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 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 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 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.
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.
Objective To study the expressions of Wnt5a, MMP2, and MMP14 in the primary lesions of gastric cancer and the influences on clinicopathologic features. Methods The expressions of Wnt5a, MMP2, and MMP14 in the specimens of 106 patients with gastric cancer and 39 patients from the adjacent normal gastric tissues were detected by immunohistochemical staining, χ2 test and non-parametric test were used to analyze the relationships among them and between them and their influences on the clinicopathologic features. Results Extensive expressions of Wnt5a, MMP2, and MMP14 were demonstrated in the gastric cancer, which were significantly higher than those in the normal gastric tissues respectively (Plt;0.05). Positive expression of Wnt5a was associated with larger tumor diameter, deeper depth of invasion, higher degree of regional lymph node metastasis, later TNM stage, and higher rate of lymph node metastasis (Plt;0.05). In addition, Wnt5a expression was also associated with lymphatic infiltration and vascular infiltration (Plt;0.05). The expressions of MMP2 and MMP14 were associated with lymphatic infiltration, but not with vascular infiltration. Higher expressions of MMP2 and MMP14 were correlated with deeper tumor invasion, higher degree of regional lymph node metastasis, later TNM stage, and higher rate of lymph node metastasis (Plt;0.05). In addition, higher expression of MMP2 possesed greater tumor diameter (Plt;0.05). Spearman rank correlation analysis revealed the positive relation between Wnt5a and MMP2 （rs=0.240, P=0.014）, Wnt5a and MMP14 （rs=0.251, P=0.010）, as well as MMP2 and MMP14 （rs=0.444, P=0.000）. Conclusion Higher expressions of Wnt5a, MMP2, and MMP14 seem to promote invasion and metastasis of gastric cancer, and there are positive relations among their expressions.
ObjectiveTo study the clinical significance of the 3-hydroxyisobutyrate dehydrogenase (HIBADH) expressions in gastric adenocarcinoma tissues and its biological function in gastric cancer cells.MethodsSeventy-six patients with gastric adenocarcinoma who were hospitalized in Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiaotong University, School of Medicine between January 2006 and December 2007 were recruited in our research. Immunohistochemical (IHC) staining was used to detect the HIBADH protein in primary gastric adenocarcinoma tissues, adjacent tissues, and metastatic lymph node tissues of gastric cancer. Then, the relationships among the expression of HIBADH protein, the clinical features, and the prognosis were analyzed. The MKN45 gastric cancer cell line of HIBADH overexpression was picked up and constructed as stable HIBADH knockdown cell lines. The biological function of HIBADH protein in gastric cancer cells was confirmed through in vitro experiments such as cell proliferation assay, migration and invasion assay, and scratch-wound assay.ResultsThe positive expression rate of HIBADH protein in the 76 gastric adenocarcinoma tissues was significantly higher than that of the adjacent tissues (χ2=54.738, P<0.001). Moreover, the higher expression level of HIBADH protein was related to the larger tumor diameter, the higher tumor lymphatic invasion rate, the later pT stage, the higher the lymph node metastasis rate, and the later pTNM stage (P<0.05). HIBADH protein was also highly expressed in lymph nodes with metastatic carcinoma, and positiverate was 100% (48/48). The 10-year survival rate of patients in the HIBADH protein positive group and HIBADH protein negative group were 16.4% and 69.4%, respectively, which showed the latter group had a longer survival time (χ2=19.612, P<0.001). The migration capacity, invasion capacity, and scratch-wound capacity of the MKN45 cells were significantly decreased after HIBADH protein knockdown (P<0.05), but the proliferation capacity of the cells was not significantly changed (P>0.05).ConclusionsThe overexpression of HIBADH protein in gastric cancer suggests later tumor stage and poor prognosis. Inhibition expression of HIBADH protein can reduce the motility capacity of gastric cancer cells.
Objective To study the expression of CD133 mRNA in peripheral blood mononuclear cells （PBMCs） of patients with gastric adenocarcinoma （GC） before operation or after operation and its clinical significance. To learn the relationship of CD133 expressions in PBMCs to primary lesion of GC. Methods Fifty patients with GC，10 patients with gastric ulcer （GU）， and 10 healthy volunteers were registered in this research. Expressions of CD133 mRNA in PBMCs and in primary lesion of GC by semi-quantitative RT-PCR and expression of CD133 protein in primary lesion of GC by immunohistochemical staining were detected. Correlations of CD133 mRNA expression with clinicopathologic parameters and postoperative survival rate were analyzed. Relation between CD133 mRNA level and CD133 protein expression or lymphatic metastasis were assessed too. Results The brightness scale value （ABSV） of CD133 mRNA in PBMCs of the patients with GC before operation （0.270±0.163） was higher than that in the healthy volunteers （0.029±0.060） or in the patients with GU （0.059±0.099） （P=0.000）. The ABSV of CD133 mRNA in the PBMCs of patients with GC before operation was related to poor cell differentiation （P=0.002）， lymph vessel invasion （P=0.028），deeper tumor invasion （P=0.041），later lymph node metastasis stage （P=0.010），later TNM stage （P=0.006），and positive expression of CD133 protein in the primary lesion （P=0.011）. Relative analysis revealed that the ABSV of CD133 mRNA in the PBMCs of patients with GC before operation was related positively to metastatic lymphatic nodes ratio （rs=0.422，P=0.002），metastatic lymph node number （rs=0.398，P=0.004），and ABSV of CD133 mRNA in the primary lesion of GC （rs=0.337，P=0.017）. The ABSV of CD133 mRNA in the PBMCs of patients with GC after operation obtained from blood sample at 1 week after curative resection was higher than that in the patients before operation （P=0.021）. Patients suffered from deeper invasion inclined to have a higher ABSV of CD133 mRNA after surgery （P=0.039）. Higher expression of CD133 mRNA in patients after operation demonstrated a much poorer survival rate （P=0.013）. Conclusions Higher expressive level of CD133 mRNA in GC before operation is associated to poor cell differentiation，lymph vessel invasion，deeper invasion，higher lymph node metastasis，later TNM stage，and positive expression of CD133 protein. It is also related positively to metastatic lymphatic nodes ratio，metastatic lymph node number，and ABSV of CD133 mRNA in primary lesion of GC. The level of CD133 mRNA in PBMCs of patients with GC is higher after operation as compared with before operation，which demonstrates deeper invasion and poorer survival.