Objective:Circular ribose nudeic acids(circRNAs)are implicated in tumor progression and drug resistance of prostate cancer(PCa).The current work explored the function of circ_0005203(aircTHSD4)in the malignancy and do...Objective:Circular ribose nudeic acids(circRNAs)are implicated in tumor progression and drug resistance of prostate cancer(PCa).The current work explored the function of circ_0005203(aircTHSD4)in the malignancy and docetaxel(DTX)resistance of PCa.Methods:circTHSD4 expression within PCa as well as matched non-carcinoma samples was measured through real time reverse transcription quantitative polymerase chain reaction(RT-qPCR).In addition,a subcellular fraction assay was conducted to determine circTHSD4 subcellular localization within PCa cells.In addition,we performed a Western blot(WB)assay to detect high mobility.group A2 protein(HMGA2)levels.Besides,functional associations of two molecules were investigated through dual luciferase reporter assay.Cell Counting Kit(CCK)-8,colony formation together with Transwell assay was conducted to assess malignant phenotypes of PCa cells,whereas flow cytometry was performed to determine cell apoptosis.Furthermore,a xenograft mouse model was constructed to verify the effect of circTHSD4 on the carcinogenesis of PCa cells.Results:According to RT-qPCR results,circTHSD4 was up-regulated within PCa tissues and cells,which predicted the dismal prognostic outcome of PCa cases.circTHSD4 silencing within PCa cells markedly suppressed cell growth,migration,and colony fomation.circTHSD4 silencing remarkably elevated PCa cell apoptosis and carcinogenesis within the xenograft model.Further,circTHSD4 silencing enhanced docetaxel(DTX)sensitivity in PCa cells.Furthermore,we demonstrated that circTHSD4 modulated the malignancy of PCa cells by regulating HMGA2 expression through sponging miR 203.Conclusion:Together,our findings suggest that cirCTHSD4 overexpression could promote the malignant phenotype and DTX resistance in PCa through the regulation of the miR 203/HMGA2 axis.展开更多
A novel, simple, and sensitive Ultra Performance Liquid Chromatography (UPLC) method was developed and validated for the quantification of process-related impurities and degradants, as well as the assay of Docetaxel. ...A novel, simple, and sensitive Ultra Performance Liquid Chromatography (UPLC) method was developed and validated for the quantification of process-related impurities and degradants, as well as the assay of Docetaxel. The stability-indicating capability of the method was demonstrated through forced degradation studies and a comprehensive mass balance evaluation. Chromatographic separation was achieved using an ACQUITY UPLC BEH C18 column (100 × 2.1 mm, 1.7 µm), with gradient elution. The mobile phase A comprised a mixture of water, methanol, and acetonitrile (500:300:200, v/v/v), while mobile phase B was acetonitrile and water (800:200, v/v). The flow rate was set at 0.4 mL/min, with detection at 232 nm using a photodiode array detector. The method exhibited excellent performance, with a tailing factor of 1.10 for Docetaxel. The method was rigorously validated for precision, accuracy, linearity, LOD, LOQ, ruggedness, specificity, and robustness. Forced degradation studies confirmed the method’s suitability for stability analysis. Stability testing on the drug substance was conducted following ICH guidelines.展开更多
BACKGROUND The tongue squamous cell carcinoma(TSCC)is an oral malignant tumor arising from the squamous epithelium of the tongue mucosa,characterized by a high malignant degree,invasive growth,early lymph node metasta...BACKGROUND The tongue squamous cell carcinoma(TSCC)is an oral malignant tumor arising from the squamous epithelium of the tongue mucosa,characterized by a high malignant degree,invasive growth,early lymph node metastasis,and poor prognosis.Paclitaxel,represented by docetaxel,is now the standard first-line treatment for head and neck squamous cell carcinoma.Docetaxel,which belongs to the class of drugs known as paclitaxel,is an antitumor drug that inhibits cell mitosis and proliferation.Its adverse effects include myelosuppression,hair loss,gastrointestinal reactions,fluid retention,and allergic reactions.However,hypokalemia is rare,most cases are mild or moderate,and severe hypokalemia is seldom reported.symptoms of adverse effects early.It is necessary to be considerate regarding individual differences between patients when selecting chemotherapy regimens and adhere to the principle of individualized treatment.Following multiple cycles of chemotherapy,patients should be aware of the accumulation of toxic side effects and receive blood tests reviewed within 24 hours of completion.It is essential to monitor electrolyte levels in patients suffering from severe gastrointestinal reactions to avoid complications that may result in death.展开更多
Background:This study was conducted to evaluate the efficacy and safety of docetaxel/S-1(TS)compared with docetaxel/capecitabine(TX)as a first-line treatment for advanced breast cancer.Methods:Patients with advanced m...Background:This study was conducted to evaluate the efficacy and safety of docetaxel/S-1(TS)compared with docetaxel/capecitabine(TX)as a first-line treatment for advanced breast cancer.Methods:Patients with advanced metastatic breast cancer were randomly divided into the TS group(n=54)and the TX group(n=57)for first-line chemotherapy from August 2015 to April 2019(ClinicalTrials.org registration no.NCT02947061).Following the completion of combination therapy,patients without progression received S-1 or capecitabine maintenance treatment.The primary end point was progression-free survival(PFS).Results:Among 111 enrolled patients,the median PFS did not differ significantly between the TS group and the TX group(TS vs.TX,9.0 vs.7.4 months,P=0.365,95%confidence interval[CI]:0.50-1.11,hazard ratio[HR]:0.75).There was also no statistically significant difference in median overall survival(OS)between the two groups(TS vs.TX,40.2 vs.41.3 months,P=0.976).In addition,visceral metastasis and metastasis sites,such as the liver or lung,did not lead to a significant effect on PFS and OS.The two regimens showed no significant difference in adverse events,except hand-foot syndrome,which predominated in the TX group(38.6%vs.7.4%,P=0.001),and diarrhea(24.1%vs.3.6%,P=0.003)and elevation of aspartate aminotransferase(AST)/alanine aminotransferase(ALT)levels(14.8%vs.3.5%,P=0.049),which were more frequent in the TS group.Conclusions:The TS and TX regimens demonstrated similar efficacy and safety for the first-line treatment of advanced breast cancer.The TS regimen had fewer cases of severe hand-foot syndrome than the TX regimen,representing an effective alternative option to the TX regimen.Further studies are warranted to define the efficacy and safety of this strategy in real-world settings.展开更多
基金Fujian Provincial Health and Middleaged and Young Backbone Talents Training Project“The role and Mechanism of C53 in mcRPC Treatment of Drug Resistance”(2019-ZQN-77).
文摘Objective:Circular ribose nudeic acids(circRNAs)are implicated in tumor progression and drug resistance of prostate cancer(PCa).The current work explored the function of circ_0005203(aircTHSD4)in the malignancy and docetaxel(DTX)resistance of PCa.Methods:circTHSD4 expression within PCa as well as matched non-carcinoma samples was measured through real time reverse transcription quantitative polymerase chain reaction(RT-qPCR).In addition,a subcellular fraction assay was conducted to determine circTHSD4 subcellular localization within PCa cells.In addition,we performed a Western blot(WB)assay to detect high mobility.group A2 protein(HMGA2)levels.Besides,functional associations of two molecules were investigated through dual luciferase reporter assay.Cell Counting Kit(CCK)-8,colony formation together with Transwell assay was conducted to assess malignant phenotypes of PCa cells,whereas flow cytometry was performed to determine cell apoptosis.Furthermore,a xenograft mouse model was constructed to verify the effect of circTHSD4 on the carcinogenesis of PCa cells.Results:According to RT-qPCR results,circTHSD4 was up-regulated within PCa tissues and cells,which predicted the dismal prognostic outcome of PCa cases.circTHSD4 silencing within PCa cells markedly suppressed cell growth,migration,and colony fomation.circTHSD4 silencing remarkably elevated PCa cell apoptosis and carcinogenesis within the xenograft model.Further,circTHSD4 silencing enhanced docetaxel(DTX)sensitivity in PCa cells.Furthermore,we demonstrated that circTHSD4 modulated the malignancy of PCa cells by regulating HMGA2 expression through sponging miR 203.Conclusion:Together,our findings suggest that cirCTHSD4 overexpression could promote the malignant phenotype and DTX resistance in PCa through the regulation of the miR 203/HMGA2 axis.
文摘A novel, simple, and sensitive Ultra Performance Liquid Chromatography (UPLC) method was developed and validated for the quantification of process-related impurities and degradants, as well as the assay of Docetaxel. The stability-indicating capability of the method was demonstrated through forced degradation studies and a comprehensive mass balance evaluation. Chromatographic separation was achieved using an ACQUITY UPLC BEH C18 column (100 × 2.1 mm, 1.7 µm), with gradient elution. The mobile phase A comprised a mixture of water, methanol, and acetonitrile (500:300:200, v/v/v), while mobile phase B was acetonitrile and water (800:200, v/v). The flow rate was set at 0.4 mL/min, with detection at 232 nm using a photodiode array detector. The method exhibited excellent performance, with a tailing factor of 1.10 for Docetaxel. The method was rigorously validated for precision, accuracy, linearity, LOD, LOQ, ruggedness, specificity, and robustness. Forced degradation studies confirmed the method’s suitability for stability analysis. Stability testing on the drug substance was conducted following ICH guidelines.
基金Supported by the Chongqing medical scientific research project(a joint project of the Chongqing Health Commission and Science and Technology),No.2020ZY023716.
文摘BACKGROUND The tongue squamous cell carcinoma(TSCC)is an oral malignant tumor arising from the squamous epithelium of the tongue mucosa,characterized by a high malignant degree,invasive growth,early lymph node metastasis,and poor prognosis.Paclitaxel,represented by docetaxel,is now the standard first-line treatment for head and neck squamous cell carcinoma.Docetaxel,which belongs to the class of drugs known as paclitaxel,is an antitumor drug that inhibits cell mitosis and proliferation.Its adverse effects include myelosuppression,hair loss,gastrointestinal reactions,fluid retention,and allergic reactions.However,hypokalemia is rare,most cases are mild or moderate,and severe hypokalemia is seldom reported.symptoms of adverse effects early.It is necessary to be considerate regarding individual differences between patients when selecting chemotherapy regimens and adhere to the principle of individualized treatment.Following multiple cycles of chemotherapy,patients should be aware of the accumulation of toxic side effects and receive blood tests reviewed within 24 hours of completion.It is essential to monitor electrolyte levels in patients suffering from severe gastrointestinal reactions to avoid complications that may result in death.
文摘Background:This study was conducted to evaluate the efficacy and safety of docetaxel/S-1(TS)compared with docetaxel/capecitabine(TX)as a first-line treatment for advanced breast cancer.Methods:Patients with advanced metastatic breast cancer were randomly divided into the TS group(n=54)and the TX group(n=57)for first-line chemotherapy from August 2015 to April 2019(ClinicalTrials.org registration no.NCT02947061).Following the completion of combination therapy,patients without progression received S-1 or capecitabine maintenance treatment.The primary end point was progression-free survival(PFS).Results:Among 111 enrolled patients,the median PFS did not differ significantly between the TS group and the TX group(TS vs.TX,9.0 vs.7.4 months,P=0.365,95%confidence interval[CI]:0.50-1.11,hazard ratio[HR]:0.75).There was also no statistically significant difference in median overall survival(OS)between the two groups(TS vs.TX,40.2 vs.41.3 months,P=0.976).In addition,visceral metastasis and metastasis sites,such as the liver or lung,did not lead to a significant effect on PFS and OS.The two regimens showed no significant difference in adverse events,except hand-foot syndrome,which predominated in the TX group(38.6%vs.7.4%,P=0.001),and diarrhea(24.1%vs.3.6%,P=0.003)and elevation of aspartate aminotransferase(AST)/alanine aminotransferase(ALT)levels(14.8%vs.3.5%,P=0.049),which were more frequent in the TS group.Conclusions:The TS and TX regimens demonstrated similar efficacy and safety for the first-line treatment of advanced breast cancer.The TS regimen had fewer cases of severe hand-foot syndrome than the TX regimen,representing an effective alternative option to the TX regimen.Further studies are warranted to define the efficacy and safety of this strategy in real-world settings.
