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multistage carcinogenesis

Sunil Kumar Dhatwalia, Manoj Kumar, Devinder K Dhawan
Lung cancer is a prominent form among various types of cancers, irrespective of the sex worldwide. Treatment of lung cancer involves the intensive phase of chemotherapy/radiotherapy which is associated with high rate of adverse events. There is a need of safe and reliable treatment/adjunctive therapy to apprehend the cancer by reducing the undesirable outcome of primary therapy. Epigallocatechin-3-gallate (EGCG), which is a potent antioxidant and anticancer compound extracted from the plant camellia sinensis has proved to be a novel agent to control or reduce lung tumorigenesis by affecting the signaling molecules of cell cycle regulation and apoptotic pathways...
March 23, 2018: Nutrition and Cancer
Josh Hiller, James Keesling
We examine basic asymptotic properties of relative risk for two families of generalized Erlang processes (where each one is based off of a simplified Armitage and Doll multistage model) in order to predict relative risk data from cancer. The main theorems that we are able to prove are all corroborated by large clinical studies involving relative risk for former smokers and transplant recipients. We then show that at least some of these theorems do not extend to other Armitage and Doll multistage models. We conclude with suggestions for lifelong increased cancer screening for both former smoker and transplant recipient subpopulations of individuals and possible future directions of research...
January 30, 2018: Bulletin of Mathematical Biology
V Pavithra, Karuna Kumari, Vanishri C Haragannavar, Roopa S Rao, Shwetha Nambiar, Dominic Augustine, S V Sowmya
Introduction: Oral carcinoma is a global health problem. India accounts for one-third of world burden with high prevalence rate of 2.5 million and mortality rate of 5.5 lacs per year. Oral carcinogenesis is a multistage process that frequently involves invasion and metastasis that needs early detection and treatment to improve the overall quality of life. The ability of Oral Squamous Cell Carcinoma (OSCC) to metastasize to lymph nodes does not always show a relationship with clinical staging...
September 2017: Journal of Clinical and Diagnostic Research: JCDR
Suresh H Moolgavkar
No abstract text is available yet for this article.
October 1, 2017: International Journal of Epidemiology
Cristina Aguirre-Portolés, Lara P Fernández, Ana Ramírez de Molina
Cancer is a multistage and multifactorial condition with genetic and environmental factors modulating tumorogenesis and disease progression. Nevertheless, cancer is preventable, as one third of cancer deaths could be avoided by modifying key risk factors. Nutrients can directly affect fundamental cellular processes and are considered among the most important risk factors in colorectal cancer (CRC). Red and processed meat, poultry consumption, fiber, and folate are the best-known diet components that interact with colorectal cancer susceptibility...
September 28, 2017: Nutrients
Takafumi Nakayama, Tomoko Sawai, Ikuko Masuda, Shinya Kaneko, Kazumi Yamauchi, Benjamin J Blyth, Yoshiya Shimada, Akira Tachibana, Shizuko Kakinuma
DNA mutations play a crucial role in the origins of cancer, and the clonal expansion of mutant cells is one of the fundamental steps in multistage carcinogenesis. In this study, we correlated tumor incidence in B6C3F1 mice during the period after exposure to N-ethyl-N-nitrosourea (ENU) with the persistence of ENU-induced mutant clones in transgenic gpt delta B6C3F1 mice. The induced gpt mutations afforded no selective advantage in the mouse cells and could be distinguished by a mutational spectrum that is characteristic of ENU treatment...
October 2017: Environmental and Molecular Mutagenesis
Manchao Kuang, Jieyao Cheng, Chengli Zhang, Lin Feng, Xue Xu, Yajing Zhang, Ming Zu, Jianfang Cui, Hang Yu, Kaitai Zhang, Aiming Yang, Shujun Cheng
Many basic properties of the T-cell receptor (TCR) repertoire require clarification, and the changes occurring in the TCR repertoire during carcinogenesis, especially during precancerous stages, remain unclear. This study used deep sequencing analyses to examine 41 gastric tissue samples at different pathological stages, including low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, early gastric cancer and matched adjacent tissues, to define the characteristics of the infiltrating TCRβ repertoire during gastric carcinogenesis...
August 10, 2017: Scientific Reports
James E Trosko, Giuseppe Carruba
It has been proposed that many human cancers are generated by intrinsic mechanisms that produce "Bad Luck" mutations by the proliferation of organ-specific adult stem cells. There have been serious challenges to this interpretation, including multiple extrinsic factors thought to be correlated with mutations found in cancers associated with these exposures. While support for both interpretations provides some validity, both interpretations ignore several concepts of the multistage, multimechanism process of carcinogenesis, namely, (1) mutations can be generated by both "errors of DNA repair" and "errors of DNA replication," during the "initiation" process of carcinogenesis; (2) "initiated" stem cells must be clonally amplified by nonmutagenic, intrinsic or extrinsic epigenetic mechanisms; (3) organ-specific stem cell numbers can be modified during in utero development, thereby altering the risk to cancer later in life; and (4) epigenetic tumor promoters are characterized by species, individual genetic-, gender-, developmental state-specificities, and threshold levels to be active; sustained and long-term exposures; and exposures in the absence of antioxidant "antipromoters...
April 2017: Dose-response: a Publication of International Hormesis Society
Sin-Aye Park, Young-Joon Surh
The tumor microenvironment provides a niche in which cancer cells and their surrounding stromal cells reside and in which their interactions occur. The cross talk between cancer and stromal cells in the tumor microenvironment promotes many biological processes to support cancer cell growth, invasion, angiogenesis, and metastasis. Recently, not only cancer cells but also multiple types of surrounding stromal cells, including endothelial cells, immune cells, and fibroblasts in the tumor microenvironment, have been recognized to be attractive targets for reducing resistance to anticancer therapy and tumor recurrence...
August 2017: Annals of the New York Academy of Sciences
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...
July 2017: 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...
July 2017: 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
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