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 roles of tumor initiating cells （TICs） and epithelial-mesenchymal transition （EMT） in tumor metastasis and drug resistance. Methods Domestic and international publications online which involving TICs，EMT，and its roles in tumor metastasis and drug resistance in recent years were reviewed. Results TICs were self-renewal cells and had the ability to give rise to more differentiated cell types，and played an important role in tumor metastasis and drug resistance. Various markers had been used to identify TICs，such as CD133，CD44，and so on. EMT was the process by which epithelial cells losed polarity and detach from the epithelial sheet， and acquired a motile mesenchymal phenotype，usually observed in embryo development and wound healing. It also could promote tumor progression and metastasis，and may also be responsible for the ability of tumors to evade the body’s immune response. EMT may be the reasons of TICs that drived tumor metastasis and recurrence. TICs or EMT as a target for treatments may effectively prevent tumor recurrence and improve patient’s survival. Conclusions EMT is probably the mechanism that TICs promote tumor metastasis and drug resistance. More effective target therapies for cancer may be found if we know more about TICs and EMT.
Objective To summarize the development of gallbladder carcinoma related resistance genes and targeted therapy. Methods Domestic and international publications online involving resistance genes and targeted therapy of gallbladder carcinoma in recent years were collected and reviewed. Results Recent studies had shown that chemotherapy drug resistance of gallbladder carcinoma mainly involved lysosome protein transmembrane β4 （LAPTM4B） gene， NF-E2-related factor 2 （Nrf2） gene， and cancer stem cells （CSCs）. While the latest gene targets of treatment for gallbladder carcinoma mainly involved LAPTM4B， Nemo-like kinase （NLK）， tissue factor way inhibitor-2 （TFPI-2）， vascular endothelial growth factor-D （VEGF-D）， epidermal growth factor receptor （EGFR）， and melanoma differentiation-associated gene 7/interleukin 24 （mda-7/IL-24） gene. Conclusion The research involving resistance genes and targeted therapy of gallbladder carcinoma has make a certain progress， which broaden the concept of traditional treatment of gallbladder carcinoma.
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 status of tumor stem cells investigations in gastrointestinal carcinoma. Methods Domestic and international publications online involving tumor stem cells of gastrointestinal carcinoma in recent years were collected and reviewed. Results There are a small quantity of cancer cells shown some stem cell characteristics. They are named tumor stem cell and play an important role in tumorigenesis, proliferation, metastasis and recurrence. And also, tumor stem cells can resist the effect of antineoplastic drugs and lead to tumor recurrence. These tumor-initiating cells are CD133-positive in the gastrointestinal carcinomas, especially in colorectal cancers. CD133-positive colorectal cancer cells have the abilities of clone, proliferation, differentiation and form metastases. And a high CD133 mRNA content was found in the blood of patients who suffered from bone metastases. Conclusion The characteristics of CD133-positive cancer cell and the mechanisms of stem cell-niche system are the basis of developing better methods to tumor diagnosis and treatment, and provide theoretical basis of new methods, such as targeted therapy.
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 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 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.
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.