Background:While the treatment of metastatic renal cell carcinoma(mRCC)is evolving due to immune checkpoint inhibitors(ICIs),optimal strategies for later lines of therapy have yet to be defined.The combination of lenv...Background:While the treatment of metastatic renal cell carcinoma(mRCC)is evolving due to immune checkpoint inhibitors(ICIs),optimal strategies for later lines of therapy have yet to be defined.The combination of lenvatinib and everolimus represents a viable option,and the present review aimed to summarize its activity,effectiveness,and safety.Methods:A systematic review of the literature was conducted using PubMed,targeting studies published between 2018 and 2025.Eligible studies included English-language prospective and retrospective trials reporting survival outcomes in mRCC patients treated with lenvatinib and everolimus after at least one ICI-containing regimen.Results:Nine studies met the inclusion criteria,encompassing a total of 441 patients.The lenvatinib and everolimus combination was primarily used in the third and subsequent lines of therapy.Median overall survival ranged from 7.5 to 24.5 months,while median progression-free survival was more consistent,between 6.1 and 6.7 months,except for one study reporting 12.9 months.Objective response rates varied widely(14.0%–55.7%).Adverse events of grade≥3 did not exceed the expected rate,with diarrhoea and proteinuria as the most reported events.Dose reductions and treatment discontinuations due to toxicity occurred but were generally lower than in prior pivotal trials.Conclusions:Real-world evidence suggests that lenvatinib and everolimus represent an effective and safe option after ICI failure in mRCC patients.Nevertheless,the lack of randomized phase III trials and the heterogeneity of existing studies highlight the need for more robust prospective research to guide post-ICI therapeutic strategies.展开更多
macrophages in tumors are a major problem. They are dynamic and heterogeneous cells, and their differenti- ation, tissue distribution and responsiveness to stimuli are governed by distinct mechanisms. In response to c...macrophages in tumors are a major problem. They are dynamic and heterogeneous cells, and their differenti- ation, tissue distribution and responsiveness to stimuli are governed by distinct mechanisms. In response to certain signals, macrophages can undergo either M1- or M2-type activation, which result in two distinct functional phenotypes.展开更多
Glioblastoma multiforme is considered one of the most common malignant primary intracranial tumors.Despite treatment with a combination of surgery,chemotherapy and radiotherapy,patients with glioblastoma multiform hav...Glioblastoma multiforme is considered one of the most common malignant primary intracranial tumors.Despite treatment with a combination of surgery,chemotherapy and radiotherapy,patients with glioblastoma multiform have poor prognosis.It has been widely accepted that the occurrence,progression,and even recurrence of glioblastoma multiforme strictly depends on the presence of glioma cancer stem cells.The presence of glioma stem cells reduces the efficacy of standard therapies,thus increasing the imperative to identify new targets and therapeutic strategies in glioblastoma patients.In this regard,the p21^(Cip1)pathway has been found to play an important role in the maintenance of the glioma stem cells.It has been shown that this pathway regulates cancer stem cell pool by preventing hyperproliferation and exhaustion.MicroRNAs,endogenous small non-coding RNAs,and long non-coding RNAs,regulate post-transcription gene expression.These are not only altered in glioma,but also in other cancer types,and are involved in tumor development and progression.Notably,they have also been shown to modulate the expression of proteins in the p21^(Cip1)signaling pathway.This review highlights the extent and complexity of cross-talk between microRNAs,long non-coding RNAs and the p21^(Cip1)pathway,and demonstrates how such interplay orchestrates the regulation of protein expression and functions in glioma and glioma stem cells.展开更多
Aim:Primary lung cancer is the leading cause of human cancer deaths worldwide,and squamous cell carcinoma(SCC)is one of the most frequent histologic subtypes.The aim of our study was to analyze clinical factors potent...Aim:Primary lung cancer is the leading cause of human cancer deaths worldwide,and squamous cell carcinoma(SCC)is one of the most frequent histologic subtypes.The aim of our study was to analyze clinical factors potentially affecting the overall outcome of advanced lung SCC patients.Methods:A series of 72 consecutive patients with advanced SCC undergoing chemotherapy at our institution between January 2007 and July 2013 were eligible for our analysis.Results:By univariate analysis,a better overall survival(OS)was related to response to first-line chemotherapy:median OS were 19.7 vs.7.17 months,respectively,for responders and nonresponders patients(P<0.0001).Eastern Cooperative Oncology Group performance status,gender,and surgery were other prognostic factors.No signifi cant relationship between OS and smoking status,age,body mass index,or type of treatment was found.In the third-line setting,a better OS was associated with objective response to second-line treatment(P=0.015).Conclusion:Our results suggest that differences in OS seem strictly associated with clinical response to previous treatments.These data should be considered in the therapeutic strategy and management of patients with SCC of the lung.展开更多
Cardiac transplantation is currently the preferred choice of treatment for end-stage cardiac disease. Despite great advances have been made in the prevention and treatment of acute transplant rejection, accelerated ca...Cardiac transplantation is currently the preferred choice of treatment for end-stage cardiac disease. Despite great advances have been made in the prevention and treatment of acute transplant rejection, accelerated cardiac allograft vasculopathy （CAV） still limits the long-term success of heart transplantation. CAV is a rapidly progressive form of atherosclerosis described by vascular remodeling of the graft coronary arteries that occurs uniquely in transplant recipi- ents. In the early stages, CAV is characterized by intimal proliferation, while luminal stenosis of epicardial branches, occlusion of smaller arteries and myocardial infarction occur in the later stages.展开更多
文摘Background:While the treatment of metastatic renal cell carcinoma(mRCC)is evolving due to immune checkpoint inhibitors(ICIs),optimal strategies for later lines of therapy have yet to be defined.The combination of lenvatinib and everolimus represents a viable option,and the present review aimed to summarize its activity,effectiveness,and safety.Methods:A systematic review of the literature was conducted using PubMed,targeting studies published between 2018 and 2025.Eligible studies included English-language prospective and retrospective trials reporting survival outcomes in mRCC patients treated with lenvatinib and everolimus after at least one ICI-containing regimen.Results:Nine studies met the inclusion criteria,encompassing a total of 441 patients.The lenvatinib and everolimus combination was primarily used in the third and subsequent lines of therapy.Median overall survival ranged from 7.5 to 24.5 months,while median progression-free survival was more consistent,between 6.1 and 6.7 months,except for one study reporting 12.9 months.Objective response rates varied widely(14.0%–55.7%).Adverse events of grade≥3 did not exceed the expected rate,with diarrhoea and proteinuria as the most reported events.Dose reductions and treatment discontinuations due to toxicity occurred but were generally lower than in prior pivotal trials.Conclusions:Real-world evidence suggests that lenvatinib and everolimus represent an effective and safe option after ICI failure in mRCC patients.Nevertheless,the lack of randomized phase III trials and the heterogeneity of existing studies highlight the need for more robust prospective research to guide post-ICI therapeutic strategies.
文摘macrophages in tumors are a major problem. They are dynamic and heterogeneous cells, and their differenti- ation, tissue distribution and responsiveness to stimuli are governed by distinct mechanisms. In response to certain signals, macrophages can undergo either M1- or M2-type activation, which result in two distinct functional phenotypes.
基金PRIN 2017 and Fondazione Umberto Veronesi(Post-doctoral Fellowship 2019 to Morelli MB).
文摘Glioblastoma multiforme is considered one of the most common malignant primary intracranial tumors.Despite treatment with a combination of surgery,chemotherapy and radiotherapy,patients with glioblastoma multiform have poor prognosis.It has been widely accepted that the occurrence,progression,and even recurrence of glioblastoma multiforme strictly depends on the presence of glioma cancer stem cells.The presence of glioma stem cells reduces the efficacy of standard therapies,thus increasing the imperative to identify new targets and therapeutic strategies in glioblastoma patients.In this regard,the p21^(Cip1)pathway has been found to play an important role in the maintenance of the glioma stem cells.It has been shown that this pathway regulates cancer stem cell pool by preventing hyperproliferation and exhaustion.MicroRNAs,endogenous small non-coding RNAs,and long non-coding RNAs,regulate post-transcription gene expression.These are not only altered in glioma,but also in other cancer types,and are involved in tumor development and progression.Notably,they have also been shown to modulate the expression of proteins in the p21^(Cip1)signaling pathway.This review highlights the extent and complexity of cross-talk between microRNAs,long non-coding RNAs and the p21^(Cip1)pathway,and demonstrates how such interplay orchestrates the regulation of protein expression and functions in glioma and glioma stem cells.
文摘Aim:Primary lung cancer is the leading cause of human cancer deaths worldwide,and squamous cell carcinoma(SCC)is one of the most frequent histologic subtypes.The aim of our study was to analyze clinical factors potentially affecting the overall outcome of advanced lung SCC patients.Methods:A series of 72 consecutive patients with advanced SCC undergoing chemotherapy at our institution between January 2007 and July 2013 were eligible for our analysis.Results:By univariate analysis,a better overall survival(OS)was related to response to first-line chemotherapy:median OS were 19.7 vs.7.17 months,respectively,for responders and nonresponders patients(P<0.0001).Eastern Cooperative Oncology Group performance status,gender,and surgery were other prognostic factors.No signifi cant relationship between OS and smoking status,age,body mass index,or type of treatment was found.In the third-line setting,a better OS was associated with objective response to second-line treatment(P=0.015).Conclusion:Our results suggest that differences in OS seem strictly associated with clinical response to previous treatments.These data should be considered in the therapeutic strategy and management of patients with SCC of the lung.
文摘Cardiac transplantation is currently the preferred choice of treatment for end-stage cardiac disease. Despite great advances have been made in the prevention and treatment of acute transplant rejection, accelerated cardiac allograft vasculopathy （CAV） still limits the long-term success of heart transplantation. CAV is a rapidly progressive form of atherosclerosis described by vascular remodeling of the graft coronary arteries that occurs uniquely in transplant recipi- ents. In the early stages, CAV is characterized by intimal proliferation, while luminal stenosis of epicardial branches, occlusion of smaller arteries and myocardial infarction occur in the later stages.
