ObjectiveTo review cancer associated fibroblasts(CAFs) and its role in the evolution of gastrointestinal neoplasms. MethodDomestic and international publications in relation to CAFs and its role in the evolution of gastrointestinal neoplasms were collected and reviewed. ResultsIn the gastrointestinal cancers, as the largest number and the most important stromal cells of the tumor microenvironment, CAFs induce the homeostasis of cell microenviron-ment out of balance, promote the remodeling of the tumor metabolism and extracellular matrix(ECM), and thus impulse the generation, proliferation, invasion and metastasis of the tumor by secreting different kinds of cytokines. ConclusionsThe key role CAFs playing in the tumor generation and evolution makes themselves and the multiple relatively specific molecules they secrete a new target for prognosis and targeted therapy, and this gives us a new idea for the combined treatment of gastrointestinal tumor or any other tumors.
Objective To summarize the role of matrix metalloproteinases (MMPs) in occurrence and development of gastric cancer. Methods Domestic and international publications online involving MMPs of gastric cancer in recent years were collected and reviewed. Results The occurrence and development of gastric cancer was a multi-step and multi-factorial complicated progress, whose etiology and pathogenesis were still unclarified. MMPs were a class of proteolytic enzymes, which played an important role in the proliferation, metastasis, angiogenesis of gastric cancer and apoptosis of tumor cells and their surrounding normal cells by regulating the microenvironment of the growth of tumor. Conclusion MMPs promote the evolution of gastric cancer in variable ways, the mechanisms of which should be comprehended to provide a theoretical basis for the future treatment of gastric cancer.
Objective To investigate the role of vascular endothelial growth factor-C (VEGF-C) and its receptors in the formation of lymphatic vessels and lymphatic metastasis in gastric cancer. Methods By the domestic and overseas literatures review, the expressions of VEGF-C and its receptors in gastric cancer, their role in tumor lymphatic metastasis and prospect in treatment of gastric cancer were summarized.Results There was a significant correlation between VEGF-C and its receptors and the formation of lymphatic vessels and lymphatic metastasis in gastric cancer. VEGF-C high expression might be an early event in lymphatic metastasis and could be considered as an independent predictive factor of lymphaticmicrometastasis. By inhibition of gastric cancer cell from secrete VEGF-C or blockage of the interaction of VEGF-C with VEGFR3, it was possible to inhibit tumor angiogenesis and the invasion and distant spread of cancer cells, thereby decreased mortality and improve survival. ConclusionVEGF-C and its receptors may promote the formation of lymphatic vessels and lymphatic metastasis in gastric cancer. It may be an effective way to gastric cancer for the treatments against VEGF-C and its receptors.
Objective To summarize the relationships between chemokines or chemokine receptors, especially CCL19/CCL21-CCR7 and CXCL12-CXCR4 axis and occurrence and development of gastric cancer. Methods Domestic and international publications online involving the relationships between chemokines, chemokine recepotors and gastric cancer in recent years were collected and reviewed. Results By regulating the microenvironment of the growth of gastric cancer, CCL19/CCL21-CCR7 played an important role in lymph node metastasis and CXCL12-CXCR4 axis played a key role in the development of peritoneal carcinomatosis. CCR7 might function as a specific prognostic marker for lymph node metastasis of gastric cancer. Blocking the CXCL12-CXCR4 axis might be useful for the future development of a more effective therapeutic strategy for gastric cancer involved in peritoneal dissemination. Conclusions Chemokines and chemokine receptors promote the evolution of gastric cancer in variable ways, so the mechanisms of which should be comprehended to provide a theoretical basis for the future treatment. As new therapeutic targets, chemokines and chemokine receptors have a prosperity for the clinic evaluation and treatment of gastric cancer.
ObjectiveTo summarize the role of epithelial-mesenchymal-transition （EMT） in occurrence and development of gastrointestinal cancer. MethodsDomestic and international publications online involving EMT of gastrointestinal cancer in recent years were collected and reviewed. ResultsEMT was a highly conserved process that has been well characterised in embryogenesis. Studies had shown that the aberrant activation of EMT in adult epithelia could promote tumour metastasis by repressing cell adhesion molecules. E-cadherin， one of the epithelial cell markers, maybe involved in the process of the EMT, especially of the Ecadherin transcriptional repressors， these transcriptional repressors significantly increased in the gastrointestinal cancer. Further more， EMT might involve in the process of gastrointestinal cancer stem cells formation. ConclusionsEMT and it’s regulators play a very important role in gastrointestinal cancer， and may provide a newsight into the gastrointestinal cancer. It also can provide a novel clinical targets to treat the gastrointestinal cancer.
Objective To review the role of mTOR signal pathway in chemo-resistance of gastric cancer. Methods Domestic and international publications related mTOR signal pathway in chemo-resistance of gastric cancer in recent years were collected and reviewed. Results mTOR was a central signaling molecule of mTOR signal pathway， which regulated key cellular processes such as cell growth， cell proliferation， cell metabolism， and angiogenesis. Signaling molecules of mTOR signal pathway were overexpressed in gastric cancer. Moreover， mTOR signal pathway might play an important role in chemo-resistance of gastric cancer， and tumor stem cells were involved in it too. Conclusion As mTOR signal pathway plays an important role in chemo-resistance of gastric cancer， the combination of mTOR inhibitors and chemotherapy drugs may overcome the chemo-resistance of gastric cancer.
Objective To summarize the research progress of gastrointestinal stem cells and its role in gastric neoplasms. Methods The literatures related effect of gastrointestinal stem cells niche， gastrointestinal stem cells markers，and the cancer stem cell theory in the gastric neoplasms were retrieved through PubMed， the research progress of gastrointestinal stem cells and cancer stem cells in the gastric neoplasms was explored. Results The cancer stem cell theory arose a decade ago. Gastrointestinal stem cells played a very important role in the gastric neoplasms， which had specific markers and their niches included many kinds of tissue factors. Inflammation could induce gastrointestinal stem cells dysplasia and become cancer stem cells， which promoted the growth， invasion， and metastasis of the gastric neoplasms. Conclusions Gastric cancer stem cells could be one of an effective target in treatment for gastric neoplasms， and it may be provide a new breakthrough in treatment for gastric neoplasms.
ObjectiveTo study the expression and role of homeobox transcription antisense intergenic ribose nucleic acid (HOTAIR) in CD133-positive gastric cancer cells, which was classified to long non-coding RNA (LncRNA). MethodsImmune magnetic cell sorting (MACS) was performed to sort CD133-positive and CD133-negative cells of KATO-Ⅲgastric cancer cells, then reverse transcription polymerase chain reaction (RT-PCR) was performed to detect the expressions of HOTAIR mRNA and CD133 mRNA. After the intervention of small interfering RNA (siRNA) for CD133-positive KATO-Ⅲcells, RT-PCR method was performed to detect the expression of HOTAIR mRNA to select siRNA who had the best silent effect. The selected-siHOTAIR was used to silent the expression of HOTAIR, then the expressions of CD133 mRNA, E-cadherin mRNA, and N-cadherin mRNA were detected by RT-PCR. At last, Transwell experiments were performed to detect the migration ability and invasion ability. Results①?RT-PCR test results showed that, the expression levels of CD133 mRNA and HOTAIR mRNA in CD133-positive group were significantly higher than those of CD133-negative group and no separation group (P < 0.05).②?After interference of siHOTAIR, the expression levels of HOTAIR mRNA in siHOTAIR1 group, siHOTAIR2 group, and siHOTAIR3 group were all significantly lower than those of blank control group and negative control group (P < 0.05), and the expression levels of HOTAIR mRNA in siHOTAIR2 group was lower than those of siHOTAIR1 group and siHOTAIR3 group (P < 0.05). The results indicated that siHOTAIR2 had the best interference efficiency.③?The expression levels of CD133 mRNA and N-cadherin mRNA in siHOTAIR2 group were lower than those corresponding indicators of blank control group and negative control group (P < 0.05), but the expression level of E-cadherin mRNA was higher than those of blank control group and negative control group (P < 0.05). Transwell experiment results showed that, number of cells which through the cell membrane in siHOTAIR2 group was lower than those of blank control group and negative control group (P < 0.05). ConclusionThe expression of HOTAIR mRNA in CD133-positive KATO-Ⅲgastric cancer cells was higher than that of CD133-negative cells, interfering the expression of HOTAIR mRNA can reduce the expression of CD133 mRNA in CD133-positive KATO-Ⅲgastric cancer cells, and can inhibit cell migration and invasion.
ObjectiveTo summarize the recent years' researches of the role of microRNAs (miRNAs) in gastric cancer. MethodsDomestic and international publications related to miRNAs biological functions and its role in gastric cancer in recent years were collected and reviewed. ResultsMiRNAs are binded to some target mRNAs which are related to gastric cancer, then result in these mRNAs silence and target-genes abnormal expression. Conciusions MiRNAs play a crucial role in tumorigenesis and development of gastric cancer, and act as a oncogene or anti-oncogene in gastric cancer.