Background and Objective: The outcome of locally advanced and metastatic urothelial carcinoma LA/mUC has improved over the past years with a plethora of new treatments and the approval of immune checkpoint inhibitors ...Background and Objective: The outcome of locally advanced and metastatic urothelial carcinoma LA/mUC has improved over the past years with a plethora of new treatments and the approval of immune checkpoint inhibitors (ICIs), antibody-drug conjugates, and targeted agents, to identify locally advanced metastatic urothelial carcinoma’s current management practices in Lebanon and the implication of the ongoing economic crisis on the medical practice. Methods: An online questionnaire was used to survey ten Lebanese oncologists from six different hospitals, between July 5 and July 11, 2022, requesting information pertaining to their current clinical practice in the pharmacological treatment of locally advanced metastatic urothelial carcinoma. Key Findings: Cisplatin-based chemotherapy was the most frequently reported initial treatment of locally advanced metastatic urothelial carcinoma. Participants reported using immune checkpoint inhibitors in platinum-ineligible patients and those with PDL1 positive tumors. Also, they would not consider the concomitant use of immunotherapy and chemotherapy in the first-line setting. Participants believed that avelumab maintenance is effective in the absence of progression after first-line platinum-based chemotherapy;they would consider initiating it 2 - 10 weeks after completion of chemotherapy. Conclusions and Clinical Implications: After comparing with current international guidelines, this study shows that Lebanese oncologists follow international guidelines and have deep knowledge of recent clinical trials for the management of locally advanced metastatic urothelial carcinoma, regardless of economic crisis challenges.展开更多
Bladder cancer is one of the most common cancers in the world, and about 80%-90% of bladder cancers are urothelial cancer. Neoadjuvant platinum-based combination chemotherapy is considered to be the standard treatment...Bladder cancer is one of the most common cancers in the world, and about 80%-90% of bladder cancers are urothelial cancer. Neoadjuvant platinum-based combination chemotherapy is considered to be the standard treatment for bladder cancer. However, the use of this treatment has clinical disadvantages such as small overall benefit, toxic effects on the target population, and inability to select the most beneficial patients. This phenomenon has been improved by the presence of immunological checkpoint inhibitors, of which PD-1/PDL-1 inhibitors are one of them. The use of PD-1/ PD-L1 in urinary cancer is a new treatment and offers new hope for the treatment of platinum-refractory metastatic urothelial bladder cancer. Related drugs have now been approved for use in patients with refractory or unqualified platinum-based chemotherapy drugs. Clinical trials are currently underway to determine how best to use these drugs, and whether they should be used alone or in combination with other treatments. This article will review the research progress of PD-1/PDL-1 inhibitors in bladder tumors.展开更多
Background:Ferroptosis is an iron dependent form of cell death,which plays an important role in the pathogenesis of a variety of urinary malignancies.The down-regulation of DECR1 gene causes the accumulation of polyun...Background:Ferroptosis is an iron dependent form of cell death,which plays an important role in the pathogenesis of a variety of urinary malignancies.The down-regulation of DECR1 gene causes the accumulation of polyunsaturated fatty acids(PUFAs),increases the susceptibility to lipid peroxidation,and finally leads to cell death.Methods:We first searched the data to find reductase 1(DECR1)expression in bladder uroepithelial carcinoma and healthy surrounding tissues in the Cancer Genome Atlas(TCGA),and we then confirmed DECR1 expression with additional independent cohorts in the Gene Expression Omnibus(GEO)database and the Human Protein Atlas(HPA).In order to determine the link between DECR1 expression and clinical traits and overall survival(OS),as well as to create nomograms,multivariate analysis and Kaplan Meier survival curves were utilized.Through the use of an online string website,the network of proteins that interact with DECR1 was created.Through an online string website,the protein network interacting with DECR1 was built.Finally,we looked at the association between aggressive immune cells and the marker genes that belong to them and DECR1 expression.Results:When compared to normal tissues,bladder tumor tissues had higher DECR1 expression(P=0.002).Low DECR1 expression was linked with tumor grade and stage in tumor cells.BLCA patients with low DECR1 expression had a lower overall survival than BLCA patients with high DECR1 expression,according to a survival study(P=0.008).The protein network’s HSD17B4 and DECR1 connections are crucial.The expression of regulatory T cells,regulatory B cells,and their markers were decreased when DECR1 was missing in bladder cancer.Conclusion:Decreased DECR1 expression was associated with BLCA progression,poor prognosis and impaired infiltration of some immune cells.展开更多
文摘Background and Objective: The outcome of locally advanced and metastatic urothelial carcinoma LA/mUC has improved over the past years with a plethora of new treatments and the approval of immune checkpoint inhibitors (ICIs), antibody-drug conjugates, and targeted agents, to identify locally advanced metastatic urothelial carcinoma’s current management practices in Lebanon and the implication of the ongoing economic crisis on the medical practice. Methods: An online questionnaire was used to survey ten Lebanese oncologists from six different hospitals, between July 5 and July 11, 2022, requesting information pertaining to their current clinical practice in the pharmacological treatment of locally advanced metastatic urothelial carcinoma. Key Findings: Cisplatin-based chemotherapy was the most frequently reported initial treatment of locally advanced metastatic urothelial carcinoma. Participants reported using immune checkpoint inhibitors in platinum-ineligible patients and those with PDL1 positive tumors. Also, they would not consider the concomitant use of immunotherapy and chemotherapy in the first-line setting. Participants believed that avelumab maintenance is effective in the absence of progression after first-line platinum-based chemotherapy;they would consider initiating it 2 - 10 weeks after completion of chemotherapy. Conclusions and Clinical Implications: After comparing with current international guidelines, this study shows that Lebanese oncologists follow international guidelines and have deep knowledge of recent clinical trials for the management of locally advanced metastatic urothelial carcinoma, regardless of economic crisis challenges.
基金The National Natural Science Foundation of China.Project No:81672519.
文摘Bladder cancer is one of the most common cancers in the world, and about 80%-90% of bladder cancers are urothelial cancer. Neoadjuvant platinum-based combination chemotherapy is considered to be the standard treatment for bladder cancer. However, the use of this treatment has clinical disadvantages such as small overall benefit, toxic effects on the target population, and inability to select the most beneficial patients. This phenomenon has been improved by the presence of immunological checkpoint inhibitors, of which PD-1/PDL-1 inhibitors are one of them. The use of PD-1/ PD-L1 in urinary cancer is a new treatment and offers new hope for the treatment of platinum-refractory metastatic urothelial bladder cancer. Related drugs have now been approved for use in patients with refractory or unqualified platinum-based chemotherapy drugs. Clinical trials are currently underway to determine how best to use these drugs, and whether they should be used alone or in combination with other treatments. This article will review the research progress of PD-1/PDL-1 inhibitors in bladder tumors.
文摘Background:Ferroptosis is an iron dependent form of cell death,which plays an important role in the pathogenesis of a variety of urinary malignancies.The down-regulation of DECR1 gene causes the accumulation of polyunsaturated fatty acids(PUFAs),increases the susceptibility to lipid peroxidation,and finally leads to cell death.Methods:We first searched the data to find reductase 1(DECR1)expression in bladder uroepithelial carcinoma and healthy surrounding tissues in the Cancer Genome Atlas(TCGA),and we then confirmed DECR1 expression with additional independent cohorts in the Gene Expression Omnibus(GEO)database and the Human Protein Atlas(HPA).In order to determine the link between DECR1 expression and clinical traits and overall survival(OS),as well as to create nomograms,multivariate analysis and Kaplan Meier survival curves were utilized.Through the use of an online string website,the network of proteins that interact with DECR1 was created.Through an online string website,the protein network interacting with DECR1 was built.Finally,we looked at the association between aggressive immune cells and the marker genes that belong to them and DECR1 expression.Results:When compared to normal tissues,bladder tumor tissues had higher DECR1 expression(P=0.002).Low DECR1 expression was linked with tumor grade and stage in tumor cells.BLCA patients with low DECR1 expression had a lower overall survival than BLCA patients with high DECR1 expression,according to a survival study(P=0.008).The protein network’s HSD17B4 and DECR1 connections are crucial.The expression of regulatory T cells,regulatory B cells,and their markers were decreased when DECR1 was missing in bladder cancer.Conclusion:Decreased DECR1 expression was associated with BLCA progression,poor prognosis and impaired infiltration of some immune cells.
