Circ_0091579 exerts an oncogenic role in hepatocellular carcinoma via mediating miR-136-5p/TRIM27.

BACKGROUND: Circular RNAs (circRNAs) act as crucial regulators in tumorigenesis. In this study, the working mechanism of circ_0091579 in hepatocellular carcinoma (HCC) progression was investigated. METHODS: The expression of RNA and protein was measured via RT-qPCR and Western blot assay. Cell proliferation ability was analyzed via CCK8, EdU and colony formation assays. Cell migration and invasion abilities were detected via transwell assays. Flow cytometry was applied to assess cell cycle and apoptosis. The target relation between miR-136-5p and circ_0091579 or tripartite motif containing 27 (TRIM27) was certified using dual-luciferase reporter assay. Xenograft tumor model was utilized to assess the role of circ_0091579 in tumor growth in vivo. The protein level of Ki67 in tumor tissues was analyzed by immunohistochemistry (IHC) assay. RESULTS: Circ_0091579 expression was elevated in HCC tissues and cell lines. HCC patients with high circ_0091579 expression displayed low survival rate. Circ_0091579 knockdown suppressed the proliferation, migration, invasion, cell cycle progression and epithelial-mesenchymal transition (EMT) and induced apoptosis of HCC cells. Circ_0091579 acted as a molecular sponge for miR-136-5p, and circ_0091579 silencing-mediated effects were largely overturned by the knockdown of miR-136-5p in HCC cells. MiR-136-5p interacted with the 3' untranslated region (3'UTR) of TRIM27, and TRIM27 overexpression largely counteracted miR-136-5p overexpression-induced influences in HCC cells. Circ_0091579 sponged miR-136-5p to up-regulate TRIM27 expression in HCC cells. Circ_0091579 silencing suppressed xenograft tumor growth in vivo. CONCLUSION: Circ_0091579 exhibited an oncogenic role to enhance the malignant potential of HCC cells through mediating miR-136-5p/TRIM27 axis in vitro and in vivo.

The relationship between pneumonitis and programmed cell death-1/programmed cell death ligand 1 inhibitors among cancer patients: A systematic review and meta-analysis.

BACKGROUND: We put the meta-analysis into practice to reveal the relationship between the incidence risk of immune-related pneumonitis and the use of programmed cell death-1 (PD-1) and ligand 1 (PD-L1) inhibitors related pneumonitis in cancer patients. METHOD: The meta-analysis was put into practice according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Odds ratio (OR) was evaluated by random effect model. RESULTS: After screening and eligibility assessment, 33 clinical trials involving 19,854 patients were selected and used for the final meta-analysis after selection criteria checked. Compared with chemotherapy, the use of PD-1/PD-L1 inhibitors alone increased the incidence risk of all-grade (OR = 4.29, 95% confidence interval: [2.97, 6.19], P < .00001) and grade 3 to 5 immune-related pneumonitis (OR = 3.53, 95% confidence interval: [2.04, 6.11], P < .00001). Similar trend could also be found when PD-1/PD-L1 inhibitors were prescribed alone or in combination with other anti-tumor therapies. CONCLUSION: Whether PD-1/PD-L1 inhibitors were used alone or combined with other antitumor drugs, the incidence risk of immune-related pneumonitis would be increased.

The Risk Ratio of Immune-Related Colitis, Hepatitis, and Pancreatitis in Patients With Solid Tumors Caused by PD-1/PD-L1 Inhibitors: A Systematic Review and Meta-Analysis.

Purpose: The meta-analysis was put into practice in evaluating the risk ratio of immune-related digestive system inflammation in patients with solid tumors caused by PD-1/PD-L1 inhibitors. Method: The process of the meta-analysis was performed by us according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Results: After screening and eligibility assessment, a total of 26 clinical trials involving 16,409 patients were selected for the final quantitative synthesis. Immune-related digestive system inflammations, including colitis, hepatitis, pancreatitis, were evaluated separately. Compared with chemotherapy, PD-1/PD-L1 inhibitors led to an increase in the incidence risk of all grade colitis (RR = 2.43, 95% CI: [1.23, 4.82], P = 0.01). Similar incidence trend could also be seen when PD-1/PD-L1 inhibitors were combined with chemotherapy (RR = 2.62, 95% CI: [1.25, 5.48], P = 0.01). Whether compared with Nivolumab plus Ipilimumab or Ipilimumab alone, the incidence risk of colitis in the Nivolumab group was significantly lower than that of the control group. Similar analysis results could also be seen in the incidence risk of hepatitis. We did not find a statistically significant effect on the incidence of immune-related pancreatitis after the use of PD-1/PD-L1 inhibitors. Conclusion: The use of PD-1/PD-L1 inhibitors increased the incidence risk of immune-related colitis and hepatitis, but this potential to increase the incidence risk of the disease was weaker than Ipilimumab.

Odds ratio of programmed cell death-1 or ligand 1 inhibitor-related endocrine dysfunction in patients with lung cancer: A systematic review and meta-analysis.

PURPOSE: We designed the study to investigate the incidence risk of Programmed Cell Death-1 (PD-1) or Ligand 1 (PD-L1) inhibitor-related endocrine dysfunction in patients with lung cancer. METHOD: All the data were collected by 1 primary reviewer and then independently reviewed by 2 secondary reviewers according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISM) guidelines. Incidence risk of all-grade and grade 3-5 PD-1/PD-L1 inhibitors related endocrine dysfunction in patients with lung cancer were taken into account. RESULTS: Overall, 12 clinical trials comprising 6108 patients were identified in this systematic review and meta-analysis. The incidence risk of hypothyroidism, hyperthyroidism and adrenal insufficiency was higher in NSCLC patients receiving combination treatments. The incidence rate of all-grade of hypothyroidism was lower in PD-1/PD-L1 inhibitor subgroup compared to chemotherapy (OR = 22.62, 95%CI:9.79-52.25), while the similar result was seen in another treatment regimen (PD-1 + platinum-based chemotherapy vs platinum-based chemotherapy) (OR = 2.93, 95%CI: [2.08, 4.11). The different result can be seen in the group related to the other treatment regimen (1PD-1/PD-L1 inhibitor vs 2 PD-1/PD-L1 inhibitors) (OR = 0.40, 95%CI:0.21-0.76). All the results of the above analysis were considered to be statistical significant. Similar result could also be seen in meta-analysis related to hyperthyroidism and adrenal insufficiency. CONCLUSION: The incidence risk of endocrine dysfunctions, including hypothyroidism, hyperthyroidism and adrenal insufficiency, were higher for PD-1/PD-L1 inhibitors group.

The Association Between the Incidence Risk of Peripheral Neuropathy and PD-1/PD-L1 Inhibitors in the Treatment for Solid Tumor Patients: A Systematic Review and Meta-Analysis.

Purpose: We conducted this study to determine the relationship between PD-1/PD-L1 inhibitors and the incidence risk of peripheral neuropathy in patients with solid tumors. Method: The process of the meta-analysis was performed by us according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Incidence of all-grade and grade 3-5 treatment-related peripheral neuropathy in patients with solid tumors were taken into account. Results: After screening and eligibility assessment, a total of 17 clinical trials involving 10,500 patients were selected for the final meta-analysis. The incidence risk of peripheral neuropathy for all grade was significantly lower in the PD-1/PD-L1 inhibitor group than that of the control group, either monotherapy (OR = 0.08, 95%CI:[0.03, 0.19]) or chemotherapy (OR = 0.05, 95%CI:[0.03, 0.11]). Similar incidence trend could also be seen for the incidence risk of grade 3-5 peripheral neuropathy. When PD-1/PD-L1 inhibitors were used in combination with chemotherapy, the incidence risk of peripheral neuropathy was higher than in the control chemotherapy group, whether it was all-grade (OR = 1.22, 95%CI:[1.00, 1.49]) or grade 3-5 degree (OR = 1.74, 95%CI:[1.03, 2.92]). Conclusion: Compared with chemotherapy, incidence risk of peripheral neuropathy related to PD-1/PD-L1 inhibitor was significantly lower than that of the chemotherapy group, while PD-1/PD-L1 inhibitor increased the incidence risk of peripheral neuropathy when it was combined with chemotherapy.

The overall safety evaluation of programmed cell death/programmed cell death ligand 1 (PD-1/PD-L1) treatment for lung cancer patients: An updated systematic review and meta-analysis.

BACKGROUND: We performed the meta-analysis to evaluate the overall safety of programmed cell death-1 (PD-1) or ligand 1 (PD-L1) inhibitor treatment for lung cancer patients. METHOD: Randomized controlled trials were collected according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Risk ratio (RR) of PD-1/PD-L1 inhibitor treatment-related death, treatment-related adverse events, any serious events, and any events leading to discontinuation were all taken into account for the final evaluation. RESULTS: Fourteen studies were collected for the meta-analysis. The RR of treatment-related death for PD-1/PD-L1 was significantly lower than that of the control group (RR = 0.37, 95% confidence interval, CI: [0.21, 0.66]). Similar analysis results could also be seen for the RR of treatment-related adverse events and adverse events leading to discontinuation. When PD-1/PD-L1 was combined with chemotherapy, it increased the RR of adverse events leading to discontinuation (RR = 1.68, 95% CI: [1.22, 3.32]). The RR of overall treatment-related adverse events was lower in nivolumab (PD-1) than that of the control group (nivolumab + ipilimumab) (RR = 0.77, 95% CI: [0.65, 0.90]). Similar analysis results could also be seen in the RR of treatment-related adverse events for grade 3 to 5 and adverse events leading to discontinuation. CONCLUSION: Compared with chemotherapy, RR of the treatment-related deaths associated with PD-1/PD-L1 inhibitor was significantly lower than that of the chemotherapy group, while it did not increase the RR when they were combined with chemotherapy or other drugs. When PD-1/PD-L1 was combined with chemotherapy, it increased the RR of adverse events leading to discontinuation.

Methotrexate, doxorubicin, and cisplatinum regimen is still the preferred option for osteosarcoma chemotherapy: A meta-analysis and clinical observation.

BACKGROUND: We designed the study to investigate whether methotrexate, doxorubicin, and cisplatinum (MAP) chemotherapy strategy was still the preferred option for the survival of osteosarcoma patients. METHOD: We collected some trials of osteosarcoma to make a meta-analysis first. Then, we retrospectively collected data from 115 patients with osteosarcoma and performed further analysis to verify the impact of MAP regimen on the survival of patients. RESULTS: Seven studies including 3433 participants met the preliminary inclusion criteria. Meta-analysis of the 3-year disease-free survival (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 0.88-1.28; P = .52) and overall survival (OR = 1.21, 95% CI: 0.70-2.11; P = .54), 5-year disease-free survival (OR = 1.07, 95% CI: 0.87-1.30; P = .54) and overall survival (OR = 0.86, 95% CI: 0.65-1.12; P = .26), and mortality rate (OR = 0.90, 95% CI: 0.70-1.17; P = .44), showed no statistically significant differences. The most common grade 3/4 adverse events were neutropenia (498 [85.9%] patients in MAP vs 533 [93.3%] in MAP plus ifosfamide and etoposide, or other adjuvant therapy drugs [MAP]). MAP was associated with less frequent toxicities than MAP group with statistical significance in thrombocytopenia, febrile neutropenia, anemia, and hypophosphatemia. The same phenomenon could also be seen in the analysis of clinical data. CONCLUSION: MAP regimen remains the preferred option for osteosarcoma chemotherapy.

Incidence risk of PD-1/PD-L1 related diarrhea in non-small cell lung cancer (NSCLC) patients: a systematic review and meta-analysis.

Purpose: We designed the study to illustrate the OR of programmed cell death-1 (PD-1) or ligand 1 (PD-L1) inhibitor-related diarrhea in patients with non-small cell lung cancer. Method: This systematic review and meta-analysis were put into practice according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Incidence of all grades for PD-1/PD-L1 inhibitor-related diarrhea in NSCLC was taken into account. Results: After screening and eligibility assessment of 57 articles, a total of 12 clinical trials involving 6,659 participants were collected for the final meta-analysis. The incidence risk of diarrhea for all grades was lower in PD-1 inhibitor monotherapy compared to monochemotherapy of docetaxel (OR=0.31, 95% CI [0.24, 0.41]; I2=0%, Z=8.23 (p<0.00001)), while a similar result could also be seen in PD-L1 inhibitor monotherapy group (OR=0.41, 95% CI [0.27, 0.64]; I2=59%, Z=3.92 [p<0.00001]). The opposite result can be seen when PD-1/PD-L1 inhibitor combined chemotherapy was compared to chemotherapy alone (OR=1.51, 95% CI [1.22, 1.87]; I2=0%, Z=3.77 [p<0.00001]). Similar incidence trend could also be seen in the meta-analysis of diarrhea for grade 1-2 and grade 3-5. Conclusion: The incidence risk of diarrhea associated with PD-1/-PD-L1 inhibitor monotherapy was significantly lower than that of docetaxel monotherapy group. However it was higher in PD-1/PD-L1 inhibitor combined with chemotherapy group compared with the chemotherapy alone group.

Hyper expression of MTBP may be an adverse signal for the survival of some malignant tumors: A data-based analysis and clinical observation.

To explore the relationship between mouse double minute 2 binding protein (MTBP) and the prognosis of cancer patients, a databank-based reanalysis was conducted and a clinical observation about lung adenocarcinoma was taken to verify the result of data analysis.We reanalyzed all the downloaded data in order to make a conclusion about the relationship between MTBP and the prognosis of cancer patients. At last, we collected 112 lung cancer patients with MTBP information to verify the results of data analysis (GSE30219).The overall Kaplan-Meier curve results of 6 eligible data groups were shown in Fig. 1. The Kaplan-Meier curve result of GSE16011 was shown in Fig. 1A (concordance index = 59.48, Log-Rank Equal Curves [P = 5.942e-05], R = 0.045/1, risk groups hazard ratio = 1.69 [conf. int. 1.3-2.9], P = 7.344e-05), while the stratification results were displayed independently in Figs. 2 and 3. The similar results could be seen in other 5 data groups. The tissue sections of 112 patients with lung adenocarcinoma were collected and immunohistochemically stained. The hyper expression rate of MTBP in adenocarcinoma was 23.21% (26/112). The results showed that patients with hyper expression of MTBP had significantly worse prognosis than the control group, and the survival curves were clearly separated from each other (Fig. 4B, P = .000).Hyper expression of MTBP maybe an adverse event for the survival of some cancer patients, especially in glioblastoma, kidney cancer, and lung cancer patients, which has been verified in 112 lung cancer patients with MTBP status.

[Effect of sequential intratumoral injection of xenogeneic antigens for immunotherapy in immunized mice bearing S180 tumor].

OBJECTIVE: To investigate the therapeutic effect of sequential intratumoral injection of xenogeneic antigens in immunized tumor-bearing mice. METHODS: Sequential intratumoral injection of the xenoantigens was performed in immunized mice bearing S180 tumor. The tumor size changes were observed, and the tumor-infiltrating lymphocytes (TIL) including CD3+CD4+T, CD3+CD8+T, and CD3+CD4+CD25+T lymphocytes were counted with flow cytometry. The concentrations of IL-2 and TNF-alpha in the tumor was measured using ELISA. RESULTS: No significant difference was found in the number of CD3+T lymphocytes in the TILs between different groups. After the immunotherapy, the percentages of CD3+CD4+T, CD3+CD8+T and CD3+CD4+CD25+T lymphocytes were 54%, 22% and 2.91%, respectively, with the CD4+/CD8+ ratio of 2.49, significantly different from that in the control group (P<0.05). The concentrations of IL-2 and TNF-alpha were 100.61 pg/ml and 54.114 pg/ml, respectively, significantly different from those in the control group (P<0.05). CONCLUSION: Sequential intratumoral injection of heteragenetic antigena can significantly increase the amount of effector cells and cytokines in the micro-environment of the tumor, and decrease the expression of T regulatory.