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Objective To investigate the influence of renal failure on the area under curve (AUC) and adverse reactions of docetaxel in breast cancer patients, and provide evidence for the dosage of docetaxel in renal failure patients. Methods A retrospective study was conducted on 24 patients with breast cancer who had undergone radical mastectomy and received AC-T adjuvant chemotherapy in our hospital from January 2019 to November 2021. According to renal function cases, the patients were divided into two groups: renal failure group (n=5) and normal renal function group (n=19). The clinical characteristics such as gender, age, body weight and body surface area of patients in two groups, docetaxel dose, blood concentration, area under the curve, liver and kidney function, white blood cell count and absolute value of neutrophil before chemotherapy were collected. Single factor linear regression was used to analyze the influencing factors of the AUC of docetaxel. Adverse reactions after chemotherapy with docetaxel including nausea and vomiting, bone marrow suppression, constipation and liver function injury were collected. CTCAE 4.0 evaluation standard was used to evaluate adverse reactions. Results The clinical characteristics of creatinine [908.0 (819.0, 1018.0) μmol/L vs 54.8 (52.0, 65.0) μmol/L] and creatinine clearance rate [4.9 (4.3, 5.4) ml /min vs 86.3 (59.3, 92.5) ml/min] of the renal failure group and the normal renal function group have significant difference (P<0.001), while no significant difference (P>0.05) were found in the body surface area [1.4 (1.4, 1.5) m2 vs 1. 6 (1.5, 1.6) m2], docetaxel dose [70.4 (69.4, 73.0) mg/m2 vs 74.4 (72.3, 91.2) mg/m2], body weight [(51.4±3.8) kg vs (51.5±5.5) kg]. Liver function, white blood cells and neutrophils were within the normal range before chemotherapy with docetaxel. There was no significant difference in AUC value [(1.6±0.6) mg·h/L vs (1.8±0.8) mg·h/L] between the two groups after chemotherapy with docetaxel (P>0.05). Linear univariate regression analysis indicated that the blood concentration at the end of docetaxel infusion was significantly associated with AUC of docetaxel (P<0.001), while the body surface area, dose of docetaxel, body weight, liver and kidney function were not correlated with AUC of docetaxel (P>0.05). After chemotherapy with docetaxel, adverse reactions of patients in the two groups: nausea and vomiting (grade I incidence: 40% vs. 57.9%, grade II incidence: 60% vs. 42.1%), myelosuppression (grade I incidence: 60% vs. 84.2%, grade II incidence: 20% vs 15.8%) and constipation (all mild constipation) had no significant difference (P>0.05). Conclusion Renal failure did not affect the exposure of docetaxel and the adverse reactions after chemotherapy with docetaxel in breast cancer patients.
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Objective:To investigate the effects and underlying mechanisms of XRCC3 on esophageal squamous-cell carcinoma (ESCC) radiotherapy response. Methods:Expression levels of XRCC3 were detected by reverse transcription PCR, Western blot, and immunohistochemistry. We knocked down XRCC3 with lentiviral infection in ESCC cells. Cell apoptosis was examined by flow cytom-etry. DNA damage and telomere dysfunction-induced foci were determined by immunofluorescence. Results:The expression levels of XRCC3 in ESCC cells and tissues were higher than those in normal esophageal epithelial cells and corresponding adjacent noncancer-ous esophageal tissues. Knockdown of XRCC3 in ESCC cells substantially increased the therapeutic efficacy of radiation. We demon-strated that the radiation resistance of XRCC3 was attributed to the XRCC3-maintaining telomere stability, which reduced ESCC cell death through radiation-induced apoptosis. Conclusion: Our data suggested that XRCC3 protects ESCC cells from ionizing radia-tion-induced DNA damage and death by enhancing telomere stability. Thus, XRCC3 can be used as a promising therapeutic target for ESCCs.
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Objective To investigate the impacts of pyruvate kinase M2 isoform (PKM2) silencing on the radiosensitivity of lung adenocarcinoma cell line (A549 cells) and the radiation synergy of xenografts, and to explore their mechanisms. Methods Plasmid pshRNA?PKM2 for interference with PKM2 expression was transfected into A549 cells, and empty vector?transfected cells and untransfected cells were set as con?trols. The silencing efficiency of pshRNA?PKM2 and the expression level of microtubule?associated protein 1 light chain 3(LC3) were measured by Western blot assay. The radiosensitizing effects in A549 cells and xen?ografts after PKM2 silencing were determined by colony?forming assay and xenografts growth curves. Autoph?agy formation in A549 cells and xenografts was analyzed by transmission electron microscopy, and the ex?pression level of PKM2 in xenografts was measured by immunohistochemistry. Comparison between groups was made by Student′s t?test, and the body weights of nude mice and xenograft volumes were subjected to a?nalysis of variance for continuous variables. Results Stable A549 cell lines transfected with pshRNA?PKM2 were successfully produced. Transfection with pshRNA?PKM2 significantly down?regulated PKM2 expression in A549 cells and xenografts (P= 0?? 001;P= 0?? 000). The sensitizer enhancement ratios for A549 cells and xenografts were 1?? 47 and 2?? 00, respectively. Interference with PKM2 expression enhanced radiation?in duced autophagy formation and significantly increased the ratio of LC 3 ? II / I ( P= 0.000 1 ) . Conclusions Silencing of PKM2 expression may enhance the radiosensitivity of A549 cells and xenografts by regulation of autophagy, which holds promise for becoming an effective radiosensitizing target for non?small cell lung canc?er, but still needs to be confirmed by further studies.