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Publisher: Biomed Central Ltd.   (Total: 302 journals)

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Showing 1 - 200 of 302 Journals sorted alphabetically
Acta Neuropathologica Communications     Open Access   (Followers: 1, SJR: 2.683, CiteScore: 5)
Acta Veterinaria Scandinavica     Open Access   (Followers: 2, SJR: 0.655, CiteScore: 1)
Addiction Science & Clinical Practice     Open Access   (Followers: 8, SJR: 1.224, CiteScore: 3)
Advances in Rheumatology     Open Access  
Advances in Simulation     Open Access   (Followers: 4)
Agriculture & Food Security     Open Access   (Followers: 15, SJR: 0.575, CiteScore: 2)
AIDS Research and Therapy     Open Access   (Followers: 14, SJR: 1.08, CiteScore: 2)
Algorithms for Molecular Biology     Open Access   (Followers: 4, SJR: 1.333, CiteScore: 2)
Allergy, Asthma and Clinical Immunology     Open Access   (Followers: 26, SJR: 0.732, CiteScore: 2)
Alzheimer's Research & Therapy     Open Access   (Followers: 3, SJR: 2.449, CiteScore: 6)
Animal Biotelemetry     Open Access   (Followers: 1, SJR: 1.067, CiteScore: 2)
Annals of Clinical Microbiology and Antimicrobials     Open Access   (Followers: 11, SJR: 1.104, CiteScore: 3)
Annals of General Psychiatry     Open Access   (Followers: 24, SJR: 0.784, CiteScore: 2)
Annals of Occupational and Environmental Medicine     Open Access   (Followers: 10, SJR: 0.452, CiteScore: 1)
Annals of Surgical Innovation and Research     Open Access   (Followers: 3, SJR: 0.328, CiteScore: 1)
Antimicrobial Resistance and Infection Control     Open Access   (Followers: 8, SJR: 1.573, CiteScore: 3)
Applied Cancer Research     Open Access  
Archives of Physiotherapy     Open Access   (Followers: 11)
Archives of Public Health     Open Access   (Followers: 12, SJR: 1.244, CiteScore: 3)
Arthritis Research & Therapy     Open Access   (Followers: 14, SJR: 2.154, CiteScore: 4)
Asia Pacific Family Medicine     Open Access   (Followers: 1, SJR: 0.538, CiteScore: 1)
Asthma Research and Practice     Open Access   (Followers: 1)
Basic and Clinical Andrology     Open Access   (SJR: 0.564, CiteScore: 2)
Behavioral and Brain Functions     Open Access   (Followers: 3, SJR: 0.986, CiteScore: 3)
Big Data Analytics     Open Access   (Followers: 26)
BioData Mining     Open Access   (Followers: 5, SJR: 0.982, CiteScore: 2)
Bioelectronic Medicine     Open Access  
Biological Procedures Online     Open Access   (SJR: 1.352, CiteScore: 4)
Biological Research     Open Access   (SJR: 0.654, CiteScore: 2)
Biology Direct     Open Access   (Followers: 7, SJR: 1.694, CiteScore: 3)
Biology of Mood & Anxiety Disorders     Open Access   (Followers: 5)
Biology of Sex Differences     Open Access   (Followers: 2, SJR: 1.902, CiteScore: 4)
Biomarker Research     Open Access   (Followers: 2)
Biomaterials Research     Open Access   (Followers: 4, SJR: 0.735, CiteScore: 3)
Biomedical Dermatology     Open Access  
BioMedical Engineering OnLine     Open Access   (Followers: 7, SJR: 0.542, CiteScore: 2)
BioPsychoSocial Medicine     Open Access   (Followers: 7, SJR: 0.416, CiteScore: 1)
Biotechnology for Biofuels     Open Access   (Followers: 10, SJR: 1.899, CiteScore: 6)
BMC Anesthesiology     Open Access   (Followers: 17, SJR: 0.807, CiteScore: 2)
BMC Biochemistry     Open Access   (Followers: 15, SJR: 0.708, CiteScore: 2)
BMC Bioinformatics     Open Access   (Followers: 136, SJR: 1.479, CiteScore: 2)
BMC Biology     Open Access   (Followers: 64, SJR: 3.842, CiteScore: 5)
BMC Biophysics     Open Access   (Followers: 3, SJR: 0.682, CiteScore: 2)
BMC Biotechnology     Open Access   (Followers: 17, SJR: 1.012, CiteScore: 3)
BMC Cancer     Open Access   (Followers: 29, SJR: 1.464, CiteScore: 3)
BMC Cardiovascular Disorders     Open Access   (Followers: 21, SJR: 0.909, CiteScore: 2)
BMC Cell Biology     Open Access   (Followers: 48, SJR: 1.277, CiteScore: 3)
BMC Clinical Pathology     Open Access   (Followers: 7, SJR: 1.141, CiteScore: 3)
BMC Complementary and Alternative Medicine     Open Access   (Followers: 14, SJR: 0.858, CiteScore: 3)
BMC Dermatology     Open Access   (Followers: 13, SJR: 0.796, CiteScore: 2)
BMC Developmental Biology     Open Access   (Followers: 13, SJR: 1.43, CiteScore: 2)
BMC Ear, Nose and Throat Disorders     Open Access   (Followers: 1, SJR: 0.653, CiteScore: 2)
BMC Ecology     Open Access   (Followers: 20, SJR: 1.076, CiteScore: 2)
BMC Emergency Medicine     Open Access   (Followers: 17, SJR: 0.572, CiteScore: 1)
BMC Endocrine Disorders     Open Access   (Followers: 7, SJR: 0.965, CiteScore: 2)
BMC Evolutionary Biology     Open Access   (Followers: 73, SJR: 1.656, CiteScore: 3)
BMC Family Practice     Open Access   (Followers: 13, SJR: 1.137, CiteScore: 2)
BMC Gastroenterology     Open Access   (Followers: 14, SJR: 1.231, CiteScore: 3)
BMC Genetics     Open Access   (Followers: 25, SJR: 1.16, CiteScore: 3)
BMC Genomics     Open Access   (Followers: 89, SJR: 2.11, CiteScore: 4)
BMC Geriatrics     Open Access   (Followers: 14, SJR: 1.257, CiteScore: 3)
BMC Health Services Research     Open Access   (Followers: 16, SJR: 1.151, CiteScore: 2)
BMC Hematology     Open Access   (Followers: 3, SJR: 0.545, CiteScore: 1)
BMC Immunology     Open Access   (Followers: 10, SJR: 0.993, CiteScore: 3)
BMC Infectious Diseases     Open Access   (Followers: 18, SJR: 1.576, CiteScore: 3)
BMC Intl. Health and Human Rights     Open Access   (Followers: 6, SJR: 1.006, CiteScore: 2)
BMC Medical Education     Open Access   (Followers: 43, SJR: 0.765, CiteScore: 2)
BMC Medical Ethics     Open Access   (Followers: 21, SJR: 1.016, CiteScore: 2)
BMC Medical Genetics     Open Access   (Followers: 7, SJR: 1.109, CiteScore: 2)
BMC Medical Genomics     Open Access   (Followers: 4, SJR: 1.688, CiteScore: 3)
BMC Medical Imaging     Open Access   (Followers: 9, SJR: 0.536, CiteScore: 2)
BMC Medical Informatics and Decision Making     Open Access   (Followers: 23, SJR: 0.812, CiteScore: 2)
BMC Medical Physics     Open Access   (Followers: 6)
BMC Medical Research Methodology     Open Access   (Followers: 9, SJR: 2.221, CiteScore: 3)
BMC Medicine     Open Access   (Followers: 13, SJR: 4.219, CiteScore: 7)
BMC Microbiology     Open Access   (Followers: 14, SJR: 1.242, CiteScore: 3)
BMC Molecular Biology     Open Access   (Followers: 144, SJR: 1.216, CiteScore: 2)
BMC Musculoskeletal Disorders     Open Access   (Followers: 22, SJR: 0.951, CiteScore: 2)
BMC Nephrology     Open Access   (Followers: 8, SJR: 1.098, CiteScore: 3)
BMC Neurology     Open Access   (Followers: 21, SJR: 1.006, CiteScore: 2)
BMC Neuroscience     Open Access   (Followers: 15, SJR: 1.12, CiteScore: 2)
BMC Nursing     Open Access   (Followers: 23, SJR: 0.766, CiteScore: 2)
BMC Nutrition     Open Access   (Followers: 8)
BMC Obesity     Open Access   (Followers: 6)
BMC Ophthalmology     Open Access   (Followers: 15, SJR: 0.921, CiteScore: 2)
BMC Oral Health     Open Access   (Followers: 6, SJR: 0.867, CiteScore: 2)
BMC Palliative Care     Open Access   (Followers: 29, SJR: 1.105, CiteScore: 2)
BMC Pediatrics     Open Access   (Followers: 17, SJR: 1.278, CiteScore: 2)
BMC Pharmacology     Open Access   (Followers: 2)
BMC Pharmacology & Toxicology     Open Access   (Followers: 6, SJR: 0.785, CiteScore: 2)
BMC Physiology     Open Access   (Followers: 4, SJR: 0.936, CiteScore: 2)
BMC Plant Biology     Open Access   (Followers: 15, SJR: 1.887, CiteScore: 4)
BMC Pregnancy and Childbirth     Open Access   (Followers: 22, SJR: 1.427, CiteScore: 3)
BMC Proceedings     Full-text available via subscription   (Followers: 1, SJR: 0.302, CiteScore: 1)
BMC Psychiatry     Open Access   (Followers: 32, SJR: 1.346, CiteScore: 3)
BMC Psychology     Open Access   (Followers: 18, SJR: 0.817, CiteScore: 2)
BMC Public Health     Open Access   (Followers: 162, SJR: 1.337, CiteScore: 3)
BMC Pulmonary Medicine     Open Access   (Followers: 4, SJR: 1.373, CiteScore: 3)
BMC Research Notes     Open Access   (Followers: 4, SJR: 0.691, CiteScore: 2)
BMC Rheumatology     Open Access   (Followers: 1)
BMC Sports Science, Medicine and Rehabilitation     Open Access   (Followers: 27, SJR: 0.926, CiteScore: 2)
BMC Structural Biology     Open Access   (Followers: 8, SJR: 1.024, CiteScore: 2)
BMC Surgery     Open Access   (Followers: 10, SJR: 0.693, CiteScore: 2)
BMC Systems Biology     Open Access   (Followers: 12, SJR: 1.109, CiteScore: 2)
BMC Urology     Open Access   (Followers: 14, SJR: 0.853, CiteScore: 2)
BMC Veterinary Research     Open Access   (Followers: 16, SJR: 0.934, CiteScore: 2)
BMC Women's Health     Open Access   (Followers: 11, SJR: 0.931, CiteScore: 2)
BMC Zoology     Open Access   (Followers: 1)
Borderline Personality Disorder and Emotion Dysregulation     Open Access   (Followers: 10)
Breast Cancer Research     Open Access   (Followers: 16, SJR: 3.026, CiteScore: 6)
Burns & Trauma     Open Access   (Followers: 12)
Cancer & Metabolism     Open Access   (Followers: 6)
Cancer Cell Intl.     Open Access   (Followers: 6, SJR: 1.13, CiteScore: 3)
Cancer Communications     Open Access  
Cancer Convergence     Open Access  
Cancer Imaging     Open Access   (Followers: 2, SJR: 1.012, CiteScore: 3)
Cancer Nanotechnology     Open Access   (Followers: 2, SJR: 1.168, CiteScore: 4)
Cancers of the Head & Neck     Open Access   (Followers: 2)
Canine Genetics and Epidemiology     Open Access   (Followers: 1)
Carbon Balance and Management     Open Access   (Followers: 5, SJR: 0.977, CiteScore: 2)
Cardio-Oncology     Open Access  
Cardiovascular Diabetology     Open Access   (Followers: 10, SJR: 2.157, CiteScore: 5)
Cardiovascular Ultrasound     Open Access   (Followers: 4, SJR: 0.812, CiteScore: 2)
Cell Communication and Signaling     Open Access   (Followers: 2, SJR: 2.211, CiteScore: 4)
Cell Division     Open Access   (Followers: 1, SJR: 2.445, CiteScore: 4)
Cellular & Molecular Biology Letters     Hybrid Journal   (Followers: 3)
Cerebellum & Ataxias     Open Access   (Followers: 1)
Child and Adolescent Psychiatry and Mental Health     Open Access   (Followers: 24, SJR: 0.901, CiteScore: 2)
Chinese Medicine     Open Access   (Followers: 2, SJR: 0.57, CiteScore: 2)
Chinese Neurosurgical J.     Open Access  
Chiropractic & Manual Therapies     Open Access   (Followers: 5, SJR: 0.599, CiteScore: 2)
Cilia     Open Access   (SJR: 0.732, CiteScore: 1)
Clinical and Molecular Allergy     Open Access   (Followers: 5, SJR: 0.933, CiteScore: 3)
Clinical and Translational Allergy     Open Access   (Followers: 2, SJR: 1.425, CiteScore: 4)
Clinical Diabetes and Endocrinology     Open Access   (Followers: 20)
Clinical Epigenetics     Open Access   (Followers: 11, SJR: 2.435, CiteScore: 5)
Clinical Sarcoma Research     Open Access  
Conflict and Health     Open Access   (Followers: 7, SJR: 1.851, CiteScore: 3)
Contraception and Reproductive Medicine     Open Access  
COPD Research and Practice     Open Access   (SJR: 0.755, CiteScore: 2)
Cost Effectiveness and Resource Allocation     Open Access   (Followers: 4, SJR: 0.888, CiteScore: 2)
Critical Care     Open Access   (Followers: 56, SJR: 2.48, CiteScore: 5)
Current Opinion in Molecular Therapeutics     Full-text available via subscription   (Followers: 14)
Diabetology & Metabolic Syndrome     Open Access   (Followers: 7, SJR: 0.943, CiteScore: 2)
Diagnostic and Prognostic Research     Open Access  
Diagnostic Pathology     Open Access   (Followers: 10, SJR: 0.818, CiteScore: 2)
Disaster and Military Medicine     Open Access   (Followers: 4)
Emerging Themes in Epidemiology     Open Access   (Followers: 13, SJR: 1.003, CiteScore: 2)
Energy, Sustainability and Society     Open Access   (Followers: 16, SJR: 0.607, CiteScore: 2)
Environmental Health     Open Access   (Followers: 11, SJR: 1.662, CiteScore: 4)
Environmental Health and Preventive Medicine     Open Access   (Followers: 3, SJR: 0.5, CiteScore: 1)
Epigenetics & Chromatin     Open Access   (Followers: 8, SJR: 3.767, CiteScore: 5)
European J. of Medical Research     Open Access   (Followers: 1, SJR: 0.55, CiteScore: 1)
European Review of Aging and Physical Activity     Open Access   (Followers: 9, SJR: 1.308, CiteScore: 4)
Experimental & Translational Stroke Medicine     Open Access   (Followers: 8, SJR: 0.98, CiteScore: 3)
Experimental Hematology & Oncology     Open Access   (Followers: 3, SJR: 0.842, CiteScore: 2)
Eye and Vision     Open Access   (Followers: 1)
Fertility Research and Practice     Open Access   (Followers: 2)
Fibrogenesis & Tissue Repair     Open Access   (SJR: 1.531, CiteScore: 4)
Fisheries and Aquatic Sciences     Open Access   (Followers: 2, SJR: 0.199, CiteScore: 0)
Flavour     Open Access   (Followers: 3)
Fluids and Barriers of the CNS     Open Access   (Followers: 2, SJR: 2.054, CiteScore: 5)
Frontiers in Zoology     Open Access   (Followers: 6, SJR: 1.597, CiteScore: 3)
Genes and Environment     Open Access   (Followers: 1, SJR: 0.516, CiteScore: 1)
Genetics Selection Evolution     Open Access   (Followers: 8, SJR: 1.745, CiteScore: 4)
Genome Biology     Open Access   (Followers: 31)
Genome Medicine     Open Access   (Followers: 5, SJR: 4.537, CiteScore: 7)
Global Health Research and Policy     Open Access   (Followers: 4)
Globalization and Health     Open Access   (Followers: 5, SJR: 1.262, CiteScore: 2)
Gut Pathogens     Full-text available via subscription   (Followers: 5, SJR: 1.066, CiteScore: 3)
Gynecologic Oncology Research and Practice     Open Access   (Followers: 1)
Harm Reduction J.     Open Access   (SJR: 1.445, CiteScore: 3)
Head & Face Medicine     Open Access   (Followers: 1, SJR: 0.62, CiteScore: 2)
Health and Quality of Life Outcomes     Open Access   (Followers: 14, SJR: 1.069, CiteScore: 3)
Health Research Policy and Systems     Open Access   (Followers: 14, SJR: 1.11, CiteScore: 2)
Hereditary Cancer in Clinical Practice     Open Access   (SJR: 0.848, CiteScore: 2)
Hereditas     Open Access   (Followers: 1, SJR: 0.278, CiteScore: 1)
Human Genomics     Open Access   (Followers: 3, SJR: 1.501, CiteScore: 3)
Human Resources for Health     Open Access   (Followers: 9, SJR: 1.301, CiteScore: 2)
Immunity & Ageing     Open Access   (Followers: 10, SJR: 1.218, CiteScore: 3)
Implementation Science     Open Access   (Followers: 18, SJR: 2.443, CiteScore: 4)
Infectious Agents and Cancer     Open Access   (SJR: 0.855, CiteScore: 2)
Infectious Diseases of Poverty     Open Access   (Followers: 1, SJR: 1.212, CiteScore: 3)
Inflammation and Regeneration     Open Access   (Followers: 1)
Intl. Breastfeeding J.     Open Access   (Followers: 23, SJR: 0.913, CiteScore: 3)
Intl. J. for Equity in Health     Open Access   (Followers: 6, SJR: 1.04, CiteScore: 2)
Intl. J. of Behavioral Nutrition and Physical Activity     Open Access   (Followers: 24, SJR: 2.626, CiteScore: 6)
Intl. J. of Health Geographics     Open Access   (Followers: 6, SJR: 1.385, CiteScore: 3)
Intl. J. of Mental Health Systems     Open Access   (Followers: 7, SJR: 0.721, CiteScore: 2)
Intl. J. of Pediatric Endocrinology     Open Access   (Followers: 10)
Intl. J. of Retina and Vitreous     Open Access   (Followers: 2)
Investigative Genetics     Open Access   (Followers: 1, SJR: 1.809, CiteScore: 3)
Irish Veterinary J.     Open Access   (Followers: 5, SJR: 0.657, CiteScore: 1)
Israel J. of Health Policy Research     Open Access   (SJR: 0.488, CiteScore: 1)
Italian J. of Pediatrics     Open Access   (Followers: 1, SJR: 0.685, CiteScore: 2)
J. for ImmunoTherapy of Cancer     Open Access   (Followers: 5, SJR: 2.798, CiteScore: 6)
J. of Angiogenesis Research     Open Access   (Followers: 2)
J. of Animal Science and Biotechnology     Open Access   (Followers: 4, SJR: 1.228, CiteScore: 3)
J. of Animal Science and Technology     Open Access   (Followers: 2)
J. of Biological Engineering     Open Access   (Followers: 3, SJR: 1.34, CiteScore: 4)

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Journal Cover
Journal of Experimental & Clinical Cancer Research
Journal Prestige (SJR): 2
Citation Impact (citeScore): 6
Number of Followers: 3  

  This is an Open Access Journal Open Access journal
ISSN (Print) 0392-9078 - ISSN (Online) 1756-9966
Published by Biomed Central Ltd. Homepage  [302 journals]
  • Downregulation of CLDN7 due to promoter hypermethylation is associated
           

    • Abstract: Background Metastasis is the primary cause of death in renal cell carcinoma (RCC). Loss of cell-to-cell adhesion, including tight junctions (TJs) is the initial step in the process of metastasis. Claudin-7 (CLDN7) is a major component of TJs. However, the clinical significance and its regulation of kidney tumorigenesis remain poorly understood. Methods A total of 120 fresh clear cell RCC (ccRCC) specimens and 144 primary RCC and adjacent nonmalignant renal paraffin specimens were obtained from Department of Urology, Peking University First Hospital. Expression of CLDN7 in ccRCC tissues and cell lines were determined using bioinformatic data mining, quantitative real-time PCR (qRT-PCR), Western blotting and immunostaining. The clinical significance of CLDN7 expression and promoter DNA methylation status was analyzed in ccRCC patients from Peking University First Hospital and The Cancer Genome Atlas. Additionally, the methylation specific-PCR, bisulfite genomic sequencing and demethylation analysis of CLDN7 were performed. Biological functions of CLDN7 were investigated by examining cell proliferation using MTS assays and EdU incorporation assays, cell migration by in vitro wound healing assays and transwell migration assays, cell invasion by transwell invasion assays, and cell apoptosis by flow cytometry. Mouse model experiments were performed to confirm the effects of CLDN7 on tumor growth and metastasis in vivo. The molecular mechanism of CLDN7 function was investigated using gene-set enrichment analysis (GSEA) and high-throughput cDNA sequencing (RNA-Seq) and confirmed by qRT-PCR, Western blot and immunostaining in vitro and in vivo. Results Our findings revealed that CLDN7 is frequently downregulated via hypermethylation of its promoter in ccRCC. CLDN7 can help predict aggressive tumor status and poor prognosis in ccRCC patients. Interestingly, hypermethylation of the CLDN7 promoter was related to advanced ccRCC status and poor prognosis. Moreover, overexpression of CLDN7 induced cell apoptosis, suppressed proliferation, migration and invasion abilities of ccRCC cells both in vitro and in vivo. Additionally, GSEA and RNA-Seq results showed that CLDN7 had negative effects in cancer-associated signaling pathways and (epithelial-mesenchymal transition) EMT-related pathways. These results were validated by qRT-PCR, Western blot and immunostaining. Conclusions We have demonstrated a previously undescribed role of CLDN7 as a ccRCC suppressor and suggest that loss of CLDN7 potentiates EMT and tumor progression. CLDN7 may serve as a functional tumor suppressor in tumor progression and a potential biomarker and target in patients with ccRCC.
      PubDate: 2018-11-14
       
  • CircRNA circRNA_102171 promotes papillary thyroid cancer progression
           through modulating CTNNBIP1-dependent activation of β-catenin pathway

    • Abstract: Background As a type of recently discovered noncoding RNA, circular RNAs (circRNAs) exert pivot biological functions in diverse cancers. However, the role of circRNA_102171 in papillary thyroid cancer (PTC) has not been investigated. Our study was focused on the functional investigation toward circRNA_102171 in PTC progression. And we also aimed to reveal its potential molecular mechanism. Methods The expression pattern of circRNA_102171 was determined using quantitative polymerase chain reaction (qPCR) in PTC samples and cell lines. Cell proliferation was examined utilizing CCK8, colony formation and EdU incorporation assays. Apoptosis was analyzed by Annexin V/PI staining and FACS detection. Cell migration and invasion was measured using Transwell assay. Tumor growth in vivo was determined through a xenograft assay. RNA-pulldown, RNA-IP (RIP) and RNA-EMSA were used to analyze the interaction between circRNA_102171 and CTNNBIP1. Results CircRNA_102171 expression was upregulated in tumor tissues and cell lines. CircRNA_102171 silencing suppressed PTC cell proliferation, migration and invasion while promoting apoptosis. CircRNA_102171 knockdown inhibited PTC growth in vivo. CircRNA_102171 interacted with CTNNBIP1 to block its interaction with the β-catenin/TCF3/TCF4/LEF1 complex, leading to activation of Wnt/β-catenin pathway. Conclusions CircRNA_102171 overexpression promotes PTC progression through activating Wnt/β-catenin pathway in a CTNNBIP1-dependent way.
      PubDate: 2018-11-13
       
  • Long non-coding RNA DANCR promotes malignant phenotypes of bladder cancer
           cells by modulating the miR-149/MSI2 axis as a ceRNA

    • Abstract: Background Accumulating evidences have indicated that long non-coding RNAs (lncRNAs) are potential biomarkers that play key roles in tumor development and progression. Differentiation antagonizing non-protein noding RNA (DANCR) is a novel lncRNA that acts as a potential biomarker and is involved in the development of cancers. However, the clinical significance and molecular mechanism of DANCR in bladder cancer is still unknown. Methods The relative expression level of DANCR was determined by Real-Time qPCR in a total of 106 patients with urothelial bladder cancer and in different bladder cancer cell lines. Loss-of-function experiments were performed to investigate the biological roles of DANCR on bladder cancer cell proliferation, migration, invasion and tumorigenicity. Comprehensive transcriptional analysis, RNA-FISH, dual-luciferase reporter assay and western blot were performed to explore the molecular mechanisms underlying the functions of DANCR. Results In this study, we found that DANCR was significantly up-regulated in bladder cancer. Moreover, increased DANCR expression was positively correlated with higher histological grade and advanced TNM stage. Further experiments demonstrated that knockdown of DANCR inhibited malignant phenotypes and epithelial-mesenchymal transition (EMT) of bladder cancer cells. Mechanistically, we found that DANCR was distributed mostly in the cytoplasm and DANCR functioned as a miRNA sponge to positively regulate the expression of musashi RNA binding protein 2 (MSI2) through sponging miR-149 and subsequently promoted malignant phenotypes of bladder cancer cells, thus playing an oncogenic role in bladder cancer pathogenesis. Conclusion This study is the first to demonstrate that DANCR plays a critical regulatory role in bladder cancer cell and DANCR may serve as a potential diagnostic biomarker and therapeutic target of bladder cancer.
      PubDate: 2018-11-12
       
  • LAT2 regulates glutamine-dependent mTOR activation to promote glycolysis
           and chemoresistance in pancreatic cancer

    • Abstract: Background Reprogrammed energy metabolism has become an emerging hallmark of cancer in recent years. Transporters have been reported to be amino acid sensors involved in controlling mTOR recruitment and activation, which is crucial for the growth of both normal and tumor cells. L-type amino acid transporter 2 (LAT2), encoded by the SLC7A8 gene, is a Na+-independent neutral amino acid transporter and is responsible for transporting neutral amino acids, including glutamine, which can activate mTOR. Previous studies have shown that LAT2 was overexpressed in gemcitabine-resistant pancreatic cancer cells. However, the role of LAT2 in chemoresistance in pancreatic cancer remains uncertain and elusive. Methods The effects of LAT2 on biological behaviors were analyzed. LAT2 and LDHB levels in tissues were detected, and the clinical value was evaluated. Results We demonstrated that LAT2 emerged as an oncogenic protein and could decrease the gemcitabine sensitivity of pancreatic cancer cells in vitro and in vivo. The results of a survival analysis indicated that high expression levels of both LAT2 and LDHB predicted a poor prognosis in patients with pancreatic cancer. Furthermore, we found that LAT2 could promote proliferation, inhibit apoptosis, activate glycolysis and alter glutamine metabolism to activate mTOR in vitro and in vivo. Next, we found that gemcitabine combined with an mTOR inhibitor (RAD001) could reverse the decrease in chemosensitivity caused by LAT2 overexpression in pancreatic cancer cells. Mechanistically, we demonstrated that LAT2 could regulate two glutamine-dependent positive feedback loops (the LAT2/p-mTORSer2448 loop and the glutamine/p-mTORSer2448/glutamine synthetase loop) to promote glycolysis and decrease gemcitabine (GEM) sensitivity in pancreatic cancer. Conclusion Taken together, our data reveal that LAT2 functions as an oncogenic protein and could regulate glutamine-dependent mTOR activation to promote glycolysis and decrease GEM sensitivity in pancreatic cancer. The LAT2-mTOR-LDHB pathway might be a promising therapeutic target in pancreatic cancer.
      PubDate: 2018-11-12
       
  • Tunicamycin specifically aggravates ER stress and overcomes
           chemoresistance in multidrug-resistant gastric cancer cells by inhibiting
           N-glycosylation

    • Abstract: Background Multidrug resistance remains a major obstacle to successful treatment for patients with gastric cancer (GC). Recently, glycosylation has been demonstrated to play a vital role in the acquisition of multidrug resistance. As a potent inhibitor of glycosylation, tunicamycin (Tu) has shown marked antitumor activities in various cancers. In the present study, we attempted to determine the exact effect of Tu on the chemoresistance of GC. Methods The cytotoxic effects of drugs on GC cells were evaluated by cell viability assays, and apoptosis was detected by flow cytometry. PCR, western blot analysis, immunofluorescence staining and canonical inhibitors were employed to identify the underlying mechanisms of the specific effects of Tu on multidrug-resistant (MDR) GC cells. Results For the first time, we found that MDR GC cells were more sensitive to Tu-induced cell death than the parental cells and that the increased sensitivity might correlate with basal endoplasmic reticulum (ER) stress. In addition, Tu dramatically increased chemotherapy-induced apoptosis by evoking ER stress in GC cells, particularly MDR cells. Further study indicated that these effects were highly dependent on glycosylation inhibition by Tu, rather than its role as a canonical ER stress inducer. Besides, autophagy was markedly triggered by Tu, and blocking autophagy enhanced the combined effects of Tu and chemotherapy on MDR GC cells. Conclusions Our results suggest that tumor-targeted glycosylation inhibition may be a feasible strategy to reverse chemoresistance in GC patients.
      PubDate: 2018-11-09
       
  • Correction to: PHF8 upregulation contributes to autophagic degradation of
           E-cadherin, epithelial-mesenchymal transition and metastasis in
           hepatocellular carcinoma

    • Abstract: In the publication of this article [1], there are two inadvertent errors.
      PubDate: 2018-11-07
       
  • GABA, glutamine, glutamate oxidation and succinic semialdehyde
           dehydrogenase expression in human gliomas

    • Abstract: Background Bioenergetic characterisation of malignant tissues revealed that different tumour cells can catabolise multiple substrates as salvage pathways, in response to metabolic stress. Altered metabolism in gliomas has received a lot of attention, especially in relation to IDH mutations, and the associated oncometabolite D-2-hydroxyglutarate (2-HG) that impact on metabolism, epigenetics and redox status. Astrocytomas and oligodendrogliomas, collectively called diffuse gliomas, are derived from astrocytes and oligodendrocytes that are in metabolic symbiosis with neurons; astrocytes can catabolise neuron-derived glutamate and gamma-aminobutyric acid (GABA) for supporting and regulating neuronal functions. Methods Metabolic characteristics of human glioma cell models – including mitochondrial function, glycolytic pathway and energy substrate oxidation – in relation to IDH mutation status and after 2-HG incubation were studied to understand the Janus-faced role of IDH1 mutations in the progression of gliomas/astrocytomas. The metabolic and bioenergetic features were identified in glioma cells using wild-type and genetically engineered IDH1-mutant glioblastoma cell lines by metabolic analyses with Seahorse, protein expression studies and liquid chromatography-mass spectrometry. Results U251 glioma cells were characterised by high levels of glutamine, glutamate and GABA oxidation. Succinic semialdehyde dehydrogenase (SSADH) expression was correlated to GABA oxidation. GABA addition to glioma cells increased proliferation rates. Expression of mutated IDH1 and treatment with 2-HG reduced glutamine and GABA oxidation, diminished the pro-proliferative effect of GABA in SSADH expressing cells. SSADH protein overexpression was found in almost all studied human cases with no significant association between SSADH expression and clinicopathological parameters (e.g. IDH mutation). Conclusions Our findings demonstrate that SSADH expression may participate in the oxidation and/or consumption of GABA in gliomas, furthermore, GABA oxidation capacity may contribute to proliferation and worse prognosis of gliomas. Moreover, IDH mutation and 2-HG production inhibit GABA oxidation in glioma cells. Based on these data, GABA oxidation and SSADH activity could be additional therapeutic targets in gliomas/glioblastomas.
      PubDate: 2018-11-07
       
  • MicroRNA-31-5p regulates chemosensitivity by preventing the nuclear
           location of PARP1 in hepatocellular carcinoma

    • Abstract: Background MicroRNAs (miRNAs) posttranscriptionally regulate gene expression and thereby contribute to the modulation of numerous complex and disease-relevant cellular processes, including cell proliferation, cell motility, apoptosis and stress response. miRNA-31-5p is encoded on a genomic fragile site, 9p21.3, which is reportedly lost in many hepatocellular carcinoma (HCC) tumors. Based on previous findings, we hypothesized that miR-31-5p alters chemosensitivity and that miR-31-5p mimics may influence sensitivity to chemotherapeutics in HCC as well as in a variety of other cancers. Methods MiR-31-5p and PARP1 in HCC tissues were tested by RT-PCR and histological analysis, respectively. Next, clonogenic assay and western blot were used to detect miR-31-5p and PARP1 to modulate sensitivity to OXA-based chemotherapy. The distribution of OXA in the nuclear and intracellular was detected by ICP-MS. Coimmunoprecipitation was used to characterize the protein-protein interaction between PARP1 and ABCB9. A xenograft nude mouse model was used to examine the in vivo effects of miR-31-5p. Results Reintroduction of miR-31-5p into miR-31-5p-null Hep3B cells significantly enhanced clonogenic resistance to oxaliplatin. Although miR-31-5p re-expression increased chemoresistance, it paradoxically increased the relative intracellular accumulation of oxaliplatin. This effect was coupled with a significantly decreased intranuclear concentration of oxaliplatin by ICP-MS. miR-31-5p prevents the nuclear location of PARP1 detected by immunofluorescence, histological analysis and Western blotting analysis. We subsequently identified an indirect miR-31-5p-mediated upregulation of ABCB9, which is a transporter associated with drug accumulation in lysosomes, along with an increased uptake of oxaliplatin to lysosomes; these phenomena were associated with a downregulation of PARP1, a bipotential transcriptional regulator with multiple miR-31-5p binding sites. However, the indirect overexpression of ABCB9 promoted cellular chemosensitivity, suggesting that miR-31-5p promotes chemoresistance largely via an ABCB9-independent mechanism. Conclusions Overall, our data suggest that the loss of miR-31-5p from HCC tumors promotes chemosensitivity, and this knowledge may be prognostically beneficial in the context of therapeutic sensitivity.
      PubDate: 2018-11-06
       
  • Vitexin compound 1, a novel extraction from a Chinese herb, suppresses
           melanoma cell growth through DNA damage by increasing ROS levels

    • Abstract: Background Vitex negundo L (Verbenaceae) is an aromatic shrub that is abundant in Asian countries. A series of compounds from Vitex negundo have been used in traditional Chinese medicine for the treatment of various diseases. Cutaneous melanoma is one of the most aggressive malignancies. A significant feature of melanoma is its resistance to traditional chemotherapy and radiotherapy; therefore, there is an urgent need to develop novel treatments for melanoma. Methods We first examined the effects of VB1 (vitexin compound 1) on cell viability by CCK-8 (cell counting kit) and Colony Formation Assay; And then, we analyzed the apoptosis and cell cycle by flow cytometry, verified apoptosis by Immunoblotting. The in vivo effect of VB1 was evaluated in xenograft mouse model. Potential mechanisms of VB1’s antitumor effects were explored by RNA sequencing and the key differential expression genes were validated by real-time quantitative PCR. Finally, the intracellular reactive oxygen species (ROS) level was detected by flow cytometry, and the DNA damage was revealed by Immunofluorescence and Immunoblotting. Results In this study, we show that VB1, which is a compound purified from the seed of the Chinese herb Vitex negundo, blocks melanoma cells growth in vitro and in vivo, arrests the cell cycle in G2/M phase and induces apoptosis in melanoma cell lines, whereas the effects are not significantly observed in normal cells. To study the details of VB1, we analyzed the alteration of gene expression profiles after treatment with VB1 in melanoma cells. The findings showed that VB1 can affect various pathways, including p53, apoptosis and the cell cycle pathway, in a variety of melanoma cell lines. Furthermore, we confirmed that VB1 restored the P53 pathway protein level, and then we demonstrated that VB1 significantly induced the accumulation of ROS, which resulted in DNA damage in melanoma cell lines. Interestingly, our results showed that VB1 also increased the ROS levels in BRAFi (BRAF inhibitor)-resistant melanoma cells, leading to DNA cytotoxicity, which caused G2/M phase arrest and apoptosis. Conclusions Taken together, our findings indicate that vitexin compound 1 might be a promising therapeutic Chinese medicine for melanoma treatment regardless of BRAFi resistance.
      PubDate: 2018-11-06
       
  • Correction to: Liver cancer cell lines distinctly mimic the metabolic gene
           expression pattern of the corresponding human tumours

    • Abstract: In the publication of this article (1), there is an error in Fig. 5b. This has now been updated in the original article (1).
      PubDate: 2018-11-02
       
  • The role of cellular reactive oxygen species in cancer chemotherapy

    • Abstract: Most chemotherapeutics elevate intracellular levels of reactive oxygen species (ROS), and many can alter redox-homeostasis of cancer cells. It is widely accepted that the anticancer effect of these chemotherapeutics is due to the induction of oxidative stress and ROS-mediated cell injury in cancer. However, various new therapeutic approaches targeting intracellular ROS levels have yielded mixed results. Since it is impossible to quantitatively detect dynamic ROS levels in tumors during and after chemotherapy in clinical settings, it is of increasing interest to apply mathematical modeling techniques to predict ROS levels for understanding complex tumor biology during chemotherapy. This review outlines the current understanding of the role of ROS in cancer cells during carcinogenesis and during chemotherapy, provides a critical analysis of the methods used for quantitative ROS detection and discusses the application of mathematical modeling in predicting treatment responses. Finally, we provide insights on and perspectives for future development of effective therapeutic ROS-inducing anticancer agents or antioxidants for cancer treatment.
      PubDate: 2018-11-01
       
  • Nobel committee honors tumor immunologists

    • Abstract: This commentary wishes to highlight the 2018 Nobel Prize in Medicine awarded to two cancer immunotherapy scientists, Prof James Allison and Prof Tasuku Honjo, for their discovery on unleashing the body’s immune system to attack cancer. Their studies have led to the development of an entire class of drugs that hopefully will bring lasting remissions to many patients who had run out of options.
      PubDate: 2018-10-30
       
  • Carbonyl reductase 1 is a new target to improve the effect of radiotherapy
           on head and neck squamous cell carcinoma

    • Abstract: Background Human carbonyl reductase 1 (CBR1) plays major roles in protecting cells against cellular damage resulting from oxidative stress. Although CBR1-mediated detoxification of oxidative materials increased by stressful conditions including hypoxia, neuronal degenerative disorders, and other circumstances generating reactive oxide is well documented, the role of CBR1 under ionising radiation (IR) is still unclear. Methods The formalin-fixed and paraffin-embedded tissues of 85 patients with head and neck squamous cell carcinoma (HNSCC) were used to determine if CBR1 expression effects on survival of patients with treatment of radiotherapy. Subsequently colony formation assays and xenograft tumor mouse model was used to verify the relationship between CBR1 expression and radiosensitivity in HNSCC cells. Publicly-available data from The Cancer Genome Atlas (TCGA) was analysed to determine if CBR1 expression affects the survival of patients with HNSCC. To verify CBR1-mediated molecular signalling pathways, cell survival, DNA damage/repair, reactive oxygen species (ROS), cell cycle distribution and mitotic catastrophe in HNSCC cells with modulated CBR1 expression by knockdown or overexpression were measured using by colony formation assays, flow cytometry, qRT-PCR and western blot analysis. Results HNSCC patients with low CBR1 had a significantly higher survival rate than the high CBR1 expression (84.2% vs. 57.8%, p = 0.0167). Furthermore, HNSCC patients with low CBR1 expression showed a good prognosis for IR compared to patients with highly expressed CBR1. Also, we found that IR upregulated CBR1 mRNA via Nrf2 activation in HNSCC cells and patients. In vitro analysis, we found that CBR1-specific siRNA or inhibitor significantly enhanced radiosensitivity after IR, while CBR1 overexpression decreased. CBR1 inhibition by siRNA or inhibitor treatment accumulated cellular ROS leading to aberrant DNA damage repair and an increase of mitotic catastrophe. Moreover, the combination of CBR1 depletion with IR dramatically inhibited primary tumour growth in a xenograft tumor mouse model. Conclusion Our findings indicate that CBR1 has a key role in DNA damage response through regulation of IR-mediated ROS generation. Consistently, CBR1 expression is highly correlated with patient survival after and susceptibility to radiation therapy. Therefore, CBR1 inhibition with IR might be a potent therapeutic strategy for HNSCC treatment.
      PubDate: 2018-10-30
       
  • Over-expressed lncRNA HOTAIRM1 promotes tumor growth and invasion through
           up-regulating HOXA1 and sequestering G9a/EZH2/Dnmts away from the HOXA1
           gene in glioblastoma multiforme

    • Abstract: Background Glioblastoma multiforme (GBM) is the common primary brain tumor classified the most malignant glioma. Long non-coding RNAs (LncRNAs) are important epigenetic regulators with critical roles in cancer initiation and progression. LncRNA HOTAIRM1 transcribes from the antisense strand of HOXA gene cluster which locus in chromosome 7p15.2. Recent studies have shown that HOTAIRM1 is involved in acute myeloid leukemia and colorectal cancer. Here we sought to investigate the role of HOTAIRM1 in GBM and explore its mechanisms of action. Methods The expressions of HOTAIRM1 and HOXA1 in GBM tissues and cells were determined by qRT-PCR, and the association between HOTAIRM1, HOXA1 transcription and tumor grade were analyzed. The biological function of HOTAIRM1 in GBM was evaluated both in vitro and in vivo. Chromatin immunoprecipitation (ChIP) assay and quantitative Sequenom MassARRAY methylation analysis were performed to explore whether HOTAIRM1 could regulate histone and DNA modification status of the HOXA1 gene transcription start sites (TSS) and activate its transcription. ChIP and RNA-ChIP were further performed to determine the molecular mechanism of HOTAIRM1 in epigenetic regulation of the HOXA1 gene. Results HOTAIRM1 was abnormally up-regulated in GBM tissues and cells, and this up-regulation was correlated with grade malignancy in glioma patients. HOTAIRM1 silencing caused tumor suppressive effects via inhibiting cell proliferation, migration and invasion, and inducing cell apoptosis. In vivo experiments showed knockdown of HOTAIRM1 lessened the tumor growth. Additionally, HOTAIRM1 action as regulating the expression of the HOXA1 gene. HOXA1, as an oncogene, it’s expression levels were markedly elevated in GBM tissues and cell lines. Mechanistically, HOTAIRM1 mediated demethylation of histone H3K9 and H3K27 and reduced DNA methylation levels by sequester epigenetic modifiers G9a and EZH2, which are H3K9me2 and H3K27me3 specific histone methyltransferases, and DNA methyltransferases (DnmTs) away from the TSS of HOXA1 gene. Conclusions We investigated the potential role of HOTAIRM1 to promote GBM cell proliferation, migration, invasion and inhibit cell apoptosis by epigenetic regulation of HOXA1 gene that can be targeted simultaneously to effectively treat GBM, thus putting forward a promising strategy for GBM treatment. Meanwhile, this finding provides an example of transcriptional control over the chromatin state of gene and may help explain the role of lncRNAs within the HOXA gene cluster.
      PubDate: 2018-10-30
       
  • ATF3 inhibits the tumorigenesis and progression of hepatocellular
           carcinoma cells via upregulation of CYR61 expression

    • Abstract: Background Hepatocellular carcinoma (HCC) is one of the most common malignant cancers with a high incidence and high mortality in East Asia. Identifying biomarkers and clarifying the regulatory mechanisms of HCC are of great importance. Herein, we report the role and mechanism of activating transcription factor 3 (ATF3), a member of the ATF/cAMP-responsive element-binding protein family of transcription factors in HCC. Methods ATF3 overexpression vector and shRNAs were transfected into HCC cancer cells to upregulate or downregulate ATF3 expression. In vitro and in vivo assays were performed to investigate the functional role of ATF3 in hepatocellular carcinoma. RNA-Seq was performed to screen the differentially expressed genes downstream of ATF3. The dual-luciferase reporter assay, chromatin immunoprecipitation (Ch-IP) analysis and functional rescue experiments were used to confirm the target gene regulated by ATF3. Tissue microarrays (TMAs) comprising 236 human primary HCC tissues were obtained and immunohistochemical staining were carried out to analyze the clinical significance of ATF3. Results The results indicate that ATF3 significantly inhibited the proliferation and mobility of HCC cells both in vitro and in vivo. Cysteine-rich angiogenic inducer 61 (CYR61) is a key target for transcriptional regulation by ATF3. Both ATF3 and CYR61 were consistently downregulated in human HCC tissues, and their expression levels were significantly and positively correlated with each other. Conclusions Our findings indicate that ATF3 functions as a tumor suppressor in HCC through targeting and regulating CYR61.
      PubDate: 2018-10-30
       
  • Lentinan inhibits tumor angiogenesis via interferon γ and in a T cell
           independent manner

    • Abstract: Background Antiangiogenic agents are commonly used in lung and colon cancer treatments, however, rapid development of drug resistance limits their efficacy. Methods Lentinan (LNT) is a biologically active compound extracted from Lentinus edodes. The effects of LNT on tumor angiogenesis were evaluated by immunohistochemistry in murine LAP0297 lung and CT26 colorectal tumor models. The impacts of LNT on immune cells and gene expression in tumor tissues were determined by flow cytometry, qPCR, and ELISA. Nude mice and IFNγ blockade were used to investigate the mechanism of LNT affecting on tumor angiogenesis. The data sets were compared using two-tailed student’s t tests or ANOVA. Results We found that LNT inhibited tumor angiogenesis and the growth of lung and colon cancers. LNT treatments elevated the expression of angiostatic factors such as IFNγ and also increased tumor infiltration of IFNγ-expressing T cells and myeloid cells. Interestingly, IFNγ blockade, but not T cell deficiency, reversed the effects of LNT treatments on tumor blood vessels. Moreover, long-lasting LNT administration persistently suppressed tumor angiogenesis and inhibited tumor growth. Conclusions LNT inhibits tumor angiogenesis by increasing IFNγ production and in a T cell-independent manner. Our findings suggest that LNT could be developed as a new antiangiogenic agent for long-term treatment of lung and colon cancers.
      PubDate: 2018-10-29
       
  • Apigenin suppresses PD-L1 expression in melanoma and host dendritic cells
           to elicit synergistic therapeutic effects

    • Abstract: Background The PD-L1/PD-1 pathway blockade-mediated immune therapy has shown promising efficacy in the treatment of multiple cancers including melanoma. The present study investigated the effects of the flavonoid apigenin on the PD-L1 expression and the tumorigenesis of melanoma. Methods The influence of flavonoids on melanoma cell growth and apoptosis was investigated using cell proliferation and flow cytometric analyses. The differential IFN-γ-induced PD-L1 expression and STAT1 activation were examined in curcumin and apigenin-treated melanoma cells using immunoblotting or immunofluorescence assays. The effects of flavonoid treatment on melanoma sensitivity towards T cells were investigated using Jurkat cell killing, cytotoxicity, cell viability, and IL-2 secretion assays. Melanoma xenograft mouse model was used to assess the impact of flavonoids on tumorigenesis in vivo. Human peripheral blood mononuclear cells were used to examine the influence of flavonoids on PD-L1 expression in dendritic cells and cytotoxicity of cocultured cytokine-induced killer cells by cell killing assays. Results Curcumin and apigenin showed growth-suppressive and pro-apoptotic effects on melanoma cells. The IFN-γ-induced PD-L1 upregulation was significantly inhibited by flavonoids, especially apigenin, with correlated reductions in STAT1 phosphorylation. Apigenin-treated A375 cells exhibited increased sensitivity towards T cell-mediated killing. Apigenin also strongly inhibited A375 melanoma xenograft growth in vivo, with enhanced T cell infiltration into tumor tissues. PD-L1 expression in dendritic cells was reduced by apigenin, which potentiated the cytotoxicity of cocultured cytokine-induced killer cells against melanoma cells. Conclusions Apigenin restricted melanoma growth through multiple mechanisms, among which its suppression of PD-L1 expression exerted a dual effect via regulating both tumor and antigen presenting cells. Our findings provide novel insights into the anticancer effects of apigenin and might have potential clinical implications.
      PubDate: 2018-10-29
       
  • Hydroxychloroquine induced lung cancer suppression by enhancing
           chemo-sensitization and promoting the transition of M2-TAMs to M1-like
           macrophages

    • Abstract: Background Lysosome-associated agents have been implicated as possible chemo-sensitizers and immune regulators for cancer chemotherapy. We investigated the potential roles and mechanisms of hydroxychloroquine (HCQ) in combination with chemotherapy in lung cancer treatment. Methods The effects of combined treatment on non-small cell lung cancer (NSCLC) were investigated using cell viability assays and animal models. The influence of HCQ on lysosomal pH was evaluated by lysosomal sensors and confocal microscopy. The effects of HCQ on the tumour immune microenvironment were analysed by flow cytometry. Results HCQ elevates the lysosomal pH of cancer cells to inactivate P-gp while increasing drug release from the lysosome into the nucleus. Furthermore, single HCQ therapy inhibits lung cancer by inducing macrophage-modulated anti-tumour CD8+ T cell immunity. Moreover, HCQ could promote the transition of M2 tumour-associated macrophages (TAMs) into M1-like macrophages, leading to CD8+ T cell infiltration into the tumour microenvironment. Conclusions HCQ exerts anti-NSCLC cells effects by reversing the drug sequestration in lysosomes and enhancing the CD8+ T cell immune response. These findings suggest that HCQ could act as a promising chemo-sensitizer and immune regulator for lung cancer chemotherapy in the clinic.
      PubDate: 2018-10-29
       
  • The deubiquitinating enzyme UCHL1 is a favorable prognostic marker in
           neuroblastoma as it promotes neuronal differentiation

    • Abstract: Background Neuroblastoma (NB) is the most common pediatric solid tumor that originates from neural crest-derived sympathoadrenal precursor cells that are committed to development of sympathetic nervous system. The well differentiated histological phenotype of NB tumor cells has been reportedly associated with favorable patient outcome. Retinoic acid (RA) can effectively induce NB cell differentiation, thereby being used in the clinic as a treatment agent for inducing the differentiation of high-risk NB. However, the underlying molecular mechanisms of regulating differentiation remain elusive. Methods The correlation between clinical characteristics, survival and the deubiquitinating enzyme ubiquitin C-terminal hydrolase 1 (UCHL1) expression were assessed using a neuroblastic tumor tissue microarray, and then validated in three independent patient datasets. The different expression of UCHL1 in ganglioneuroblastoma, ganglioneuroma and NB was detected by immunohistochemistry, mass spectra and immunoblotting analysis, and the correlation between UCHL1 expression and the differentiated histology was analyzed, which was also validated in three independent patient datasets. Furthermore, the roles of UCHL1 in NB cell differentiation and proliferation and the underlying mechanisms were studied by using short hairpin RNA and its inhibitor LDN57444 in vitro. Results Based on our neuroblastic tumor tissue microarrays and three independent validation datasets (Oberthuer, Versteeg and Seeger), we identified that UCHL1 served as a prognostic marker for better clinical outcome in NB. We further demonstrated that high UCHL1 expression was associated with NB differentiation, indicated by higher UCHL1 expression in ganglioneuroblastomas/ganglioneuromas and well-differentiated NB than poorly differentiated NB, and the positive correlation between UCHL1 and differentiation markers. As expected, inhibiting UCHL1 by knockdown or LDN57444 could significantly inhibit RA-induced neural differentiation of NB tumor cells, characterized by decreased neurite outgrowth and neural differentiation markers. This effect of UCHL1 was associated with positively regulating RA-induced AKT and ERK1/2 signaling activation. What’s more, knockdown of UCHL1 conferred resistance to RA-induced growth arrest. Conclusion Our findings identify a pivotal role of UCHL1 in NB cell differentiation and as a prognostic marker for survival in patients with NB, potentially providing a novel therapeutic target for NB.
      PubDate: 2018-10-25
       
  • Aberrant miRNAs expressed in HER-2 negative breast cancers patient

    • Abstract: Background Breast cancer is a highly heterogeneous pathology, exhibiting a number of subtypes commonly associated with a poor outcome. Due to their high stability, microRNAs are often regarded as non-invasive cancer biomarkers, having an expression pattern specific for their ‘cell of origin’. Method Triple negative breast cancer (TNBC: ER-, PR-, Her-2-) and double positive breast cancer (DPBC: ER+, PR+, Her-2) miRNA expression patterns were obtained by analysis of the TCGA (The Cancer Genome Atlas) data, followed by PCR-array analysis on plasma samples from 20 TNBC patients, 14 DPBC patients and 11 controls. Results Three downregulated and nine upregulated miRNAs were obtained from the TNBC analysis. Five overexpressed miRNAs were identified in the DPBC group. Four of the dysregulated miRNAs (miR-10a, miR-125b, miR-210 and miR-489) were common for both groups. The cluster miR-17-92 (miR-17, miR-20a, miR-20b, and miR-93), along with miR-130, miR-22 and miR-29a/c, were found to differentiate between TNBC and DPBC. A panel of five transcripts (miR-10a, miR-125, miR-193b, miR-200b and miR-489) was validated in a new set of plasma samples. The overlapping of TCGA and plasma profiling data revealed miR-200b, miR-200c, miR-210 and miR-29c as common signature. MiR-200b was validated on additional normal and tumor tissue samples. The expression level of this transcript from the TCGA data was correlated with lung and bone metastatic genes. Conclusion The miR-200b presents a great potential for the future advancements in the diagnostic/prognostic and therapeutic approach of TNBC, along with other coding or non-coding transcripts. However, this needs to be further integrated in a regulatory network that acts in conjunction with other markers that affect the patients’ prognosis or response to therapy.
      PubDate: 2018-10-20
       
 
 
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