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multistage carcinogenesis

Junko Kuramoto, Eri Arai, Ying Tian, Nobuaki Funahashi, Masaki Hiramoto, Takao Nammo, Yuichi Nozaki, Yoriko Takahashi, Nanako Ito, Ayako Shibuya, Hidenori Ojima, Aoi Sukeda, Yosuke Seki, Kazunori Kasama, Kazuki Yasuda, Yae Kanai
The aim of this study was to clarify the significance of DNA methylation alterations during non-alcoholic steatohepatitis (NASH)-related hepatocarcinogenesis. Single-CpG-resolution genome-wide DNA methylation analysis was performed on 264 liver tissue samples using the Illumina Infinium HumanMethylation450 BeadChip. After Bonferroni correction, 3331 probes showed significant DNA methylation alterations in 113 samples of non-cancerous liver tissue showing NASH (NASH-N) as compared with 55 samples of normal liver tissue (NLT)...
March 1, 2017: Carcinogenesis
Andrew F Brouwer, Rafael Meza, Marisa C Eisenberg
Many cancers are understood to be the product of multiple somatic mutations or other rate-limiting events. Multistage clonal expansion (MSCE) models are a class of continuous-time Markov chain models that capture the multi-hit initiation-promotion-malignant-conversion hypothesis of carcinogenesis. These models have been used broadly to investigate the epidemiology of many cancers, assess the impact of carcinogen exposures on cancer risk, and evaluate the potential impact of cancer prevention and control strategies on cancer rates...
March 2017: PLoS Computational Biology
Vazhappilly Cijo George, Graham Dellaire, H P Vasantha Rupasinghe
Carcinogenesis is a multistage process that involves a series of events comprising of genetic and epigenetic changes leading to the initiation, promotion and progression of cancer. Chemoprevention is referred to as the use of nontoxic natural compounds, synthetic chemicals or their combinations to intervene in multistage carcinogenesis. Chemoprevention through diet modification, i.e., increased consumption of plant-based food, has emerged as a most promising and potentially cost-effective approach to reducing the risk of cancer...
November 28, 2016: Journal of Nutritional Biochemistry
Sharada H Sharma, Senthilkumar Thulasingam, Sangeetha Nagarajan
Multistep model of colon carcinogenesis has provided the framework to advance our understanding of the molecular basis of colon cancer. This multistage process of carcinogenesis takes a long period to transform from a normal epithelial cell to invasive carcinoma. Thus, it provides enough time to intervene the process of carcinogenesis especially through dietary modification. In spite of the in-depth understanding of the colon cancer etiology and pathophysiology and its association with diet, colon cancer remains a major cause of cancer mortality worldwide...
January 15, 2017: European Journal of Pharmacology
Josh Hiller, Celeste Vallejo, Leo Betthauser, James Keesling
We investigate and classify several patterns in cancer incidence and relative risk data which persist across different countries and multiple published studies. We then explore biological hypotheses as well as many mathematical models in the literature that attempt to explain these patterns. A general modeling framework is presented which is general enough to model most of observed behaviors. It is our belief that this model has sufficient flexibility to be adapted to new information as it is discovered. As one application of this framework, we give a model for the effect of aging on the process of carcinogenesis...
March 2017: Progress in Biophysics and Molecular Biology
Maarten J Wensink
There is significant recent interest in Peto's paradox and the related problem of the evolution of large, long-lived organisms in terms of cancer robustness. Peto's paradox refers to the expectation that large, long-lived organisms have a higher lifetime cancer risk, which is not the case: a paradox. This paradox, however, is circular: large, long-lived organisms are large and long-lived because they are cancer robust. Lifetime risk, meanwhile, depends on the age distributions of both cancer and competing risks: if cancer strikes before competing risks, then lifetime risk is high; if not, not...
September 14, 2016: Proceedings. Biological Sciences
Andrew F Brouwer, Rafael Meza, Marisa C Eisenberg
Multistage clonal expansion (MSCE) models of carcinogenesis are continuous-time Markov process models often used to relate cancer incidence to biological mechanism. Identifiability analysis determines what model parameter combinations can, theoretically, be estimated from given data. We use a systematic approach, based on differential algebra methods traditionally used for deterministic ordinary differential equation (ODE) models, to determine identifiable combinations for a generalized subclass of MSCE models with any number of preinitation stages and one clonal expansion...
September 9, 2016: Risk Analysis: An Official Publication of the Society for Risk Analysis
Hyung Sik Kim, Sam Kacew, Byung Mu Lee
The main goal of cancer chemoprevention is to prevent or halt the progression of carcinogenesis with the administration of synthetic or natural compounds. Fundamental chemopreventive strategies include inhibition of genetic damage, anti-proliferation/cell cycle regulation, and induction of apoptosis and anti-inflammatory processes, which may be critical for carcinogenesis intervention. Recently, a new paradigm for identifying chemopreventive agents has been implemented. It focuses on defining new biomarkers that can be used to evaluate chemopreventive efficacy based on multistage carcinogenesis...
October 2016: Archives of Toxicology
Andrea Janz Moreira, Graziella Ramos Rodrigues, Silvia Bona, Leila Xavier Sinigaglia Fratta, Giovana Regina Weber, Jaqueline Nascimento Picada, Jorge Luiz Dos Santos, Carlos Thadeu Cerski, Claudio Augusto Marroni, Norma Possa Marroni
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is characterized by multistage formation. The presence of ductular reaction, cytokeratin 7 positivity (PCK7), and increased levels of gamma glutamyltransferase (γGT) has been observed during liver carcinogenesis and contribute to tumor progression. Our goal was to evaluate the ductular reaction in multistage carcinogenesis and to correlate PCK7 and γGT levels with tumor incidence, histological characteristics, liver DNA damage index, and the expression of oxidative stress proteins...
March 2017: Protoplasma
Payal Katakwar, Rashmi Metgud, Smitha Naik, Rashu Mittal
Oxygen derived species such as hydrogen peroxide, superoxide anion radical, hydroxyl radical (OH-), and singlet oxygen are well known to be cytotoxic and have been implicated in the etiology of a wide array of human diseases, including cancer. Various carcinogens may also partly exert their effect by generating reactive oxygen species (ROS) during their metabolism. Oxidative damage to cellular DNA can lead to mutations and may, therefore, play an important role in the initiation and progression of multistage carcinogenesis...
April 2016: Journal of Cancer Research and Therapeutics
Stefanie Marczok, Birgit Bortz, Chong Wang, Heike Pospisil
Carcinogenesis is a complex multifactorial, multistage process, but the precise mechanisms are not well understood. In this study, we performed a genome-wide analysis of the copy number variation (CNV), breakpoint region (BPR) and fragile sites in 2,737 tumor samples from eight tumor entities and in 432 normal samples. CNV detection and BPR identification revealed that BPRs tended to accumulate in specific genomic regions in tumor samples whereas being dispersed genome-wide in the normal samples. Hotspots were observed, at which segments with similar alteration in copy number were overlapped along with BPRs adjacently clustered...
2016: PloS One
Siddavaram Nagini, Jaganathan Kowshik
The hamster buccal pouch (HBP) carcinogenesis model is one of the most well-characterized animal tumor models used as a prelude to investigate multistage oral carcinogenesis and to assess the efficacy of chemointervention. Hamster buccal pouch carcinomas induced by 7,12-dimethylbenz[a]anthracene (DMBA) show extensive similarities to human oral squamous cell carcinomas. The HBP model offers a number of advantages including a simple and predictable tumor induction procedure, easy accessibility for examination and follow-up of lesions, and reproducibility...
2016: Methods in Molecular Biology
Fang Peng, Ying Huang, Mao-Yu Li, Guo-Qing Li, Hui-Chao Huang, Rui Guan, Zhu-Chu Chen, Song-Ping Liang, Yong-Heng Chen
AIM: To discover novel biomarkers for early diagnosis, prognosis or treatment of human colorectal cancer. METHODS: iTRAQ 2D LC-MS/MS analysis was used to identify differentially expressed proteins (DEPs) in the human colonic epithelial carcinogenic process using laser capture microdissection-purified colonic epithelial cells from normal colon, adenoma, carcinoma in situ and invasive carcinoma tissues. RESULTS: A total of 326 DEPs were identified, and four DEPs (DMBT1, S100A9, Galectin-10, and S100A8) with progressive alteration in the carcinogenic process were further validated by immunohistochemistry...
May 14, 2016: World Journal of Gastroenterology: WJG
Melissa A Merritt, Howard D Strickler, Mark H Einstein, Hannah P Yang, Mark E Sherman, Nicolas Wentzensen, Jurriaan Brouwer-Visser, Maria Jose Cossio, Kathleen D Whitney, Herbert Yu, Marc J Gunter, Gloria S Huang
PURPOSE: Experimental and observational data link insulin, insulin-like growth factor (IGF), and estrogens to endometrial tumorigenesis. However, there are limited data regarding insulin/IGF and sex hormone axes protein and gene expression in normal endometrial tissues, and very few studies have examined the impact of endometrial cancer risk factors on endometrial tissue biology. METHODS: We evaluated endometrial tissues from 77 premenopausal and 30 postmenopausal women who underwent hysterectomy for benign indications and had provided epidemiological data...
2016: Cancer Causes & Control: CCC
Stella Logotheti, Nikolas Khoury, Spiros A Vlahopoulos, Elena Skourti, Dimitra Papaevangeliou, Triantafyllos Liloglou, Vassilis Gorgoulis, Irina Budunova, Anthony M Kyriakopoulos, Vassilis Zoumpourlis
Glucocorticoids (GCs) are frequently used in anticancer combination regimens; however, their continuous use adds selective pressure on cancer cells to develop GC-resistance via impairment of the glucocorticoid receptor (GR), therefore creating a need for GC-alternatives. Based on the drug repurposing approach and the commonalities between inflammation and neoplasia, drugs that are either in late-stage clinical trials and/or already marketed for GC-refractory inflammatory diseases could be evaluated as GC-substitutes in the context of cancer...
July 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
Mark P Little, Jolyon H Hendry, Jerome S Puskin
BACKGROUND: A recent paper by Tomasetti and Vogelstein (Science 2015 347 78-81) suggested that the variation in natural cancer risk was largely explained by the total number of stem-cell divisions, and that most cancers arose by chance. They proposed an extra-risk score as way of distinguishing the effects of the stochastic, replicative component of cancer risk from other causative factors, specifically those due to the external environment and inherited mutations. OBJECTIVES: We tested the hypothesis raised by Tomasetti and Vogelstein by assessing the degree of correlation of stem cell divisions and their extra-risk score with radiation- and tobacco-associated cancer risk...
2016: PloS One
Andrew F Brouwer, Marisa C Eisenberg, Rafael Meza
Differences in prognosis in HPV-positive and HPV-negative oral (oropharyngeal and oral cavity) squamous cell carcinomas (OSCCs) and increasing incidence of HPV-related cancers have spurred interest in demographic and temporal trends in OSCC incidence. We leverage multistage clonal expansion (MSCE) models coupled with age-period-cohort (APC) epidemiological models to analyze OSCC data in the SEER cancer registry (1973-2012). MSCE models are based on the initiation-promotion-malignant conversion paradigm in carcinogenesis and allow for interpretation of trends in terms of biological mechanisms...
2016: PloS One
Marvin J Núñez, Ignacio A Jiménez, Cristina R Mendoza, Marvin Chavez-Sifontes, Morena L Martinez, Eiichiro Ichiishi, Ryo Tokuda, Harukuni Tokuda, Isabel L Bazzocchi
Inhibition of tumour promotion in multistage chemical carcinogenesis is considered a promising strategy for cancer chemoprevention. In an ongoing investigation of bioactive secondary metabolites from Celastraceae species, five new dihydro-β-agarofuran sesquiterpenes (1-5), named Chiapens A-E, and seventeen known ones, were isolated from Maytenus chiapensis. Their structures were elucidated by extensive NMR spectroscopic and mass spectrometric techniques, and their absolute configurations were determined by circular dichroism studies, chemical correlations and biogenic means...
March 23, 2016: European Journal of Medicinal Chemistry
Manuela Cesaretti, Alban Zarzavadjian LE Bian
Gastric cancer is one of the most common cancers with an important related-mortality worldwide. It is preceded by a multistage pathological state arising from environmental and dietary factors. These factors influence intracellular molecular changes associated with the gastric carcinogenesis. Gastroenterology imaging, such as endoscopy, is essential for an early diagnosis as patients are typically asymptomatic at the onset of gastric cancer. Recent technological advances have allowed the development of novel imaging devices such as narrow-band imaging or high-definition endoscopy...
August 2016: Minerva Chirurgica
Tong Wu, Yun Hong, Lihua Jia, Jie Wu, Juan Xia, Juan Wang, Qinchao Hu, Bin Cheng
Head and neck squamous cell carcinoma (HNSCC) development is a multistage process includes the normal, dysplasia and squamous cell carcinoma (SCC) stages. Recently, increasing evidence has suggested that the tumor microenvironment (TME) is an integral part of malignant transformation. Exploring certain key node genes in TME for future intervention in dysplasia to interrupt oral carcinogenesis was the primary goal of this research. To achieve this goal, systems biology approaches were first applied to the epithelia and fibroblasts collected at sequential stages in a 4-nitroquinoline-1-oxide (4NQO) -induced rat oral carcinogenesis model...
February 1, 2016: Scientific Reports
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