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    The role of histone deacetylase 1 in distant metastasis of pancreatic ductal cancer.
    Cancer Sci 2018 Jun 19. Epub 2018 Jun 19.
    Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University.
    Current therapies for pancreatic ductal cancer (PDAC) do not sufficiently control distant metastasis. Thus, new therapeutic targets are urgently needed. Numerous studies have suggested that the epithelial-mesenchymal transition (EMT) is pivotal for metastasis of carcinomas. Read More

    FH inactivation in hereditary leiomyomatosis and renal cell cancer is synthetic lethal with ferroptosis induction.
    Cancer Sci 2018 Jun 19. Epub 2018 Jun 19.
    Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ, 85721, USA.
    Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a hereditary cancer syndrome characterized by inactivation of the Krebs cycle enzyme fumarate hydratase (FH). HLRCC patients are at a high risk of developing kidney cancer of type 2 papillary morphology that is refractory to current radio-, immuno-, and chemo- therapies. Hence, an effective therapy for this deadly form of cancer is urgently needed. Read More

    Phase II Trial of Biweekly Cetuximab and Irinotecan as Third-Line Therapy for Pretreated KRAS Exon 2 Wild-Type Colorectal Cancer.
    Cancer Sci 2018 Jun 16. Epub 2018 Jun 16.
    Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
    Efficacy and safety of biweekly cetuximab plus irinotecan were evaluated to provide guidance for its use in Japan as third-line treatment for pretreated metastatic colorectal cancer patients harboring wild-type KRAS Exon 2. Objective response rate was used as primary endpoint based on an expected proportion of 0.23 with confidence width of 0. Read More

    Exosomes in cancer development and clinical applications.
    Cancer Sci 2018 Jun 16. Epub 2018 Jun 16.
    Department of Plant Pathology and Microbiology & Center for Biotechnology, National Taiwan University, Taipei, 10617, Taiwan.
    Exosomes participate in cancer progression and metastasis by transferring bioactive molecules between cancer and varied cells in the local and distant microenvironments. Such intercellular cross-talks result in changes in multiple cellular and biological functions in recipient cells. Several hallmarks of cancer have been reportedly impacted by this exosome-mediated cell-to-cell communication, including modulating immune responses, re-programming stromal cells, re-modeling the architecture of extracellular matrix, or even endowing cancer cells with characteristics of drug resistance. Read More

    AMPK-dependent mTOR pathway is involved in flavokawain B-induced autophagy in thyroid cancer cells.
    Cancer Sci 2018 Jun 16. Epub 2018 Jun 16.
    Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, 250012, China.
    Flavokawain B (FKB), a naturalkava chalcone, displays potent anti-tumor activity in various types of cancer, though the mechanism of action remains unclear. In this study, we report that FKB has profound effects on the metabolic state of human thyroid cancer (TCa) cells, leading to high autophagy flux via upregulation of AMPK, which in turn inhibits mTOR and activates Beclin-1 in TCa cells. We further demonstrate that the autophagy induced by FKB plays a pro-survival role in TCa cells both in vitro and in vivo. Read More

    PIK3CA-mutation profiling in patients with breast cancer, using a highly sensitive detection system.
    Cancer Sci 2018 Jun 15. Epub 2018 Jun 15.
    Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
    PIK3CA mutations are common activating mutations associated with breast cancer (occurring in 20-30% of all cases) and are potent predictive markers for responses to PI3K inhibitors. Thus, it is important to develop sensitive methods to detect these mutations. We established a novel detection method using a quenching probe (QP) system to identify PIK3CA mutations, using DNA from 309 breast cancer tissues. Read More

    Nab-paclitaxel interrupt cancer-stromal interaction through CXCL10 mediated IL-6 down-regulation in vitro.
    Cancer Sci 2018 Jun 14. Epub 2018 Jun 14.
    Department of Surgery, Institute of Biomedical Sciences, Tokushima University of Graduate School, Tokushima, 770-8503, Japan.
    Cancer-associated fibroblasts (CAFs), which derived from cancer tissues stroma, interact with cancer cells and play an important role in cancer initiation, growth and metastasis. Nab-paclitaxel (nab-PTX) is the 130nm albumin binding paclitaxel and recommended for many kinds of cancer chemotherapy. It has been reported that nab-PTX stromal disrupting effect during pancreatic cancer treatment. Read More

    Autophagy inhibition synergizes with calcium mobilization to achieve efficient therapy of malignant gliomas.
    Cancer Sci 2018 Jun 14. Epub 2018 Jun 14.
    Division of Molecular Genetics, Cancer and Stem Cell Research Program, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa, 920-1192, Japan.
    Autophagy plays a critical role in tumorigenesis, but how autophagy contributes to cancer cells' responses to chemotherapeutics remains controversial. To investigate the roles of autophagy in malignant gliomas, we used CRISPR/CAS9 to knock out the ATG5 gene, which is essential for autophagosome formation, in tumor cells derived from glioblastoma patients. While ATG5 disruption inhibited autophagy, it did not change the phenotypes of glioma cells and did not alter their sensitivity to temozolomide, an agent used for glioblastoma patient therapy. Read More

    Integrin β1 is an essential factor on vasculogenic mimicry in human cancer cells.
    Cancer Sci 2018 Jun 14. Epub 2018 Jun 14.
    Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
    Vasculogenic mimicry (VM) formation by cancer cells is known to play a crucial role in tumor progression, whereas the detailed mechanism of which has been unclear. In this study, we focused on integrin β1 (ITGB1) and assessed the role of ITGB1 on VM formation. We used in vitro methods to seed cancer cells on Matrigel to evaluate the capability of VM formation. Read More

    Isolation and molecular analysis of circulating tumor cells from lung cancer patients using a microfluidic chip type cell sorter.
    Cancer Sci 2018 Jun 14. Epub 2018 Jun 14.
    Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Shizuoka, japan.
    Circulating tumor cells (CTCs) are a tumor-derived material utilized for liquid-based biopsy; however, capturing rare CTCs for further molecular analysis remains technically challenging, especially in non-small cell lung cancer. Here, we report the results of a clinical evaluation of On-chip Sort, a disposable microfluidic chip-based cell sorter, for capture and molecular analysis of CTCs from patients with lung adenocarcinoma. Peripheral blood was collected from 30 metastatic lung adenocarcinoma patients to enumerate CTCs using both On-chip Sort and CellSearch in a blind manner. Read More

    Role of caveolin-1 in hepatocellular carcinoma arising from non-alcoholic fatty liver disease.
    Cancer Sci 2018 Jun 13. Epub 2018 Jun 13.
    Second Department of Surgery.
    The molecular features of hepatocellular carcinoma arising from non-alcoholic fatty liver disease (NAFLD-HCC) are not well known. In this study, we investigated the mechanism by which NAFLD-HCC survives in a fat-rich environment. We found that caveolin (CAV)-1 was overexpressed in clinical specimens from NAFLD-HCC patients. Read More

    CDK2 positively regulates aerobic glycolysis by suppressing SIRT5 in gastric cancer.
    Cancer Sci 2018 Jun 13. Epub 2018 Jun 13.
    Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China.
    Although significant progress has been made in the diagnosis and treatment of gastric cancer, the overall survival rate of the disease remains unchanged at approximately 20-25%. Thus, there is an urgent need for a better understanding of the molecular biology aspects of the disease, in the hope of discovering novel diagnosis and treatment strategies. Recent years have witnessed the decisive roles of aberrant cancer cell metabolism in the maintenance of malignant hallmarks of cancers, and cancer cell metabolism has been regarded as a novel target for the treatment of cancer. Read More

    TNFSF15 promotes lymphatic metastasis via up-regulation of VEGFC in a mouse model of lung cancer.
    Cancer Sci 2018 Jun 11. Epub 2018 Jun 11.
    Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, China.
    Lymphatic metastasis is facilitated by lymphangiogenic growth factor VEGFC that is secreted by some primary tumors. We previously identified tumor necrosis factor superfamily 15 (TNFSF15), a blood vascular endothelium-derived cytokine, in lymphatic endothelial cells, as a key molecular modulator during lymphangiogenesis. However, the effect of TNFSF15 on tumor lymphatic metastasis and the underlying molecular mechanisms remain unclear. Read More

    High-affinity PD-1 molecules deliver improved interaction with PD-L1 and PD-L2.
    Cancer Sci 2018 Jun 11. Epub 2018 Jun 11.
    State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, China.
    The inhibitory checkpoint molecule programmed death (PD)-1 plays a vital role in maintaining immune homeostasis upon binding to its ligands, PD-L1 and PD-L2. Several recent studies have demonstrated that soluble PD-1 (sPD-1) can block the interaction between membrane PD-1 and PD-L1 to enhance the anti-tumor capability of T cells. However, the affinity of natural sPD-1 binding to PD-L1 is too low to permit therapeutic applications. Read More

    Genetic compensation of RUNX family transcription factors in leukemia.
    Cancer Sci 2018 Jun 8. Epub 2018 Jun 8.
    Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan.
    RUNX1 is a transcription factor belonging to the Core Binding Factor (CBF) family. It is considered to be a master regulator of hematopoiesis and has been regarded as a tumor suppressor because it is essential for definitive hematopoiesis in vertebrates. It is one of the most frequent target genes of chromosomal translocation in leukemia, and germ line mutation of RUNX1 causes familial platelet disorder with associated myeloid malignancies (FPDMM). Read More

    Current state of therapeutic development for rare cancers in Japan, and proposals for improvement.
    Cancer Sci 2018 May;109(5):1731-1737
    Subcommittee on Rare Cancers, The Science Board to the Pharmaceuticals and Medical Devices Agency, Tokyo, Japan.
    This article discusses current obstacles to the rapid development of safe and effective treatments for rare cancers, and considers measures required to overcome these challenges. In order to develop novel clinical options for rare cancers, which tend to remain left out of novel therapeutic development because of their paucity, efficient recruitment of eligible patients, who tend to be widely dispersed across the country and treated at different centers, is necessary. For this purpose, it is important to establish rare cancer registries that are linked with clinical studies, to organize a central pathological diagnosis system and biobanks for rare cancers, and to consolidate patients with rare cancers to facilities that can conduct clinical studies meeting international standards. Read More

    Japanese Society of Medical Oncology Clinical Guidelines: Molecular Testing for Colorectal Cancer Treatment, Third Edition.
    Cancer Sci 2018 Jun;109(6):2074-2079
    Division of Translational Research, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan.
    The Japanese Society of Medical Oncology (JSMO) previously published 2 editions of the clinical guidelines: "Japanese guidelines for testing of KRAS gene mutation in colorectal cancer" in 2008 and "Japanese Society of Medical Oncology Clinical Guidelines: RAS (KRAS/NRAS) mutation testing in colorectal cancer patients" in 2014. These guidelines have contributed to the proper use of KRAS and RAS mutation testing, respectively. Recently, clinical utility, particularly for colorectal cancer (CRC) patients with BRAF V600E mutation or DNA mismatch-repair (MMR) deficiency, has been established. Read More

    The CD47-SIRPα signaling system and its application to cancer immunotherapy.
    Cancer Sci 2018 Jun 6. Epub 2018 Jun 6.
    Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
    Tumor cells evade immune surveillance through direct or indirect interactions with various types of immune cell, with much recent attention having focused on modifying immune cell responses as the basis for the development of new cancer treatments. Signal regulatory protein α (SIRPα) and CD47 are both transmembrane proteins that interact with each other and constitute a cell-cell communication system. SIRPα is particularly abundant in myeloid cells such as macrophages and dendritic cells, whereas CD47 is expressed ubiquitously and its expression level is elevated in cancer cells. Read More

    Yin Yang 1 promotes the Warburg effect and tumorigenesis via glucose transporter GLUT3.
    Cancer Sci 2018 Jun 5. Epub 2018 Jun 5.
    The Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China.
    Cancer cells typically shift their metabolism to aerobic glycolysis to fulfil the demand of energy and macromolecules in order to support their proliferation. Glucose transporter (GLUT) family-mediated glucose transport is the pacesetter of aerobic glycolysis, and thus is critical for tumor cell metabolism. Yin Yang 1 (YY1) is an oncogene crucial for tumorigenesis; however, its role in tumor cell glucose metabolism remains unclear. Read More

    DEAD box protein DDX1 promotes colorectal tumorigenesis through transcriptional activation of the LGR5 gene.
    Cancer Sci 2018 Jun 5. Epub 2018 Jun 5.
    Stem Cell Project and 4Core Technology and Research Center, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan.
    DDX1, a member of the DEAD box RNA helicase family, plays a critical role in testicular tumors. However, it remains to be clarified whether DDX1 is involved in other types of malignant tumors such as colorectal cancer. We disrupted the DDX1 gene in a human colorectal cancer cell line LoVo using the CRISPR/Cas9-mediated gene-targeting system. Read More

    HNRNPLL stabilizes mRNAs for DNA replication proteins and promotes cell cycle progression in colorectal cancer cells.
    Cancer Sci 2018 Jun 5. Epub 2018 Jun 5.
    Division of Pathophysiology, Aichi Cancer Center Research Institute, Nagoya, Japan.
    HNRNPLL (heterogeneous nuclear ribonucleoprotein L-like), an RNA-binding protein that regulates alternative splicing of pre-mRNAs, has been shown to regulate differentiation of lymphocytes, as well as metastasis of colorectal cancer cells. Here we show that HNRNPLL promotes cell cycle progression and hence proliferation of colorectal cancer cells. Functional annotation analysis of those genes whose expression levels were changed by three-fold or more in RNA sequencing analysis between SW480 cells overexpressing HNRNPLL and those knocked down for HNRNPLL revealed enrichment of DNA replication-related genes by HNRNPLL overexpression. Read More

    HuR stabilizes TFAM mRNA in an ATM/p38 dependent manner in ionizing irradiated cancer cells.
    Cancer Sci 2018 Jun 1. Epub 2018 Jun 1.
    Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Chinese Academy of Sciences, No. 350 of Shushanhu Road, Hefei, PR China, 230031.
    Mitochondrial transcription factor A (TFAM) plays key roles in transcription and maintenance of mitochondrial DNA (mtDNA). It has been reported that TFAM could promote the proliferation and tumorigenesis of cells under stressed conditions. Previous evidence showed ionizing radiation stimulated the expression of TFAM, the replication of mtDNA and the activity of mtDNA encoded cytochrome C oxidase. Read More

    Multicenter retrospective analysis of systemic chemotherapy for unresectable combined hepatocellular and cholangiocarcinoma.
    Cancer Sci 2018 Jun 1. Epub 2018 Jun 1.
    Department of Medical Oncology, Kyorin University, Faculty of Medicine, Tokyo, Japan.
    We conducted a multicenter retrospective analysis to evaluate the efficacy of systemic chemotherapy for unresectable combined hepatocellular and cholangiocarcinoma. Thirty-six patients with pathologically proven, unresectable combined hepatocellular and cholangiocarcinoma treated with systemic chemotherapy were enrolled. The log-rank test determined the significance of each prognostic factor. Read More

    APOBEC family genes activation and regulation during tumorigenesis.
    Cancer Sci 2018 Jun 1. Epub 2018 Jun 1.
    Translational Medical Center, Central Hospital Affiliated to Zhengzhou University.
    Cancer is currently viewed as a disease of evolving genomic instability and abnormal epigenomic modifications. Most solid cancers harbor oncogenic gene mutations driven by both extrinsic and intrinsic factors. Apolipoprotein B mRNA editing catalytic polypeptide-like family (APOBECs) enzymes have an intrinsic deamination activity to convert cytosine to uracile during RNA editing and retrovirus or retrotransposon restriction. Read More

    Reappraisal of nodal Epstein-Barr Virus-negative cytotoxic T-cell lymphoma: identification of indolent CD5 diseases.
    Cancer Sci 2018 May 29. Epub 2018 May 29.
    Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan.
    Nodal cytotoxic molecule (CM)-positive peripheral T-cell lymphoma (CTL) has recently been recognized as a clinicopathologically distinct disease. To further characterize this disease, here we compared 58 patients with Epstein-Barr virus (EBV)-negative CTL to 48 patients with EBV-positive CTL. The two groups did not differ in histopathology, T-cell receptor (TCR) expression or rearrangement incidences, or survival curves. Read More

    Oncogenic roles of EZH1/2 in hematological malignancies.
    Cancer Sci 2018 May 29. Epub 2018 May 29.
    Division of Hematological Malignancy, National Cancer Center Research Institute, Tokyo, Japan.
    Polycomb group (PcG) proteins regulate the expression of target genes by modulating histone modifications and are representative epigenetic regulators that maintain the stemness of embryonic and hematopoietic stem cells. The histone methyltransferases enhancer of zeste homolog 1 and 2 (EZH1/2), which are subunits of polycomb repressive complexes (PRCs), are recurrently mutated or highly expressed in many hematological malignancies. EZH2 has a dual function in tumorigenesis as an oncogene and tumor suppressor gene, and targeting PRC2, in particular EZH1/2, for anticancer therapy has been extensively developed in the clinical setting. Read More

    CXCR4-mediated osteosarcoma growth and pulmonary metastasis is suppressed by MicroRNA-613.
    Cancer Sci 2018 May 30. Epub 2018 May 30.
    Department of orthopedic surgery, Xiangya Hospital, Central South University, Changsha, China.
    Osteosarcoma is the most common primary bone malignancy. Recently, studies showed chemokine receptor 4 (CXCR4) played a critical role in osteosarcoma. However, the regulation of CXCR4 is not fully understood. Read More

    HTLV-1 Tax-specific T cell exhaustion in HTLV-1-infected individuals.
    Cancer Sci 2018 May 29. Epub 2018 May 29.
    Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences.
    Adult T-cell leukemia/lymphoma (ATL) is caused by human T-cell lymphotropic/leukemia virus type 1 (HTLV-1), and a higher HTLV-1 provirus load in peripheral blood mononuclear cells (PBMC) is a risk factor for ATL development. Here, we document a significant inverse correlation between the function of HTLV-1 Tax-specific cytotoxic T-cells (Tax-CTL), as assessed by ex vivo cytokine production in response to cognate peptide, and the HTLV-1 provirus load in PBMC in both HTLV-1 asymptomatic carriers (AC) (Spearman rank correlation coefficient [Rs] = -0.494, P = 0. Read More

    ASP8273 tolerability and antitumor activity in TKI-naive Japanese patients with EGFR mutation-positive non-small cell lung cancer.
    Cancer Sci 2018 May 28. Epub 2018 May 28.
    Kindai University Hospital, Osaka, Japan.
    Epidermal growth factor receptor (EGFR) activating mutations occur in approximately 50% of East Asian patients with non-small cell lung cancer (NSCLC) and confer sensitivity to tyrosine kinase inhibitors (TKI). ASP8273 is an orally administered, irreversible EGFR-TKI that inhibits EGFR activating mutations and has demonstrated clinical activity in patients with EGFR mutation-positive NSCLC. EGFR-TKI-naïve Japanese adult patients (≥20 years) with NSCLC harboring EGFR mutations were enrolled in this open-label, single-arm, Phase 2 study (NCT02500927). Read More

    Vaccine immunotherapy with ARNAX induces tumor-specific memory T cells and durable anti-tumor immunity in mouse models.
    Cancer Sci 2018 May 23. Epub 2018 May 23.
    Department of Vaccine Immunology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
    Immunological checkpoint blockade therapies benefit a limited population of cancer patients. We have previously shown that vaccine immunotherapy with Toll-like receptor (TLR)3-adjuvant and tumor antigen overcomes anti-programmed death ligand-1 (PD-L1) resistance in mouse tumor models. In the present study, 4 different ovalbumin (OVA)-expressing tumor cell lines were implanted into syngeneic mice and subjected to anti-tumor immunotherapy using ARNAX and whole OVA protein. Read More

    Synergy between peroxisome proliferator-activated receptor γ agonist and radiotherapy in cancer.
    Cancer Sci 2018 May 23. Epub 2018 May 23.
    Department of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
    Angiogenesis and inflammation are crucial processes through which the tumor microenvironment (TME) influences tumor progression. In this study, we showed that peroxisome proliferator-activated receptor γ (PPARγ) is not only expressed in CT26 and 4T1 tumor cell lines but also in cells of TME, including endothelial cells and tumor-associated macrophages (TAM). In addition, we showed that rosiglitazone may induce tumor vessel normalization and reduce TAM infiltration. Read More

    Long non-coding RNA NEAT1 promoted ovarian cancer cells' metastasis via regulating of miR-382-3p/ROCK1 axial.
    Cancer Sci 2018 May 23. Epub 2018 May 23.
    Department of Nuclear Medicine, First Affiliated Hospital of Dalian Medical University, Dalian, P.R.China.
    Long non-coding RNAs (lncRNAs) are extensively involved in various malignant tumors including ovarian cancer (OC). In the present study, we focused on the expression and function of nuclear enriched abundant transcript 1 (NEAT1) work on ovarian cancer cells' metastasis. We demonstrated that NEAT1 was up-regulated in OC tissue specimens and cell lines. Read More

    Generation and application of human induced-stem cell memory T (iT ) cells for adoptive immunotherapy.
    Cancer Sci 2018 May 23. Epub 2018 May 23.
    Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
    Adoptive T cell therapy is an effective strategy for cancer immunotherapy. However, infused T cells frequently become functionally exhausted, and consequently offer a poor prognosis after transplantation into patients. Adoptive transfer of tumor antigen-specific stem cell memory T (T ) cells is expected to overcome this shortcoming since T cells are close to naïve T cells, but are also highly proliferative, long-lived, and produce a large number of effector T cells in response to antigen stimulation. Read More

    USP22 acts as an oncoprotein to maintain glioma malignancy through deubiquitinating BMI1 for stabilization.
    Cancer Sci 2018 May 22. Epub 2018 May 22.
    Institute of Nano Biomedicine and Engineering, Department of Instrument Science and Engineering, Key Lab. for Thin Film and Microfabrication Technology of Ministry of Education, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China.
    USP22 is a member of "death-from-cancer" signature, which plays a key role in cancer progression. Although previous evidence has shown that USP22 is overexpressed and correlated with poor prognosis in glioma. The effect and mechanism of USP22 in glioma malignancy especially cancer stemness remain elusive. Read More

    Increase in incidental detection of thyroid cancer in Osaka, Japan.
    Cancer Sci 2018 May 22. Epub 2018 May 22.
    Department of Surgery, Saiseikai Senri Hospital, Suita, Osaka, Japan.
    Using Osaka Cancer Registry data, we examined age-specific and age-adjusted incidence rates of thyroid cancer according to the route of thyroid cancer detection from 1992 to 2012. The detection routes were categorized into "symptomatic" and "incidental detection." Age-specific incidence rates of incidentally-detected thyroid cancer consistently increased during the study period, especially after 2001, for all sex and age groups other than childhood. Read More

    MicroRNA 493 is a prognostic factor in triple-negative breast cancer.
    Cancer Sci 2018 May 19. Epub 2018 May 19.
    Key Laboratory of Breast Cancer in Shanghai Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
    Breast cancer is one of the most common malignant diseases in women, in which triple-negative breast cancer (TNBC) exhibits higher aggressiveness and recurrence rates, while there are no effective targets or tailored treatments for patients with this subtype. Thus, finding effective prognostic markers for TNBC might help clinicians in their ability to care for their patients. We used tissue microarrays (TMAs) to detect miR-493 expression in breast cancer samples. Read More

    Potassium octatitanate fibers induce persistent lung and pleural injury and are possibly carcinogenic in male Fischer 344 rats.
    Cancer Sci 2018 May 17. Epub 2018 May 17.
    Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
    Potassium octatitanate fibers (K O•8TiO , POT fibers) are widely used as an alternative to asbestos. We investigated the pulmonary and pleural toxicity of POT fibers with reference to 2 non-fibrous titanium dioxide nanoparticles (nTiO ), photo-reactive anatase (a-nTiO ) and inert rutile (r-nTiO ). Ten-week old male F344 rats were administered 0. Read More

    The Emerging Roles of Long Non-coding RNA in Cancer.
    Cancer Sci 2018 May 17. Epub 2018 May 17.
    Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
    Since comprehensive analysis of the mammalian genome has revealed that the vast majority of genomic products are transcribed in long non-coding RNAs (lncRNAs), increasing attention has been paid towards these transcripts. The applied next-generation sequencing technologies have provided accumulating evidence of dysregulated lncRNAs in cancer. The implication of this finding may be seen in many forms and at multiple levels. Read More

    Evaluation of two prognostic indices for adult T-cell leukemia/lymphoma in the subtropical endemic area, Okinawa, Japan.
    Cancer Sci 2018 May 17. Epub 2018 May 17.
    Division of Endocrinology, Diabetes and Metabolism, Hematology and Rheumatology, Second Department of Internal Medicine, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan.
    Aggressive adult T-cell leukemia/lymphoma (ATL) has an extremely poor prognosis and is hyperendemic in Okinawa, Japan. This study evaluated two prognostic indices (PIs) for aggressive ATL, the ATL-PI and Japan Clinical Oncology Group (JCOG)-PI, in a cohort from Okinawa. The PIs were originally developed using two different Japanese cohorts that included few patients from Okinawa. Read More

    Combination of IFITM1 knockdown and radiotherapy inhibits the growth of oral cancer.
    Cancer Sci 2018 May 16. Epub 2018 May 16.
    Head and Neck Tumor Research Center, No. 3 Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province & Yunnan Cancer Center), Kunming, 650118, Yunnan, China.
    This research aimed to analyze the effect of IFITM1 on the radioresistance of oral neoplasm. IFITM1 emerged using multi-group heat map from GSE9716 analysis of GEO database as the relevant radioresistance gene. IFITM1 was screened by TCGA database before its expression was analyzed. Read More

    NCTD enhances antitumor immunity of GM-CSF prostate cancer cells vaccine by inducing apoptosis of regulatory T cells.
    Cancer Sci 2018 May 16. Epub 2018 May 16.
    Institute of Biotherapy, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
    Norcantharidin (NCTD) is a promising antitumor drug with low toxicity. It was reported to be able to regulate immunity, but the mechanism is not yet clear. Here we explored whether NCTD could enhance the antitumor immunity induced by prostate cancer cells vaccine. Read More

    Concomitant administration of radiation with eribulin improves the survival of mice harboring intracerebral glioblastoma.
    Cancer Sci 2018 May 14. Epub 2018 May 14.
    Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo, Japan.
    Glioblastoma is the most common and devastating type of malignant brain tumor. We recently found that eribulin suppresses glioma growth in vitro and in vivo and that eribulin is efficiently transferred into mouse brain tumors at a high concentration. Eribulin is a non-taxane microtubule inhibitor approved for breast cancer and liposarcoma. Read More

    Loss of protein phosphatase 6 in mouse keratinocytes enhances K-ras -driven tumor promotion.
    Cancer Sci 2018 May 14. Epub 2018 May 14.
    Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Miyagi, Japan.
    Here, we address the function of protein phosphatase 6 (PP6) loss on K-ras-initiated tumorigenesis in keratinocytes. To do so, we developed tamoxifen-inducible double mutant (K-ras -expressing and Ppp6c-deficient) mice in which K-ras expression is driven by the cytokeratin 14 (K14) promoter. Doubly-mutant mice showed early onset tumor formation in lip, nipples, external genitalia, anus and palms, and had to be sacrificed by three weeks after induction by tamoxifen, while comparably-treated K-ras -expressing mice did not. Read More

    IDH-mutated astrocytomas with 19q-loss constitute a subgroup that confers better prognosis.
    Cancer Sci 2018 May 12. Epub 2018 May 12.
    Department of Neurosurgery, Dokkyo Medical University, Mibu, Japan.
    IDH-mutant gliomas are classified into astrocytic or oligodendroglial tumors by 1p/19q status in the WHO 2016 classification, with the latter presenting with characteristic morphology and better prognosis in general. However, the morphological and genetic features within each category are varied, and there might be distinguishable subtypes. We analyzed 170 WHO grade II-IV gliomas resected in our institution. Read More

    Therapies based on targeting Epstein-Barr virus lytic replication for EBV-associated malignancies.
    Cancer Sci 2018 May 11. Epub 2018 May 11.
    Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, China.
    In recent years, Epstein-Barr virus (EBV) lytic infection has been shown to significantly contribute to carcinogenesis. Thus, therapies aimed at targeting the EBV lytic cycle have been developed as novel strategies for treatment of EBV-associated malignancies. In this review, focusing on the viral lytic proteins, we describe recent advances regarding the involvement of the EBV lytic cycle in carcinogenesis. Read More

    Stromal barriers to nanomedicine penetration in the pancreatic tumor microenvironment.
    Cancer Sci 2018 May 8. Epub 2018 May 8.
    Department of Pharmaceutical Biomedicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
    Pancreatic cancer is known for its dismal prognosis despite efforts to improve therapeutic outcome. Recently, cancer nanomedicine, application of nanotechnology to cancer diagnosis and treatment, has gained interest for treatment of pancreatic cancer. The enhanced permeability and retention (EPR) effect that promotes selective accumulation of nanometer-sized molecules within tumors is the theoretical rationale of treatment. Read More

    Metabolomics research on potential role for 9-cis-Retinoic acid in breast cancer progression.
    Cancer Sci 2018 May 8. Epub 2018 May 8.
    Department of Clinical Laboratory, Third Central Hospital of Tianjin, Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry, 83 Jintang Road, Hedong District, Tianjin, China.
    Deciphering the molecular networks that discriminate organ-confined breast cancer from metastatic breast cancer may lead to the identification of critical biomarkers for breast cancer invasion and aggressiveness. Here metabolomics, a global study of metabolites, has been applied to explore the metabolic alterations that characterize breast cancer progression. We profiled a total of 693 metabolites across 87 serum samples related to breast cancer (46 clinically localized and 41 metastatic breast cancer) and 49 normal samples. Read More

    Blockade of ONECUT2 expression in ovarian cancer inhibited tumor cell proliferation, migration, invasion and angiogenesis.
    Cancer Sci 2018 May 8. Epub 2018 May 8.
    Guangdong Province Engineering Research Center for Antibody Drug and Immunoassay, Department of Biology, Jinan University, Guangzhou, China.
    One cut homeobox 2 (ONECUT2 or OC-2) is a newly discovered transcription factor. Aberrant expression of OC-2 is closely related to cell proliferation, migration, invasion, and angiogenesis. In this study, we found that OC-2 expression was upregulated in ovarian adenocarcinoma cells, by Western blot analysis. Read More

    Long non-coding RNA FOXD2-AS1 contributes to colorectal cancer proliferation through its interaction with microRNA-185-5p.
    Cancer Sci 2018 May 8. Epub 2018 May 8.
    Departments of Oncology, Henan Provincial People's Hospital, Zhengzhou, China.
    Emerging evidence has indicated that long non-coding RNA plays an important role in carcinogenesis at the transcriptional and post-translational levels. The regulation of carcinogenesis-related effectors is potent in the determination of tumor initiation and progression. In the current study, FOXD2-AS1 was found to interact with microRNA (miR)-185-5p to modulate proliferation, migration, and invasion of colorectal cancer (CRC) cells. Read More

    HSPC159 promotes proliferation and metastasis by inducing epithelial-mesenchymal transition and activating the PI3K/Akt pathway in breast cancer.
    Cancer Sci 2018 May 8. Epub 2018 May 8.
    Department of Diagnostic Pathology, Weifang Medical University, Weifang, China.
    HSPC159 is a novel human galectin-related protein that has been shown to be involved in carcinogenesis. Little is known about HSPC159 expression and function in breast cancer. Herein we showed that HSPC159 was aberrantly expressed in both breast cancer cell lines and tumor tissues and that its expression was associated with poor prognosis of breast cancer patients. Read More

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