Objective
To study relationship between integrins and carcinogenesis, development, treatment or prognosis of gastric cancer.
Methods
The literatures about integrins and gastric cancer in recent years were reviewed and analyzed.
Results
The current study found that the β1 subunit integrins and αν subline integrins are closely associated with the gastric cancer. The β1 subunit integrins are associated with the invasion and metastasis of the gastric cancer, the αν subline integrins are associated with the typing, grading, and staging of the gastric cancer, and the ανβ3, ανβ5 and ανβ6 are associated with the prognosis of the gastric cancer, further more, the ανβ6 could be used as an independent effective prognostic factor.
Conclusions
Integrins are associated with occurrence, development, treatment, and prognosis of gastric cancer. It′s mechanism such as signal transduction pathway is not completely clarified. With further in-depth research, it′s molecular mechanism would be gradually elucidated and provide new ideas and methods for diagnosis, treatment, and prognosis of gastric cancer.
ObjectiveTo investigate the association between polymorphism of V4,F+1 in ADAM33 (adisintegrin and metalloproteinase 33) gene and COPD in a northwestern Uighur population.
MethodsA total of 100 Uighur COPD patients and 140 healthy volunteers were recruited in the study. Genotypes were determined by restriction fragment lengthpolymorphism(PCR-RFLP). All subjects had a epidemiological investigation including modified british medical research council(mMRC),COPD assessment test(CAT),and pulmonary function test. The 100 Uighur COPD patients were assessed by revised GOLD2011.
ResultsAssessed by revised GOLD2011,the patients of A,B and C grade accounted for 22%,35% and 30%,respectively. There was no statistical significance in the distributions of the V4,F+1 alleles between the patients and the controls(P>0.05). There was no statistical significance between SNPs in ADAM33(V4 and F+1) with the decreased lung function and the grade of COPD(P>0.05).
ConclusionThere was no association between polymorphism of V4,F+1 in ADAM33 gene and COPD in a northwestern Uighur population.
Low shear stress is a component of the tumor microenvironment in vivo and plays a key role in regulating cancer cell migration and invasion. The integrin, as a mechano-sensors mediating and integrating mechanical and chemical signals, induce the adhesion between cells and extracellular matrix (ECM). The purpose of this study is to investigate the effect of low shear stress(1.4 dyn/cm2)on the migration of HepG2 cells and the expression of integrin. Scratch wound migration assay was performed to examine the effect of low shear stress on the migration of HepG2 cells at 0 h, 1 h, 2 h and 4 h, respectively. F-actin staining was used to detect the expression of F-actin in HepG2 cells treated with low shear stress at 2 h and 4 h. Western blot analysis was carried out to determine the effect of low shear stress on the expression of integrin at different durations. The results showed that the migrated distance of HepG2 cells and the expression of F-actin increased significantly compared with the controls. The integrin α subunits showed a different time-dependent expression, suggesting that various subunits of integrin exhibit different effects in low shear stress regulating cancer cells migration.
ObjectiveTo summarize the relationship between integrins, tumor metabolism, and tumor cells with pancreatic stellate cells in the tumor microenvironment, in order to provide targets and ideas for the treatment of pancreatic ductal adenocarcinoma.MethodTo review the literatures on pancreatic stellate cells, integrins, and amino acid metabolism as therapeutic targets for pancreatic ductal adenocarcinoma in the domestic and overseas.ResultsThe drug research for pancreatic ductal adenocarcinoma was currently under vigorous development, but remain in the animal and clinical test stage. As a new therapeutic protein, ProAgio could inhibit the expression of integrin αvβ3, activation and secretion of pancreatic stellate cells, and alanine metabolism in the microenvironment of pancreatic ductal adenocarcinoma, so as to achieve the dual effects of anti-fibrosis and anti-tumor.ConclusionsThe roles of activated pancreatic stellate cells, ProAgio, integrin αvβ3, and alanine metabolism in pancreatic ductal adenocarcinoma have been partially elucidated, but the specific mechanism still needs further investigation and may become a completely new therapeutic target someday.
Objective
To investigate the inhibition effect of silence of a disintegrin and metalloproteinase 17 (ADAM17) gene on proliferation and apoptosis of HT29 colon cancer cells and its possible mechanism.
Methods
HT29cells were divided into 3 groups: cells of interference group were transfected with recombinant lentivirus vector, cells of negative control group were transfected with negative recombinant lentivirus vector, and cells of blank control group were treated with PBS. The expression of ADAM17 mRNA was detected by real-time PCR, the expressions of ADAM17 protein, caspase3, protein kinase B (Akt), glycogen synthase kinase-3β (GSK3β), phospho-protein kinase B (P-Akt), phospho-glycogen synthase kinase-3β (P-GSK3β) protein were detected by Western blot method, the cell proliferation was detected by MTT assay, and the apoptosis rate was detected by Annexin V-FITC/PI cell death detection kit.
Results
Compared with the control group and the negative control group, the interference group was related to low expressions of ADAM17 mRNA and its protein, low optical density value at the same time point (24, 48, and 72 h), high apoptosis rate, high expression level of caspase3 protein, but low expression levels of P-Akt and P-GSK3β protein (P<0.05).
Conclusion
Silent ADAM17 gene could significantly induces apoptosis and inhibits the proliferation of HT29 cells, which maybe via inhibiting Akt/GSK3β signaling pathway.
Objective Epidermal stem cells (ESCs) can actively partici pate in wound heal ing and enhance reepithel ial ization. To establ ish ideal diabetes mell itus (DM) rat models and to investigate the expression of keratin 19 (K19),β1-integrin, β-catenin, and prol iferating cell nuclear antigen (PCNA) in ESCs of DM rat model, then to study the potential mechanism of difficult recovering wounds of diabetic skin. Methods Twenty male SD rats (weighing 250-300 g) were dividedinto DM group and normal control group randomly (n=10). The DM rat model was made by intraperitoneal injected 65 mg/kg streptozocin (STZ), the normal control group was not treated. At 4 weeks after injection, pancreatic tissue was harvested for HE staining in two groups. The ESCs isolated from full-thickness skins of the back of two group rats were culutured and identified. The 2nd passage of ESCs were obtained for immunocytochemical staining of K19, β1-integrin, β-catenin, and PCNA. Meanwhile, the cell cycle were measured by flow cytometry. The cell colony formation rates were detected after 1 week. Results The achievement ratio of DM rat model was 90% with good stabil ity. HE staining showed that the number of islet cells significantly decreased with degeneration and necrosis in DM group; the structure of islet cell was clear without degeneration and necrosis in normal control group. The integral absorbance values of positive expression for K19, β1-integrin, β-catenin, and PCNA in ESCs of DM group (82.63 ± 14.77, 21.59 ± 4.71, 6.49 ± 6.58, and 90.77 ± 12.44, respectively) were significantly lower than those in the normal control group (151.24 ± 42.83, 54.48 ± 17.43, 116.39 ± 9.26, and 110.62 ± 20.67, respectively) (P lt; 0.01). The clone forming efficiency of ESCs in DM group (6.43% ± 1.01% ) was significantly lower than that in the normal control group (11.37% ± 1.62%) (P lt; 0.01). Flow cytometry indicated that 88.89% of cultured ESCs in the DM group were in resting state/ pre-DNA-synthetic gap (G0/G1), and the apoptosis rate was 3.98%; 91.50% in the normal control group and the apoptosis rate was 0. Conclusion The DM rat model can be effectively induced by intraperitoneal injected 65 mg/ kg STZ. The decreased amount and the low prol iferation and differentiation capacity of ESCs may be one of the important mechanisms of difficult recovering wounds of DM rats.
Objective To investigate the role of calcium- and integrin-binding protein-1（CIB1） in oxidized lowdensity lipoprotein（OX-LDL） inhibiting migration of mouse macrophages. Methods To silence CIB1 express of mouse macrophages by RNA interference, then incubating mouse macrophages with OX-LDL, cell migration and cell spreading of mouse macrophages were analyzed. Results At 24-72h after macrophages transfected CIB1 siRNA, the express of CIB1 protein was restrained obviously. To silence CIB1 express could increase migration and spreading of mouse macrophages significantly. Conclusions CIB1 plays the important role in intracellular modulating mechanism of OX-LDL inhibiting mouse macrophages migration.
ObjectiveTo investigate the expression of a disintegrin and metalloproteinase with thrombospondin typeⅠmotif (ADAMTS1) in colorectal cancer tissues, and to study the relationship with clinicopathological features and prognosis of it.
MethodsExpression of ADAMTS1 was evaluated by immunohistochemistry (SP method) in 65 specimens, which obtained by resection from patients with colorectal cancer, including corresponding adjacent benign tissues. Chi-square test was used for analyzing the relationship between expression of ADAMTS1 and clinicopathological features of colorectal cancer tissues. Cox proportional hazard model was used to explore the relationship between expression of ADAMTS1, other clinicopathological parameters, and patients' survival situation.
ResultsThe positive expression rate of ADAMTS1 was 40% (26/65) in the colorectal cancer tissues and 85% (55/65) in the adjacent benign tissues, which was significantly higher in adjacent benign tissues (χ2=27.546, P < 0.001). The positive expression rate of ADAMTS1 was significantly lower in the colorectal cancer tissues with lymph node metastasis than that of the colorectal cancer without lymph node metastasis (χ2=5.329, P=0.021). Results of survival analysis showed that median survival time were 27 months in the ADAMTS1-negative group and 70 months in the ADAMTS1-positive group respectively, and the survival situation was better in latter group (χ2=10.151, P=0.001). Results of multivariable prognostic analysis of Cox proportional hazard model showed that colorectal cancer withⅠ-Ⅱstage (RR=3.782, 95% CI:1.509-9.476, P=0.005), without lymph node metastasis (RR=3.107, 95% CI:1.186-8.138, P=0.021), and with positive-expression of ADAMTS1 (RR=2.020, 95% CI:1.071-3.809, P=0.030) had better survival situation.
ConclusionsExpression of ADAMTS1 is down-regulated in colorectal cancer tissues and it is associated with lymph node metastasis. The prognosis of patients in ADAMTS1-positive group is better than that of ADAMTS1-negative group, suggesting that ADAMTS1 may be an independent prognostic factor in colorectal cancer.
OBJECTIVE: To investigate the selection and identification of human keratinocyte stem cells(KSC) in vitro. METHODS: According to the characteristics of KSC which can adhere to extracellular matrix very fast, we selected 3 groups of different time(5 minutes, 20 minutes and 60 minutes) and unselected as control group. And the cells were identified by monoclone antibody of beta 1-integrin and cytokeratin 19 (Ck19), then the image analysis was done. Furthermore we analyzed the cultured cells with flow cytometer(FCM) and observed the ultrastructure of the cell by transmission electron microscope(TEM). RESULTS: The cell clones formed in all groups after 10 to 14 days, while the cells of 5 minute group grew more slowly than those of the other groups, however, the clones of this group were bigger. The expression of beta 1-integrin and Ck19 were found in all groups. The positive rate of beta 1-integrin was significant difference between 5 minute group and the other groups (P lt; 0.05). And the expression of Ck19 was no significant difference between 5 minute group and 20 minute group(P gt; 0.05), and between 60 minute group and control group. But significant difference was observed between the former and the later groups(P lt; 0.05). The result of FCM showed that most cells of the 5 minute group lied in G1 period of cell cycle, which was different from those of the other groups. At the same time, the cells of 5 minute group were smaller and contained fewer organelles than those of the other groups. CONCLUSION: The above results demonstrate that the cells of 5 minute group have a slow cell cycle, characteristics of immaturity, and behaving like clonogenic cells in vitro. The cells have the general anticipated properties for KSC. So the KSC can be selected by rapid attachment to extracellular matrix and identified by monoclone antibody of beta 1-integrin and Ck19.
Mechanical stress modulates almost all functions of cells. The key to exploring its biological effects lies in studying the perception of mechanical stress and its mechanism of mechanotransduction. This article details the perception and mechanotransduction mechanism of mechanical stress by extracellular matrix, cell membrane, cytoskeleton and nucleus. There are two main pathways for the perception and mechanotransduction of mechanical stress by cells, one is the direct transmission of force, and the other is the conversion of mechanical signal into chemical signal. The purpose of this study is to provide some reference for the exploration of precise treatment of mechanical stress-related diseases and the optimization of construction of tissue engineered organs by mechanical stress.
