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Objective:To investigate the effects of cabazitaxel on lung cancer cell metastasis and proliferation and the related mechanisms.Methods:Lung cancer cells A549 were divided into two groups. The experimental group were cultured with a low concentration of 50 μg/ml cabazitaxel, and the control group were cultured with an equal volume of a solution of cabazitaxel. The proliferation ability of the two groups of cells was examined using CCK8 and plate cloning experiments. The migration ability of A459 cells was verified by transwell and cell scratch experiments. The expression levels of MMP2/9, CDK4/6, and P16 protein were detected by Western blotting.Results:Compared with the control group, the cell proliferation ability of the A549 cell was weakened in the experimental group. The plate clone formation rate of the experimental group was 17.5%±2.3%, and A549 cell clone formation rate of the control group was 74.8%±4.5%. The cloning ability was reduced in the experimental group. Western blot results showed that the expression of CDK4/6 in the experimental group was down-regulated and the expression of P16 was up-regulated. The scratch healing percentage of the cells in the experimental group was 56.2%±3.8%, and the scratch healing percentage of the cells in the control group was 86.8%±5.2%. The scratch healing ability of the cells in the experimental group decreased. The transwell results showed that the experimental group had 35±4 cells per field of view, while it was 78±9 in the control group. The cell migration ability of the experimental group was decreased. Western blot results showed that the expression of MMP2/9 in the experimental group was down-regulated.Conclusion:Cabazitaxel leads to a decrease in the metastasis ability of lung cancer cells A549 through the extracellular matrix pathway, and inhibits cell proliferation by up-regulating P16.
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Objective:To investigate the induction of specific T lymphocyte by bispecific monoclonal antibody in pancreatic cancer and its killing effects on KIF20A positive pancreatic cancer PANC1 cell line.Methods:CD 3/KIF20A bispecific monoclonal antibody was prepared and concentrated by chemical cross-linking method and purified by Sephrose-25 gel chromatography. Peripheral blood samples of healthy volunteers were collected, and monocytes were isolated using lymphocyte separation solution, and then cultured as dendritic cells (DC) and T cells respectively, and then co-cultured as DC-T cells. Meanwhile vitamin C was used to treat DC-T cells (vcDC-T cells). The levels of IFN-γ, IL-2, IL-4 and IL-12 in the supernatants and T cell subsets were detected by flow cytometry. About 1×10 5 T cells, DC-T cells, and vcDC-T cells with 10, 50, 100 and 300 ng CD 3/KIF20A antibody loaded were cocultured with PANC1 cells (20∶1) for 2, 6 and 10 hours to determine the highest killing rate dosage of CD 3/KIF20A antibody loaded cells. DC-T cells and DC-T cells, vcDC-T cells loaded with the highest killing rate dosage of CD 3/KIF20A antibody were cocultured with PANC1 cells (20∶1) for 2, 6, 8, 10 and 12 hours. The aggregation effect of effector cells on target cells was observed under inverted microscope, the killing rate of tumor cells was detected by LDH method. Results:The molecular weight of CD 3/KIF20A antibody was 130 000 measured and validated by SDS gel electrophoresis. The ratio of CD 8+ CD 28+ and CD40L subsets of vcDC-T cells was increased [(47.6±15.8)% vs (38.2±7.6)%, (52.1±4.9)% vs (44.7±3.2)% ] compared with that of DC-T cells, the ratio of negative regulatory cells (Treg) was decreased [(4.3±0.8)% vs (8.3±1.1)%]; the release of IL-2, IFN-γ and IL-12 was increased [(201.2±17.3) ng/L, (163.4±13.1)ng/L, (303.3±22.6)ng/L vs 221.8±17.6)ng/L, (190.4±11.7)ng/L vs (80.3±8.6)ng/L]. All the differences were statistically significant ( P<0.01). 100 ng CD 3/KIF20A loaded T cells were observed under microscope, which obviously targeted KIF20A + pancreatic cancer PANC1 cells and had a strongest killing power. At the killing cells to targeting cells ratio of 20∶1 with 4-hour coculture, the killing rate of CD 3/KIF20A-vcDC-T cells on PANC1 cells was (88.6±2.6)%, which was significantly higher than (68.4±3.4)% and (39.2±2.1)% in the CD3/KIF20A-DC-T group and (39.2±2.1)% in the DC-T group, increasing by 20% and at lease 45%, respectively. Conclusions:DC-T cells loaded with CD 3/KIF20A antibody can significantly increase the killing rate of KIF20A positive pancreatic cancer PANC1 cells, and vitamin C intervention can further enhance the killing ability of antibody loaded T cells.
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Objective:To investigate the safety and efficacy of anlotinib in treatment of advanced malignant tumors.Methods:The clinical data of 65 patients with advanced malignant tumors after the failure of the second-line treatment in Shanxi Bethune Hospital from July 2018 to July 2019 were retrospectively analyzed, including 32 cases of non-small cell lung cancer, 12 cases of small cell lung cancer, 15 cases of ovarian cancer, and 6 cases of peritoneal cancer. The objective total remission rate (ORR), disease control rate (DCR), progression-free survival (PFS) time, and the related adverse events were also analyzed.Results:ORR in non-small cell lung cancer group was 43.7% (14/32), DCR was 68.8% (22/32); ORR in small cell lung cancer group was 8.3% (1/12), and DCR was 25.0% (3/12). ORR in ovarian cancer group was 33.3% (5/15), DCR was 73.3% (11/15). In peritoneal carcinoma group, ORR was 0 (0/6) and DCR was 33.3% (2/6). The median PFS time was 8.0 months (95% CI 6.2-9.8 months) in the non-small cell lung cancer group, 3.0 months (95% CI 1.9-4.1 months) in the small cell lung cancer group, 5.0 months (95% CI 3.1-6.9 months) in the ovarian cancer group, and 2.0 months (95% CI 0.0-5.6 months) in the peritoneal cancer group. Hypertension was the most common non-hematology-related adverse event, and there were 6 cases (9.2%) of grade Ⅰ-Ⅱ adverse event and 1 case (1.5%) of grade Ⅲ-Ⅳ adverse event. Among the hematology-related adverse events, thrombocytopenia was the most common, and there were 8 cases (12.3%) of grade Ⅰ-Ⅱ adverse event and 1 case (1.5%) of grade Ⅲ-Ⅳ adverse event. All patients could tolerate the adverse reactions. Conclusion:Anlotinib is one of the options for the treatment of advanced malignant tumors, with mild drug-related adverse reactions and definite efficacy.
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Objective To investigate the safety and efficacy of low-dose apatinib in treatment of advanced malignant tumors. Methods The clinical data of 54 patients with advanced malignant tumors who were admitted to Shanxi Dayi Hospital from March 2015 to March 2018 were analyzed retrospectively. These patients were treated with apatinib at doses of 250 mg (29 cases) and 500 mg (25 cases) after initial treatment or failure of multi-line treatment. There were 15 cases of gastric cancer, 11 cases of lung cancer, 9 cases of ovarian cancer, 7 cases of liver cancer, 6 cases of soft tissue sarcoma, 3 cases of esophageal cancer, 2 cases of melanoma, and 1 case of peritoneal cancer. The objective response rate (ORR), disease control rate (DCR), progress free survival (PFS) and overall survival (OS) were analyzed, and the efficacy and related adverse reactions were evaluated. Results The adverse reactions of 54 patients could be evaluated. Non-hematological drug-related adverse reactions were most common with hypertension, hand-foot skin reaction and proteinuria, while hematologic drug-related adverse reactions were most common with leukopenia and thrombocytopenia. All patients were well tolerated. The incidence of drug-related adverse reactions in the 250 mg dose group was lower than that in the 500 mg dose group, and the incidence of grade Ⅰ-Ⅱhypertension between the two groups was statistically different (χ2 = 6.268, P= 0.012). Short-term efficacy:ORR of the patients in the 250 mg and 500 mg dose groups was 6.9％ (2/29) and 12.0％ (3/25), respectively;DCR was 41.4％ (12/29) and 52.0％ (13/25), respectively; and the 500 mg dose group was superior to the250 mg dose group, but the differences were not statistically significant (ORR: χ2= 0.416, P= 0.519; DCR:χ2= 0.609, P= 0.435). Long-term efficacy: the 500 mg dose group had a slight advantage over the 250 mg dose group in both median PFS time (3.9 months vs. 3.6 months) and median OS time (7.8 months vs. 7.6 months), but the differences were not statistically significant (PFS:χ2=0.472, P=0.492; OS:χ2=0.261, P=0.609). Conclusions Low-dose apatinib can be used to treat advanced malignant tumors. The drug-related adverse reactions are small, the curative effects are exact, the adverse reactions are easy to tolerate, and it is convenient for long-term use. Low-dose apatinib is one of the treatment options for advanced malignant tumors.
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In recent years,the biological therapy of ovarian cancer has made great progress.Immunotherapy including tumor vaccine and adoptive immunity cell therapy can improve immune recognition capability,while the applications of molecular targeted drugs such as monoclonal antibodies and tyrosine kinase inhibitors for different target spots during the tumor cells growth progresses achieve significant clinical benefit,as well as hormone replacement therapy and Chinese medicine treatment improve the life quality of patients with ovarian cancer to a certain degree.