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    Establishment of a dog primary prostate cancer organoid using the urine cancer stem cells.
    Cancer Sci 2017 Oct 10. Epub 2017 Oct 10.
    Laboratory of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Yamaguchi University.
    Dog spontaneously develops prostate cancer (PC) like human. Since most dogs with PC have poor prognosis, they are expected to become a translational model for human advanced PC. Stem cell-derived 3D organoid culture could recapitulate organ structures and physiology. Read More

    Identification of ZIC5 as a Survival Factor of Prostate and Colorectal Cancer Cells.
    Cancer Sci 2017 Oct 10. Epub 2017 Oct 10.
    Laboratory of Genome and Biosignals, Tokyo University of Pharmacy and Life Sciences, Hachioji-shi, Tokyo, 192-0392, Japan.
    The identification of specific drug targets is very important for cancer therapy. We recently identified zinc finger protein of the cerebellum 5 (ZIC5) as a factor that promotes melanoma aggressiveness via platelet-derived growth factor D (PDGFD) expression. However, its roles in other cancer types remain largely unknown. Read More

    Esophageal adenocarcinoma microenvironment: peritumoral adipose tissue effects associated with chemoresistance.
    Cancer Sci 2017 Oct 6. Epub 2017 Oct 6.
    Esophageal and Digestive Tract Surgical Unit, Veneto Institute of Oncology (IOV-IRCCS), 35128, Padova, Italy.
    Peritumoral microenvironment affects cancer development and chemoresistance, and visceral adipose tissue may play a critical role. We aimed to identify depot-specific adipose characteristics associated with carcinogenesis and resistance to neoadjuvant therapy, in esophageal adenocarcinoma (EAC). We analysed: 1) the peritumoral adipose tissue of rats, following the induction of esophageal carcinogenesis; 2) the peritumoral and distal (omental) adipose tissue of patients affected by EAC; 3) adipose-derived stem cells (ADSCs) isolated from healthy patients and treated with conditioned medium (CM), collected from tumoral and adipose tissue of patients with EAC. Read More

    A double-edged sword: the world according to Capicua in cancer.
    Cancer Sci 2017 Oct 6. Epub 2017 Oct 6.
    Division of Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
    CIC/Capicua is a HMG-box transcription factor that is well conserved during evolution. CIC recognizes the T(G/C)AATG(A/G)A sequence and represses its target genes such as PEA3 family genes. The RTK/RAS/MAPK signals downregulate CIC and relieves CIC's target genes from the transrepressional activity, and CIC thus acts as an important downstream molecule of the pathway and as a tumor suppressor. Read More

    Endocrine sensitivity of estrogen receptor-positive breast cancer is negatively correlated with aspartate-β-hydroxylase expression.
    Cancer Sci 2017 Oct 6. Epub 2017 Oct 6.
    Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
    Although prognostic markers for early estrogen receptor (ER)-positive breast cancer have been extensively developed, predictive markers for adjuvant endocrine therapy are still lacking. Focusing on the mechanisms underlying endocrine resistance, we investigated whether the endocrine sensitivity of ER-positive breast cancer cells was correlated with the expression of aspartate-β-hydroxylase (ASPH), which is involved in the development of hepatocellular carcinoma. ASPH expression in ER-positive and tamoxifen-resistant breast cancer cells was upregulated by the MAPK and phosphoinositide-3 kinase (PI3K) pathways, which both play pivotal roles in endocrine resistance. Read More

    The expression level of CXCL7 in peripheral blood cells is a potential biomarker for the diagnosis of renal cell carcinoma.
    Cancer Sci 2017 Oct 6. Epub 2017 Oct 6.
    Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
    There are no blood biomarkers for the diagnosis of renal cell carcinoma (RCC) in routine clinical use. We focused on the gene expression profile of peripheral blood cells obtained from RCC patients to discover novel biomarkers for RCC diagnosis. Using microarray analysis and quantitative verification, CXCL7 was shown to be significantly up-regulated in the peripheral blood cells of RCC patients. Read More

    Augmented O-GlcNAcylation of AMP-activated kinase promotes the proliferation of LoVo cells, a colon cancer cell line.
    Cancer Sci 2017 Oct 3. Epub 2017 Oct 3.
    Department of Pharmacology, Faculty of Medicine, Osaka Medical College, 2-7, Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
    Increasing incidence of various cancers has been reported in diabetic patients. O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins at serine/threonine residues (O-GlcNAcylation) is an essential post-translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. However, the mechanisms by which O-GlcNAcylation promotes tumor growth remain unclear. Read More

    Requisite role of vasohibin-2 in spontaneous gastric cancer formation and accumulation of cancer-associated fibroblasts.
    Cancer Sci 2017 Sep 27. Epub 2017 Sep 27.
    Department of Vascular Biology, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Miyagi, Japan.
    The vasohibin (VASH) family consists of two genes, VASH1 and VASH2. VASH1 is mainly expressed in vascular endothelial cells and suppresses angiogenesis in an autocrine manner whereas VASH2 is mainly expressed in cancer cells and exhibits pro-angiogenic activity. Employing adenomatous polyposis coli gene mutant mice, we have recently reported the role of Vash2 in the spontaneous formation of intestinal tumors. Read More

    Comprehensive genomic profiling of lung cancer using a validated panel to explore therapeutic targets in East Asian patients.
    Cancer Sci 2017 Sep 26. Epub 2017 Sep 26.
    State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, Guangzhou, 510120, China.
    People of East Asian ethnicity show unique clinical characteristics, tumour histology, and different prevalence of oncogenic mutations. However, only limited studies have explored the landscape of genomic alterations in lung adenocarcinoma derived from Asian patients thus far. In this single centre study, with an aim to elucidate the mutational profile of lung cancer in people of Chinese ethnicity and to use the obtained information to guide decision making for treatment, we employed a well-validated assay to perform comprehensive genomic characterization of tumour specimens from 306 Chinese lung cancer patients. Read More

    A phase 1/2 study of the WT1 peptide cancer vaccine WT4869 in patients with myelodysplastic syndrome.
    Cancer Sci 2017 Sep 26. Epub 2017 Sep 26.
    Department of Hematology, Nagasaki University, Nagasaki, Japan.
    WT4869 is a synthetic peptide vaccine derived from the Wilms' tumor gene 1 (WT1) protein. This phase 1/2 open-label study evaluated the safety and efficacy of WT4869, and biomarkers for response, in patients with myelodysplastic syndrome. WT4869 (5-1200 μg/dose) was administered intradermally every 2 weeks, according to a 3+3 dose-escalation method in higher-risk (International Prognostic Scoring System score ≥1. Read More

    Inactivated Sendai Virus Particles upregulate cancer cell ICAM-1 expression with enhancing NK cell sensitivity on cancer cell.
    Cancer Sci 2017 Sep 25. Epub 2017 Sep 25.
    Division of Gene Therapy Science, Graduate School of Medicine Osaka University, Osaka, Japan.
    We have already reported that the inactivated Sendai virus (hemagglutinating virus of Japan; HVJ) envelope (HVJ-E) has multiple anti-cancer effects, including induction of cancer-selective cell death and activation of anti-cancer immunity. HVJ-E stimulates dendritic cells (DCs) to produce cytokines and chemokines such as IFN-β, IL-6, CCL5 and CXCL10, which activate both CD8(+) T cells and NK cells and recruit them to the tumor microenvironment. However, the effect of HVJ-E on modulating the sensitivity of cancer cells to immune cell attack has yet to be investigated. Read More

    Differences in the Impact of Prognostic Factors for Hepatocellular Carcinoma Over Time.
    Cancer Sci 2017 Sep 25. Epub 2017 Sep 25.
    Department of Epidemiology Infectious Disease Control and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
    To evaluate the prognostic significance of serum markers that reflect tumor progression, liver function, or liver fibrosis in patients with hepatocellular carcinoma (HCC), focusing on how their impact changes over time after diagnosis. Alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), albumin-bilirubin (ALBI) score, aspartate aminotransferase to platelet ratio index (APRI), and FIB-4 index were measured at the time of initial non-recurrent HCC diagnosis in 1669 patients between 1997 and 2016. Survival rates after diagnosis were compared after stratifying patients by these markers. Read More

    Characterization of ascites-derived tumor cells from an endometrial cancer patient.
    Cancer Sci 2017 Sep 25. Epub 2017 Sep 25.
    Department of Breast Surgery and oncology, The Second Hospital of Dalian Medical University, Dalian, China.
    Improved treatment outcomes for the endometrial cancer patient required precision methods to investigate the biology of this disease and clinically relevant models to test treatment drugs. Hence, we applied a personalized platform to investigate whether in vitro and in vivo models could accurately predict effective treatment regimens. We successfully expanded ascites-derived tumor cells from an endometrial cancer patient with malignant ascites using ascites collected prior to chemotherapy treatment. Read More

    Epirubicin suppresses proliferative and metastatic potential by down-regulating TGFBI expression in urothelial carcinoma.
    Cancer Sci 2017 Sep 22. Epub 2017 Sep 22.
    Department of Pathology, Capital Medical University, Beijing, China.
    Transforming growth factor-β-induced (TGFΒI) is considered to be a vital gene in several carcinomas. In this study we determined the effect of TGFBI on the proliferative and metastatic potential of human urothelial carcinoma (UC) cells as well as its mRNA and protein expression, which were detected by RT-PCR and Western blot, respectively. UC cell proliferation was analyzed by WST-1 assay and Hoechst 33258 staining. Read More

    Personalized peptide vaccination as second-line treatment for metastatic upper tract urothelial carcinoma.
    Cancer Sci 2017 Sep 22. Epub 2017 Sep 22.
    Department of Urology, Kurume University School of Medicine, Kurume, Japan.
    This study investigated the applicability of personalized peptide vaccination (PPV) for patients with metastatic upper tract urothelial cancer (mUTUC) after failure of platinum-based chemotherapy. In this single arm, open-label, phase II clinical trial, patients with mUTUC received PPV at a single institution. Personalized peptide vaccination treatment used a maximum of four peptides chosen from 27 candidate peptides according to human leukocyte antigen types and peptide-reactive IgG titers, for six s. Read More

    The antifibrotic effects of pentoxifylline improve the efficacy of gemcitabine in human pancreatic tumor xenografts.
    Cancer Sci 2017 Sep 23. Epub 2017 Sep 23.
    Department of Biomedicine & Health Science, College of Medicine, The Catholic University of Korea, 222 Banpo-daero Seocho-ku, Seoul, 06591, Republic of Korea.
    We investigated the combinatorial effects of pentoxifylline (PTX) on the efficacy of gemcitabine (GEM) in a human pancreatic tumor xenograft model. PTX significantly improved the efficacy of GEM, as shown by a 50% reduction in tumor growth rate at 4 weeks of treatment compared with that in animals given GEM alone. The fluorescent drug doxorubicin (DOX) was used to test whether drug delivery was improved by PTX, contributing to the improved efficacy of GEM. Read More

    miR-203 inhibits cell proliferation, invasion, and migration of non-small-cell lung cancer by downregulating RGS17.
    Cancer Sci 2017 Sep 16. Epub 2017 Sep 16.
    Department of Emergency Medicine, Shanghai Pudong New Area Gongli Hospital, The Second Military Medical University, Shanghai, China.
    Involvement of the RGS17 oncogene in the promotion of non-small-cell lung cancer (NSCLC) has been reported, but the regulation mechanism in NSCLC remains unclear. MicroRNAs (miRNAs) negatively regulate gene expression, and their dysregulation has been implicated in tumorigenesis. To understand the role of miRNAs in Regulator of G Protein Signaling 17 (RGS17)-induced NSCLC, we showed that miR-203 was downregulated during tumorigenesis, and inhibited the proliferation and invasion of lung cancer cells. Read More

    Cancer-specific mortality of high-risk prostate cancer after carbon-ion radiotherapy plus long-term androgen deprivation therapy.
    Cancer Sci 2017 Sep 16. Epub 2017 Sep 16.
    Hospital of the National Institute of Radiological Sciences National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
    The treatment outcomes of patients with high-risk localized prostate cancer (PC) after carbon-ion radiotherapy (CIRT) combined with long-term androgen deprivation therapy (LTADT) were analyzed, and compared with those of other treatment modalities, focusing on PC-specific mortality (PCSM). A total of 1247 patients were enrolled in three phase II clinical trials of fixed-dose CIRT between 2000 and 2013. Excluding patients with T4 disease, 608 patients with high- or very-high-risk PC, according to the National Comprehensive Cancer Network classification system, who received CIRT with LTADT were evaluated. Read More

    WASH overexpression enhances cancer stem cell properties and correlates with poor prognosis of esophageal carcinoma.
    Cancer Sci 2017 Sep 15. Epub 2017 Sep 15.
    Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
    There is increasing evidence that cytoskeleton remodeling is involved in cancer progression. Wiskott-Aldrich syndrome protein (WASP) family represents a key regulator of actin cytoskeleton remodeling. However, the underlying mechanism of the WASP family in cancer progression remains elusive. Read More

    Epidemiological and clinical features of adult T-cell leukemia-lymphoma in Japan, 2010-2011: A nationwide survey.
    Cancer Sci 2017 Sep 14. Epub 2017 Sep 14.
    Department of Hematology, National Cancer Center Hospital East, Kashiwa, Japan.
    Adult T-cell leukemia-lymphoma (ATL) is a mature T-cell malignancy associated with human T-cell leukemia virus type 1 (HTLV-1) infection. Japan is the most endemic country for HTLV-1 and ATL in the world. Recent nationwide studies of Japanese blood donors reported that HTLV-1 carriers spread from endemic areas to non-endemic areas. Read More

    Phosphorylation of ETS-1 is a critical event in DNA polymerase iota-induced invasion and metastasis of esophageal squamous cell carcinoma.
    Cancer Sci 2017 Sep 14. Epub 2017 Sep 14.
    Suzhou Cancer Center Core Laboratory, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu, China.
    An aberrantly elevated expression of DNA polymerase ι (Pol ι) is significantly associated with poor prognosis of patients with esophageal squamous cell carcinoma (ESCC), yet the mechanisms behind this phenomenon remain obscure. Based on the RNA-Seq transcriptome and real-time PCR analysis, we identified ETS-1 as a candidate gene involved in Pol ι-mediated progression of ESCC. Wound-healing and transwell assay indicated that downregulation of ETS-1 attenuates Pol ι-mediated invasiveness of ESCC. Read More

    Immunological efficacy of herbal medicines in prostate cancer patients treated by personalized peptide vaccine.
    Cancer Sci 2017 Sep 12. Epub 2017 Sep 12.
    Division of Clinical Research, Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan.
    This randomized phase II study investigated the immunological efficacy of herbal medicines (HM) using Hochu-ekki-to and Keishi-bukuryo-gan in combination with personalized peptide vaccination (PPV) for castration-resistant prostate cancer (CRPC). Seventy patients with CRPC were assigned to two arms; PPV plus HM or PPV alone. Two to four peptides were chosen from 31 peptides derived from cancer antigens for a s. Read More

    Clinical features of cystatin A expression in patients with pancreatic ductal adenocarcinoma.
    Cancer Sci 2017 Sep 12. Epub 2017 Sep 12.
    Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan.
    Pancreatic ductal adenocarcinoma (PDAC) is the most lethal malignancy known, with an extremely poor prognosis due to the lack of an efficient diagnostic scheme and no radical treatment option, except surgery. Therefore, understanding the pathophysiology of, and finding a novel biomarker to detect, PDAC should be prioritized. We observed an increase in mRNA expression of the cysteine protease inhibitor cystatin A (CSTA) in CD4(+) T cells in peripheral blood cells of nine patients with PDAC, compared with the expression in seven healthy volunteers. Read More

    Study On The Tumor-Induced Angiogenesis Using Mathematical Models.
    Cancer Sci 2017 Sep 11. Epub 2017 Sep 11.
    School of Mathematics and Statistics, Mathematical Institute, University of St Andrews.
    We study angiogenesis using mathematical models describing the dynamics of tip cells. We review the basic ideas of angiogenesis models and its numerical simulation technique to produce realistic computer graphics images of sprouting angiogenesis. We examine the classical model of Anderson-Chaplain using fundamental concepts of mass transport and chemical reaction with ECM degradation included. Read More

    Elevated expression of ΔNp63 in advanced esophageal squamous cell carcinoma.
    Cancer Sci 2017 Sep 11. Epub 2017 Sep 11.
    Department of General Surgical Science, Gunma University, Maebashi, Japan.
    This study aims to explore the expression level of ΔNp63 in esophageal squamous cell carcinoma (ESCC). To investigate the association between ΔNp63 (p40) expression and ESCC biology, we compared the levels of ΔNp63 expression in normal and tumor tissues, with a specific focus on the diagnostic value of ΔNp63 in ESCC. We analyzed 160 consecutive patients with ESCC who underwent surgical resection without neoadjuvant chemotherapy at Gunma University Hospital (Maebashi, Japan) between September 2000 and January 2010. Read More

    A review of the biologic and clinical significance of genetic mutations in angioimmunoblastic T-cell lymphoma.
    Cancer Sci 2017 Sep 10. Epub 2017 Sep 10.
    Department of Hematology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
    Angioimmunoblastic T-cell lymphoma (AITL) is an age-related malignant lymphoma, characterized by immune system-dysregulated symptoms. Recent sequencing studies have clarified the recurrent mutations in ras homology family member A (RHOA) and in genes encoding epigenetic regulators, tet methyl cytosine dioxygenase 2 (TET2), DNA methyl transferase 3 alpha (DNMT3A), and isocitrate dehydrogenase 2, mitochondrial (IDH2), as well as those related to the T-cell receptor signaling pathway in AITL. In this review, we will focus on how this genetic information has changed the understanding of the developmental process of AITL and will in future lead to individualized therapies for AITL patients. Read More

    Japanese genome-wide association study identifies a significant colorectal cancer susceptibility locus at chromosome 10p14.
    Cancer Sci 2017 Sep 4. Epub 2017 Sep 4.
    Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
    Genome-wide association studies are a powerful tool for searching for disease susceptibility loci. Several studies identifying single nucleotide polymorphisms (SNP) connected intimately to the onset of colorectal cancer (CRC) have been published, but there are few reports of genome-wide association studies in Japan. To identify genetic variants that modify the risk of CRC oncogenesis, especially in the Japanese population, we performed a multi-stage genome-wide association study using a large number of samples: 1846 CRC cases and 2675 controls. Read More

    Antitumor effects of eribulin depend on modulation of the tumor microenvironment by vascular remodeling in mouse models.
    Cancer Sci 2017 Sep 4. Epub 2017 Sep 4.
    Division of Functional Imaging, National Cancer Center, Kashiwa, Japan.
    We previously reported that eribulin mesylate (eribulin), a tubulin-binding drug (TBD), could remodel tumor vasculature (i.e. increase tumor vessels and perfusion) in human breast cancer xenograft models. Read More

    Intersection of retinoblastoma tumor suppressor function, stem cells, metabolism, and inflammation.
    Cancer Sci 2017 Sep 29;108(9):1726-1731. Epub 2017 Jul 29.
    Division of Oncology and Molecular Biology, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan.
    The Retinoblastoma (RB) tumor suppressor regulates G1 /S transition during cell cycle progression by modulating the activity of E2F transcription factors. The RB pathway plays a central role in the suppression of most cancers, and RB mutation was initially discovered by virtue of its role in tumor initiation. However, as cancer genome sequencing has evolved to profile more advanced and treatment-resistant cancers, it has become increasingly clear that, in the majority of cancers, somatic RB inactivation occurs during tumor progression. Read More

    miR-125b-1 and miR-378a are predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer.
    Cancer Sci 2017 Aug 31. Epub 2017 Aug 31.
    Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
    Many clinical trials of peptide vaccines have been conducted. However, these vaccines have provided clinical benefits in only a small fraction of patients. The purpose of the present study was to explore microRNAs (miRNAs) as novel predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer. Read More

    Lipocalin 2 negatively regulates cell proliferation and epithelial to mesenchymal transition through changing metabolic gene expression in colorectal cancer.
    Cancer Sci 2017 Aug 31. Epub 2017 Aug 31.
    Department of Internal Medicine Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea.
    Lipocalin 2 (LCN2), a member of the lipocalin superfamily, plays an important role in oncogenesis and progression in various types of cancer. However, the expression pattern and functional role of LCN2 in colorectal cancer (CRC) is still poorly understood. The purpose of the present study was to investigate whether LCN2 is associated with proliferation and the epithelial-mesenchymal transition (EMT) in CRC and to elucidate the underlying signaling pathways. Read More

    Tumor endothelial cells with high aldehyde dehydrogenase activity show drug resistance.
    Cancer Sci 2017 Aug 29. Epub 2017 Aug 29.
    Department of Cardiovascular and Thoracic Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
    Tumor blood vessels play an important role in tumor progression and metastasis. We previously reported that tumor endothelial cells (TEC) exhibit several altered phenotypes compared with normal endothelial cells (NEC). For example, TEC have chromosomal abnormalities and are resistant to several anticancer drugs. Read More

    Therapeutic effect of cisplatin given with a lymphatic drug delivery system on false-negative metastatic lymph nodes.
    Cancer Sci 2017 Aug 28. Epub 2017 Aug 28.
    Laboratory of Biomedical Engineering for Cancer, Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan.
    Systemic administration of drugs into the blood circulation is standard treatment for prevention of metastasis. However, systemic delivery cannot maintain sufficiently high concentrations of anticancer drugs in lymph nodes (LN). Here, we show that giving cisplatin (CDDP) using a lymphatic drug delivery system (LDDS) has the potential to treat false-negative metastatic LN. Read More

    Synergistic activity of sorafenib and betulinic acid against clonogenic activity of non-small cell lung cancer cells.
    Cancer Sci 2017 Aug 28. Epub 2017 Aug 28.
    Department of Experimental Oncology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy Polish Academy of Science, Wroclaw, Poland.
    The highly selective multi-targeted agent sorafenib is an inhibitor of a number of intracellular signaling kinases with anti-proliferative, anti-angiogenic and pro-apoptotic effects in various types of tumors, including human non-small cell lung cancer (NSCLC). Betulin displays a broad spectrum of biological and pharmacological properties, including anticancer and chemopreventive activity. Combination of drugs with different targets is a logical approach to overcome multilevel cross-stimulation among key signaling pathways in NSCLC progression. Read More

    Survivin: A novel marker and potential therapeutic target for human angiosarcoma.
    Cancer Sci 2017 Aug 28. Epub 2017 Aug 28.
    Division of Cancer Biology, National Cancer Center Research Institute, Tokyo, Japan.
    Human angiosarcoma is a rare malignant vascular tumor associated with extremely poor clinical outcome and generally arising in skin of the head and neck region. However, little is known about the molecular pathogeneses and useful immunohistochemical markers of angiosarcoma. To investigate the mechanisms of angiosarcoma progression, we collected 85 cases of human angiosarcoma specimens with clinical records and analyzed ISO-HAS-B patient-derived angiosarcoma cells. Read More

    Diagnostic and prognostic role of urinary collagens in primary human bladder cancer.
    Cancer Sci 2017 Aug 24. Epub 2017 Aug 24.
    Department of Urology, Nara Medical University, Nara, Japan.
    Collagen type 4 alpha 1 (COL4A1) and collagen type 13 alpha 1 (COL13A1) produced by urothelial cancer cells support the vital oncogenic property of tumor invasion. We investigated the diagnostic and prognostic capability of COL4A1 and COL13A1 in voided urine and compared the observed values with those of fragments of cytokeratin-19 (CYFRA21-1), nuclear matrix protein 22 (NMP-22), and voided urine cytology in bladder cancer (BCa). We collected voided urine samples from 154 patients newly diagnosed with BCa, before surgery and from 61 control subjects. Read More

    Lipoxygenase-mediated generation of lipid peroxides enhances ferroptosis induced by erastin and RSL3.
    Cancer Sci 2017 Aug 24. Epub 2017 Aug 24.
    Secretion Biology Laboratory, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
    In cancer cells the small compounds erastin and RSL3 promote a novel type of cell death called ferroptosis, which requires iron-dependent accumulation of lipid reactive oxygen species. Here we assessed the contribution of lipid peroxidation activity of lipoxygenases (LOX) to ferroptosis in oncogenic Ras-expressing cancer cells. Several 12/15-LOX inhibitors prevented cell death induced by erastin and RSL3. Read More

    Chromobox homolog 8 is a predictor of muscle invasive bladder cancer and promotes cell proliferation by repressing the p53 pathway.
    Cancer Sci 2017 Aug 24. Epub 2017 Aug 24.
    State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
    Chromobox homolog 8 (CBX8), also known as human polycomb 8, is a repressor that maintains the transcriptionally repressive state in various cellular genes, and has been reported to promote tumorigenesis. In the present study, we examined CBX8 expression in eight pairs of muscle invasive bladder cancer tissues and adjacent non-tumor tissues, and found that CBX8 was frequently upregulated in muscle invasive bladder cancer tissues when compared to adjacent non-tumor tissues. Analysis showed that high expression of CBX8 in 152 muscle invasive bladder cancer specimens was associated with progression of the T, N, and M stages (P = 0. Read More

    Elevated expression of JAM-A promotes neoplastic properties of lung adenocarcinoma.
    Cancer Sci 2017 Aug 24. Epub 2017 Aug 24.
    Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
    A cell-cell adhesion protein, junctional adhesion molecule-A (JAM-A), has been shown to be involved in neoplasia of various organs. However, the fundamental role of JAM-A in tumorigenesis is still under debate because dysregulated expression of this protein has distinct effects, playing opposite roles in carcinogenesis depending on the target tissues. In the present study, we found elevated levels of JAM-A expression in lung adenocarcinoma and its preinvasive lesions, including atypical adenomatous hyperplasia and adenocarcinoma in situ by immunohistochemistry. Read More

    Phase 1 study of veliparib with carboplatin and weekly paclitaxel in Japanese patients with newly diagnosed ovarian cancer.
    Cancer Sci 2017 Aug 24. Epub 2017 Aug 24.
    Department of Obstetrics and Gynecology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
    This phase 1, open-label, dose-escalation study was conducted to determine the safety, tolerability, pharmacokinetics and preliminary efficacy of veliparib with carboplatin and weekly paclitaxel in Japanese women with newly diagnosed, advanced ovarian cancer. Patients received veliparib at 100 or 150 mg b.i. Read More

    c-Jun N-terminal kinase in pancreatic tumor stroma augments tumor development in mice.
    Cancer Sci 2017 Aug 24. Epub 2017 Aug 24.
    Department of Gastroenterology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
    Pancreatic ductal adenocarcinoma (PDAC) is a life-threatening disease and there is an urgent need to develop improved therapeutic approaches. The role of c-Jun N-terminal kinase (JNK) in PDAC stroma is not well defined even though dense desmoplastic reactions are characteristic of PDAC histology. We aimed to explore the role of JNK in PDAC stroma in mice. Read More

    Solasodine inhibits human colorectal cancer cells through suppression of the AKT/glycogen synthase kinase-3β/β-catenin pathway.
    Cancer Sci 2017 Aug 13. Epub 2017 Aug 13.
    Department of Integrated Traditional and Western Medicine, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
    Solasodine is a main active component isolated from Solanum incanum L. that performs a wide range of functions containing anti-oxidant, anti-infection, and neurogenesis promotion. In this study, we explored the influence of solasodine on three types of human colorectal cancer (CRC) cell lines. Read More

    Persistent detection of alternatively spliced BCR-ABL variant results in a failure to achieve deep molecular response.
    Cancer Sci 2017 Aug 12. Epub 2017 Aug 12.
    Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan.
    Treatment with tyrosine kinase inhibitors (TKI) may sequentially induce TKI-resistant BCR-ABL mutants in chronic myeloid leukemia (CML). Conventional PCR monitoring of BCR-ABL is an important indicator to determine therapeutic intervention for preventing disease progression. However, PCR cannot separately quantify amounts of BCR-ABL and its mutants, including alternatively spliced BCR-ABL with an insertion of 35 intronic nucleotides (BCR-ABL(I)(ns35bp) ) between ABL exons 8 and 9, which introduces the premature termination and loss of kinase activity. Read More

    Modeling phenotypes of malignant gliomas.
    Cancer Sci 2017 Aug 10. Epub 2017 Aug 10.
    Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
    Malignant gliomas are primary tumors of the central nervous system characterized by diffuse infiltration into the brain and a high recurrence rate. Advances in comprehensive genomic studies have provided unprecedented insight into the genetic and molecular heterogeneity of these tumors and refined our understanding of their evolution from low to high grade. However, similar levels of phenotypic characterization are indispensable to understanding the complexity of malignant gliomas. Read More

    Long non-coding RNAs and prostate cancer.
    Cancer Sci 2017 Aug 10. Epub 2017 Aug 10.
    Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
    Long non-coding RNAs (lncRNAs) are RNA transcripts larger than 200 nucleotides that do not code for proteins the aberrant expression of which has been documented in various types of cancer, including prostate cancer. Lack of appropriate sensitive and specific biomarkers for prostate cancer has led to overdiagnosis and overtreatment, making lncRNAs promising novel biomarkers as well as therapeutic targets for the disease. The present review attempts to summarize the current knowledge of lncRNA expression patterns and mechanisms in prostate cancer, which contribute to carcinogenesis. Read More

    Complex genetic control of lung tumorigenesis in resistant mice strains.
    Cancer Sci 2017 Aug 10. Epub 2017 Aug 10.
    Department of Predictive and Preventive Medicine, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.
    The SM/J mouse strain is resistant to chemically-induced lung tumorigenesis despite having a haplotype, in the pulmonary adenoma susceptibility locus (Pas1) locus, that confers tumor susceptibility in other strains. To clarify this inconsistent genotype-phenotype correlation, we crossed SM/J mice with another resistant strain and conducted genome-wide linkage analysis in the (C57BL/6J × SM/J)F2 progeny exposed to urethane to induce lung tumors. Overall, >80% of F2 mice of both sexes developed from 1 to 20 lung tumors. Read More

    Mutation status of RAD51C, PALB2 and BRIP1 in 100 Japanese familial breast cancer cases without BRCA1 and BRCA2 mutations.
    Cancer Sci 2017 Aug 10. Epub 2017 Aug 10.
    Clinical Genetic Oncology, Cancer Institute Hospital, Japanese Foundation of Cancer Research, Tokyo, Japan.
    In addition to BRCA1 and BRCA2, RAD51C, PALB2 and BRIP1 are known as breast cancer susceptibility genes. However, the mutation status of these genes in Japanese familial breast cancer cases has not yet been evaluated. To this end, we analyzed the exon sequence and genomic rearrangement of RAD51C, PALB2 and BRIP1 in 100 Japanese patients diagnosed with familial breast and ovarian cancer and without BRCA1 and BRCA2 mutations. Read More

    Dermokine contributes to epithelial-mesenchymal transition through increased activation of signal transducer and activator of transcription 3 in pancreatic cancer.
    Cancer Sci 2017 Aug 9. Epub 2017 Aug 9.
    Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
    Dermokine (DMKN) was first identified in relation to skin lesion healing and skin carcinoma. Recently, its expression was associated with pancreatic cancer tumorigenesis, although its involvement remains poorly understood. Herein, we showed that DMKN loss of function in Patu-8988 and PANC-1 pancreatic cancer cell lines resulted in reduced phosphorylation of signal transducer and activator of transcription 3, and increased activation of ERK1/2 and AKT serine/threonine kinase. Read More

    CENP-R acts bilaterally as a tumor suppressor and as an oncogene in the two-stage skin carcinogenesis model.
    Cancer Sci 2017 Aug 9. Epub 2017 Aug 9.
    Department of Carcinogenesis Research, Division of Experimental Animal Research, Chiba Cancer Center Research Institute, Chiba, Japan.
    CENP-R is a component of the CENP-O complex, including CENP-O, CENP-P, CENP-Q, CENP-R, and CENP-U and is constitutively localized to kinetochores throughout the cell cycle in vertebrates. CENP-R-deficient chicken DT40 cells are viable and show a very minor effect on mitosis. To investigate the functional roles of CENP-R in vivo, we generated CENP-R-deficient mice (Cenp-r(-/-) ). Read More

    Combination of anti-CD4 antibody treatment and donor lymphocyte infusion ameliorates graft-versus-host disease while preserving graft-versus-tumor effects in murine allogeneic hematopoietic stem cell transplantation.
    Cancer Sci 2017 Oct 29;108(10):1967-1973. Epub 2017 Aug 29.
    Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not only a well-established immunotherapy for hematologic malignancies, but is potentially useful for treating solid tumors refractory to available therapies. However, application of allo-HSCT to solid tumors is limited, despite the beneficial antitumor effects, by the risk of graft-versus-host disease (GVHD). CD4(+) T cells have been implicated in several aspects of GVHD, and suppress antitumor CD8(+) T-cell responses. Read More

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