Epigenetic alterations in gastric carcinogenesis

Gastric cancer is believed to result in part from the accumulation of multiple genetic alterations leading to oncogeneoverexpression and tumor suppressor loss. Epigenetic alterations as a distinct and crucial mechanism to silence a varietyof methylated tissue-specific and imprinted genes, have been extensively studied in gastric carcinoma and play impor-tant roles in gastric carcinogenesis. This review will briefly discuss the basic aspects of DNA methylation and CpGisland methylation, in particular the epigenetic alterations of certain critical genes implicated in gastric carcinogenesisand its relevance of clinical implications.

Genetic screening of liver cancer:State of the art

Liver cancer,primarily hepatocellular carcinoma,remains a global health challenge with rising incidence and limited therapeutic options.Genetic factors play a pivotal role in the development and progression of liver cancer.This state-of-the-art paper provides a comprehensive review of the current landscape of genetic screening strategies for liver cancer.We discuss the genetic underpinnings of liver cancer,emphasizing the critical role of risk-associated genetic variants,somatic mutations,and epigenetic alterations.We also explore the intricate interplay between environmental factors and genetics,highlighting how genetic screening can aid in risk stratification and early detection via using liquid biopsy,and advancements in high-throughput sequencing technologies.By synthesizing the latest research findings,we aim to provide a comprehensive overview of the state-of-the-art genetic screening methods for liver cancer,shedding light on their potential to revolutionize early detection,risk assessment,and targeted therapies in the fight against this devastating disease.

Molecular alterations in gastric cancer with special reference to the early-onset subtype

Currently, gastric cancer(GC) is one of the most frequently diagnosed neoplasms, with a global burden of 723000 deaths in 2012. It is the third leading cause of cancer-related death worldwide. There are numerous possible factors that stimulate the procarcinogenic activity of important genes. These factors include genetic susceptibility expressed in a singlenucleotide polymorphism, various acquired mutations(chromosomal instability, microsatellite instability, somatic gene mutations, epigenetic alterations) and environmental circumstances(e.g., helicobcter pylori infection, EBV infection, diet, and smoking). Most of the aforementioned pathways overlap, and authors agree that a clear-cut pathway for GC may not exist. Thus, the categorization of carcinogenic events is complicated. Lately, it has been claimed that research on early-onset gastric carcinoma(EOGC) and hereditary GC may contribute towards unravelling some part of the mystery of the GC molecular pattern because young patients are less exposed to environmental carcinogens and because carcinogenesis in this setting may be more dependent on genetic factors. The comparison of various aspects that differ and coexist in EOGCs and conventional GCs might enable scientists to: distinguish which features in the pathway of gastric carcinogenesisare modifiable, discover specific GC markers and identify a specific target. This review provides a summary of the data published thus far concerning the molecular characteristics of GC and highlights the outstanding features of EOGC.

Role of mitophagy in the hallmarks of aging

Aging, subjected to scientific scrutiny, is extensively defined as a time-dependent decline in functions that involves the majority of organisms. The time-dependent accretion of cellular lesions is generally a universal trigger of aging, while mitochondrial dysfunction is a sign of aging. Dysfunctional mitochondria are identified and removed by mitophagy, a selective form of macroautophagy. Increased mitochondrial damage resulting from reduced biogenesis and clearance may promote the aging process. The primary purpose of this paper is to illustrate in detail the effects of mitophagy on aging and emphasize the associations between mitophagy and other signs of aging, including dietary restriction, telomere shortening, epigenetic alterations, and protein imbalance.The evidence regarding the effects of these elements on aging is still limited. And although the understanding of relationship between mitophagy and aging has been long-awaited, to analyze details of such a relationship remains the main challenge in aging studies.

Pathogenetic mechanisms in gastric cancer

Gastric cancer(GC) is a major public health issue as the fourth most common cancer and the second leading cause of cancer-related death. Recent advances have improved our understanding of its molecular pathogenesis,as best exemplified by elucidating the fundamental role of several major signaling pathways and related molecular derangements. Central to these mechanisms are the genetic and epigenetic alterations in these signaling pathways,such as gene mutations,copy number variants,aberrant gene methylation and histone modification,nucleosome positioning,and microRNAs. Some of these genetic/epigenetic alterations represent effective diagnostic and prognostic biomarkers and therapeutic targets for GC. This information has now opened unprecedented opportunities for better understanding of the molecular mechanisms of gastric carcinogenesis and the development of novel therapeutic strategies for this cancer. The pathogenetic mechanisms of GC are the focus of this review.

Promoter hypermethylation of death-associated protein kinase gene in cholangiocarcinoma

BACKGROUND: Death-associated protein kinase (DAPK) is a Ca2+/calmodulin-regulated Ser/Thr kinase which is involved in apoptosis. The aberrant methylation of its promoter region CpG islands may be one of the important mechanisms of carcinogenesis. We studied the relationship of methylation status and expression of the DAPK gene with the clinical findings in cholangiocarcinoma. METHODS: Target DNA was modified by sodium bisulfite, coverting all unmethylated, but not methylated, cytosines to uracil, and subsequently detected by methylation-specific PCR. Moreover, mRNA expression of the DAPK gene was assessed by RT-PCR. RESULTS: Aberrant methylation of the DAPK gene was detected in 11 (30.6%) of 36 tissue specimens of cholangiocarcinoma, and in 2 (5.6%) of 36 specimens of adjacent normal tissues. DAPK mRNA was not expressed in tumor and adjacent tissues with hypermethylation of the DAPK promoter. There were no statistical differences in the extent of differentiation and invasion, lymph node metastasis or pathologic type between the methylated and unmethylated tissues. CONCLUSIONS: The frequency of DAPK gene methylation in cholangiocarcinoma is high and it may offer an effective means for earlier auxiliary diagnosis of the malignancy. The DAPK gene is probably suppressed by methylation, and it could become resistant to apoptosis and immunological surveillance. The DAPK gene epigenetically affected by methylation may be associated with the carcinogenesis of cholangiocarcinoma.

Mineralogy,Fluid Inclusion and H-O-C-S Stable Isotopes of Mengqiguer Uranium Deposit in the Southern Yili Basin,Xinjiang:Implication for Ore Formation

The Mengqiguer deposit in the southern Yili basin Ili Basin is a large interlayer-oxidation-zone type uranium deposit.In this paper,we applied multiple methods including microscopic observation,scanning electron microscope and electronic probe,to analyze the systematical alteration characteristics of the ore-bearing sandstone layer.Fluid inclusion and stable isotope studies on the ore-bearing sandstone have also been carried out to discuss the internal relations between fluid activities,epigenetic alteration and the uranium mineralization.Major epigenetic alteration include clay alteration,carbonatization and pyritization,of which biogenetic pyritization is most closely related to the uranium mineralization.This suggests the existence of microorganism during the uranium mineralization process.The mineralization fluids of low temperature,medium density but varied salinities are suggested to be derived from multi-source,including the meteoric water and organic acidic vapor components from coal-bearing strata.Uranium mineralization,grain-dispersed kaolinite,limonite,colloidal pyrite,and the carbonate cements associated with sulfate-reducing bacteria were formed by meteoric water and vermicular-shaped kaolinite,autologous pyrite,and the carbonate cementation associated with the dehydroxylation of organic matter was formed by organic acidic.Based on these results,we consider that the uranium mineralization and epigenetic alteration both resulted from the reciprocity of organic–inorganic fluid and fluid–rock during the formation of the interlayer oxidation zone.

Epigenetic changes in gastrointestinal cancers

Epigenetic alterations,including DNA methylation,histone modification,loss of genome imprinting,chromatin remodeling and non-coding RNAs,are associated with human carcinogenesis.Among them,DNA methylation is a fundamental epigenetic process to modulate gene expression.In cancer cells,altered DNA methylation includes hypermethylation of site-specific CpG island promoter and global DNA hypo-methylation.Detection of aberrant gene promoter methylation has been applied to the clinic to stratify risk in cancer development,detect early cancer and predict clinical outcomes.Environmental factors associated with carcinogenesis are also significantly related to aberrant DNA methylation.Importantly,epigenetic changes,including altered DNA methylation,are reversible and thus,used as targets for cancer therapy or chemoprevention.An increasing number of recent studies reported DNA methylation level to be a useful biomarker for diagnosis,risk assessment and prognosis prediction for gastrointestinal(GI)cancers.This review summarized the accumulated evidence for clinical application to use aberrant DNA methylation levels in GI cancers,including colorectal,gastric and esophageal cancer.

Cancers chemoprevention by dietary phytochemicals and traditional Chinese medicines: epigenetics and cellular signaling pathways

The incidence and mortality of cancer have been increasing alarmingly in China and worldwide.Unlike other chronic diseases such as metabolic,cardiovascular,and neuropathies,most cancers,especially metastatic ones,are still essentially uncontrollable in spite of significant progresses such as early diagnosis and immunotherapies.

Field cancerization in the colon:a role for aberrant DNA methylation?

Colorectal cancer is the third most common cancer worldwide and arises secondary to the progressive accumulation of genetic and epigenetic alterations in normal colon cells,which results in a polyp-to-cancer progression sequence.It is known that individuals with a personal history of colon adenomas or cancer are at increased risk for metachronous colon neoplasms.One explanation for this increased risk could be field cancerization,which is a phenomenon in which the histologically normal tissue in an organ is primed to undergo transformation.Epigenetic alterations appear to be promising markers for field cancerization.In this review,we discuss field cancerization in the colon and the data supporting the use of methylated DNA as a biomarker for this phenomenon.

Risk factors and molecular mechanisms of esophageal cancer: differences between the histologic subtypes

The two major histologic subtypes of esophageal cancer have different risk factors as well as different molecular mechanisms.In this review,the differences in risk factors and genetic/epigenetic alterations between esophageal squamous cell carcinoma(ESCC)and esophageal adenocarcinoma(EAC)will be discussed.Cigarette smoking and alcohol consumption are risk factors for ESCC,while gastroesophageal refl ux,cigarette smoking,and obesity are the main EAC risk factors.Commonly mutated genes of both subtypes are TP53 and PIK3CA.Recent genome-wide analysis revealed that the activation of the RAC1 pathway may contribute to EAC tumorigenesis.Clustered abnormality in copy number was observed in several genes in ESCC,whereas a few genes were specifically altered at high frequency in EAC.Epigenetic changes,such as DNA methylation,histone modifications,and altered expression of microRNAs,have been revealed to influence carcinogenesis and progression of both ESCC and EAC.