Outlook on Epigenetic Therapeutic Approaches for Treatment of Gastric Cancer

2017 ◽  
Vol 18 (1) ◽  
pp. 65-88 ◽  
Author(s):  
Petra Hudler
Keyword(s):  
Gastric Cancer ◽  
Cpg Island ◽  
Diagnostic Procedures ◽  
Tumour Suppressor Genes ◽  
Treatment Regimens ◽  
Cell Functions ◽  
Molecular Events ◽  
Aberrant Dna Methylation ◽  
Epigenetic Modulation ◽  
Specific Symptoms

The incidence of gastric cancer has been declining globally in the last decades. Despite the improvements in the diagnostic procedures, most cases are still detected at advanced stages due to lack of specific symptoms associated with early phases of tumour development. Consequently, gastric cancer poses a major health burden worldwide due to high mortality rates. Continuing advances in high-throughput technologies are revealing an intricate network of genetic and epigenetic changes associated with carcinogenesis. In addition, several risk factors, both environmental and genetic, have been recognized, which promote accumulation of diverse alterations affecting the expression of oncogenes, tumour suppressor genes, DNA repair genes, and other genes, implicated in normal gastric cell functions. A plethora of aberrant molecular events found in patients with this disease and intragenic heterogeneity of tumours from individuals are delaying the development of targeted biological therapies. Frequent occurrence of characteristic CpG island methylator phenotypes (CIMP phenotypes) in gastric cancers, particularly in association with Helicobacter pylori or EBV infection, could lead to introduction of epigenetic modulators into standard treatment regimens used against early and advanced forms of adenocarcinomas. This review highlights aberrant DNA methylation events in the development of gastric tumours and addresses the different aspects associated with the application of therapeutic epigenetic modulation in the management of the disease.

scholarly journals Molecular Events in Primary and Metastatic Colorectal Carcinoma: A Review

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Rani Kanthan ◽  
Jenna-Lynn Senger ◽  
Selliah Chandra Kanthan
Keyword(s):  
Colorectal Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Cpg Island ◽  
Genetic Alterations ◽  
Tumour Suppressor Genes ◽  
Metastatic Colorectal Carcinoma ◽  
Cpg Island Methylator Phenotype ◽  
Mesenchymal Transition ◽  
Sequence Of Events ◽  
Molecular Events

Colorectal cancer (CRC) is a heterogeneous disease, developing through a multipathway sequence of events guided by clonal selections. Pathways included in the development of CRC may be broadly categorized into (a) genomic instability, including chromosomal instability (CIN), microsatellite instability (MSI), and CpG island methylator phenotype (CIMP), (b) genomic mutations including suppression of tumour suppressor genes and activation of tumour oncogenes, (c) microRNA, and (d) epigenetic changes. As cancer becomes more advanced, invasion and metastases are facilitated through the epithelial-mesenchymal transition (EMT), with additional genetic alterations. Despite ongoing identification of genetic and epigenetic markers and the understanding of alternative pathways involved in the development and progression of this disease, CRC remains the second highest cause of malignancy-related mortality in Canada. The molecular events that underlie the tumorigenesis of primary and metastatic colorectal carcinoma are detailed in this manuscript.

DIFFERENTIAL DIAGNOSTICS OF GASTRIC CANCER AND PRECANCEROUS CHANGES OF THE GASTRIC MUCOSA USING ANALYSIS OF EXPRESSION OF SIX MICRORNAS

2020 ◽  
Vol 65 (2) ◽  
pp. 131-136 ◽  
Author(s):  
S. E. Titov ◽  
V. V. Anishchenko ◽  
T. L. Poloz ◽  
Yu. A. Veryaskina ◽  
A. A. Arkhipova ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Mucosa ◽  
Decision Tree ◽  
Diagnostic Procedures ◽  
Normal Mucosa ◽  
Gastric Ulcers ◽  
Differential Diagnostics ◽  
Diagnostic Significance ◽  
Diagnostic Characteristics ◽  
Specific Symptoms

The lack of specific symptoms for the early detection of gastric cancer leads to the fact that it is often diagnosed at a late stage, when the prognosis is unfavorable. The analysis of molecular markers in addition to standard diagnostic procedures is a promising approach for improving the preoperative diagnosis of both gastric cancer and precancerous changes in the mucosa. Therefore, the aim of our study was to analyze the diagnostic significance of using miRNA expression to diagnosis gastric cancer and precancerous conditions (dysplasia) in histological material. In this work, 122 samples of archival histological material in the form of paraffin blocks were used: 34 samples of gastric adenocarcinoma, 54 samples of gastric ulcers with dysplasia and 34 samples of normal gastric mucosa obtained from patients after bariatric surgery. The expression level of miRNA-145-5p, -150-5p, -20a-5p, -21-5p, -31-5p, -34a-5p, -375 was determined using real-time RT-PCR. Samples were stratified into different groups using the C-RT decision tree algorithm. All miRNAs, except miRNA-20a, were included in the decision tree, which allows stratification of samples for normal mucosa, dysplasia, and gastric cancer. Normal mucosa can be distinguished from gastric cancer only by miRNA-34a, -21, -375. Diagnostic characteristics for the detection of dysplasia: specificity - 97%, sensitivity - 87%; for the detection of gastric cancer: specificity - 91%, sensitivity - 93%. The sufficiently high values of the diagnostic characteristics for detecting dysplasia of the gastric mucosa and gastric cancer obtained in our study indicate the possibility of using expression data of a small amount of miRNAs for the effective separation of samples with tumor and precancerous changes in the stomach tissue.

Multimode light microscopy and fluorescence-based reagents as tools for the study of chemical and molecular dynamics of living cells and tissues

1992 ◽  
Vol 50 (1) ◽  
pp. 418-419
Author(s):  
D. L. Taylor
Keyword(s):  
Living Cells ◽  
Cellular Level ◽  
Molecular Techniques ◽  
Cellular Functions ◽  
Macromolecular Assemblies ◽  
Cell Functions ◽  
Molecular Events ◽  
Yield Information ◽  
Full Knowledge ◽  
Structural Methods

Cells function through the complex temporal and spatial interplay of ions, metabolites, macromolecules and macromolecular assemblies. Biochemical approaches allow the investigator to define the components and the solution chemical reactions that might be involved in cellular functions. Static structural methods can yield information concerning the 2- and 3-D organization of known and unknown cellular constituents. Genetic and molecular techniques are powerful approaches that can alter specific functions through the manipulation of gene products and thus identify necessary components and sequences of molecular events. However, full knowledge of the mechanism of particular cell functions will require direct measurement of the interplay of cellular constituents. Therefore, there has been a need to develop methods that can yield chemical and molecular information in time and space in living cells, while allowing the integration of information from biochemical, molecular and genetic approaches at the cellular level.

Association Between Cyclin D1 Polymorphism with CpG Island Promoter Methylation Status of Tumor Suppressor Genes in Gastric Cancer

2010 ◽  
Vol 55 (12) ◽  
pp. 3449-3457 ◽  
Author(s):  
Tomomitsu Tahara ◽  
Tomoyuki Shibata ◽  
Masakatsu Nakamura ◽  
Hiromi Yamashita ◽  
Daisuke Yoshioka ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Suppressor ◽  
Cyclin D1 ◽  
Promoter Methylation ◽  
Tumor Suppressor Genes ◽  
Cpg Island ◽  
Methylation Status ◽  
Suppressor Genes ◽  
Promoter Methylation Status

scholarly journals Epigenetic modulation associated with carcinogenesis and prognosis of human gastric cancer

2017 ◽  
Vol 13 (5) ◽  
pp. 3363-3368 ◽  
Author(s):  
Fuminori Sonohara ◽  
Yoshikuni Inokawa ◽  
Masamichi Hayashi ◽  
Yasuhiro Kodera ◽  
Shuji Nomoto
Keyword(s):  
Gastric Cancer ◽  
Human Gastric Cancer ◽  
Epigenetic Modulation

scholarly journals Occurrence of HHIP gene CpG island methylation in gastric cancer

2014 ◽  
Vol 8 (5) ◽  
pp. 2340-2344 ◽  
Author(s):  
YU SONG ◽  
YUN ZUO
Keyword(s):  
Gastric Cancer ◽  
Cpg Island ◽  
Cpg Island Methylation

Molecular medicine of gastric adenocarcinomas

2005 ◽  
Vol 7 (17) ◽  
pp. 1-13 ◽  
Author(s):  
Gisela Keller ◽  
Heinz Höfler ◽  
Karl-Friedrich Becker
Keyword(s):  
Gastric Cancer ◽  
Molecular Basis ◽  
Locally Advanced ◽  
Germline Mutations ◽  
Molecular Medicine ◽  
Tumour Suppressor Genes ◽  
Gi Tract ◽  
Incurable Disease ◽  
Gastric Adenocarcinomas ◽  
Upper Gastrointestinal

Upper gastrointestinal (GI) tract malignancies, including carcinomas of the esophagus, the GI junction and the stomach, are among the most common cancers worldwide. Overall survival is poor because many patients present with locally advanced and often incurable disease. This review focuses on the pathogenesis of adenocarcinomas of the stomach. It summarises recent findings on genetic predisposition to gastric cancer, in particular in relation to germline mutations in the E-cadherin gene. It also describes the molecular basis of sporadic gastric cancer, including alterations in oncogenes, tumour suppressor genes and growth factors, and discusses how these findings might be used in the clinic for improved diagnosis and therapy.

Sign in / Sign up

Export Citation Format

Share Document