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    Expression profile analysis of long noncoding RNA in Acute Myeloid Leukemia by microarray and bioinformatics.
    Cancer Sci 2017 Dec 8. Epub 2017 Dec 8.
    Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710000, China.
    Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides, which are involved in tumorigenesis and play a key role in cancer progression. To determine whether lncRNAs are involved in acute myeloid leukemia (AML), we analyzed the expression profile of lncRNAs and mRNAs in AML. 5 pairs of AML patients and iron deficiency anemia (IDA) controls were screened by microarray. Read More

    Helicobacter pylori induces CDX2 and COX2 expression by modulating microRNAs in esophageal epithelial cells.
    Cancer Sci 2017 Dec 7. Epub 2017 Dec 7.
    Department of Gastroenterology, Peking University First Hospital, Beijing, 100034, China.
    Dysregulation of microRNAs (miRNAs) has been linked to virulence factors of Helicobacter pylori (H. pylori). The role of H. Read More

    Breast cancer: The translation of big genomic data to cancer precision medicine.
    Cancer Sci 2017 Dec 7. Epub 2017 Dec 7.
    Department of Medicine, Center for Personalized Therapeutics The University of Chicago, USA.
    Cancer is a complex genetic disease that consequence from the accumulation of genomic alterations, in which germline variations predispose individuals to cancer and somatic alterations initiate and trigger the progression of cancer. For the past two decades, genomic research has advanced remarkably, evolving from single-gene to whole-genome screening by using genome-wide association study (GWAS) and next generation sequencing (NGS) that contributing to big genomic data. International collaborative efforts have contributed in curating these data to identify clinically significant alterations that could be used in the clinical settings. Read More

    Combined Annotation Dependent Depletion (CADD) Score for BRCA1/2 variants in patients with Breast and/or Ovarian Cancer.
    Cancer Sci 2017 Dec 7. Epub 2017 Dec 7.
    Genome Analysis Center, Yamanashi Central Hospital.
    The utility of Combined Annotation Dependent Depletion (CADD) Score was recently reported to rank the pathogenicity as C-scores ranging 1 to 99 for both convinced deleterious mutations and missense mutations. Using C-scores for BRCA1/2 variants, we tried to constitute the classification system for Variant of Uncertain Significance (VUS), which had been major problem of genetic testing for Hereditary Breast and/or Ovarian Cancer (HBOC). We analyzed BRCA1/2 genes for 283 patients with breast and/or ovarian cancer. Read More

    Testicular orphan receptor 4 promotes tumor progression and implies poor survival through AKT3 regulation in seminoma.
    Cancer Sci 2017 Dec 2. Epub 2017 Dec 2.
    Department of Urology and Chawnshang Chang Liver Cancer Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China, 310016.
    Seminoma is recognized as the most common testicular germ cell tumor which mainly occurs in the 15-35-year-old young men worldwide. Early studies have indicated that testicular nuclear receptor 4 (TR4) firstly cloned from testis is involved in the invasion and metastasis of several human tumors, however, little attention is paid to the function of TR4 in Seminoma. Our Immunohistochemical (IHC) staining results showed that patients who underwent advanced stage tended to higher expression of TR4. Read More

    Downregulation of DYRK2 promotes tumor cell proliferation and invasion by enhancing CDK14 expression in breast cancer.
    Cancer Sci 2017 Nov 28. Epub 2017 Nov 28.
    Department of Biochemistry, Jikei University School of Medicine, Tokyo, Japan.
    Tumor progression is the main cause of death in patients with breast cancer. Accumulating evidence suggests that dual-specificity tyrosine-regulated kinase 2 (DYRK2) functions as a tumor suppressor by regulating cell survival, differentiation, proliferation, and apoptosis. However, little is known about the mechanisms of transcriptional regulation by DYRK2 in cancer progression, particularly with respect to cancer proliferation and invasion. Read More

    Phlebotomy as a preventive measure for crocidolite-induced mesothelioma in male rats.
    Cancer Sci 2017 Nov 29. Epub 2017 Nov 29.
    Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
    Malignant mesothelioma (MM) is a rare but socially important neoplasm due to its association with asbestos exposure. While MM is difficult to diagnose at an early stage, there are no particularly effective treatments available at the advanced stage, thus necessitating efficient strategies to prevent MM in individuals already exposed to asbestos. We previously showed that persistent oxidative damage caused by foreign body reaction and affinity of asbestos both to hemoglobin and histones is one of the major pathogeneses. Read More

    Childhood cancer incidence and survival in Japan and England: A population-based study (1993-2010).
    Cancer Sci 2017 Nov 24. Epub 2017 Nov 24.
    Cancer Survival Group, London School of Hygiene & Tropical Medicine, London, UK.
    This study aimed to compare cancer incidence and trends in survival for children diagnosed in Japan and England, using population-based cancer registry data. The analysis was based on 5,192 children with cancer (age 0-14 years) from six prefectural cancer registries in Japan and 21,295 children diagnosed in England during 1993-2010. Differences in incidence rates between the two countries were measured with Poisson regression models. Read More

    PRDM14 directly interacts with heat shock proteins HSP90α and GRP78.
    Cancer Sci 2017 Nov 24. Epub 2017 Nov 24.
    The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.
    PRDM14 is overexpressed in various cancers and can regulate cancer phenotype under certain conditions. Inhibiting PRDM14 expression in breast and pancreatic cancers has been reported to reduce cancer stem-like phenotypes, which are associated with aggressive tumor properties. Therefore, PRDM14 is considered a promising target for cancer therapy. Read More

    Proliferation genes in lung development associated with the prognosis of lung adenocarcinoma but not squamous cell carcinoma.
    Cancer Sci 2017 Nov 23. Epub 2017 Nov 23.
    State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
    There are many similarities between embryonic development and tumorigenesis, and gene expression profiles show that certain correlations exist between the gene signature during development and the clinical phenotypes of different cancers. Our group previously reported the gene expression profiles of human lung development, and the expression of one group of proliferation-related genes (named as PTN1 genes) steadily decreased during lung development. Here, we examined the prognostic value of PTN1 genes in five independent lung adenocarcinoma (ADC) and five lung independent squamous cell carcinoma (SCC) microarray datasets and found that the expression levels of PTN1 genes were associated with survival in lung ADC but not lung SCC. Read More

    HOXC13 promotes proliferation of esophageal squamous cell carcinoma via repressing transcription of CASP3.
    Cancer Sci 2017 Nov 23. Epub 2017 Nov 23.
    Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
    Esophageal squamous cell carcinoma (ESCC), the dominant subtype of esophageal cancer, is one of the most common digestive tumors worldwide. In this study, we confirmed that HOXC13, a member of the homeobox HOXC gene family, was significantly upregulated in ESCC and its overexpression was associated with poorer clinical characteristics and worse prognosis. Moreover, knockdown of HOXC13 inhibited proliferation and induced apoptosis of ESCC via upregulating CASP3. Read More

    PRIMA-1 induces p53-madiated apoptosis by upregulating Noxa in esophageal squamous cell carcinoma with TP53 missense mutation.
    Cancer Sci 2017 Nov 23. Epub 2017 Nov 23.
    Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita city, 565-0871, Osaka, Japan.
    TP53 is associated with the resistance of cytotoxic treatment and patient prognosis, and the mutation rate of TP53 in esophageal squamous cell carcinoma (ESCC) is extraordinarily high, at over 90%. PRIMA-1 (p53 re-activation and induction of massive apoptosis) has recently been reported to restore the function of mutant TP53; however, its antitumor effect and mechanism in ESCC remain unclear. After evaluating the TP53 mutation status of a panel of eleven ESCC cell lines by Sanger sequencing, we assessed the in vitro effect of PRIMA-1 administration on cells with different p53 status by conducting cell viability and apoptosis assays. Read More

    DNA replication stress and cancer chemotherapy.
    Cancer Sci 2017 Nov 23. Epub 2017 Nov 23.
    Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
    DNA replication is one of the fundamental biological processes in which dysregulation can cause genome instability. This instability is one of the hallmarks of cancer and confers genetic diversity during tumorigenesis. Numerous experimental and clinical studies have indicated that most tumors have experienced and overcome the stresses caused by the perturbation of DNA replication, which is also referred to as DNA replication stress (DRS). Read More

    miR-335 inhibited cell proliferation of lung cancer cells by target Tra2β.
    Cancer Sci 2017 Nov 21. Epub 2017 Nov 21.
    Departments of Cardio-Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, P.R. China.
    Accumulating evidence has suggested that the dysregulation of miRNAs is an important factor in the pathogenesis of lung cancer. Here, we demonstrate that miR-335 expression is reduced in non-small cell lung cancer (NSCLC) tumors relative to non-cancerous adjacent tissues, whilst the expression of Tra2β is increased. In addition, clinical data revealed that the increased Tra2β and decreased miR-335 expression observed in NSCLC cells was associated with poor patient survival rates. Read More

    MicroRNA 26b promotes colorectal cancer metastasis by down-regulating PTEN and WNT5A.
    Cancer Sci 2017 Nov 21. Epub 2017 Nov 21.
    Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University.
    Invasion and metastasis are crucially important factors in the survival of malignant tumors. The epithelial-mesenchymal transition (EMT) is an early step in metastatic progression and the presence of cancer stem cells is closely related to tumor survival, proliferation, metastasis, and recurrence. Here we report that ectopic overexpression of microRNA 26b (miR-26b) in colorectal cancer (CRC) cell lines promoted EMT and stem cell-like phenotypes in vitro. Read More

    Detection of circulating tumor cells in cervical cancer using a conditionally replicative adenovirus targeting telomerase-positive cells.
    Cancer Sci 2017 Nov 19. Epub 2017 Nov 19.
    Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
    Circulating tumor cells (CTC) are newly discovered biomarkers of cancers. Although many systems detect CTC, a gold standard has not yet been established. We analyzed CTC in uterine cervical cancer patients using an advanced version of conditionally replicative adenovirus targeting telomerase-positive cells, which was enabled to infect coxsackievirus-adenovirus receptor-negative cells and to reduce false-positive signals in myeloid cells. Read More

    ASCT2 defined by enzyme-mediated activation of radical sources enhances malignancy of GD2-plus small cell lung cancer.
    Cancer Sci 2017 Nov 19. Epub 2017 Nov 19.
    Department of Biomedical Sciences, Chubu University College of Life Health Sciences, 1200 Matsumoto, Kasugai, Aichi, 487-8501.
    Ganglioside GD2 is specifically expressed in small cell lung cancer (SCLC) cells, leading to enhancement of malignant phenotypes, such as cell proliferation and migration. However, how GD2 promotes malignant phenotypes in SCLC cells is not well known. In this study, to reveal mechanisms by which GD2 increases malignant phenotypes in SCLC cells, we performed enzyme-mediated activation of radical sources combined with mass spectrometry in GD2 positive (+) SCLC cells. Read More

    Clinical significance of disease-specific MYD88 mutations in circulating DNA in primary central nervous system lymphoma.
    Cancer Sci 2017 Nov 19. Epub 2017 Nov 19.
    Department of Hematology, Graduate School of Comprehensive Human Sciences, University of Tsukuba.
    Recent sequencing studies demonstrated the MYD88 L265P mutation in more than 70% of primary central nervous system lymphomas (PCNSL), and the clinical significance of this mutation has been proposed as diagnostic and prognostic markers in PCNSL. On the other hand, mutational analyses using cell-free DNAs have been reported in a variety of systemic lymphomas. To investigate how sensitively the MYD88 L265P mutation can be identified in cell-free DNA from PCNSL patients, we performed droplet digital PCR (ddPCR) and targeted deep sequencing (TDS) in consecutive 14 PCNSL patients from whom paired tumor-derived DNA and cell-free DNA was available at diagnosis. Read More

    Downregulation of dual-specificity phosphatase 4 enhances cell proliferation and invasiveness in colorectal carcinomas.
    Cancer Sci 2017 Nov 18. Epub 2017 Nov 18.
    Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan.
    It is widely accepted that aberrant activation of the Wnt signaling pathway is responsible for the development of precursor lesions of colorectal cancer (CRC). However, the molecular mechanisms involved in the process of progression from these precursor lesions to invasive lesions of CRC are not fully understood. Recently, we reported that constitutive activation of MAPK accompanied by downregulation of dual-specificity phosphatase 4 (DUSP4), a MAPK phosphatase, contributes to the progression of precursor lesions in the pancreas. Read More

    Oncogenic spiral by infectious pathogens: Cooperation of multiple factors in cancer development.
    Cancer Sci 2017 Nov 15. Epub 2017 Nov 15.
    Laboratory of Virus Control, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
    Chronic infection is one of the major causes of cancer, and there are several mechanisms for infection-mediated oncogenesis. Some pathogens encode gene products that behave like oncogenic factors, hijacking cellular pathways to promote the survival and proliferation of infected cells in vivo. Some of these viral oncoproteins trigger a cellular damage defense response leading to senescence; however, other viral factors hinder this suppressive effect, suggesting that cooperation of those viral factors is important for malignant transformation. Read More

    Clinical characteristics and outcomes of Castleman disease: a multicenter study of 185 Chinese patients.
    Cancer Sci 2017 Nov 9. Epub 2017 Nov 9.
    Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine.
    Castleman disease (CD) is a rare lymphoproliferative disorder. To assess the clinical features, outcomes, and prognostic factors of this disease, we retrospectively analyzed 185 HIV-negative CD patients from four medical centers in southern China. The median age was 37 years. Read More

    Altered intracellular signaling by imatinib increases the anti-cancer effects of tyrosine kinase inhibitors in chronic myelogenous leukemia cells.
    Cancer Sci 2017 Nov 9. Epub 2017 Nov 9.
    Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
    Tyrosine kinase inhibitors (TKI), including imatinib (IM), improve the outcome of CML therapy. However, TKI treatment is long-term and can induce resistance to TKI, which often leads to a poor clinical outcome in CML patients. Here, we examined the effect of continuous IM exposure on intracellular energy metabolism in K562 cells, a human Philadelphia chromosome-positive CML cell line, and its subsequent sensitivity to anti-cancer agents. Read More

    Xanthohumol inhibits angiogenesis by suppressing nuclear factor-κB activation in pancreatic cancer.
    Cancer Sci 2017 Nov 9. Epub 2017 Nov 9.
    Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
    Xantohumol, a prenylated chalcone from hops (Humulus lupulus L.), has been shown to inhibit proliferation in some cancers. However, little is known regarding the effects of xanthohumol in pancreatic cancer. Read More

    Investigating the hepatitis B virus life cycle using engineered reporter hepatitis B viruses.
    Cancer Sci 2017 Nov 9. Epub 2017 Nov 9.
    Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
    Chronic infection with hepatitis B virus (HBV) increases the risk of developing fibrosis, cirrhosis or hepatocellular carcinoma. Current therapies are limited to type-I interferons and/or nucleos(t)ide analogues; however, these are only partially effective. The development of novel anti-HBV agents for new treatment strategies has been hampered by the lack of a suitable system that allows the in vitro replication of HBV. Read More

    Efficacy and safety of trametinib in Japanese patients with advanced biliary tract cancers refractory to gemcitabine.
    Cancer Sci 2017 Nov 9. Epub 2017 Nov 9.
    Department of Medical Oncology, Kyorin University, Tokyo, Japan.
    Gemcitabine-based therapy remains the mainstay of treatment for patients with biliary tract cancers (BTCs) with no second-line treatment(s) established yet. Aberrant activation of the MAPK pathway in patients with BTC indicates its importance in BTC. Trametinib is a potent, highly selective, allosteric non-competitive inhibitor of MEK1/MEK2. Read More

    Potential utility of a longitudinal relative dose intensity of molecularly targeted agents in phase 1 dose-finding trials.
    Cancer Sci 2017 Nov 8. Epub 2017 Nov 8.
    Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institute of Health, Rockville, MD, USA.
    Phase 1 trials of molecularly targeted agents (MTA) often do not use toxicity data beyond the first cycle of treatment to determine a recommended phase 2 dose (RP2D). We investigated the potential utility of longitudinal relative dose intensity (RDI) that may be a better new way of determining a more accurate RP2D as a lower dose that is presumably more tolerable over the long term without compromising efficacy. All consecutive patients who were initially treated using a single MTA at the conventional RP2D or at one level lower dose (OLLD) of that RP2D in 9 phase 1 trials sponsored by the National Cancer Institute were included. Read More

    Towards understanding the mechanisms of actions of CEACAM6 in cancer progression.
    Cancer Sci 2017 Nov 7. Epub 2017 Nov 7.
    Department of Biological & Environmental Sciences, College of Arts and Science, Qatar University, Doha, Qatar.
    Human carcinoembryonic antigen (CEA) is the prototypic member of highly related cell surface glycoproteins that includes Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) and others. CEACAM6 (formerly NCA) that belongs to the immunoglobulin superfamily, is a cell adhesion proteins of the CEA family. It is normally expressed on the epithelial surfaces and the surface of myeloid (CD66c). Read More

    Downregulation of CD24 suppresses bone metastasis of lung cancer.
    Cancer Sci 2017 Nov 2. Epub 2017 Nov 2.
    Department of Biochemistry, Jikei University School of Medicine, Tokyo, Japan.
    Suppression of bone metastasis can improve patient quality of life. Current drugs for bone metastasis have been shown to prolong progression-free survival but not overall survival; therefore, other potential therapeutic targets for bone metastasis should be investigated. Cell-surface antigens, such as CD24, have been recently shown to be involved in the metastasis of various cancers. Read More

    Rac GTPase activating protein 1 promotes oncogenic progression of epithelial ovarian cancer.
    Cancer Sci 2017 Nov 2. Epub 2017 Nov 2.
    Department of Obstetrics and Gynecology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
    Rac GTPase activating protein 1 (RacGAP1) can regulate cytokinesis and cell differentiation. The oncogenic role of RacGAP1 has been partially studied in gastric cancer, colorectal cancer, and breast cancer. In the present study, we endeavor to evaluate its expression and functions in epithelial ovarian cancer (EOC). Read More

    Immune-suppressive effects of interleukin-6 on T-cell-mediated anti-tumor immunity.
    Cancer Sci 2017 Nov 1. Epub 2017 Nov 1.
    Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
    Accompanied by the growing clinical applications of immunotherapy in the treatment of cancer patients, development of novel therapeutic approaches to reverse the immune-suppressive environment in cancer patients is eagerly anticipated, because the success of cancer immunotherapy is currently limited by immune-suppressive effects in tumor-bearing hosts. Interleukin (IL)-6, a pleotropic proinflammatory cytokine, participates in tumor cell-autonomous processes that are required for their survival and growth, and is therefore known as a poor prognostic factor in cancer patients. In addition, an emerging role of IL-6 in modulating multiple functions of immune cells including T cells, dendritic cells, and macrophages is responsible for the dysfunction of innate and adaptive immunity against tumors. Read More

    Clinical significance of tryptophan catabolism in Hodgkin lymphoma.
    Cancer Sci 2017 Oct 28. Epub 2017 Oct 28.
    Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
    Indoleamine 2,3-dioxygenase 1 (IDO) is an enzyme catabolizing tryptophan (Trp) into the kynurenine (Kyn) pathway. The purpose of the present study was to determine the clinical significance of Trp catabolism in newly diagnosed Hodgkin lymphoma (HL) patients. We quantified serum Trp and Kyn in 52 HL patients, and analyzed their associations with different clinical parameters including serum soluble CD30 concentration. Read More

    Dual inhibition of the mTORC1 and mTORC2 signaling pathways is a promising therapeutic target for adult T-cell leukemia.
    Cancer Sci 2017 Oct 27. Epub 2017 Oct 27.
    Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
    Adult T-cell leukemia (ATL) has a poor prognosis as a result of severe immunosuppression and rapid tumor progression with resistance to conventional chemotherapy. Recent integrated-genome analysis has revealed mutations in many genes involved in the T-cell signaling pathway, suggesting that the aberration of this pathway is an important factor in ATL pathogenesis and ATL-cell proliferation. We screened a siRNA library to examine signaling-pathway functionality and found that the PI3K/Akt/mTOR pathway is critical to ATL-cell proliferation. Read More

    Increased T-helper 17 cell differentiation mediated by exosome-mediated microRNA-451 redistribution in gastric cancer infiltrated T cells.
    Cancer Sci 2017 Oct 23. Epub 2017 Oct 23.
    Department of Clinical Laboratory, the 359th Hospital of PLA, Zhenjiang, China.
    MicroRNA (miR)-451 is a cell metabolism-related miRNA that can mediate cell energy-consuming models by several targets. As miR-451 can promote mechanistic target of rapamycin (mTOR) activity, and increased mTOR activity is related to increased differentiation of T-helper 17 (Th17) cells, we sought to investigate whether miR-451 can redistribute from cancer cells to infiltrated T cells and enhance the distribution of Th17 cells through mTOR. Real-time PCR was used for detecting expression of miR-451 in gastric cancer, tumor infiltrated T cells and exosomes, and distribution of Th17 was evaluated by both flow cytometry and immunohistochemistry (IHC). Read More

    Phase I study of single-agent ribociclib in Japanese patients with advanced solid tumors.
    Cancer Sci 2017 Oct 23. Epub 2017 Oct 23.
    National Cancer Center Hospital, Tokyo, Japan.
    The cyclin D-CDK4/6-INK4-Rb pathway is frequently dysregulated in cancers. Ribociclib, an orally available, selective CDK4/6 inhibitor, showed preliminary clinical activity in a phase I study in the USA and Europe for patients with solid tumors and lymphomas. The present study aimed to determine the single-agent maximum tolerated dose (MTD) and recommended dose for expansion (RDE) in Japanese patients with advanced solid tumors. Read More

    Dasatinib cessation after deep molecular response exceeding 2 years and natural killer cell transition during dasatinib consolidation.
    Cancer Sci 2017 Oct 23. Epub 2017 Oct 23.
    Department of Hematology, Nippon Medical School, Tokyo, Japan.
    Tyrosine kinase inhibitors (TKI) improve the prognosis of patients with chronic myelogenous leukemia (CML) by inducing substantial deep molecular responses (DMR); some patients have successfully discontinued TKI therapy after maintaining DMR for ≥1 year. In this cessation study, we investigated the optimal conditions for dasatinib discontinuation in patients who maintained DMR for ≥2 years. This study included 54 patients with CML who were enrolled in a D-STOP multicenter prospective trial, had achieved DMR, and had discontinued dasatinib after 2-year consolidation. Read More

    Everolimus in advanced, progressive, well-differentiated, non-functional neuroendocrine tumors: RADIANT-4 lung subgroup analysis.
    Cancer Sci 2017 Oct 21. Epub 2017 Oct 21.
    University of Texas MD Anderson Cancer Center, Houston, TX, USA.
    In the phase III RADIANT-4 study, everolimus improved median progression-free survival (PFS) by 7.1 months in patients with advanced, progressive, well-differentiated (grade 1 or grade 2), non-functional lung or gastrointestinal neuroendocrine tumors (NETs) vs placebo (hazard ratio, 0.48; 95% confidence interval [CI], 0. Read More

    Predictive value of BRCA1/2 mRNA expression for response to neoadjuvant chemotherapy in BRCA-negative breast cancers.
    Cancer Sci 2017 Oct 19. Epub 2017 Oct 19.
    Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, Beijing Cancer Hospital & Institute, Peking University Cancer Hospital, Beijing, China.
    It is well known that BRCA1 and BRCA2 play a central role in DNA repair, but the relationship between BRCA1 and BRCA2 mRNA expression and response to neoadjuvant chemotherapy in sporadic breast cancer patients has not been well established. Here, we investigate the association between BRCA1 or BRCA2 mRNA expression levels and pathological response in 674 BRCA1/2 mutation-negative breast cancer patients who received neoadjuvant chemotherapy. BRCA1 and BRCA2 mRNA expression were assessed using quantitative real-time polymerase chain reaction in core biopsy breast cancer tissue obtained prior to the initiation of neoadjuvant chemotherapy. Read More

    Involvement of local renin-angiotensin system in immunosuppression of tumor microenvironment.
    Cancer Sci 2017 Oct 16. Epub 2017 Oct 16.
    Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
    To improve current cancer immunotherapies, strategies to modulate various immunosuppressive cells including myeloid derived suppressor cells (MDSC) which were shown to be negative factors in immune-checkpoint blockade therapy, need to be developed. In the present study, we evaluated the role of the local renin-angiotensin system (RAS) in the tumor immune-microenvironment using murine models bearing tumor cell lines in which RAS was not involved in their proliferation and angiogenetic ability. Giving angiotensin II receptor blockers (ARB) to C57BL/6 mice bearing murine colon cancer cell line MC38 resulted in significant enhancement of tumor antigen gp70 specific T cells. Read More

    PD-L1 expression is mainly regulated by interferon gamma associated with JAK-STAT pathway in gastric cancer.
    Cancer Sci 2017 Oct 16. Epub 2017 Oct 16.
    Department of Gastrointestinal Tract Surgery, Fukushima Medical University, Fukushima, Japan.
    Despite multidisciplinary treatment for patients with advanced gastric cancer, their prognosis remains poor. Therefore, the development of novel therapeutic strategies is urgently needed, and immunotherapy utilizing anti-programmed death 1/-programmed death ligand-1 mAb is an attractive approach. However, as there is limited information on how programmed death ligand-1 is upregulated on tumor cells within the tumor microenvironment, we examined the mechanism of programmed death ligand-1 regulation with a particular focus on interferon gamma in an in vitro setting and in clinical samples. Read More

    Ursolic acid enhances the therapeutic effects of oxaliplatin in colorectal cancer by inhibition of drug resistance.
    Cancer Sci 2017 Oct 16. Epub 2017 Oct 16.
    Department of Endoscopy Surgery, Wuxi People's Hospital, Affiliated to Nanjing Medical University, Wuxi, China.
    It has been reported that ursolic acid has anti-tumor activity and it enhances the therapeutic effect of oxaliplatin in colorectal cancer (CRC). However, the underlying mechanisms remain unknown. In the present study, the mechanisms of the enhancement of therapeutic effects through use of ursolic acid were investigated. Read More

    Correlation between CXCR4/CXCR7/CXCL12 chemokine axis expression and prognosis in lymph-node-positive lung cancer patients.
    Cancer Sci 2017 Oct 15. Epub 2017 Oct 15.
    Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
    The CXCR4/CXCR7/CXCL12 chemokine axis plays important roles in the migration of tumor cells during cancer development by modulating site-specific distant metastasis including to regional lymph nodes. We investigated the correlation of these chemokine expressions to prognosis in lymph-node-positive non-small-cell lung cancer (NSCLC) patients. A total of 140 surgically resected specimens of primary site (PS) and metastatic lymph nodes (MLN) of NSCLC involving hilar and/or mediastinal lymph nodes (N1-2) were collected. Read More

    Pyruvate kinase isozyme M2 and glutaminase might be promising molecular targets for the treatment of gastric cancer.
    Cancer Sci 2017 Dec 27;108(12):2462-2469. Epub 2017 Nov 27.
    Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
    The aim of this study was to analyze the significance of glucose metabolism-related enzymes in the proliferation of gastric cancer under hypoxia. Four hypoxia-resistant gastric cancer cell lines and four parent cell lines were used. Reverse transcription-PCR was used to evaluate the mRNA expression levels of the following metabolism-related enzymes: pyruvate kinase isozyme M2 (PKM2), glutaminase (GLS), enolase 1 (ENO1), glucose-6-phosphate dehydrogenase (G6PDH), and PKM1. Read More

    Identification and characterization of a metastatic suppressor BRMS1L as a target gene of p53.
    Cancer Sci 2017 Dec 6;108(12):2413-2421. Epub 2017 Nov 6.
    Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan.
    The tumor suppressor p53 and its family members, p63 and p73, play a pivotal role in the cell fate determination in response to diverse upstream signals. As transcription factors, p53 family proteins regulate a number of genes that are involved in cell cycle arrest, apoptosis, senescence, and maintenance of genomic stability. Recent studies revealed that p53 family proteins are important for the regulation of cell invasion and migration. Read More

    Establishment of a dog primary prostate cancer organoid using the urine cancer stem cells.
    Cancer Sci 2017 Dec 6;108(12):2383-2392. Epub 2017 Nov 6.
    Laboratory of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.
    Dog spontaneously develop prostate cancer (PC) like humans. Because most dogs with PC have a poor prognosis, they could be used as a translational model for advanced PC in humans. Stem cell-derived 3-D organoid culture could recapitulate organ structures and physiology. Read More

    Identification of zinc finger protein of the cerebellum 5 as a survival factor of prostate and colorectal cancer cells.
    Cancer Sci 2017 Dec 25;108(12):2405-2412. Epub 2017 Oct 25.
    Laboratory of Genome and Biosignals, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
    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 by 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 Dec 4;108(12):2393-2404. Epub 2017 Nov 4.
    Esophageal and Digestive Tract Surgical Unit, Veneto Institute of Oncology (IOV-IRCCS), 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 analyzed: (i) the peritumoral adipose tissue of rats following the induction of esophageal carcinogenesis; (ii) the peritumoral and distal (omental) adipose tissue of patients affected by EAC; (iii) adipose-derived stem cells (ADSC) 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 Dec 25;108(12):2319-2325. Epub 2017 Oct 25.
    Division of Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
    CIC/Capicua is an 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 receptor tyrosine kinase/RAS/MAPK signals downregulate CIC and relieves CIC's target genes from the transrepressional activity; 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 Dec 21;108(12):2454-2461. Epub 2017 Oct 21.
    Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Suita, 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

    Expression level of CXCL7 in peripheral blood cells is a potential biomarker for the diagnosis of renal cell carcinoma.
    Cancer Sci 2017 Dec 25;108(12):2495-2502. Epub 2017 Oct 25.
    Department of Urology, Osaka University Graduate School of Medicine, Suita, 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 upregulated 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 Dec 21;108(12):2373-2382. Epub 2017 Oct 21.
    Department of Pharmacology, Faculty of Medicine, Osaka Medical College, Takatsuki, 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

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