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Wei Wang, Jiang-Jiang Qin, Xin Li, Guanyu Tao, Qiang Wang, Xuming Wu, Jianwei Zhou, Xiaolin Zi, Ruiwen Zhang
Prostate cancer remains a major health problem in the US and worldwide. There is an urgent need to develop novel approaches to preventing primary and metastatic prostate cancer. We have identified 25-OCH3-protopanaxadiol (GS25), the most active ginsenoside that has been identified so far; it has potent activity against human cancers, including prostate cancer. However, it has not been proven if GS25 could be a safe and effective agent for cancer prevention. In the present study, we used the TRAMP model and clearly demonstrated that GS25 inhibited prostate tumorigenesis and metastasis with minimal host toxicity...
May 12, 2018: Carcinogenesis
Feng Wang, Zhi-Yu Song, Xian-Jun Qu, Feng Li, Liang Zhang, Wen-Bao Li, Shu-Xiang Cui
Chronic gut inflammation disposes to an increased risk of colitis-associated cancer (CAC). Chemoprevention is an attractive complementary strategy. We aimed to evaluate the chemopreventive effects of M10, a novel derivative of Myricetin, in the murine azoxymethane (AOM)/dextran sodium sulfate (DSS) model. Oral administration of M10 at 50-100 mg/kg once a day for consecutive 12 weeks significantly prevented ulcerative colitis and colorectal tumor. Pathological analysis of intestines showed that M10 reduced the degree of chronic inflammation and prevented the progression of colorectal tumorigenesis...
May 11, 2018: Carcinogenesis
Peng Deng, Jiongke Wang, Xuefeng Zhang, Xingyu Wu, Ning Ji, Jing Li, Min Zhou, Lu Jiang, Xin Zeng, Qianming Chen
Super elongation complex (SEC) controls gene transcription by releasing Pol II from pausing. Previous studies have shown that dysfunction of SEC was associated with multiple human cancers, such as leukemia and breast cancer. However, the role of SEC in head and neck squamous cell carcinoma (HNSCC) development remains largely unknown. In this study, we found expression of AF4/FMR2 family member 4 (AFF4), the core component of SEC, was upregulated dramatically in HNSCC cell lines and tumor tissues. By using siRNA-mediated depletion and overexpression of AFF4, we demonstrated AFF4 promoted proliferation, migration and invasion of HNSCC cells...
May 8, 2018: Carcinogenesis
Jian-Min Yuan, Steven G Carmella, Renwei Wang, Yu-Ting Tan, Jennifer Adams-Haduch, Yu-Tang Gao, Stephen S Hecht
It has been hypothesized that the pathogenesis of lung cancer induced by cigarette smoking involves oxidative damage by free radicals. Epidemiological data on biomarkers of oxidative damage and risk of lung cancer development are sparse. A nested case-control study of 610 lung cancer cases and 610 matched controls was conducted within a prospective cohort of 18,244 Chinese men in Shanghai, China. The concentrations of 8-epi-prostaglandin F2α (8-epiPGF2α), a biomarker of oxidative stress, were determined in baseline urine samples using a validated mass-spectrometry assay...
May 3, 2018: Carcinogenesis
Jennifer A Freedman, Yanru Wang, Xuechan Li, Hongliang Liu, Patricia G Moorman, Daniel J George, Norman H Lee, Terry Hyslop, Qingyi Wei, Steven R Patierno
Prostate cancer is a clinically and molecularly heterogeneous disease, with variation in outcomes only partially predicted by grade and stage. Additional tools to distinguish indolent from aggressive disease are needed. Phenotypic characteristics of stemness correlate with poor cancer prognosis. Given this correlation, we identified single nucleotide polymorphisms (SNPs) of stemness-related genes and examined their associations with prostate cancer survival. SNPs within stemness-related genes were analyzed for association with overall survival of prostate cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial...
May 3, 2018: Carcinogenesis
Xin Dai, Nan Zhang, Ying Cheng, Ti Yang, Yingnan Chen, Zhenzhong Liu, Zhishan Wang, Chengfeng Yang, Yiguo Jiang
Circular RNAs (circRNAs) are widespread and diverse endogenous RNAs distinct from traditional linear RNAs, which may regulate gene expression in eukaryotes. However, the function of human circRNAs, including their potential role in lung cancer, remains largely unknown. We screened the circRNA circ0006916, which was evidently down-regulated in 16HBE-T cells (anti-benzopyrene-trans-7, 8-dihydrodiol-9, 10-epoxide-transformed human bronchial epithelial cells), and in A549 and H460 cell lines. Silencing of circ0006916, but not its parental gene homer scaffolding protein 1 (HOMER1), promoted cell proliferation via speeding up the cell cycle process rather than by inhibiting apoptosis; conversely, overexpression of circ0006916 had the opposite effect...
May 3, 2018: Carcinogenesis
Lindsay Reed, Volker M Arlt, David H Phillips
Many chemical carcinogens require metabolic activation via xenobiotic-metabolising enzymes in order to exert their genotoxic effects. Evidence from numerous in-vitro studies, utilising reconstituted systems, microsomal fractions and cultured cells, implicate cytochrome P450 enzymes as being the predominant enzymes responsible for the metabolic activation of many procarcinogens. With the development of targeted gene disruption methodologies, knockout mouse models have been generated that allow investigation of the in-vivo roles of P450 enzymes in the metabolic activation of carcinogens...
May 3, 2018: Carcinogenesis
Ayman Alhamdow, Christian Lindh, Jessika Hagberg, Pål Graff, Håkan Westberg, Annette M Krais, Maria Albin, Per Gustavsson, Håkan Tinnerberg, Karin Broberg
Some polycyclic aromatic hydrocarbons (PAH) are known carcinogens and workplace PAH exposure may increase the risk of cancer. Monitoring early cancer-related changes can indicate whether the exposure is carcinogenic. Here, we enrolled 151 chimney sweeps, 152 controls, and 19 creosote-exposed male workers from Sweden. We measured urinary PAH metabolites using LC/MS/MS, the cancer-related markers telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) using qPCR, and DNA methylation of lung cancer-related genes F2RL3 and AHRR using pyrosequencing...
May 2, 2018: Carcinogenesis
Xuelian Chen, Qin Wen, Andres Stucky, Yunjing Zeng, Shengjia Gao, William G Loudon, Hector W Ho, Mustafa H Kabeer, Shengwen Calvin Li, Xi Zhang, Jiang F Zhong
Glioblastoma multiforme (GBM) remains an incurable brain tumor. The highly malignant behavior of GBM may, in part, be attributed to its intraclonal genetic and phenotypic diversity (subclonal evolution). Identifying the molecular pathways driving GBM relapse may provide novel, actionable targets for personalized diagnosis, characterization of prognosis and improvement of precision therapy. We screened single-cell transcriptomes, namely RNA-seq data of primary and relapsed GBM tumors from a patient, to define the molecular profile of relapse...
April 28, 2018: Carcinogenesis
Marjaana Pussila, Petri Törönen, Elisabet Einarsdottir, Shintaro Katayama, Kaarel Krjutškov, Liisa Holm, Juha Kere, Päivi Peltomäki, Markus J Mäkinen, Jere Linden, Minna Nyström
Colorectal cancer (CRC) genome is unstable and different types of instabilities, such as chromosomal instability (CIN) and microsatellite instability (MSI) are thought to reflect distinct cancer initiating mechanisms. Although 85% of sporadic CRC reveal CIN, 15% reveal mismatch repair (MMR) malfunction and MSI, the hallmarks of Lynch syndrome with inherited heterozygous germline mutations in MMR genes. Our study was designed to comprehensively follow genome-wide expression changes and their implications during colon tumorigenesis...
April 26, 2018: Carcinogenesis
Preethi Ravindranathan, Divya Pasham, Uthra Balaji, Jacob Cardenas, Jinghua Gu, Shusuke Toden, Ajay Goel
Although the anticancer properties of oligomeric proanthocyanidins (OPCs) from grape seeds have been well recognized, the molecular mechanisms by which they exert anticancer effects are poorly understood. In this study, through comprehensive RNA-sequencing-based gene expression profiling in multiple colorectal cancer cell lines, we for the first time illuminate the genome-wide effects of OPCs from grape seeds in colorectal cancer. Our data revealed that OPCs affect several key cancer-associated genes. In particular, genes involved in cell cycle and DNA replication were most significantly and consistently altered by OPCs across multiple cell lines...
April 19, 2018: Carcinogenesis
Jenn-Ren Hsiao, Chan-Chi Chang, Wei-Ting Lee, Cheng-Chih Huang, Chun-Yen Ou, Sen-Tien Tsai, Ken-Chung Chen, Jehn-Shyun Huang, Tung-Yiu Wong, Yu-Hsuan Lai, Yuan-Hua Wu, Wei-Ting Hsueh, Shang-Yin Wu, Chia-Jui Yen, Jang-Yang Chang, Chen-Lin Lin, Ya-Ling Weng, Han-Chien Yang, Yu-Shan Chen, Jeffrey S Chang
Poor oral hygiene may lead to overgrowth of pathogenic oral bacteria, which may induce chronic inflammation to promote the oncogenesis of oral squamous cell carcinoma (OSCC). This study investigated the association between oral bacterial profile and OSCC risk in a case-control study of 138 OSCC cases and 151 controls (88 cases and 90 controls for the discovery group and 50 cases and 61 controls for the validation group). Oral bacterial profiles were characterized by targeted sequencing of the 16S rRNA gene...
April 13, 2018: Carcinogenesis
Jiyae Jung, Youngmi Kim, Jinhoi Song, Yae Jin Yoon, Da-Eun Kim, Joo Ae Kim, Yena Jin, Yu-Jin Lee, Seokho Kim, Byoung-Mog Kwon, Dong Cho Han
We hypothesized that Octamer-binding transcription factor 4 (OCT4) inhibition would have therapeutic benefits in Testicular germ cell tumors (TGCT). To identify inhibitors of OCT4, a chemical library was screened using a luciferase reporter system under the control of an OCT4 response element. A compound named KRIBB53 was identified based on its blocking of OCT4-dependent luciferase activation. When NCCIT cells were exposed to KRIBB53, the expression levels of OCT4 target genes, such as NANOG and USP44, were inhibited with an IC50 of 13 and 15 μM, respectively...
April 13, 2018: Carcinogenesis
Krishna B Singh, Su-Hyeong Kim, Eun-Ryeong Hahm, Subrata K Pore, Bruce L Jacobs, Shivendra V Singh
Increased de novo synthesis of fatty acids is a rather unique and targetable mechanism of human prostate cancer. We have shown previously that oral administration of sulforaphane (SFN) significantly inhibits the incidence and/or burden of prostatic intraepithelial neoplasia and well-differentiated adenocarcinoma in TRansgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice. The present study used cellular models of prostate cancer and archived plasma/adenocarcinoma tissues and sections from the TRAMP study to demonstrate inhibition of fatty acid synthesis by SFN treatment in vitro and in vivo...
April 13, 2018: Carcinogenesis
Zhen Lian, Jinsong Han, Lin Huang, Chengming Wei, Yongyong Fan, Jiake Xu, Mengyu Zhou, Haotian Feng, Qian Liu, Lingzi Chen, Zhaoning Li, Haichun Cheng, Guixin Yuan, Xixi Lin, Fangming Song, Yiji Su, Chao Wang, Guopeng Huang, An Qin, Yunlong Song, Guanfeng Yao
Osteosarcoma is the most frequent primary bone tumor in children and adolescents. The phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway is an attractive anticancer target because it plays key roles in the regulation of cell growth, division and differentiation. In this study, we demonstrated high expression of PI3K/mTOR signaling pathway-related genes in patients with osteosarcoma. We thus investigated the effects of A005, a newly synthesized dual PI3K/mTOR inhibitor, on osteosarcoma cells and in a mouse xenograft tumor model...
April 4, 2018: Carcinogenesis
Xiang Shu, Jianchun Gu, Maosheng Huang, Nizar M Tannir, Surena F Matin, Jose A Karam, Christopher G Wood, Xifeng Wu, Yuanqing Ye
Genome-wide association studies (GWAS) have identified 13 susceptibility loci for renal cell carcinoma (RCC). Additional genetic loci of risk remain to be explored. Moreover, the role of germline genetic variants in predicting RCC recurrence and overall survival (OS) is less understood. In this study, we focused on 127 significantly mutated genes from The Cancer Genome Atlas (TCGA) Pan-Cancer Analysis across 12 major cancer sites to identify potential genetic variants predictive of RCC risk and clinical outcomes...
April 4, 2018: Carcinogenesis
Jay H Fowke, Saundra S Motley
The roles of obesity, metabolic dysregulation, and systemic inflammation to advance prostate carcinogenesis are unclear. This study investigates metabolic and inflammatory factors in the transition from high-grade prostatic intraepithelial neoplasia (HGPIN) to prostate cancer (PC). We prospectively followed 160 men diagnosed with HGPIN at biopsy, and therefore at high-risk and clinically monitored for PC. Analyses investigated body mass index (BMI), waist circumference, waist-hip ratio, height, fat mass, lean mass % body fat, NSAIDs, statins, metformin, diabetes, hypertension, hypercholesterolemia representing metabolic dysregulation on the risk of a PC diagnosis during follow-up...
April 3, 2018: Carcinogenesis
Akiko Furusawa, Morikazu Miyamoto, Masashi Takano, Hitoshi Tsuda, Yong Sang Song, Daisuke Aoki, Naoyuki Miyasaka, Johji Inazawa, Jun Inoue
Amino acids (AAs) are biologically important nutrient compounds necessary for the survival of any cell. Of the 20 AAs, cancer cells depend on the uptake of several extracellular AAs for survival. However, which extracellular AA is indispensable for the survival of cancer cells and the molecular mechanism involved have not been fully defined. In this study, we found that the reduction of cell survival caused by glutamine (Gln) depletion is inversely correlated with the expression level of glutamine synthetase (GS) in ovarian cancer (OVC) cells...
April 2, 2018: Carcinogenesis
Ana de la Cueva, Michael Emmerling, Sarah L Lim, Shi Yang, Philip C Trackman, Gail E Sonenshein, Kathrin H Kirsch
The propeptide (LOX-PP) domain of the lysyl oxidase proenzyme (Pro-LOX) was shown to inhibit the transformed phenotype of breast, lung and pancreatic cells in culture and the formation of Her2/neu-driven breast cancer in a xenograft model. A single nucleotide polymorphism (SNP, rs1800449) positioned in a highly conserved region of LOX-PP results in an Arg158Gln substitution (humans). This ArgGln substitution profoundly impaired the ability of LOX-PP to inhibit the invasive phenotype and xenograft tumor formation...
March 22, 2018: Carcinogenesis
Dongyu Zhang, Alpana Kaushiva, Yuzhi Xi, Tengteng Wang, Nan Li
Ovarian cancer (OC) accounts for 4% of female malignancies worldwide and its prognosis is unfavorable. Currently available epidemiologic data suggest that non-herbal tea consumption may reduce OC risk but these evidences are inconsistent. A comprehensive literature search for observational epidemiologic studies reporting associations between non-herbal tea consumption and OC risk was conducted in electronic databases. A random-effects model was used to synthesize effect measures in binary meta-analysis, and adjusted indirect comparison was used to compare if there was a difference in effects between green tea (GT) and black tea (BT)...
March 20, 2018: Carcinogenesis
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