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Sarcoma is a rare mesenchymal malignancy that comprises more than 50 histological subtypes. Because of the rarity and diversity of sarcomas, their differential diagnosis is difficult, and there is still a need for biomarkers to support pathological diagnoses. Micro RNAs (miRNAs) are small noncoding RNAs that regulate the behavior of tumors, such as invasion and metastasis. The expression patterns of miRNAs reflect the origin of malignancy and are considered to be candidate biomarkers. To understand the molecular background of those histological subtypes, we investigated the miRNA expression in 89 tumor tissues of eight subtypes. The correlation coefficients between each sarcoma subtype on the basis of miRNA expression values were mostly higher than 0.7, reflecting the common mesenchymal origin. By contrast, hierarchical clustering and principal component analysis showed that three types of sarcoma with chromosomal translocation (i.e., dermatofibrosarcoma protuberans, myxoid liposarcoma, and synovial sarcoma) were grouped according to their histological subtypes, whereas five types with complex karyotypes (i.e., myxofibrosarcoma, malignant peripheral nerve sheath tumor, undifferentiated pleomorphic sarcoma, dedifferentiated liposarcoma, and pleomorphic liposarcoma) were not. Notably, the number of miRNAs whose expression pattern was unique to histological subtypes with statistical significance was higher in sarcomas with chromosome translocation than in those with complex karyotypes. Hence, it can be concluded that the miRNAs unique to histological subtypes are candidate biomarkers for the differential diagnosis of sarcomas, particularly in those with chromosomal translocation. [ABSTRACT FROM AUTHOR]

Regulation of kinase activity plays a crucial role in carcinogenesis and cancer progression. Mutations in the activity domain of kinases are extensively investigated as therapeutic targets. We examined anti-proliferative anti-cancer drugs and drug targets via the multi-omics approach: (i) comprehensive kinase activity assay, (ii) high-throughput drug screening, and (iii) genomic sequencing. Two osteosarcomas cell lines, NCC-OS1-C1 and NCC-ESOS1-C1 derived from bone and soft tissue respectively, were used. Genetic alterations were examined by NCC Oncopanel based on the next-generation sequencing technology and SNP array. One hundred kinases were monitored by the PamStation 12, an in vitro kinase assay. The anti-proliferative effects of 214 FDA-approved anti-cancer drugs were examined. Mutation of PIK3CA and deletion of CDKN2A were identified in NCC-ESOS1-C1 and druggable genetic alterations were not identified in the NCC-OS1-C1. PI3K-AKT pathway or CDKN2A inhibitors did not show significant effects on these cell lines. Comprehensive kinomic assay revealed no remarkable differences on these osteosarcoma cells (R2=0.99). The two cells shared similar kinase activity profiles for FES, FER, PDGFR-ß, VEGFR2, and Wee1. Anti-proliferative effects of anti-cancer drugs on NCC-OS1-C1 and NCC-ESOS1 cells showed remarkable differences. Significant responses to romidepsin and trabectedin were observed for both. Eribulin was effective on NCCOS1- C1; ifosfamide and dacarbazine were effective on NCC-ESOS1-C1 only. Hence, investigating kinase activities and genetic alterations will lead to predict the effects of kinase inhibitors. The different status of kinase mutations, activities, and response to inhibitors should be integrated. Multi-omics experiments and data integration are crucial in understanding cancer progression and developing novel therapies. [ABSTRACT FROM AUTHOR]

Clear cell carcinoma (CCC) is a rare subtype of ovarian cancer resistant to standard platinum chemotherapy, which leads to a poor prognosis for patients with CCC. Kinases are targets for anticancer drugs; few studies have profiled kinase activity to identify kinase inhibitors as novel anticancer drugs. In this study, we aimed to identify novel anticancer drugs for the treatment of CCC with comprehensive kinase activity assay and drug screening. Using ascites from a 51-year old patient, we established and characterized the NCC-cOV1-C1 cell line. We screened the antiproliferative effects of 152 small anticancer compounds and conducted comprehensive kinase activity assays with the PamStation12 platform. The NCC-cOV1-C1 cells harbor copy number variation of HFN1ß amplification, and exhibit constant growth, spheroid formation, and invasion capability. NCC-cOV1-C1 cells responded remarkably to idarubicin HCl and vorinostat. The kinase activity assay revealed that SRC and EGFR were highly activated in NCC-cOV1-C1 cells; the SRC inhibitor dasatinib and the EGFR inhibitor lapatinib exhibited antiproliferative effects and downregulation of downstream signaling. The NCC-cOV1-C1 cell line will be a useful tool for basic and preclinical study of CCC, and the clinical utility of idarubicin HCl, vorinostat, dasatinib, lapatinib is worthy of further investigation. [ABSTRACT FROM AUTHOR]

Tumor biology can no longer be understood simply by focusing on the characteristics of the tumor cells, but instead must encompass the contributions of the "tumor microenvironment". Although the tumor microenvironment contains multiple natural extracellular matrices (ECMs), only single or specific ECMs are presently used to assess the behavioral characteristics of tumor cells in vitro. Recently, the use of decellularized tissue gels (DTGs) has gained attention, as they represent a new platform to provide multiple ECM components of the cellular microenvironment. However, as tissues contain unique components of ECMs, it is essential to reproduce the tissue-specific landscape when evaluating tumor functions in vitro. We hypothesized that DTGs affect the in vitro tumor cell behavior and that their protein composition varies between tissues. To test this, we created lung and liver DTGs via freeze-thawing and investigated the effects of DTGs on tumor cell migration. DTGs regulated the migration of tumor cells when these were cultured on DTG-coated plates. The proteins present in the DTGs were separated via SDS-PAGE, and multiple bands were observed using silver staining. Noteworthy, the band pattern varied depending on the tissue from which the DTGs were derived. In summary, this study shows that certain DTGs modulate the behavioral characteristics of tumor cells, which may have potential applications in cancer studies and therapy development. Hence, DTGs are worth investigating as useful tools for tumor cell culture and in vitro assays. [ABSTRACT FROM AUTHOR]

Objectives: We investigated the prediction of outcomes of patients with dermatomyositis with acute/subacute interstitial pneumonia (DM-A/SIP) on the basis of chest computed tomography (CT) images. Methods: In 20 patients with DM-A/SIP (13 survivors; seven deaths), the relationships between prognostic outcomes and chest high-resolution CT (HRCT) findings or limited three-level thinsection CT scoring on the first examination were retrospectively investigated. Results: No significant difference was noted in chest HRCT findings between the survivor group and death group. The ground-glass opacity (GGO) scores of the right upper and middle lobes and left upper lobe, and the fibrosis score of the right middle lobe were significantly higher in the death group than in the survivor group (p=0.01, 0.001, 0.02, and 0.02, respectively). The influence of the GGO score of the right middle lobe on death from IP was the strongest among the items examined, and it was independently significant (p=0.01). A right middle lobe GGO score of -3 (GGO-25% of the lobe) was determined to be the best cut-off value for a poor prognosis (sensitivity: 85.7%, specificity: 85.7%), and the survival rate after 24 weeks was significantly lower in patients with a right middle lobe GGO score of -3 (survival rate: 0.0%) than in those with a score of53 (92.9%) (p50.0001). Conclusions: The prognosis of patients with DM-A/SIP was poor when the range of right middle lobe GGO was 25% or higher on limited three-level thin-section CT. [ABSTRACT FROM AUTHOR]

The tumor microenvironment determines tumor characteristics, and its recapitulation via in vitro tissue culture conditions is necessary for better understanding of molecular mechanisms of tumor behaviors and development of novel therapy. Rhabdomyosarcoma is a mesenchymal tumor that originates limb muscles. To assess the possible utility of the decellularized materials that contain native components of the microenvironment for the optimal humanized spheroid formation, we demonstrated co-culture of decellularized muscle extracts and rhabdomyosarcoma cells. The decellularized muscle extracts were prepared using a detergent, solubilized via pepsin digestion, and used for the spheroid culture of rhabdomyosarcoma cells in a low-attachment tissue culture plate. Here, we confirmed that these extracts contained proteins whose expression was unique to muscles. When rhabdomyosarcoma cells formed spheroids with decellularized muscle extracts, they exhibited heterogeneous morphology and a unique protein expression pattern. We conclude that in vitro cancer models established using decellularized tissue extracts from the originating organ have the potential to recapitulate features of in vivo tumor cells by providing the components of the tumor microenvironment. The precise molecular mechanisms for the interaction of cells and decellularized tissues are worth further investigation. [ABSTRACT FROM AUTHOR]