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Manuel Gentiluomo, Paula Puchalt García, Alice Alessandra Galeotti, Renata Talar-Wojnarowska, Christine Tjaden, Francesca Tavano, Oliver Strobel, Juozas Kupcinskas, John Neoptolemos, Péter Hegyi, Eithne Costello, Raffaele Pezzilli, Cosimo Sperti, Rita T Lawlor, Gabriele Capurso, Andrea Szentesi, Pavel Soucek, Pavel Vodicka, Martin Lovecek, Thilo Hackert, Giulia Martina Cavestro, Anna Caterina Milanetto, Federico Canzian, Campa Daniele
Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis, caused by various factors, such as the aggressiveness of the disease, the limited therapeutic options and the lack of early detection and risk markers. The ATP binding cassette subfamily C member 2 (ABCC2) protein plays a critical role in response to various drugs and is differentially expressed in gemcitabine sensitive and resistant cells. Moreover, Single Nucleotide Polymorphisms (SNPs) in the gene have been associated with differential outcomes and prognosis in several tumour types...
January 9, 2019: Carcinogenesis
Huaxin Zhou, Jacob Saliba, George E Sandusky, Catherine R Sears
Cigarette smoke (CS) contains hundreds of carcinogens and is a potent inducer of oxidative and bulky DNA damage, which when insufficiently repaired leads to activation of DNA damage response and possibly mutations. The DNA repair protein xeroderma pigmentosum group C (XPC) is primed to play an important role in CS-induced DNA damage due to its function in initiating repair of both bulky oxidative DNA damage. We hypothesized that loss of XPC function will increase susceptibility to developing CS-carcinogen induced lung cancer through impaired repair of oxidative DNA damage...
January 8, 2019: Carcinogenesis
Patricia Zamorano, Tania Koning, Claudia Oyanadel, Gonzalo A Mardones, Pamela Ehrenfeld, Mauricio P Boric, Alfonso González, Andrea Soza, Fabiola A Sánchez
The permeability of endothelial cells is regulated by the stability of the adherens junctions, which is highly sensitive to kinase-mediated phosphorylation and nitric oxide synthase (eNOS)-mediated S-nitrosylation of its protein components. Solid tumors can produce a variety of factors that stimulate these signaling pathways leading to endothelial cell hyperpermeability. This generates stromal conditions that facilitate tumoral growth and dissemination. Galectin-8 (Gal-8) is over-expressed in several carcinomas and has a variety of cellular effects that can contribute to tumor pathogenicity, including angiogenesis...
January 8, 2019: Carcinogenesis
Hanna Najgebauer, Triantafillos Liloglou, Puthen V Jithesh, Olivier T Giger, Andrea Varro, Christopher M Sanderson
There is increasing evidence that stromal myofibroblasts play a key role in tumour development, however the mechanisms by which they become reprogrammed to assist in cancer progression remain unclear. As cultured Cancer Associated Myofibroblasts (CAMs) retain an ability to enhance the proliferation and migration of cancer cells in vitro, it is possible that epigenetic reprogramming of CAMs within the tumour microenvironment may confer long-term pro-tumorigenic changes in gene expression. This study reports the first comparative multi-omics analysis of cancer-related changes in gene expression and DNA-methylation in primary myofibroblasts derived from gastric and oesophageal tumours...
January 8, 2019: Carcinogenesis
Jian-Min Yuan, Menno Grouls, Steven G Carmella, Renwei Wang, Alisa Heskin, Yang Jiang, Yu-Ting Tan, Jennifer Adams-Haduch, Yu-Tang Gao, Stephen S Hecht
Chronic inflammation and oxidative stress play pivotal roles in the pathogenesis of hepatocellular carcinoma (HCC). We conducted a nested case-control study of 347 HCC cases and 691 matched controls within a prospective cohort of 18 244 Chinese men in Shanghai, China. The concentrations of 8-epi-prostaglandin F2α (8-epi-PGF2α), a biomarker of oxidative stress, and prostaglandin E2 (PGE2) metabolite (PGE-M), a biomarker of the inflammation mediator PGE2, were determined in baseline urine samples using validated mass spectrometry assays...
January 5, 2019: Carcinogenesis
Jason Harquail, Nicolas LeBlanc, Rodney J Ouellette, Gilles A Robichaud
Recent studies have enabled the identification of important factors regulating cancer progression, such as Pax-5. This transcription factor has consistently been associated to B cell cancer lesions and more recently solid tumors including breast carcinoma. Although Pax-5 downstream activity is relatively well characterized, aberrant Pax-5 expression in a cancer specific context is poorly understood. To investigate the regulation of Pax-5 expression, we turned to micro-RNAs (miRNAs), small non-coding RNA molecules that regulate key biological processes...
January 3, 2019: Carcinogenesis
Xiaomeng Wang, Hongliang Liu, Yinghui Xu, Jichun Xie, Dakai Zhu, Christopher I Amos, Shenying Fang, Jeffrey E Lee, Xin Li, Hongmei Nan, Yanqiu Song, Qingyi Wei
Remodeling or deregulation of the calcium signaling pathway is a relevant hallmark of cancer including cutaneous melanoma (CM). In the present study, using data from a published genome-wide association study (GWAS) from The University of Texas M.D. Anderson Cancer Center, we assessed the role of 41,377 common single nucleotide polymorphisms (SNPs) of 167 calcium signaling pathway genes in CM survival. We used another GWAS from Harvard University as the validation dataset. In the single-locus analysis, 1,830 SNPs were found to be significantly associated with CM-specific survival (CMSS) (P ≤ 0...
December 29, 2018: Carcinogenesis
Preethi Ravindranathan, Divya Pasham, Ajay Goel
Multidrug resistance is a major hindrance in managing cancer. By performing a series of experiments in chemoresistant colorectal cancer cell lines, we demonstrate that oligomeric proanthocyanidins (OPCs) from grape seed extracts can sensitize both acquired (HCT116-FOr cells) and innately chemoresistant (H716 cells) cancer cells to chemotherapeutic drugs, 5-fluorouracil (5FU) and oxaliplatin, by inhibiting ABC transporter proteins. When combined with chemotherapeutic drugs, OPCs significantly inhibited growth of the chemoresistant cells (p<0...
December 29, 2018: Carcinogenesis
Inês Direito, Margarida Fardilha, Luisa A Helguero
Resistant Breast and Prostate cancer remain a major clinical problem and new therapeutic approaches and better predictors of therapeutic response are clearly needed. Due to the involvement of the Unfolded Protein Response (UPR) in cell proliferation and apoptosis evasion, an increasing number of publications support the hypothesis that impairments in this network trigger and/or exacerbate cancer. Moreover, UPR activation could contribute to the development of drug-resistance phenotypes in both breast and prostate cancers...
December 28, 2018: Carcinogenesis
Tao Cui, Stefan Enroth, Adam Ameur, Inger Gustavsson, David Lindquist, Ulf Gyllensten
Invasive cervical cancer (ICC) with very low titer of high-risk human papillomavirus (HPV) has worse clinical outcome than cases with high titer, indicating a difference in molecular etiology. Fresh-frozen ICC tumors (n=49) were classified into high and low HPV titer cases using real-time PCR-based HPV genotyping. The mutation spectra were studied using the AmpliSeq Comprehensive Cancer Panel and the expression profiles using total RNA-sequencing, and the results validated using the AmpliSeq Transcriptome assay...
December 28, 2018: Carcinogenesis
Sarrah E Widatalla, Olga Y Korolkova, Diva S Whalen, J Shawn Goodwin, Kevin P Williams, Josiah Ochieng, Amos M Sakwe
The epidermal growth factor receptor (1) is a major oncogene in triple negative breast cancer (TNBC), but the use of EGFR targeted tyrosine kinase inhibitors (TKI) and therapeutic monoclonal antibodies is associated with poor response and acquired resistance. Understanding the basis for the acquired resistance to these drugs and identifying biomarkers to monitor the ensuing resistance remains a major challenge. We previously showed that reduced expression of annexin A6 (AnxA6), a calcium dependent membrane binding tumor suppressor, not only promoted the internalization and degradation of activated EGFR but also sensitized TNBC cells to EGFR TKIs...
December 27, 2018: Carcinogenesis
Juncheng Dai, Zhihua Li, Christopher I Amos, Rayjean J Hung, Adonina Tardon, Angeline Andrew, Chu Chen, David C Christiani, Demetrios Albanes, Erik H F M van der Heijden, Eric Duell, Gadi Rennert, Mckay D James, Jian-Min Yuan, John K Field, Manjer Jonas, Kjell Grankvist, Loic Le Marchand, M Dawn Teare, Matthew B Schabath, Melinda C Aldrich, Ming-Sound Tsao, Philip Lazarus, Lam Stephen, Stig E Bojesen, Arnold Susanne, Xifeng Wu, Aage Haugen, Janout Vladimir, Mikael Johansson, Brhane Yonathan, Ana Fernandez-Somoano, Lambertus A Kiemeney, Michael Davies, Shanbeh Zienolddiny, Zhibin Hu, Hongbing Shen
DNase I hypersensitive sites (DHS) are abundant in regulatory elements, such as promoter, enhancer and transcription factor binding sites. Many studies have revealed that disease-associated variants were concentrated in DHS related regions. However, limited studies are available on the roles of DHS-related variants in lung cancer. In the current study, we performed a large-scale case-control study with 20,871 lung cancer cases and 15,971 controls to evaluate the associations between regulatory genetic variants in DHS and lung cancer susceptibility...
December 24, 2018: Carcinogenesis
Fabia de Oliveira Andrade, Kelly Silva Furtado, Renato Heidor, Silvana Sandri, Cristina Bichels Hebeda, Mayara Lilian Paulino Miranda, Laura Helena Gasparini Fernandes, Roberto Carvalho Yamamoto, Maria Aderuza Horst, Sandra Helena Poliselli Farsky, Fernando Salvador Moreno
Agents that inhibit angiogenic factors may prevent the development of hepatocellular carcinoma. Thus, the objective of this study was to kinetically evaluate the anti-angiogenic activity of tributyrin (TB), a butyric acid prodrug, in the promotion stage of hepatocarcinogenesis. For this purpose, the resistant hepatocyte model was used for induction of preneoplastic lesions in Wistar rats. During the promotion phase, the animals received TB or maltodextrin (MD) as control daily. The rats were euthanized at three different time-points (P1, P2, P3)...
December 24, 2018: Carcinogenesis
Teresa T Liu, Jonathan A Ewald, Emily A Ricke, Robert Bell, Colin Collins, William A Ricke
Detailed mechanisms involved in prostate cancer (CaP) development and progression are not well understood. Current experimental models used to study CaP are not well suited to address this issue. Previously, we have described the hormonal progression of non-tumorigenic human prostate epithelial cells (BPH1) into malignant cells via tissue recombination. Here, we describe a method to derive human cell lines from distinct stages of CaP that parallel cellular, genetic, and epigenetic changes found in patient cancers...
December 22, 2018: Carcinogenesis
Aki Sakatani, Fuminori Sonohara, Ajay Goel
Background: 5-fluorouracil (5-FU) has been established as the first-line chemotherapy for advanced colorectal cancer (CRC); however, acquired chemoresistance is often the cause of poor therapeutic response. Melatonin is a molecule which is associated with circadian rhythms. Although antitumor effects of melatonin have been shown, the underlying mechanism(s) for its activity and its effect, if any, in chemoresistant CRC has not been studied. We aimed to investigate antitumor effects of melatonin, and more specifically its effect on molecular mechanisms in 5-FU resistant CRC cells...
December 22, 2018: Carcinogenesis
Wen-Chun Lin, Li-Han Chen, Yao-Chin Hsieh, Pei-Wen Yang, Liang-Chuan Lai, Eric Y Chuang, Jang-Ming Lee, Mong-Hsun Tsai
Esophageal cancer is one of the leading causes of cancer death in the male population of Eastern Asia. In addition, esophageal squamous cell carcinoma (ESCC) is the major type of esophageal cancer among the world. Due to the poor overall 5-year survival rate, novel effective treatment strategies are needed. miRNAs are important gene regulators which are dysregulated in many cancer types. In our previous study, we applied next generation sequencing to demonstrate that miR-338-5p was down-regulated in the tumor tissue of patients with versus without recurrence...
December 20, 2018: Carcinogenesis
Sharleen V Menezes, Leyla Fouani, Michael L H Huang, Bekesho Geleta, Sanaz Maleki, Alexander Richardson, Des R Richardson, Zaklina Kovacevic
The metastasis suppressor, N-myc down-stream regulated gene-1 (NDRG1), plays multifaceted roles in inhibiting oncogenic signaling and can suppress the epithelial mesenchymal transition (EMT), a key step in metastasis. In this investigation, NDRG1 inhibited the oncogenic effects of transforming growth factor-β (TGF-β) in PANC-1 pancreatic cancer cells, promoting expression and co-localization of E-cadherin and β-catenin at the cell membrane. A similar effect of NDRG1 at supporting E-cadherin and β-catenin co-localization at the cell membrane was also demonstrated for HT-29 colon and CFPAC-1 pancreatic cancer cells...
December 18, 2018: Carcinogenesis
Enrico Oddone, Benedetto Terracini, Dario Mirabelli, Carolina Mensi, Dario Consonni, Francesco Barone-Adesi
No abstract text is available yet for this article.
December 18, 2018: Carcinogenesis
Laura Carminati, Denise Pinessi, Patrizia Borsotti, Lucia Minoli, Raffaella Giavazzi, Maurizio D'Incalci, Dorina Belotti, Giulia Taraboletti
Trabectedin is a marine-derived anti-neoplastic drug. Besides targeting the cancer cells, trabectedin has a peculiar activity on the tumor microenvironment with marked effects on the vasculature and the immune response. Since a favorable microenvironment is a key factor in the progression of cutaneous melanoma, we hypothesized that trabectedin might affect the growth and metastasis of this highly aggressive cancer.This study shows that trabectedin inhibited the subcutaneous growth of the murine melanoma B16-BL6 and K1735-M2...
December 13, 2018: Carcinogenesis
Praveen Pandey, Deepika Singh, Mohammad Hasanain, Raghib Ashraf, Mayank Maheshwari, Kuldeep Choyal, Akhilesh Singh, Dipak Datta, Brijesh Kumar, Jayanta Sarkar
Sphaeranthus indicus Linn. is commonly used in Indian traditional medicine for management of multiple pathological conditions. However, there are limited studies on anti-cancer activity of this plant and its underlying molecular mechanisms. Here, we isolated an active constituent, 7-hydroxyfrullanolide (7-HF), from the flowers of this plant which showed promising chemotherapeutic potential. The compound was more effective in inhibiting in vitro proliferation of colon cancers cells through G2/M phase arrest than other cancer cell lines that were used in the present study...
December 8, 2018: Carcinogenesis
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