A Statistics about the Causes of Delay in the Diagnosis of Stomach Cancer

Kurokawa, Toshio; Masuda, Takashi

doi:10.1620/tjem.54.294

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“…Gastric cancer has few or no symptoms in the early stages thus ~ 65% patients present as advanced cancers (T3, T4) [ 33 , 34 ]. Treatment outcomes for gastric cancer (by cisplatin/fluoropyrimidine or by trastuzumab in combination with chemotherapy for HER2-positive advanced gastric cancer) are unsatisfying; the 5-year survival rate of patients with advanced gastric cancer is below 20% and has not been improved in recent 20 years [ 35 – 37 ]. Although several chemical drugs (such as taxane and irinotecan [ 38 ]) or monoclonal antibodies (such as pembrolizumab and ramucirumab [ 39 , 40 ]) are currently tested in phase II and III clinical trials, increasing reports indicates that these drugs do not significantly improve the therapeutic outcome over conventional chemotherapy [ 41 – 44 ] and the prognosis remains poor.…”

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confidence: 99%

Blockade of ITGA2 Induces Apoptosis and Inhibits Cell Migration in Gastric Cancer

Chuang

Lin

et al. 2018

Biol Proced Online

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BackgroundGastric cancer is currently the fourth leading cause of cancer-related death worldwide. Gastric cancer is often diagnosed at advanced stages and the outcome of the treatment is often poor. Therefore, identifying new therapeutic targets for this cancer is urgently needed. Integrin alpha 2 (ITGA2) subunit and the beta 1 subunit form a heterodimer for a transmembrane receptor for extracellular matrix, is an important molecule involved in tumor cell proliferation, survival and migration. Integrin α2β1 is over-expressed on a variety of cancer cells, but is low or absent in most normal organs and resting endothelial cells.ResultsIn this report, we assessed the ITGA2 as the potential therapeutic target with the bioinformatics tools from the TCGA dataset in which composed of 375 gastric cancer tissues and 32 gastric normal tissues. According to the information from the Cancer Cell Line Encyclopedia (CCLE) database, the AGS cell line with ITGA2 high expression and the SUN-1 cell line with low expression were chosen for the further investigation. Interestingly, the anti-ITGA2 antibody (at 3 μg/ml) inhibited approximately 50% survival of the AGS cells (over-expressed ITGA2), but had no effect in SNU-1 cells (ITGA2 negative). The extents of antibody-mediated cancer inhibition positively correlated with the expression levels of the ITGA2. We further showed that the anti-ITGA2 antibody induced apoptosis by up-regulating the RhoA-p38 MAPK signaling to promote the expressions of Bim, Apaf-1 and Caspase-9, whereas the expressions of Ras and Bax/Bcl-2 were not affected. Moreover, blocking ITGA2 by the specific antibody at lower doses also inhibited cell migration of gastric cancer cells. Blockade of ITGA2 by a specific antibody down-regulated the expression of N-WASP, PAK and LIMK to impede actin organization and cell migration of gastric cancer cells.ConclusionsHere, we showed that the mRNA expression levels of ITGA2 comparing to normal tissues significantly increased. In addition, the results revealed that targeting integrin alpha 2 subunit by antibodies did not only inhibit cell migration, but also induce apoptosis effect on gastric cancer cells. Interestingly, higher expression level of ITGA2 led to significant effects on apoptosis progression during anti-ITGA2 antibody treatment, which indicated that ITGA2 expression levels directly correlate with their functionality. Our findings suggest that ITGA2 is a potential therapeutic target for gastric cancer.Electronic supplementary materialThe online version of this article (10.1186/s12575-018-0073-x) contains supplementary material, which is available to authorized users.

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