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Human epidermal growth factor receptor 2 (HER2), programmed death-1 and programmed death-ligand 1 are related to the proliferation, invasion and metastasis of various tumor cells. A variety of antibodies and small molecule drugs targeting HER2 have achieved considerable results in clinical practice. Immune checkpoint inhibitors targeting programmed death-1 and programmed death-ligand 1 have significant effects in clinical application. In the KEYNOTE-811 trial, the combination of immune checkpoint inhibitors and targeted therapy has achieved encouraging results in HER2-positive advanced gastric cancer.
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Cervical cancer is a common malignant tumor of female reproductive system. The treatment of cervical cancer is based on surgery and radiotherapy (or concurrent chemoradiation). Lower extremity lymphedema (LEL) is a frequent complication after cervical cancer treatment, which significantly affects the quality of life of patients. Both pelvic surgery and radiation for cervical cancer can lead to LEL. The risk factors for LEL are complicated and involving characteristics regarding patient (age, comorbidities, lifestyle, etc.), tumor [International Federation of gynecology and Obstetrics (FIGO) stage, lymph node metastasis, etc.], and treatment (number of resected lymph nodes, removal of circumflex iliac nodes, adjuvant therapy, etc.). Comprehensive measures are proposed to prevent cervical cancer patients from LEL, and further investigations in terms of effectiveness are warranted.
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The miR-34 family plays an important role in gastric cancer, and the inactivation or reduced expression of the miR-34 family is detected in gastric cancer cell lines and gastric cancer tissues compared with normal gastric mucosa tissues, indicating it is associated with the occurrence and development of gastric cancer. Studies have shown that miR-34 plays a key role in inhibiting gastric cancer progression by regulating IGF2BP3, survivin, Bcl-2 and epithelial-mesenchymal transition-related pathway, indicating that miR-34 is an important target for gastric cancer treatment. In terms of clinical treatment, miR-34 has not only been proved to have radiochemotherapy sensitization, but also achieved good curative effect in tumor clinical trials. With the emergence of miR-34 vectors targeting gastric cancer, it is possible to use it for gastric cancer treatment. Deep understanding of the molecular basis and clinical efficacy of miR-34 for gastric cancer treatment can help to evaluate the potential of the miR-34 family as a new therapeutic target for gastric cancer.
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Objective:To investigate the effects of programmed death-ligand 1 (PD-L1) expression on the biological behaviors of gastric cancer cell line MKN45.Methods:The PD-L1 gene of gastric cancer cell line MKN45 was silenced by RNA interference technique. MKN45 cells were divided into blank control group, si-NC group (transfected with siRNA-NC) and si-PD-L1 group (transfected with siRNA-PD-L1). Quantitative real-time PCR was used to detect the mRNA expressions of PD-L1 and epithelial-mesenchymal transformation (EMT)-related proteins E-cadherin, Vimentin and Snail in MKN45 cells, and Western blotting was used to detect the expression levels of PD-L1 protein in MKN45 cells of each group. Transwell migration test, Transwell invasion test and MTT test were used to detect the migration, invasion and adhesion abilities of MKN45 cells.Results:The relative expression levels of PD-L1 mRNA in the blank control group, si-NC group and si-PD-L1 group were 1.002±0.092, 1.005±0.121 and 0.237±0.017, respectively, with a statistically significant difference ( F=75.61, P<0.001). The protein expression levels of PD-L1 in the three groups were 0.944±0.028, 1.008±0.088 and 0.269±0.015, respectively, with a statistically significant difference ( F=172.99, P<0.001). The mRNA and protein expression levels of PD-L1 in the si-PD-L1 group were lower than those in the other two groups (all P<0.001), but there were no statistically significant differences between the blank control group and si-NC group (all P>0.05). The cell migration rates of the blank control group, si-NC group and si-PD-L1 group were (1.000±0.020)%, (1.012±0.084)% and (0.488±0.050)%, respectively, with a statistically significant difference ( F=80.73, P<0.001). The cell invasion rates of the three groups were (0.929±0.087)%, (0.924±0.208)% and (0.300±0.100)%, respectively, with a statistically significant difference ( F=19.37, P<0.001), and the cell adhesion rates of the three groups were (100.000±5.407)%, (99.280±4.845)% and (59.723±2.674)%, respectively, with a statistically significant difference ( F=79.87, P<0.001). Compared with the blank control group and si-NC group, the migration, invasion and adhesion abilities of MKN45 cells in the si-PD-L1 group decreased significantly (all P<0.001). The expression levels of E-cadherin mRNA of the three groups were 1.000±0.023, 0.981±0.051, 3.618±0.201, the expression levels of Vimentin mRNA were 1.000±0.043, 1.108±0.150, 0.328±0.011, the expression levels of Snail mRNA were 1.061±0.103, 1.090±0.110, 0.304±0.043, respectively, with statistically significant differences ( F=477.17, P<0.001; F=65.97, P<0.001; F=72.70, P<0.001). Compared with the blank control group and si-NC group, the mRNA expression levels of Vimentin and Snail of MKN45 cells in the si-PD-L1 group decreased, while the expression level of E-cadherin mRNA increased, with statistically significant differences (all P<0.001). Conclusion:Silencing the expression of PD-L1 can reduce the migration, invasion and adhesion abilities of MKN45 cells, and the mechanism may be related to the effect of PD-L1 on the EMT pathway of gastric cancer.
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Objective To investigate the changes of hypoxia-inducible factor (HIF-1α, HIF-2α) expression level in lung cancer A-549 cells under normoxic conditions, different hypoxia durations, and different oxygen concentrations. Methods A549 cells were divided into normoxic group, time control group, and oxygen concentration control group. Western blot was used to detect the expression of HIF-1α and HIF-2α in A-549 cells.Results The expression of HIF-1α and HIF-2α protein were lower under normoxia and significantly increased under hypoxic conditions. The difference was statistically significant. The lower the oxygen concentration, the more HIF-1α and HIF-2α protein expression levels were. The differences between high and high were statistically significant. The expression of HIF-1α protein increased at 2 h after hypoxia, peaked at 8 h, appeared plateau at 8 to 16 h, and decreased at 32 h, with a statistically significant difference. HIF-2α proteins gradually increased with prolonged hypoxia. Conclusions Under hypoxic conditions, the expression of HIF-1α and HIF-2α are increased, and the expression of HIF-2α has a time-dependent pattern, which may have more important biological significance.
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Objective To investigate the effect of isosorbide mononitrate on the levels of NO,iNOS,IL-1 and IL-6 in lung tissue of spontaneously hypertensive rats (SHR).Methods Fourteen-week-old Wistar and SHR male rats were randomly divided into the W0,W1,S0 and S1 group,with 10 rats ineach group.Rats in the W0 and S0 group were fed with the normal saline and the ordinary food,rats in the W1 and S1 group were fed with isosorbide mononitrate and the ordinary food.Twelve weeks later,levels of NO,iNOS,IL-1 and IL6 in rat lung tissue were detected.Results Compared with the W0 group,levels of NO,iNOS,IL-1 and IL6 were significantly increased in the W1 groups (P < 0.05,respectively).Compared with the SO group,levels of NO,iNOS,IL-1 and IL6 were significantly increased in the S1 group (P < 0.05,respectively).In the W1 and S1 group,levels of iNOS and NO were positively correlated with IL-1 and IL-6.Conclusion 1.Isosorbide mononitrate may lead to increases of NO,iNOS,IL-1 and IL6 in lung tissue of Wistar rats,which indicates the presence of chronic inflammation.2.Longterm feeding of isosorbide mononitrate may lead to increases of inflammatory factors in SHR rats,contributing to the inflammatory state in rats.
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Objective To investigate the safety and clinical efficacy of recombinant human endostatin injection (endostar) continuous pumping combine with chemotherapy injection in the treatment of advanced malignancies . Methods 156 patients with advanced cancer were divided into the chemotherapy group (78 cases) and the chemotherapy combined with endostar group (78 cases). The two groups were similar in the tumor types, the neoplasm staging, the KPS and the chemotherapy agents. After two cycles chemotherapy, the efficacy was evaluated according to RECIST criteria and the quality of life (QOL) was assessed by KPS scores. Results The objective response rate (RR) of the chemotherapy combined with endostar group was 39.74%(31/78). The RR of the chemotherapy group was 17.95%(14/78). There was statistics significance in the RRs of the two groups (P0.05), and all patients can tolerate. Conclusion The QOL of patients with advanced malignant tumors are improved by endostar combined with chemotherapy which is safe and effective. It is worthy further clinical observation.