multistage carcinogenesis

BACKGROUND: Cancer, an uncontrolled multistage process causing swift division of cells, is a leading disease with the highest mortality rate. Cellular heterogeneity, evading growth suppressors, resisting cell death, and replicative immortality drive the tumor progression by resisting therapeutic action of existing anticancer drugs through a series of intrinsic and extrinsic cellular interactions. The innate cellular mechanisms also regulate the replication process as a fence against proliferative signaling, enabling replicative immortality through telomere dysfunction...

CONTEXT: Carcinogenesis causes much human misery. It is a process involving multistage alterations. Medicinal plants are candidates for beneficial anticancer agents. OBJECTIVES: Investigation of anticancer proficiencies of the plant Dicliptera roxburghiana . MATERIAL AND METHODS: Crude extract and derived fractions were inspected for their inhibitory potential against nuclear factor KB (NFκB), nitric oxide synthase inhibition, aromatase inhibition and induction of quinone reductase 1 (QR 1)...

A 55-year-old woman became aware of a tumor on the left side of the head in July, 2020 and was referred to our hospital in September because of its rapid growth. A head CT showed a neoplastic lesion of the skull. A CT from the neck to the pelvis revealed an ascending colon tumor and multiple lesions in the liver, which was suspected as metastasis. A colonoscopy also showed a type 2 like lesion in the ascending colon, and a biopsy showed adenocarcinoma. A pedunculated polyp had been pointed out in the ascending colon at another hospital four years previously, and the pathological result was an adenoma, but endoscopic mucosal resection was not performed...

Colorectal carcinoma (CRC) is a common disease, the incidence of which is increasing according to Western lifestyle; it remains to have a poor prognosis. Western nutriments are presumed to induce mild inflammation within the colonic mucosa, resulting in the accumulation of DNA alterations in colonocytes through a multistage carcinogenesis process. This suggests that most CRCs are related to the environment. Of interest, fecal microbiota composition has been shown yielding a novel approach regarding how environment changes may impact health and disease...

Locoregional recurrence after surgery is a major unresolved issue in cancer treatment. Premalignant lesions are considered a cause of cancer recurrence. A study showed that premalignant lesions surrounding the primary tumor drove a high local cancer recurrence rate after surgery in head and neck cancer. Based on the multistage theory of carcinogenesis, cells harboring an intermediate number of mutations are not cancer cells yet but have a higher risk of becoming cancer than normal cells. This study constructed a mathematical model for cancer initiation and recurrence by combining the Moran and branching processes in which cells require two specific mutations to become malignant...

The age-specific trend of cancer incidence rates, but not its magnitude, is well described employing the multistage theory of carcinogenesis by Armitage and Doll in combination with the senescence model of Pompei and Wilson. We derived empirical parameters of the multistage-senescence model from U.S. Surveillance, Epidemiology, and End Results (SEER) incidence data from 2000-2003 and 2010-2013 for The Cancer Genome Atlas (TCGA) cancer types. Under the assumption of a constant tumor-specific transition rate between stages, there is an extremely strong linear relationship ( P < 0...

PURPOSE: There has been an increase in the incidence of signet ring cell cancer (SRCC) of the stomach and gastro-esophageal junction (GEJ). The multistage carcinogenesis involving genetic and epigenetic aberrations may have a major role in the increasing incidence of SRCC. Although there are numerous studies on the prognostic value of SRCC, they are markedly inconsistent in their results, making it impossible to draw any meaningful conclusions. We aimed to examine the available evidences on molecular alterations and stage-stratified treatment approaches in SRCC of the stomach and GEJ...

BACKGROUND: Evidence has accumulated showing that an increase in thyroid cancer incidence reflects overdiagnosis of clinically unimportant lesions due to the rise in the use of neck ultrasonography. In the manuscript we examine the hypothesis that the rise in thyroid cancer incidence in Russia is largely caused by overdiagnosis. MATERIALS AND METHODS: Incidence and mortality rates of thyroid cancer for Russia overall and its administrative regions were abstracted from the statistical database of the Ministry of Health of Russia...

Photoaging is a complex and multistage process triggered mainly by ultraviolet (UV) radiation due to exposure to sunlight. Photoaging induces DNA damage and oxidative stress that initiate an inflammatory response and an increase of matrix metalloproteinases (MMPs) expression, which results in cumulative changes in skin appearance, structure, and functions, and eventually causes skin carcinogenesis. Dietary polysaccharides from bio-resources have been utilized as functional ingredients in healthy food, cosmetics, and drug due to their good bioactivities...

Patterns of cancer incidence, viewed over extended time periods, reveal important aspects of multistage carcinogenesis. Here we show how a multistage clonal expansion (MSCE) model for cancer can be harnessed to identify biological processes that shape the surprisingly dynamic and disparate incidence patterns of esophageal squamous cell carcinoma (ESCC) in the US population. While the dramatic rise in esophageal adenocarcinoma (EAC) in the US has been largely attributed to reflux related increases in the prevalence of Barrett's esophagus (BE), the premalignant field in which most EAC are thought to arise, only scant evidence exists for field cancerization contributing to ESCC...

A recent hypothesis proposed that the total number of stem cell divisions in a tissue (TSCD model) determine its intrinsic cancer risk; however, a different model-the multistage model-has long been used to understand how cancer originates. Identifying the correct model has important implications for interpreting the frequency of cancers. Using worldwide cancer incidence data, we applied three tests to the TSCD model and an evolutionary multistage model of carcinogenesis (EMMC), a model in which cancer suppression is recognized as an evolving trait, with natural selection acting to suppress cancers causing a significant mean loss of Darwinian fitness...

We have previously reported that the deletion of BMAL1 gene has opposite effects in respect to its contribution to the pathways that are effective in the multistage carcinogenesis process. BMAL1 deletion sensitized nearly normal breast epithelial (MCF10A) and invasive breast cancer cells (MDA-MB-231) to cisplatin- and doxorubicin-induced apoptosis, while this deletion also aggravated the invasive potential of MDA-MB-231 cells. However, the mechanistic relationship of the seemingly opposite contribution of BMAL1 deletion to carcinogenesis process is not known at genome-wide level...

Amorphous silica nanoparticles (SiO2 NPs) have been widely used in medicine including targeted drug/DNA delivery, cancer therapy, and enzyme immobilization. Nevertheless, SiO2 NPs should be used with caution due to safety concerns associated with unique physical and chemical characteristics. The objective of this study was to determine the effects of SiO2 NPs on genotoxic and non-genotoxic mechanisms associated with abnormal gap junctional intercellular communication (GJIC) in multistage carcinogenesis. The SiO2 NPs exhibited negative responses in standard genotoxicity tests including the Ames test, chromosome aberration assay, and micronucleus assay...

The intrinsic risk of cancer increases with body size and longevity; however, big long-lived species do not exhibit this increase, a contradiction named Peto's paradox. Five hypotheses potentially resolving this paradox were modeled using the multistage model of carcinogenesis. The five hypotheses were based on (1) intrinsic changes in metabolic rate with body size; adaptive increase in immune policing of (2) cancer cells or (3) cells with driver mutations; or adaptive increase in cancer suppression via (4) decreased somatic mutation rate, or (5) increased genetic control...

BK polyomavirus (BKPyV)-associated cancer after transplantation has gained increasing attention. However, the role of BKPyV integration on oncogenesis is still unclear. In this study, next-generation virome capture sequencing of primary and metastatic tumors were performed in three patients with BKPyV-associated urothelial carcinoma after renal transplantation. As a result, a total of 332 viral integration sites were identified in the six tumors. Integration of BKPyV in both primary and metastatic tumors followed the mechanism of microhomology-mediated end joining mostly, since microhomologies between human and BKPyV genomes were significantly enriched in flanking regions of 84% of the integration sites...

Helicobacter pylori (H. pylori)-negative gastric cancer (HPNGC) usually shows a gastric mucin phenotype, but there are a few case reports of HPNGC with an intestinal mucin phenotype. We herein report a case of multiple HPNGC with an intestinal mucin phenotype showing a gastritis-like appearance. A 68-year-old H. pylori-uninfected man was suspected of having antral gastritis on endoscopy, but a histologic examination revealed multiple well-differentiated adenocarcinomas with positive-CDX2/MUC2/CD10 and negative-MUC5AC/MUC6...

Gastric and esophageal cancers are multifactorial and multistage-involved malignancy. While the impact of gut microbiota on overall human health and diseases has been well documented, the influence of gastric and esophageal microbiota on gastric and esophageal cancers remains unclear. This review will discuss the reported alteration in the composition of gastric and esophageal microbiota in normal and disease conditions, and the potential role of dysbiosis in carcinogenesis and tumorigenesis. This review will also discuss how dysbiosis stimulates local and systemic immunity, which may impact on the immunotherapy for cancer...

Lung cancer is the most often diagnosed cancer in the world and the most frequent cause of cancer death. The prognosis for lung cancer is relatively poor and 75% of patients are diagnosed at its advanced stage. The currently used diagnostic tools are not sensitive enough and do not enable diagnosis at the early stage of the disease. Therefore, searching for new methods of early and accurate diagnosis of lung cancer is crucial for its effective treatment. Lung cancer is the result of multistage carcinogenesis with gradually increasing genetic and epigenetic changes...

The potential of natural products in cancer prevention and treatment has received worldwide interest in recent years from the nutraceutical and pharmaceutical industry point of view. Medicinal plants have been traditionally used as they exhibit a wide range of therapeutic effects due to their phytoconstituents which play an active role against oxidative stress-associated diseases such as cancer. They may block or suppress multistage carcinogenesis mainly through mechanistic regulation of the myriad of deregulated cellular pathways...

Gastric cancer (GC) is one of the most common malignancies worldwide and it is the fourth leading cause of cancer-related death. GC is a multifactorial disease, where both environmental and genetic factors can have an impact on its occurrence and development. The incidence rate of GC rises progressively with age; the median age at diagnosis is 70 years. However, approximately 10% of gastric carcinomas are detected at the age of 45 or younger. Early-onset gastric cancer is a good model to study genetic alterations related to the carcinogenesis process, as young patients are less exposed to environmental carcinogens...