment.

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by a germline mutation of the TP53. The lifetime risk of cancer in individuals with LFS is ≥ 70% for men and ≥ 90% for women. Undifferentiated pleomorphic sarcoma (UPS) is one of the core cancers associated with LFS. UPS is a subtype of undifferentiated soft tissue sarcoma that shows no identifiable line of differentiation. The standard curative treatment for UPS is complete surgical resection. However, local recurrence and distant metastasis to the lung can usually be found after resection of the UPS. Therefore, a novel treatment strategy for patients with UPS is required. Although well characterized, patient-derived tumor cell lines facilitate the high-throughput screening of a large number of drugs, and no sarcoma cell lines derived from a patient with LFS have been registered in public cell banks. Thus, this study aimed to establish a novel, well-characterized UPS cell line from a patient with LFS. From surgically resected UPS tumor tissues, we established the first UPS cell line from a patient with LFS and named it NCC-UPS4-C1. NCC-UPS4-C1 harbored copy number alterations and had the TP53 tumor suppressor gene mutation. The cells exhibited constant cell growth and invasive ability. This well-characterized NCC-UPS4-C1 cell line was then utilized for high-throughput screening of 214 anti-cancer drugs, and two effective drugs were identified. One of the two drugs, romidepsin, was commonly effective for the NCC-UPS1-C1, NCC-UPS2-C1, and NCC-UPS3-C1 cell lines that we previously reported; a potential drug for the treatment of UPS was suggested using well-characterized UPS cell lines. These data indicate that NCC-UPS4-C1, which is the first sarcoma cell line established from a patient with LFS, enables researchers to conduct vigorous preclinical research on UPS.

(1) Background: CIC-DUX4 sarcoma is a rare mesenchymal small round cell tumor which belongs to rare cancers that occupy a significant percentage of cancer cases as a whole, despite each being rare. Importantly, each rare cancer type has different features, and thus there is a need to develop a model that mimics the features of each of these cancers. We evaluated the idea that the chicken chorioallantoic membrane assay (CAM), a convenient and versatile animal model, can be established for the CIC-DUX4 sarcoma. (2) Methods: Patient-derived cell lines of CIC-DUX4 were applied. These cells were transplanted onto the CAM membrane and tumor formation was examined by H&amp, E staining, immunohistochemistry and Western blotting. The CAM tumor was transferred onto a fresh CAM and was also used to form organoids. Retention of the fusion gene was examined. (3) Results: H&amp, E staining as well as molecular characterization demonstrated the formation of the CIC-DUX4 tumor on the CAM membrane. Expression of cyclin D2 and ETV4 was identified. The CAM tumor was transferred to a fresh CAM to form the second-generation CAM tumor. In addition, we were successful in forming tumor organoids using the CAM tumor. Retention of the fusion gene CIC-DUX4 in the CAM, second-generation CAM, and in the CAM-derived organoids was confirmed by RT-PCR. (4) Conclusions: The CAM assay provides a promising model for CIC-DUX4 sarcoma.

Giant cell tumor of bone (GCTB) is a rare osteolytic intermediate bone tumor that harbors a pathogenic H3F3A gene mutation and exhibits characteristic histology. The standard curative treatment for GCTB is complete surgical resection, but it frequently results in local recurrence and, more rarely, metastasis. Therefore, effective multidisciplinary treatment is needed. Although patient-derived tumor cell lines are promising tools for preclinical and basic research, there are only four available cell lines for GCTB in public cell banks. Thus, the aim of this study was to establish a novel GCTB cell line. Using surgically resected tumor tissues from a patient with GCTB, we established a cell line named NCC-GCTB4-C1. The cells harbored the typical H3F3A gene mutation and exhibited constant proliferation and invasive capabilities. After characterizing NCC-GCTB4-C1 cell behaviors, we conducted high-throughput screening of 214 anti-tumor drugs and identified seven effective drugs. Comparing the results of high-throughput screening using NCC-GCTB4-C1 cell line with the results using NCC-GCTB1-C1, NCC-GCTB2-C1, and NCC-GCTB3-C1 cell lines that we previously established, four drugs were in common effective. This study showed potential drugs for the treatment of GCTB. These data indicate that NCC-GCTB4-C1 has the potential to be a powerful tool in preclinical and basic research on GCTB.

Malignant peripheral nerve sheath tumors (MPNSTs) are a rare subtype of mesenchymal tumors that arise from the sheath of peripheral nerves. MPNSTs exhibit strong metastatic potential, leading to poor clinical outcomes. The clinical utility of radiation therapy and chemotherapy is marginal with respect to overall survival and effective systematic therapies for MPNSTs are still needed to improve patient outcome. Although patient-derived cell lines are an essential tool for the development of novel therapies, only a limited number of cell lines have been reported and are available from cell banks. Thus, we established the novel MPNST cell line, NCC-MPNST6-C1, using surgically resected MPNST tissue. The NCC-MPNST6-C1 cells retained copy-number alterations similar to those of the original tumors and demonstrated constant proliferation, spheroid formation, and invasion capability in vitro, which reflected the malignant features of the original tumor tissue. While the NCC-MPNST6-C1 cells did not exhibit tumorigenesis in nude mice, their use in drug screening resulted in anti-cancer agents with low IC

Undifferentiated pleomorphic sarcoma (UPS), previously termed malignant fibrous histiocytoma, is one of the most aggressive sarcomas with no identifiable line of differentiation. Although the molecular mechanism of oncogenesis in UPS has not been clarified, radiation exposure is considered to be a risk factor in the development of UPS. In the treatment of UPS, surgical treatment remains the most important modality. While chemotherapy is considered in unresectable or metastatic cases, UPS is known to be refractory to conventional chemotherapy, leading to an unfavorable prognosis. To improve the clinical outcome of this condition, novel treatment methods are urgently needed. Patient-derived cell lines are essential tools in preclinical studies. However, owing to the rarity of UPS, only four UPS cell lines are publicly available. Thus, we established a novel UPS cell line, NCC-UPS3-C1, using a surgically resected tumor from a patient with radiation-associated UPS. NCC-UPS3-C1 cells had multiple genomic deletions including the tumor suppressor genes CDKN2A and CDKN2B. NCC-UPS3-C1 cells demonstrated constant growth, spheroid formation, and aggressive invasion ability. We also conducted a screening test using 214 drugs and identified that the histone deacetylase inhibitor, romidepsin, is highly effective on NCC-UPS3-C1 cells. Thus, we concluded that the NCC-UPS3-C1 cell line is a useful tool in preclinical studies for UPS.

With the abundance of CT scanners in Japan, doctors can easily order CT scans to diagnose pneumonia. The Japanese Respiratory Society (JRS) guidelines uniquely recommend conditions for which additional CT scans should be considered at the time of diagnosis of pneumonia, a feature not found in other guidelines. In this study, we aimed to evaluate the usefulness of the recommendations in a bid to reduce the number of unnecessary CT examinations.We retrospectively reviewed the electronic medical records of consecutive patients with pneumonia hospitalized between April 2016 and March 2017 to extract patients' backgrounds and clinical courses. Conformity with the JRS guideline recommendations was also examined. In the patients who did not meet the recommendations, we investigated the proportion of them for whom an additional CT scan influenced the clinical decisions. Finally, we evaluated whether there was a difference in hospital stay depending on the additional chest CT at the time of admission.We included 363 hospitalized patients with pneumonia. Chest CT scan was performed in 306 patients (84.3%), of whom 186 (60.8%) did not meet the JRS guideline recommendations. Chest CT revealed findings requiring a change in treatment strategy in only 14 (7.5%) of the 186 patients. Among the 240 patients (66.1%) who did not meet the recommendations, no statistically significant difference was observed in the hospital stay or mortality between patients with and without CT scans.Adherence to the JRS guideline recommendations may reduce the excessive use of CT scans in the diagnosis of pneumonia.

Primary pleural melanoma is an extremely rare neoplasm, and to the best of our knowledge, there have been only 8 case reports of this condition in the English literature. We herein report a rare case in which the cytological and immunocytochemical analyses of pleural fluid and ultrasonography (US)-guided biopsy of a pleural lesion were useful for the diagnosis primary pleural melanoma. This case highlights the importance of careful physical examinations, cytomorphologic and immunocytochemical analyses of pleural fluid, as well as the utility of US-guided biopsy of the pleural lesions in the diagnosis of primary pleural melanoma.

We experienced a patient who presented with lung abscess one month after aspirating barium during a gastric cancer screening examination. The patient had no subjective symptoms suggesting a swallowing disorder. Rigorous history taking under suspicion of aspiration and a further assessment of the cause of aspiration revealed hypopharyngeal cancer. Lung abscess and hypopharyngeal cancer, both treatable but potentially fatal conditions, were not diagnosed until one month after the aspiration. This highlights the need for guidance for patients and physicians to follow in the event of barium aspiration, as it is the most common complication of a barium examination. A health checkup for one condition (gastric cancer) may also be an opportunity to diagnose another underlying condition.

Dedifferentiated liposarcoma (DDLPS) is a highly malignant subtype of liposarcoma, with characteristic amplification of MDM2 and CDK4 (12q14-15). It is caused by the dedifferentiation of well-differentiated liposarcoma. DDLPS is refractory to conventional chemotherapy; thus, surgical resection is the primary treatment modality. However, complete resection of DDLPS is difficult because of its deep location, which results in poor prognosis. Therefore, novel systemic chemotherapy is required to improve the clinical outcome. Patient-derived cell lines are important tools in the development of novel chemotherapy. However, there are no DDLPS cell lines available from public cell banks. In this study, we established a novel DDLPS cell line, NCC-DDLPS3-C1, using a surgically resected specimen from a patient with DDLPS. NCC-DDLPS3-C1 cells retained the characteristic gene amplification of MDM2 and CDK4. In addition, other gene amplifications and losses related to the poor prognosis of DDLPS were also observed in concordance with the original tumor. The cells also exhibited rapid cell proliferation, aggressive invasion ability, spheroid formation ability, and tumorigenic ability in nude mice. Furthermore, a drug-screening test showed significant antiproliferative effects of proteasome inhibitors and HDAC inhibitors. Thus, the NCC-DDLPS3-C1 cell line should be a useful tool for the development of novel chemotherapy for DDLPS.

Synovial sarcoma (SS) is defined as a monomorphic blue spindle cell sarcoma showing variable epithelial differentiation, and is characterized by a specific fusion gene, SS18-SSX. Although SS is rare, it accounts for approximately 8% of all soft tissue sarcomas, which occupies a significant proportion of soft tissue tumors. The prognosis of SS is unfavorable, with 5-year survival rate of 50-60%, and only a few anti-cancer agents are recommended for its treatment. Thus, we need to urgently establish novel treatment methods. Patient-derived cell lines are essential tools in basic research and pre-clinical studies. However, there are only 4 publicly available SS cell lines. Therefore, we established a novel SS cell line, NCC-SS4-C1, using surgically resected tumor tissues of a patient with SS. The cell line maintained the characteristic fusion gene, SS18-SSX1, and copy number alteration, in concordance with the original tumor. The cells also exhibited moderate cell proliferation, invasion ability, and spheroid formation ability. Moreover, a drug-screening test using 4 SS cell lines, including NCC-SS4-C1, demonstrated the significant anti-proliferative effects of ALK and HDAC inhibitors. Thus, we concluded that the NCC-SS4-C1 cell line is a useful tool for basic and pre-clinical studies of SS.

While aspiration pneumonia constitutes the majority of pneumonia cases in the elderly, it remains highly underdiagnosed. We experienced a case of recurrent pneumonia and chronic cough that was later diagnosed as aspiration pneumonia and diffuse aspiration bronchiolitis (DAB) due to recurrent hemorrhaging from an intramedullary cavernous malformation. The patient was finally diagnosed when life-threatening respiratory depression caused emergency attention. This is the first report of hemorrhaging from an intramedullary cavernous malformation diagnosed due to aspiration pneumonia and DAB. These findings highlight the importance of considering aspiration in cases with recurrent pneumonia or chronic chough. The underlying cause may be a life-threatening condition.

The simple suspension method (SSM), developed by Kurata in 1997, is a way to suspend tablets and capsules in warm water for decay and suspension prior to their administration. This method is safe and has various advantages such as the avoidance of tube clogging and the loss of the drug. This study aimed to investigate whether a higher percentage of commonly used drugs could pass through nutrition tubes effectively using SSM, relative to that using the conventional crushing method. A tablet or capsule was inserted into a 20 mL syringe with warm water (at 55 °C). After 10 min, it was shaken in the syringe. The suspension liquid was injected into tubes of the following sizes: 8 Fr, 10 Fr, 12 Fr, 14 Fr, 16 Fr, and 18 Fr. A total of 3686 tablets and 432 capsules that are frequently used in Japan were tested. Using SSM, 3377 (91.6%) tablets and 359 (83.1%) capsules disintegrated within 10 min and passed through the tube without clogging it in the tube passage test. With the conventional crushing method, 2117 tablets (57.4%) and 272 capsules (63.0%) could be crushed. SSM reduced the risk of tube clogging and drug loss with more drugs than that with the conventional crushing method. The number of drugs indicated for administration by SSM is greater than that indicated by the conventional crushing method. Further studies are needed to consider its utility compared to conventional methods for dysphagia patients in clinical settings.

Leiomyosarcoma (LMS) is a rare and aggressive mesenchymal malignancy, derived from smooth muscle cells or precursor mesenchymal stem cells for this tissue type. LMS has highly complex and unstable karyotypes, and the clinical outcomes in patients with LMS remain dismal as evidenced by the 5-year-survival of 64%. Novel therapeutic approaches are required to improve its clinical outcomes. Patient-derived cancer cell lines are indispensable as a tool to study the molecular mechanisms underlying clinical behaviors of tumor cells such as resistance to treatments, metastasis, and recurrence. However, only a limited number of LMS cell lines are publicly available, probably because of the rarity of patients with LMS, and a paucity of cell lines hinders the research on LMS. This study aimed to develop a patient-derived LMS cell line. We successfully established a cell line from the primary tumor tissue of a 90-year-old female patient with pleomorphic LMS, which we named NCC-LMS2-C1. NCC-LMS2-C1 cells were maintained as a monolayer culture for over 29 passages spanning 10 months. NCC-LMS2-C1 cells exhibited continuous growth, the ability to form spheroid, and invasion capability. We screened 213 anti-cancer drugs to find those that have anti-proliferation effects on NCC-LMS2-C1 cells, and identified a histone deacetylase inhibitor, romidepsin. In conclusion, we have established a novel LMS cell line, NCC-LMS2-C1, which will be a useful resource to study the mechanisms of LMS progression and perform high-throughput screening for anti-cancer drug discovery.

Myxofibrosarcoma (MFS) is among the most aggressive and complex sarcoma types that require novel therapeutic approaches for improved clinical outcomes. MFS displays highly complex karyotypes, and frequent alterations in p53 signaling and cell cycle checkpoint genes as well as loss-of-function mutations in NF1 and PTEN have been reported. The effects of radiotherapy and chemotherapy on MFS are limited, and complete surgical resection is the only curative treatment. Thus, the development of novel therapeutic strategies for MFS has long been long desired for MFS. Patient-derived cell lines are an essential tool for basic and translational research in oncology. However, public cell banks provide only a limited number of MFS cell lines. In this study, we aimed to develop a novel patient-derived MFS cell line, which was established from the primary tumor tissue of a 71-year-old male patient with MFS and was named NCC-MFS2-C1. A single-nucleotide polymorphism assay revealed that NCC-MFS2-C1 cells exhibited gain and loss of genetic loci. NCC-MFS2-C1 cells were maintained as a monolayer culture for over 24 passages for 10 months. The cells exhibited spindle-like morphology, continuous growth, and capacity for spheroid formation and invasion. Screening of 213 anticancer agents revealed that bortezomib, gemcitabine, romidepsin, and topotecan at low concentrations inhibited the proliferation of NCC-MFS2-C1 cells. In conclusion, we established a novel MFS cell line, NCC-MFS2-C1, which can be used for studying the molecular mechanisms underlying tumor development and for the in vitro screening of anti-cancer drugs.

Dedifferentiated liposarcoma (DDLPS) is one of the four subtypes of liposarcomas; it is characterized by the amplification of the 12q13-15 region, which includes MDM2 and CDK4 genes. DDLPS has an extremely high local recurrence rate and is refractory to chemotherapy and radiation, which leads to poor prognosis. Therefore, a novel therapeutic strategy should be urgently established for improving the prognosis of DDLPS. Although patient-derived cell lines are important tools for basic research, there are no DDLPS cell lines available from public cell banks. Here, we report the establishment of a novel DDLPS cell line. Using the surgically resected tumor tissue from a patient with DDLPS, we established a cell line and named it NCC-DDLPS1-C1. The NCC-DDLPS1-C1 cells contained 12q13-15, 1p32, and 1q23 amplicons and highly expressed MDM2 and CDK4 proteins. NCC-DDLPS-C1 cells exhibited constant growth, spheroid formation, aggressive invasion, and tumorigenesis in mice. By screening a drug library, we identified that the proteasome inhibitor, bortezomib, had inhibitory effects on the proliferation of NCC-DDLPS1-C1 cells. We concluded that the NCC-DDLPS1-C1 cell line may serve as a useful tool for basic and pre-clinical studies of DDLPS.

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.

Alveolar soft-part sarcoma is a mesenchymal malignancy characterized by the rearrangement of ASPSCR1 and TFE3 and a histologically distinctive pseudoalveolar pattern. Although alveolar soft-part sarcoma takes an indolent course, its long-term prognosis is poor because of late distant metastases. Currently, curative treatments have not been found for alveolar soft-part sarcoma, and hence, a novel therapeutic strategy has long been required. Patient-derived cell lines comprise an important tool for basic and preclinical research. However, few cell lines from alveolar soft-part sarcoma have been reported in the literature because it is an extremely rare malignancy, accounting for less than 1% of all soft-tissue sarcomas. This study aimed to establish a novel alveolar soft-part sarcoma cell line. Using surgically-resected tumor tissue of alveolar soft-part sarcoma, we successfully established a cell line and named it NCC-ASPS1-C1. The NCC-ASPS1-C1 cells harbored an ASPSCR1-TFE3 fusion gene and exhibited slow growth, and spheroid formation. On the other hand, NCC-ASPS1-C1 did not show the capability of invasion. We screened the antiproliferative effects of 195 anticancer agents, including Food and Drug Administration-approved anticancer drugs. We found that the MET inhibitor tivantinib and multi-kinase inhibitor orantinib inhibited the proliferation of NCC-ASPS1-C1 cells. The clinical utility and molecular mechanisms of antitumor effects of these drugs are worth investigating in the further studies, and NCC-ASPS1-C1 cells will be a useful tool for the in vitro study of alveolar soft-part sarcoma.

Dermatofibrosarcoma protuberans (DFSP) is the most common dermal sarcoma; it is characterized by the presence of the COL1A1-PDGFB translocation, which causes the constitutive activation of the platelet-derived growth factor β (PDGFB) signaling pathway. DFSP frequently exhibits local recurrence and is refractory to conventional chemotherapy. Therefore, a novel therapeutic strategy is required for improving the prognosis of DFSP. Although patient-derived cell lines are important tools for pre-clinical studies, currently, only a few such cell lines are available for DFSP in cell banks. Here, we report the establishment of a novel DFSP cell line. Using a surgically resected metastatic tumor tissue from a patient with DFSP, we established a cell line called NCC-DFSP3-C1. The NCC-DFSP3-C1 cells had a COL1A1-PDGFB translocation and retained the same copy number aberrations as the original tumor tissue. NCC-DFSP3-C1 cells exhibited constant growth, spheroid formation, and invasive ability. By screening a drug library, we identified anti-cancer agents with inhibitory effects on the proliferation of NCC-DFSP3-C1 cells; these anti-cancer agents included proteasomal, histone deacetylase, and kinase inhibitors. We concluded that the NCC-DFSP3-C1 cell line may serve as a useful tool for performing basic and pre-clinical studies on DFSP.

Spindle-cell/sclerosing rhabdomyosarcoma (ssRMS) is a rare subtype of rhabdomyosarcoma, characterized by unique pathological features. Although distinctive molecular backgrounds such as frequent mutations in MyoD1 have been reported, optimized therapy has not been fully developed, and further investigations are required. Patient-derived cancer models are critical tools for basic and pre-clinical studies. However, there is no model for ssRMS. Thus, this study aimed to develop a novel cell line from the tumor tissue of a patient with ssRMS. Using surgically resected tissue, we successfully established this cell line, named NCC-ssRMS1-C1. These cells exhibited spindle-shape morphology, consistent with the pathological observations of the original tumor tissue. Genetic studies demonstrated that NCC-ssRMS1-C1 cells retained original copy number alterations and the typical point mutation in MyoD1. Malignant phenotypes such as proliferation, spheroid formation, and invasion were confirmed in vitro by studying NCC-ssRMS1-C1 cells. Upon screening an anti-cancer agent library, sensitivity to conventional chemotherapeutic agents such as actinomycin D was revealed. We conclude that the NCC-ssRMS1-C1 cell line will be a useful resource for basic and pre-clinical studies.

Synovial sarcoma is a rare malignancy of mesenchymal origin, characterized by a chromosomal translocation, t(X;18) (p11.2;q11.2). Wide surgical resection with radiation and cytotoxic chemotherapy is established as a standard treatment; however synovial sarcoma remains a high-grade sarcoma with poor prognosis, and novel anti-cancer agents and immunological approaches are currently being developed. The patient-derived cell line is a critical tool for basic and pre-clinical research. However, only a few patient-derived synovial sarcoma cell lines are publicly available from cell banks. Thus, the aim of this study was to establish and characterize a novel cell line for synovial sarcoma. Using a surgically resected tumor tissue from a 48-year-old female patient, we successfully established a cell line, named NCC-SS3-C1. NCC-SS3-C1 cells harbor an SS18-SSX1 fusion gene and exhibit moderate growth, spheroid formation, and invasion. We examined a range of proliferation-inhibiting effects of small molecule anti-cancer compounds, including FDA-approved anti-cancer drugs, using NCC-SS3-C1 cells, and identified anti-cancer drugs which inhibited the proliferation of NCC-SS3-C1 cells at the low concentration. We concluded that NCC-SS3-C1 would be a useful tool for basic and pre-clinical synovial sarcoma research.

Nuclear protein in testis (NUT) carcinoma (NUT-C) is an exceedingly rare and aggressive neoplasm. We herein report a case of a 57-year-old man with a rapidly progressing tumor of the thorax and left pleural effusion. The pathological features and immunohistochemical staining of specimens obtained by a transbronchial lung biopsy initially indicated poorly differentiated squamous cell carcinoma. However, given the clinical presentation along with the additional histopathologic features, NUT-C was considered. Immunohistochemical staining for NUT was positive in the pleural fluid cell block, confirming the diagnosis of NUT-C. This report indicates the utility of immunohistochemical staining for diagnosing NUT in the pleural fluid cell block.

Diffuse idiopathic skeletal hyperostosis (DISH) is a relatively common progressive noninflammatory entheses disease. Patients are often asymptomatic or are undiagnosed due to minor chronic symptoms. We herein report a rare case in which the primary symptom was sudden-onset upper airway obstruction due to exuberant osteophytosis in the cervical spine. Treatment was successful with careful airway management and surgical osteophyectomy. Most DISH cases in the literature with airway obstruction have been managed with tracheotomy. However, the safety and necessity of this approach remain questionable. We herein discuss the possibility of conservative management as a choice of airway control. Airway obstruction due to DISH may be underrecognized. This highlights the importance of including DISH in the differential diagnosis of airway obstruction. In addition, a detailed evaluation and personalized care for each individual case is essential.

Objective Emphysematous cystitis (EC) has a high mortality rate compared with urinary tract infection without emphysema. However, its prognostic factors have yet to be determined. The presence of venous gas is suspected to be a rare, adverse prognostic factor of EC. However, all four previously reported cases improved. We hypothesized that venous gas is not an adverse prognostic factor of EC and aimed to assess the effect of venous gas on the EC prognosis. Methods Medical records were reviewed retrospectively. Patients The patients diagnosed with EC at Yodogawa Christian Hospital between April 2004 and September 2014 were included. Results Venous gas was present in 15 of 23 patients with EC. There was no significant difference in the background or clinical presentation between patients with or without venous gas. All patients with venous gas survived without invasive measures, whereas 50% of patients without venous gas died. Conclusion There was no marked difference in the mortality rate due to EC between the patients with and without venous gas. Venous gas may be a more common and less worrying finding in EC than assumed. It does not reflect the severity of infection, and air embolisms have not been reported so far. Venous gas may not affect the prognosis. This may be due to the differences in the mechanism of venous gas production. Gas in EC may develop due to glucose fermentation and intravesical pressurization, in contrast to the necrotizing infection seen in other emphysematous infections. This is the first study to assess the effect of venous gas on EC prognosis.

We herein report a rare case of miliary tuberculosis-associated hemophagocytic syndrome (HPS) complicated with respiratory failure. A 19-year-old Japanese woman with a fever, general malaise, and chest radiograph abnormalities was referred to our hospital. After admission, she developed respiratory failure with pancytopenia. A histological examination of lung and bone marrow biopsy samples revealed noncaseating granulomas without evidence of acid-fast bacilli or lymphoma. In addition, a bone marrow biopsy showed marked histiocyte hyperplasia with hemophagocytosis, and a bronchoalveolar lavage fluid culture grew Mycobacterium tuberculosis. Therefore, a diagnosis of miliary tuberculosis-associated HPS was made. The patient was successfully treated with antituberculous therapy.

CIC-DUX4 sarcoma (CDS), an aggressive soft tissue sarcoma, is characterized by a CIC and DUX4 rearrangement. It has a dismal clinical course and high metastatic rate and shows chemotherapy resistance; therefore, a novel therapeutic strategy is required. Patient-derived cell lines are indispensable tools for basic and preclinical research. However, only a few patient-derived CDS cell lines have been currently reported. Therefore, in this study, we aimed to establish and characterize a novel cell line of CDS. We successfully established the NCC-CDS2-C1 cell line by using surgically resected tumor tissue from a patient with CDS. The NCC-CDS2-C1 cells harbored a CIC-DUX4 fusion gene without insertion and exhibited rapid growth, spheroid formation, and invasion. We screened the antiproliferative effects of small anticancer agent compounds, which included FDA-approved anticancer drugs, on NCC-CDS2-C1 cells in comparison with those on the two previously reported patient-derived CDS cell lines, NCC-CDS1-X1-C1 and NCC-CDS1-X3-C1. The response profile of NCC-CDS2-C1 was similar to but distinct from those of the other cell lines for the small anticancer agent compounds. Therefore, we conclude that the NCC-CDS2-C1 cell line will be a useful tool for basic and preclinical studies of CDS.

The success rate of establishing human cancer cell lines is not satisfactory and the established cell lines often do not preserve the molecular and histological features of the original tissues. In this study, we developed a novel culture method which can support proliferation of almost all primary epithelial ovarian cancer cells, as well as primary normal human oviductal epithelial cells. Cancer cells from fresh or frozen specimens were enriched by the anti-EpCAM antibody-conjugated magnetic beads, plated on Matrigel-coated plate and cultivated under the optimized culture conditions. Seventeen newly established ovarian cancer cell lines, which included all four major histotypes of ovarian cancer, were confirmed to express histotype-specific markers in vitro. Some of the cell lines from all the four histotypes, except mucinous type, generated tumors in immune-deficient mice and the xenograft tumor tissues recapitulated the corresponding original tissues faithfully. Furthermore, with poorly tumorigenic cell lines including mucinous type, we developed a novel xenograft model which could reconstruct the original tissue architecture through forced expression of a set of oncogenes followed by its silencing. With combination of the novel culture method and cell-derived xenograft system, virtually every epithelial ovarian cancer can be reconstituted in mice in a timely fashion.

Predicting phenotypes at risk of chronic obstructive pulmonary disease (COPD) exacerbation is extremely important. Dysphagia is becoming recognized as one of these phenotypes. A convenient method of screening for dysphagia and COPD exacerbation risk is desired. The repetitive saliva swallowing test (RSST) is one of the least invasive dysphagia screening methods. We previously reported the possible relation between the RSST result and COPD exacerbation in a retrospective study. Based on this, we performed a prospective study to evaluate the efficacy of RSST as a predictor of COPD exacerbation and to determine its optimal cut-off value for COPD.Seventy patients with COPD were recruited. Patients underwent the following dysphagia screening tests: the 10-item Eating Assessment Tool, Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease, RSST, water swallowing test, and simple swallow provocation test. After one year, they were classified into two groups according to the presence of COPD exacerbation during the follow-up period.Twenty-seven patients had one or more exacerbations in the past year. During the follow-up period, 28 patients had one or more exacerbations (E group), and 42 had none (non-E group). There were no significant differences between the groups except for the presence of past exacerbations and the results of the RSST, when the cut-off value was set at 2, 3, 4, or 5 swallows. The number of swallows in the RSST was significantly lower in the E group than in the Non-E group. A cut-off value of 5 was the most effective. The time to first exacerbation was significantly longer in those with an RSST value of5. The RSST was more reliable for differentiating the E group and non-E group than the presence of exacerbation in the past year (hazard ratios: 13.78 and 2.70, respectively).An RSST cut-off value of 5 may be a strong predictor of COPD exacerbation.

Background Peritoneal dissemination is a critical prognostic factor in ovarian cancer. Although stabilized spheroid formation promotes cancer cell peritoneal dissemination in ovarian cancer, the associated oncogenes are unknown. In this study, we assessed the role of the KRAS oncogene in ovarian cancer cell dissemination, focusing on the stability of cells in spheroid condition, as well as the modulation of intracellular signaling following spheroid transformation. Methods We used ID8, a murine ovarian cancer cell line, and ID8-KRAS, an oncogenic KRAS (G12 V)-transduced ID8 cell line in this study. Spheroid-forming (3D) culture and cell proliferation assays were performed to evaluate the growth characteristics of these cells. cDNA microarray analysis was performed to identify genes involved in KRAS-associated signal transduction in floating condition. A MEK inhibitor was used to evaluate the effect on cancer peritoneal dissemination. Results Cell viability and proliferation in monolayer (2D) cultures did not differ between ID8 and ID8-KRAS cells. However, the proportions of viable and proliferating ID8-KRAS cells in 3D culture were approximately 2-fold and 5-fold higher than that of ID8, respectively. Spheroid-formation was increased in ID8-KRAS cells. Analysis of peritoneal floating cells obtained from mice intra-peritoneally injected with cancer cells revealed that the proportion of proliferating cancer cells was approximately 2-fold higher with ID8-KRAS than with ID8 cells. Comprehensive cDNA microarray analysis revealed that pathways related to cell proliferation, and cell cycle checkpoint and regulation were upregulated specifically in ID8-KRAS cells in 3D culture, and that some genes partially regulated by the MEK-ERK pathway were upregulated only in ID8-KRAS cells in 3D culture. Furthermore, a MEK inhibitor, trametinib, suppressed spheroid formation in 3D culture of ID8-KRAS cells, although trametinib did not affect 2D-culture cell proliferation. Finally, we demonstrated that trametinib dramatically improved the prognosis for mice with ID8-KRAS tumors in an in vivo mouse model. Conclusions Our data indicated that KRAS promoted ovarian cancer dissemination by stabilizing spheroid formation and that the MEK pathway is important for stabilized spheroid formation. Disruption of spheroid formation by a MEK inhibitor could be a therapeutic target for cancer peritoneal dissemination. Electronic supplementary material The online version of this article (10.1186/s12885-018-4922-4) contains supplementary material, which is available to authorized users.