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.
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.
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 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 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 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.
ObjectiveTo investigate the expressions of CD133 and CD44 protein in primary lesions of gastric cancer and its clinical significance. MethodsThe expressions of CD44 and CD133 protein in gastric cancer tissues of 100 patients with gastric cancer were detected by immunohistocheimcal stainings.The relation between the expressions of CD44 and CD133 protein and the clinicopathologic characters were analyzed. ResultsBoth CD44 and CD133 protein were expressed on the cell membranes.No correlation were found between CD44/CD133 and the clinicopathologic parameters include gender and age (P > 0.05), but the positive expression rate of CD44/CD133 with diameter>5 cm was significantly higher than that tumor with diameter≤5 cm (CD44 P=0.150;CD133 P=0.056), and correlated with the tissue differentiation (CD44 P=0.008;CD133 P=0.007), vascular invasion (CD44 P=0.043;CD133 P=0.023), lymphatic vessel invasion (CD44 P=0.020;CD133 P=0.044), lymph nodes metastasis (CD44 P=0.002;CD133 P=0.004), inva-sion depth of tumor (CD44 P=0.006;CD133 P=0.021), and pTNM stage (CD44 P=0.034;CD133 P=0.001).No correlation were found between the co-expression of CD44 and CD133 protein and the clinicopathologic parameters include gender, age, tissue differentiation, and vascular invasion (P > 0.05), but the positive co-expression rate of CD44 and CD133 with diameter>5 cm was significantly higher than that tumor with diameter≤5 cm (P=0.010), and correlated with lymphatic vessel invasion (P=0.003), lymph nodes metastasis (P=0.045), invasion depth of tumor (P=0.041), and pTNM stage (P=0.049).The Spearman rank correlation analysis showed that there was positive correlation between the expressions of CD44 and CD133 protein (r=0.207, P=0.039).Univariate analysis showed that lymph nodes metastasis (P < 0.001), pTNM stages (P=0.013), CD44 protein expression (P=0.005), CD133 protein expression (P=0.002), and co-expression of CD44 and CD133 protein (P < 0.001) were significantly correlated with 3-year survival rate of pati-ents with gastric cancer respectively.Logistic regression analysis revealed that lymph node metastasis (P=0.038) was independent risk factor for co-expression of CD44 and CD133 protein.Multivariate analysis with the Cox regression models showed that co-expression of CD44 and CD133 protein (P=0.003) and lymph node metastasis (P=0.006) were significantly associated with poor prognosis. ConclusionsCD44 and CD133 protein may be considered as robust cancer stem cell markers in gastric cancer.The co-expression of CD44 and CD133 protein is the independent prognosis factor for gastric cancer and strongly associated with poor prognosis when they are expressed more high.
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.