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    Anti-human SIRPα antibody is a new tool for cancer immunotherapy.
    Cancer Sci 2018 Feb 23. Epub 2018 Feb 23.
    Division of Molecular and Cellular Signaling Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
    Interaction of signal regulatory protein α (SIRPα) expressed on the surface of macrophages with its ligand CD47 expressed on target cells negatively regulates phagocytosis of the latter cells by the former. We recently showed that blocking Abs to mouse SIRPα enhanced both the Ab-dependent cellular phagocytosis (ADCP) activity of mouse macrophages for Burkitt's lymphoma Raji cells opsonized with an Ab to CD20 (rituximab) in vitro as well as the inhibitory effect of rituximab on the growth of tumors formed by Raji cells in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. However, the effects of blocking Abs to human SIRPα in preclinical cancer models have remained unclear given that such Abs have failed to interact with endogenous SIRPα expressed on macrophages of immunodeficient mice. Read More

    Cytotoxic T lymphocyte response to peptide vaccination predicts survival in stage III colorectal cancer.
    Cancer Sci 2018 Feb 23. Epub 2018 Feb 23.
    Department of Surgery, Kindai University Faculty of Medicine, Osakasayama, Osaka, 589-8511, Japan.
    We previously reported a phase I clinical trial of a peptide vaccine ring finger protein 43 (RNF43) and 34-kDa translocase of the outer mitochondrial membrane (TOMM34) combined with uracil-tegafur (UFT)/LV for patients with metastatic colorectal cancer (CRC), and demonstrated the safety and immunological responsiveness of this combination therapy. In this study, we evaluated vaccination-induced immune responses to clarify the survival benefit of the combination therapy as adjuvant treatment. We enrolled 44 patients initially in an HLA-masked fashion. Read More

    Toll-like receptor 3 signal augments radiation-induced tumor growth retardation in a murine model.
    Cancer Sci 2018 Feb 21. Epub 2018 Feb 21.
    Department of Vaccine Immunology, Graduate School of Medicine Hokkaido University, Kita 15 Nishi 7, Kita-ku, Sapporo, Japan.
    Radiotherapy induces anti-tumor immunity by induction of tumor antigens and damage-associated molecular patterns (DAMPs). DNA, a representative DAMP in radiotherapy, activates the STING pathway which enhances the immune response. However, the immune response does not always parallel the inflammation associated with radiotherapy. Read More

    In vivo optical imaging of cancer cell function and tumor microenvironment.
    Cancer Sci 2018 Feb 21. Epub 2018 Feb 21.
    Department of Molecular Medicine for Pathogenesis, Ehime University Graduate School of Medicine.
    In vivo optical imaging using fluorescence and bioluminescence is superior to other methods in terms of spatio-temporal resolution and specificity, and represents a new technology for comprehensively studying living organisms in a less invasive manner. Nowadays, it is an indispensable technology for studying many aspects of cancer biology, including dynamic invasion and metastasis. In observations of fluorescence or bioluminescence signals in a living body, various problems were caused by optical characteristics such as absorption and scattering, and therefore observation of deep tissue portion was difficult. Read More

    X-ray-enhanced cancer cell migration requires the linker of nucleoskeleton and cytoskeleton complex.
    Cancer Sci 2018 Feb 21. Epub 2018 Feb 21.
    Graduate School of Medicine and Health Science, Osaka University, Osaka, 565-0871, Japan.
    The linker of nucleoskeleton and cytoskeleton (LINC) complex is a multifunctional protein complex that is involved in various process at the nuclear envelope including nuclear migration, mechanotransduction, chromatin tethering, and DNA damage response. We recently showed that a nuclear envelope protein, Sad1 and UNC84 domain protein 1 (SUN1); a component of the LINC complex functions in cell migration. Although ionizing radiation activates cell migration and invasion in vivo and in vitro, the underlying molecular mechanism remains unknown. Read More

    Antitumor activity of pan-HER inhibitors in HER2-positive gastric cancer.
    Cancer Sci 2018 Feb 21. Epub 2018 Feb 21.
    General Thoracic Surgery, Breast and Endocrinological Surgery.
    Molecularly targeted therapy has enabled outstanding advances in cancer treatment. Whereas various anti-HER2 drugs have been developed, trastuzumab is still the only anti-HER2 drug presently available for gastric cancer. In this study, we propose novel treatment options for patients with HER2-positive gastric cancer. Read More

    The significance of tumor-infiltrating lymphocytes before and after neoadjuvant therapy for rectal cancer.
    Cancer Sci 2018 Feb 21. Epub 2018 Feb 21.
    Department of Surgical Oncology, Osaka City University Graduate School of Medicine.
    Recently, neoadjuvant therapy for locally advanced rectal cancer has been generally performed. However, biomarkers predicting the response to neoadjuvant therapy have not been established. Tumor-infiltrating lymphocytes (TILs) have a crucial effect on tumor progression and the survival outcome as the primary host immune response, and an antitumor immune effect has been reported to contribute to the response to radiotherapy and chemotherapy. Read More

    Downregulation of reticulocalbin-1 differentially facilitates apoptosis and necroptosis in human prostate cancer cells.
    Cancer Sci 2018 Feb 17. Epub 2018 Feb 17.
    Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, China.
    Reticulocalbin 1 (RCN1), an endoplasmic reticulum (ER)-resident Ca-binding protein, is dysregulated in cancers, but its pathophysiological roles are largely unclear. Here, we demonstrate that RCN1 is overexpressed in clinical prostate cancer (PCa) samples, associated with Cyclin B, not Cyclin D1 expression, compared to that of benign tissues in a Chinese Han population. Downregulation of endogenous RCN1 significantly suppresses PCa cell viability and arrests the cell cycles of DU145 and LNCaP cells at the S and G2/M phases, respectively. Read More

    The anti-malarial mefloquine inhibits NF-κB signaling and induces apoptosis in colorectal cancer cells.
    Cancer Sci 2018 Feb 17. Epub 2018 Feb 17.
    Suzhou Institute of Systems Medicine, Center for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, Jiangsu, 215123, China.
    The NF-κB signaling pathway is activated in many colorectal cancer (CRC) cells and in the tumor microenvironment, which plays a critical role in cancer initiation, development, and response to therapies. We found in the present study that the widely used antimalarial drug mefloquine was a NF-κB inhibitor that blocked the activation of IκBα kinase, leading to the reduction of IκBα degradation, decrease of p65 phosphorylation, and suppressed expression of NF-κB target genes in colorectal cancer cells. We also found that mefloquine induced growth arrest and apoptosis of colorectal cancer cells harboring phosphorylated p65 in culture and mice. Read More

    KIAA0247 inhibits growth, migration, invasion of non-small-cell lung cancer through regulating the Notch pathway.
    Cancer Sci 2018 Feb 16. Epub 2018 Feb 16.
    Department of Pathology, College of Basic Medical Sciences and First Affiliated Hospital, China Medical University, Shenyang.
    Lung cancer remains the leading cause of cancer-related death worldwide. Previous studies have shown that the novel KIAA0247 gene potentially targeted by the tumor suppressor p53 may inhibit the development of several cancers. However, the exact function of KIAA0247 in non-small-cell lung cancer (NSCLC) is unknown. Read More

    Down-regulation of LRIG1 by microRNA-20a modulates gastric cancer multidrug resistance.
    Cancer Sci 2018 Feb 16. Epub 2018 Feb 16.
    Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 210008, Nanjing, China.
    Multidrug resistance (MDR) significantly restricts the clinical efficacy of gastric cancer (GC) chemotherapy, and it is critical to search novel targets to predict and overcome MDR. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) has been proved to be correlated with drug resistance in several cancers. The present study revealed that LRIG1 was overexpressed in chemo-sensitive GC tissues and decreased expression of LRIG1 predicted poor survival in GC patients. Read More

    NRF2 Addiction in Cancer Cells.
    Cancer Sci 2018 Feb 16. Epub 2018 Feb 16.
    Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
    The KEAP1-NRF2 system is a pivotal defense mechanism against oxidative and electrophilic stress. While transient NRF2 activation in response to stress is beneficial for health, persistent NRF2 activation in cancer cells has deleterious effects on cancer-bearing hosts by conferring therapeutic resistance and aggressive tumorigenic activity on cancer cells. Because NRF2 increases the anti-oxidant and detoxification capability of cancer cells, persistently high levels of NRF2 activity enhance therapeutic resistance of the cancer cells. Read More

    Overexpression of IL-35 in intrahepatic cholangiocarcinoma isa prognostic indicator after curative resection.
    Cancer Sci 2018 Feb 15. Epub 2018 Feb 15.
    Liver Cancer Institute and Zhongshan Hospital of Fudan University, Shanghai, 200032, China.
    Interleukin-35 (IL-35) is implicated in tumorigenesis, but the exact impact on intrahepatic cholangiocarcinoma (ICC) is not clearly. The aim of present study was to explore the specific effect of IL-35 on patient prognosis. Additionally, we formulated an effective prognostic nomogram for ICC patients after curative resection. Read More

    Preclinical characterization of anlotinib, a highly potent and selective vascular endothelial growth factor receptor-2 inhibitor.
    Cancer Sci 2018 Feb 15. Epub 2018 Feb 15.
    Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
    Abrogating tumor angiogenesis by inhibiting vascular endothelial growth factor receptor-2 (VEGFR2) has been established as a therapeutic strategy for treating cancer. However, because of their low selectivity, most small molecule inhibitors of VEGFR2 tyrosine kinase exhibit unexpected adverse effects and limited anti-cancer efficacy. In this study, we detailed the pharmacologic properties of anlotinib, a highly potent and selective VEGFR2 inhibitor, in preclinical models. Read More

    Stemness and anti-cancer drug resistance in ABCG2 highly expressed pancreatic cancer is induced on 3D-culture condition.
    Cancer Sci 2018 Feb 14. Epub 2018 Feb 14.
    Research Team for Geriatric Medicine (Vascular Medicine), Tokyo Metropolitan Institute of Gerontology, Tokyo, 173-0015, Japan.
    The expression of ATP-binding cassette subfamily G member 2 (ABCG2) is related with tumorigenic cancer stem cells (CSCs) in several cancers. However, the effects of ABCG2 on CSC-related malignant characteristics in pancreatic ductal adenocarcinoma (PDAC) are not well elucidated. In this study, we compared the characteristics of low (ABCG2-) and high (ABCG2+)-ABCG2-expressing PDAC cells after cell sorting. Read More

    Establishment of an in vivo simulating co-culture assay platform for genotoxicity of multi-walled carbon nanotubes.
    Cancer Sci 2018 Feb 14. Epub 2018 Feb 14.
    Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo, 104-0045, Japan.
    Engineered nanomaterials (ENMs) are now used in a wide variety of fields, and thus their safety should urgently be assessed and secured. It has been suggested that inflammatory responses via the phagocytosis of ENMs by macrophages is a key mechanism for their genotoxicity. The present study was conducted to establish a mechanism-based assay to evaluate the genotoxicity of ENMs under conditions simulating an in vivo situation, featuring a co-culture system of murine lung resident cells (GDL1) and immune cells (RAW264. Read More

    Identification and functional analyses of differentially expressed metabolites in early stage endometrial carcinoma.
    Cancer Sci 2018 Feb 12. Epub 2018 Feb 12.
    Division of Uterine Vascular Biology, Guangzhou Institute of Pediatrics Guangzhou Women and Children's Medical Center, Guangzhou, China.
    Diagnosis of endometrial cancer is primarily based on symptoms and imaging, with early-stage disease being difficult to diagnose. Therefore, development of potential diagnostic biomarkers is required. Metabolomics, a quantitative measurement of the dynamic metabolism in living systems, can be applied to determine metabolite profiles in different disease states. Read More

    FBW7 is associated with prognosis, inhibits malignancies and enhances temozolomide sensitivity in glioblastoma cells.
    Cancer Sci 2018 Feb 10. Epub 2018 Feb 10.
    Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
    F-box and WD repeat domain-containing 7(FBW7) is a SCF-type E3 ubiquitin ligase targeting a multitude of oncoproteins for degradation. Acting as one of the most important tumor suppressor it is frequently inactivated in various tumors. In this study we aimed to evaluate the relationship of FBW7 with glioma pathology and prognosis, and examine its effect in glioma malignancies and temozolomide(TMZ)-based therapy. Read More

    Crosstalk of DNA double-strand break repair pathways in PARP inhibitor treatment of BRCA1/2-mutated Cancer.
    Cancer Sci 2018 Feb 10. Epub 2018 Feb 10.
    Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Japan.
    Germ-line mutations in breast cancer susceptibility gene 1 or 2 (BRCA1 or BRCA2) significantly increase cancer risk in hereditary breast and ovarian cancer syndrome (HBOC). Both genes function in the homologous recombination (HR) pathway of DNA double-strand break (DSB) repair process. Therefore, the DNA-repair defect characteristic in cancer cells brings therapeutic advantage for Poly(ADP-ribose) polymerase (PARP) inhibitor-induced synthetic lethality. Read More

    The stearate-to-palmitate ratio modulates endoplasmic reticulum stress and cell apoptosis in non-B non-C hepatoma cells.
    Cancer Sci 2018 Feb 10. Epub 2018 Feb 10.
    Second Department of Surgery, Hamamatsu University School of Medicine.
    The increased prevalence of hepatocellular carcinoma (HCC) without viral infection, namely, NHCC, is a major public health issue worldwide. NHCC is frequently derived from non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), which exhibit dysregulated fatty acid (FA) metabolism. This raises a possibility that NHCC evolves intracellular machineries to adapt to dysregulated FA metabolism. Read More

    Multiple roles of SIM2 in esophageal squamous cell carcinoma and its clinical implications.
    Cancer Sci 2018 Feb 10. Epub 2018 Feb 10.
    Department of Translational Oncology, National Cancer Center.
    The degree of histological differentiation is an important characteristic of cancers and may be associated with their malignant potentials. However, in squamous cell carcinomas, a key transcriptional factor to regulate tumor differentiation is largely unknown. Chemoradiotherapy (CRT) is a standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC); however, the survival rate is still below 40%. Read More

    Impact of novel oncogenic pathways regulated by anti-tumor miR-451a in renal cell carcinoma.
    Cancer Sci 2018 Feb 8. Epub 2018 Feb 8.
    Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
    Recent analyses of our microRNA (miRNA) expression signatures obtained from several types of cancer have provided novel information on their molecular pathology. In renal cell carcinoma (RCC), expression of microRNA-451a (miR-451a) was significantly downregulated in patient specimens and low expression of miR-451a was significantly associated with poor prognosis of RCC patients (p = 0.00305) based on data in The Cancer Genome Atlas (TCGA). Read More

    Mutations in the STAT family of genes in cancer.
    Cancer Sci 2018 Feb 8. Epub 2018 Feb 8.
    Stanford University, Stanford, CA, 94305.
    In recent years, it has become clear that members of the signal transducer and activator of transcription (STAT) family of genes play an important role in cancer. The STAT family consists of six genes, STAT1-4, STAT5A/ STAT5B and STAT6, that are involved in regulating cellular proliferation, apoptosis, angiogenesis and the immune system response. Constitutive activation of STAT3, via mutational changes, has been shown to be important in oncogenesis in both solid and hematopoietic cancers. Read More

    Metastatic ability and the epithelial-mesenchymal transition in induced cancer stem-like hepatoma cells.
    Cancer Sci 2018 Feb 8. Epub 2018 Feb 8.
    Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan.
    Cancer stem cells (CSCs) are thought to play important roles in cancer malignancy. Previously, we successfully induced sphere cancer stem-like cells (CSLCs) from several cell lines and observed the property of chemoresistance. In the present study, we examined the metastatic potential of these induced CSLCs. Read More

    Retraction.
    • Authors:
    Cancer Sci 2018 02 9;109(2):483. Epub 2018 Jan 9.
    'EphB3-targeted regulation of miR-149 in the migration and invasion of human colonic carcinoma HCT116 and SW620 cells' by Guodong Zhang, Xiaozhu Liu, Yinfeng Li, Yan Wang, Huankun Liang, Kangyan Li, Laiqing Li, Cuicui Chen, Wenqiao Sun, Shoulei Ren, Pengfei Zhu and Licheng Zhang. The above article from Cancer Science, first published on 3 April 2017 in Wiley Online Library (wileyonlinelibrary.com) and in Volume 108, pp. Read More

    CREPT overexpression is associated with proliferation behaviors and poor prognosis in non-small cell lung cancer.
    Cancer Sci 2018 Feb 3. Epub 2018 Feb 3.
    Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
    The cell-cycle-related and expression-elevated protein in tumor (CREPT) is overexpressed in several human malignancies. However, the clinical relevance of CREPT expression and its biological role in non-small cell lung cancer (NSCLC) remains unclear.In this study, we detected the expression of CREPT in both NSCLC tissues and cell lines by immunohistochemistry, Western Blot and RT-PCR. Read More

    The anti-tumor effects of Metformin are due to inhibiting NF-κB nuclear translocation in esophageal squamous cell carcinoma.
    Cancer Sci 2018 Feb 3. Epub 2018 Feb 3.
    Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
    Esophageal squamous cell carcinoma (ESCC) is an intractable digestive organ cancer that has proven difficult to treat despite multidisciplinary therapy, and the new treatment strategy is demanded. Metformin is used for type 2 diabetes mellitus and its antitumor effects have been reported recently. Metformin exerts antitumor effects in various respects, such as inhibiting inflammation, tumor growth and epithelial-mesenchymal transition (EMT). Read More

    Antitumor activity of antibody against cytotoxic T lymphocyte epitope peptide of lymphocyte-specific protein tyrosine kinase.
    Cancer Sci 2018 Feb 1. Epub 2018 Feb 1.
    Cancer Vaccine Center, Kurume University, Kurume, Japan.
    Although humoral responses against cytotoxic T lymphocyte epitope peptides from lymphocyte-specific protein tyrosine kinase antigen have been observed in the majority of healthy donors and cancer patients, the biological activity of the antibody has not been determined. Then we investigated the biological activity of monoclonal antibody against cytotoxic T lymphocyte epitope peptide of lymphocyte-specific protein tyrosine kinase antigen at positions 486-494 (anti-lymphocyte-specific protein tyrosine kinase-486 monoclonal antibody). This monoclonal antibody induced dendritic cell maturation from murine bone marrow cells by the immune complex form in vitro, and inhibited tumor growth in association with a suppression of tumor infiltrating T cells, including T regulatory cells in a murine model using the female BALB/cCrlCrlj mice (H-2K). Read More

    Area of residual tumor is a robust prognostic marker for patients with rectal cancer undergoing preoperative therapy.
    Cancer Sci 2018 Feb 1. Epub 2018 Feb 1.
    Department of Colorectal and Pelvic Surgery, National Cancer Center Hospital East, Chiba, Japan.
    The aim of this study was to elucidate differences in the histological features of rectal cancer between patients treated with preoperative chemoradiotherapy and those treated with preoperative chemotherapy. Area of residual tumor (ART) was also evaluated for its utility as a potential prognostic marker between them. Sixty-eight patients with rectal cancer who underwent sphincter-saving surgery were enrolled in this study. Read More

    Reverse of non-small cell lung cancer drug resistance induced by cancer associated fibroblasts via a paracrine pathway.
    Cancer Sci 2018 Jan 30. Epub 2018 Jan 30.
    Department of Interventional, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, PR, China.
    Tumor microenvironment orchestrates the sustained growth, metastasis and recurrence of cancer. As an indispensable component of tumor microenvironment, cancer associated fibroblasts (CAFs) are considered as an essential synthetic machine producing various tumor components, leading to cancer sustained stemness, drug resistance and tumor recurrence. Here, we developed a sustainable primary culture of lung cancer cells fed with lung cancer associated fibroblasts, resulting in enrichment and acquisition of drug resistance in cancer cells. Read More

    lncRNA BC005927 upregulates EPHB4 and promotes gastric cancer metastasis under hypoxia.
    Cancer Sci 2018 Jan 30. Epub 2018 Jan 30.
    Department of Oncology, Tangdu Hospital Fourth Military Medical University, 1 Xinsi Road, Xi'an, 710038, China.
    Hypoxia plays a critical role in the metastasis of gastric cancer (GC), yet the underlying mechanism remains largely unclear. It is also not known if lncRNAs are involved in the contribution of hypoxia to the GC metastasis. In this study, we found that lncRNA BC005927 can be induced by hypoxia in GC cells and mediates hypoxia-induced GC cell metastasis. Read More

    Tunicamycin inhibits cell proliferation and migration in hepatocellular carcinoma via suppression of CD44s and the ERK1/2 pathway.
    Cancer Sci 2018 Jan 29. Epub 2018 Jan 29.
    State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute Renji Hospital Shanghai Jiaotong University School of Medicine, Shanghai, China.
    Tunicamycin is an N-linked glycosylation (NLG) inhibitor with strong anti-tumor activity, the exact underlying molecular mechanism of which remains to be elucidated. In our previous studies, we found that tunicamycin reversed drug resistance and improved the efficacy of combination treatments for hepatocellular carcinomas (HCC). Here, we investigated the effects of tunicamycin on HCC cell proliferation and migration as well as mechanism of those effects. Read More

    SNCA, a novel biomarker for Group 4 medulloblastomas, can inhibit tumor invasion and induce apoptosis.
    Cancer Sci 2018 Jan 25. Epub 2018 Jan 25.
    Department of Pathology, Peking University School of Basic Medical Science, Peking University Third Hospital, Peking Univeristy Health Science Center, Beijing, China.
    Medulloblastoma (MB) is the most common malignant brain tumor in childhood. It contains at least four distinct molecular subgroups. The aim of this study is to explore novel diagnostic and potential therapeutic markers within each subgroup of MB, in particular within Group 4, the largest subgroup, to facilitate diagnosis together with gene therapy. Read More

    RBBP6 increases radioresistance and serves as a therapeutic target for preoperative radiotherapy in colorectal cancer.
    Cancer Sci 2018 Jan 25. Epub 2018 Jan 25.
    Department of General Surgery, Shanghai General Hospital School of Medicine Shanghai Jiao Tong University, Shanghai, 200080, People's Republic of China.
    Radiotherapy (RT) can be used as preoperative treatment to downstage initially unresectable locally rectal carcinoma, but the radioresistance and recurrence remain significant problems. Retinoblastoma binding protein 6 (RBBP6) has been implicated in the regulation of cell cycle, apoptosis and chemoresistance both in vitro and in vivo. This study investigated whether the inhibition of RBBP6 expression would improve radiosensitivity in human colorectal cancer cells. Read More

    Modulation of AKR1C2 by curcumin decreases testosterone production in prostate cancer.
    Cancer Sci 2018 Jan 25. Epub 2018 Jan 25.
    Department of Urology, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
    Intratumoral androgen biosynthesis has been recognized as an essential factor of castration-resistant prostate cancer. The present study investigated the effects of curcumin on the inhibition of intracrine androgen synthesis in prostate cancer. Human prostate cancer cell lines, LNCaP and 22Rv1 cells were incubated with or without curcumin after which cell proliferation was measured at 0, 24, 48 and 72 hours, respectively. Read More

    Osimertinib in patients with EGFR T790M advanced non-small cell lung cancer selected using cytology samples.
    Cancer Sci 2018 Jan 24. Epub 2018 Jan 24.
    Research and Development, AstraZeneca K.K, Osaka, Japan.
    Osimertinib is a potent, irreversible EGFR tyrosine kinase inhibitor (TKI) selective for EGFR-TKI sensitizing (EGFRm) and T790M resistance mutations. The primary objective of the cytology cohort in the AURA study was to investigate safety and efficacy of osimertinib in pretreated Japanese patients with EGFR T790M mutation-positive NSCLC, with screening EGFR T790M mutation status determined from cytology samples. The cytology cohort was included in the Phase I dose expansion component of the AURA study. Read More

    E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma: A phase 1 study.
    Cancer Sci 2018 Jan 24. Epub 2018 Jan 24.
    Department of Clinical Development, Eisai Co Ltd, Tokyo.
    E7777, a recombinant cytotoxic fusion protein comprising diphtheria toxin fragments A and B and human interleukin-2, shares an amino acid sequence with denileukin diftitox but has improved purity and an increased percentage of active protein monomer species. A phase 1 study was conducted to evaluate the tolerability, safety, pharmacokinetics and anti-tumour activity of E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma. E7777 (6, 12 and expanded 9 μg/kg/day) was administered to 13 patients via intravenous infusion on 5 consecutive days per 21-day cycle. Read More

    Serum MicroRNA Signatures and Metabolomics Have High Diagnostic Value in Colorectal Cancer by Two Novel Methods.
    Cancer Sci 2018 Jan 24. Epub 2018 Jan 24.
    Department of Gastroenterology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
    Recently, many new diagnostic biomarkers have been developed for colorectal cancer. We chose two methods with high diagnostic efficiencies, the detection of serum microRNAs and metabolomics based on gas chromatography/mass spectrometry (GC/MS), and aimed to establish appropriate models. We reviewed the diagnostic value of all microRNAs identified by previous diagnostic tests. Read More

    Expression of activating natural killer-cell receptors is a hallmark of the innate-like T-cell neoplasm in peripheral T-cell lymphomas.
    Cancer Sci 2018 Jan 24. Epub 2018 Jan 24.
    Division of Hematology & Oncology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
    Peripheral T- or natural killer (NK)-cell lymphomas are rare and difficult-to-recognize diseases. It remains arduous to distinguish between NK cell- and cytotoxic T-lymphocyte-derived lymphomas through routine histological evaluation. To clarify the cells of origin, we focused on NK-cell receptors and examined the expression using immunohistochemistry in 22 cases with T- and NK-cell neoplasms comprising angioimmunoblastic T-cell lymphoma, anaplastic lymphoma kinase (ALK)-positive and -negative anaplastic large-cell lymphomas, extranodal NK/T-cell lymphoma, nasal type, monomorphic epitheliotropic intestinal T-cell lymphoma, aggressive NK-cell leukemia, and other peripheral T-cell lymphomas. Read More

    Understanding intratumor heterogeneity by combining genome analysis and mathematical modeling.
    Cancer Sci 2018 Jan 20. Epub 2018 Jan 20.
    Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
    Cancer is composed of multiple cell populations with different genomes. Each of the populations is called a clone (or subclone) and this phenomenon is called intratumor heterogeneity (ITH). ITH is observed in various types of cancers and presumed to be a major cause leading to therapeutic resistance. Read More

    Development of a risk prediction model for lung cancer: The Japan Public Health Center-based Prospective Study.
    Cancer Sci 2018 Jan 18. Epub 2018 Jan 18.
    Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
    Although the impact of tobacco consumption on the occurrence of lung cancer is well-established, risk estimation could be improved by risk prediction models that consider various smoking habits, such as quantity, duration, and time since quitting. We constructed a risk prediction model using a population of 59 161 individuals from the Japan Public Health Center (JPHC) Study Cohort II. A parametric survival model was used to assess the impact of age, gender, and smoking-related factors (cumulative smoking intensity measured in pack-years, age at initiation, and time since cessation). Read More

    Programmed death-ligand 1 is a promising blood marker for predicting tumor progression and prognosis in patients with gastric cancer.
    Cancer Sci 2018 Jan 18. Epub 2018 Jan 18.
    Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
    Immune checkpoint inhibitor therapy has been clinically introduced for several malignancies, and its effectiveness has been confirmed by clinical trials. In particular, programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) are widely known as important immune checkpoint molecules associated with the mechanisms of immune escape by malignant tumor cells. In addition, liquid biopsy of blood specimens has the clinical benefit of providing a simple, repeatable sampling tool. Read More

    Whole Genome Sequencing Analysis for Cancer Genomics and Precision Medicine.
    Cancer Sci 2018 Jan 18. Epub 2018 Jan 18.
    Laboratory for Genome Sequencing Analysis, RIKEN Center for Integrative Medical Sciences, Tokyo, 108-8639, Japan.
    Explosive advances of next-generation sequencer (NGS) and computational analyses have been exploring somatic protein-altered mutations in most cancer types and these coding mutation data are intensively accumulated. However, there is limited information on somatic mutations in non-coding regions including introns, regulatory elements, and non-coding RNAs, structural variants and pathogen in cancer genomes remain widely unexplored. Whole genome sequencing (WGS) approaches can comprehensively explore all types of genomic alterations in cancer and help us to better understand the whole landscape of driver mutations and mutational signature in cancer genomes and elucidate functional or clinical implications of these unexplored genomic regions and mutational signature. Read More

    Present status and future perspective of peptide-based vaccine therapy for urological cancer.
    Cancer Sci 2018 Jan 18. Epub 2018 Jan 18.
    Department of Urology, Iwate Medical University School of Medicine, Morioka, Japan.
    Use of peptide-based vaccines as therapeutics aims to elicit immune responses through antigenic epitopes derived from tumor antigens. Peptide-based vaccines are easily synthesized and lack significant side-effects when given in vivo. Peptide-based vaccine therapy against several cancers including urological cancers has made progress for several decades, but there is no worldwide approved peptide vaccine. Read More

    Palbociclib in combination with letrozole as first-line treatment for advanced breast cancer: A Japanese phase II study.
    Cancer Sci 2018 Jan 18. Epub 2018 Jan 18.
    Kyoto University Graduate School of Medicine, Kyoto, Japan.
    This single-arm, open-label, phase II study in 42 Japanese postmenopausal patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer evaluated the efficacy, safety, and pharmacokinetics of first-line palbociclib (125 mg once daily, 3 weeks on/1 week off) coadministered with letrozole (2.5 mg once daily). Primary endpoint of investigator-assessed 1-year progression-free survival (PFS) probability was 75. Read More

    Drug resistance in anaplastic lymphoma kinase-rearranged lung cancer.
    Cancer Sci 2018 Jan 16. Epub 2018 Jan 16.
    Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
    The anaplastic lymphoma kinase (ALK) gene encodes a receptor tyrosine kinase, and many kinds of ALK fusion genes have been found in a variety of carcinomas. There is almost no detectable expression of ALK in adults. However, through ALK gene rearrangement, the resultant ALK fusion protein is aberrantly overexpressed and dimerized through the oligomerization domains, such as the coiled-coil domain, in the fusion partner that induces abnormal constitutive activation of ALK tyrosine kinase. Read More

    Protocadherin-8 promotes invasion and metastasis via laminin subunit γ2 in gastric cancer.
    Cancer Sci 2018 Jan 11. Epub 2018 Jan 11.
    Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
    Growing evidence suggests that protocadherins (PCDH) play crucial roles in pathogenesis and progression of cancers, including gastric cancer (GC). Protocadherin-8 (PCDH8) was previously reported to be involved in metastasis of GC, but functional studies yielded inconsistent results and the molecular mechanism remained unknown. The present study aimed to explore the clinical relevance, function and molecular mechanism of PCDH8 in GC. Read More

    Hereditary kidney cancer syndromes: Genetic disorders driven by alterations in metabolism and epigenome regulation.
    Cancer Sci 2018 Jan 11. Epub 2018 Jan 11.
    Department of Urology, Yokohama City University, Yokohama, Japan.
    Although hereditary kidney cancer syndrome accounts for approximately five percent of all kidney cancers, the mechanistic insight into tumor development in these rare conditions has provided the foundation for the development of molecular targeting agents currently used for sporadic kidney cancer. In the late 1980s, the comprehensive study for hereditary kidney cancer syndrome was launched in the National Cancer Institute, USA and the first kidney cancer-associated gene, VHL, was identified through kindred analysis of von Hippel-Lindau (VHL) syndrome in 1993. Subsequent molecular studies on VHL function have elucidated that the VHL protein is a component of E3 ubiquitin ligase complex for hypoxia-inducible factor (HIF), which provided the basis for the development of tyrosine kinase inhibitors targeting the HIF-VEGF/PDGF pathway. Read More

    Cellular stress induces cancer stem-like cells through expression of DNAJB8 by activation of heat shock factor 1.
    Cancer Sci 2018 Jan 8. Epub 2018 Jan 8.
    Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
    In a previous study, we found that DNAJB8, a heat shock protein (HSP) 40 family member is expressed in kidney cancer stem-like cells (CSC)/cancer-initiating cells (CIC) and that it has a role in the maintenance of kidney CSC/CIC. Heat shock factor (HSF) 1 is a key transcription factor for responses to stress including heat shock, and it induces HSP family expression through activation by phosphorylation. In the present study, we therefore examined whether heat shock (HS) induces CSC/CIC. Read More

    Monitoring tyrosine kinase inhibitor therapeutic responses with a panel of metabolic biomarkers in chronic myeloid leukemia patients.
    Cancer Sci 2018 Jan 8. Epub 2018 Jan 8.
    Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.
    The aim of this study is to investigate the potential biomarkers associated with chronic myeloid leukemia (CML), reveal the metabolite changes related to the continuous phases of tyrosine kinase inhibitors (TKIs), and find the potential biomarkers associated with treatment effects. Fifty-two patients with CML and 26 matched healthy people were enrolled as the discovery set. Another 194 randomly selected CML patients treated with TKI were chosen as the external validation set. Read More

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