2. CONTENT
Introduction
Molecular genetics of gastric cancer
Molecular determinants of gastric cancer invasion and metastasis
Molecular changes associated with H. pylori infection
characterization of gastric cancer
Targeted therapy in gastric cancer
Targeted agents reaching clinical development
Angiogenic signalling network and inhibition by antiangiogenic drugs
Discovery of biomarkers for gastric cancer
Types of human noncoding RNAs in gastric cancer
A novel human gastric primary cell culture system
2
5. MOLECULAR GENETICS OF GASTRIC CANCER
Inactivation of tumor
suppressor genes
• inactivation of p53 and p16
• (APC) gene mutations
• fragile histidine triad (FHIT)
• deleted in colon cancer (DCC)
• transcriptional silencing of various
genes (e.g., Ecadherin,p16, p15,
MGMT, and hMLH1)
Activation of oncogenes
• c-met proto oncogene
• c-erB2 (HER-2/neu) gene
• c-erbB3, K-sam,Ras, and c-myc,
Telomerase reactivation
MSI
• High frequency (MSI-H)
• low-frequency (MSI-L)
• stable (MSS)
5
6. MOLECULAR DETERMINANTS OF GASTRIC CANCER INVASION
AND METASTASIS
Alterations of growth
factors and cytokines
• Epidermal growth factor (EGF)
family
• Vascular endothelial growth factor
(VEGF)
• insulin-like growth factor (IGF)
• numerous cytokines, such as TGF,
IL-1,and IL-8
Apoptosis and cell-cycle
regulators
• Genes that regulate apoptosis,
such as FAS, tumor necrosis
factor(TNF), and bcl-2, contribute to
the development of cancer
• LOH at the bcl-2 locus
Alterations of adhesion
molecules
• E-cadherin
• Nitric oxide synthase
(NOS)
• Cyclooxygenase
(COX)-2
6
7. MOLECULAR CHANGES ASSOCIATED WITH H. PYLORI INFECTION
CagA(+) H. pylori
infection
Cag T4SS
Vag A(+) H.pylori
infection
Lipopolycacharids
7
9. ROLE OF HELICOBACTER PYLORI IN GASTRIC CANCER
9
DOI: 10.4251/wjgo.v8.i2.147
World J Gastrointest Oncology
10. ROLE OF HELICOBACTER PYLORI IN GASTRIC CANCER
10
DOI: 10.4251/wjgo.v8.i2.147
World J Gastrointest Oncology
11. CHARACTERIZATION OF GASTRIC CANCER
11
DOI: 10.1177/1756283X12453636
TRMOME 1136 No. of Pages 11 ,Trends In Molecular
Medicine. Cell Press.
12. KEY FEATURES OF GASTRIC CANCER SUBTYPES ACCORDING TO THE CANCER GENOME ATLAS
(TCGA)
12
http://dx.doi.org/10.1038/nrclinonc.2016.15
NATURE REVIEWS | CLINICAL ONCOLOGY
13. TARGETED THERAPY IN GASTRIC CANCER
13
Nature Reviews Clinical Oncology 10, 643
655(2013) doi:10.1038/nrclinonc.2013.170
17. TYPES OF HUMAN NONCODING RNAS IN GASTRIC CANCER
17
Hindawi Publishing Corporation .Disease Markers .Volume 2015, Article ID 503762, 14 pages
http://dx.doi.org/10.1155/2015/503762
18. A NOVEL HUMAN GASTRIC PRIMARY CELL CULTURE SYSTEM
18
Nature Cell Biology 18, 246254 (2016) doi:10.1038/ncb3312