Objective: Radical cystectomy(RC)is a standard treatment for localized muscle invasive bladder cancer and high-risk or very high-risk non-muscle invasive bladder cancer not responding to adequate endovesical therapy.I...Objective: Radical cystectomy(RC)is a standard treatment for localized muscle invasive bladder cancer and high-risk or very high-risk non-muscle invasive bladder cancer not responding to adequate endovesical therapy.In women,traditionally RC is performed with hystero-adnexectomy and resection of the anterior vaginal wall,often resulting in sexual disorders.Vaginal-sparing techniques have been developed to improve functional outcomes.The present study explores the safety and the functional outcome of vaginal-sparing techniques.Methods: We retrospectively analyzed all consecutive female patients undergoing robot-assisted RC(RARC)with neobladder diversion between October 2017 and February 2022.The indications for vaginal-sparing RC were absence of tumor on bladder neck or urethra and no sign of infiltration of posterior bladder wall at the preoperative MRI.Functional results were evaluated with the aid of five questions out of the Bladder Cancer Index questionnaire.Complications were reported according to the Clavien–Dindo classification and cancer control was evaluated by recurrence-free and cancer-specific survival.Results: A total of 22 female patients underwent RARC with neobladder diversion.Neoadjuvant chemotherapy was given in 17(77%)cases.Clavien–Dindo grades III–IV complications occurred in four(18%)cases.After a mean follow-up of 29(interquartile range 16–44)months,six(27.3%)patients developed distant metastases,and one(4.5%)woman loco-regional relapse.Sexual-sparing surgery was performed in 19(86%)patients,and in the others the anterior vaginal wall was resected,but neobladder was still performed.During daytime,no patients reported total incontinence and 73%(11/15)reported total continence or only occasional leaks.Sexual results showed that seven of 15(47%)women regained sexual activity after surgery,with a quality reported as“good”or“very good”in 40%of all 19 cases.Conclusion: RARC in female with anterior vaginal wall preservation is feasible.The approach showed a good safety profile,with satisfying results on continence and sexual activity.Sexual-sparing approaches should be carried out after correct patient selection.展开更多
Hepatocellular carcinoma(HCC)is the fifth most common cause of cancer in the world.According to Barcelona Clinic Liver Cancer modified criteria,patients with early stage disease are candidate to radiofrequency ablatio...Hepatocellular carcinoma(HCC)is the fifth most common cause of cancer in the world.According to Barcelona Clinic Liver Cancer modified criteria,patients with early stage disease are candidate to radiofrequency ablation(RFA),while patients with intermediate stage HCC are usually treated by transarterial chemoembolization(TACE).TACE and RFA induce a transient devascularisation effect followed by strong neoangiogenic stimulus.In fact,after these procedures,it has been demonstrated an up-regulation of pro-angiogenic and growth factors such as vascular endothelial growth factor-A,which might contribute to accelerated progression in patients with incomplete response.Several studies have demonstrated that MAP-kinase and AKT pathways,in addition to neo-angiogenesis,have an important role in the development of HCC.In advanced HCC,anti-angiogenic therapy and tyrosine kinases inhibitors showed potential clinical benefit.Actually,a number of clinical studies are ongoing testing these agents in combination with TACE or RFA.In this paper,we have reviewed the most recent preclinical and clinical results of such trials.展开更多
AIM: To identify suitable biomarkers of response to bevacizumab(BV)- it remains an open question. The measurement of serum vascular endothelial growth factor(VEGF) has been proposed as a predictive factor for this dru...AIM: To identify suitable biomarkers of response to bevacizumab(BV)- it remains an open question. The measurement of serum vascular endothelial growth factor(VEGF) has been proposed as a predictive factor for this drug, even if literature data are contradictory. METHODS: We prospectively evaluated the role of BV, total and not BV-bound VEGF and angiopoietin-2(Ang-2) serum levels as potential predictive factors of response for BV in combination with an oxaliplatinbased chemotherapy. BV, Ang-2, total and not BVbound VEGF levels were measured at baseline, before 2^(nd) and 5^(th) cycle of oxaliplatin-based chemotherapy in 20 consecutive metastatic colorectal cancer patients. RESULTS: Results were correlated to response to treatment. Variability in BV levels have been found, with decreased level in less responding patients. In particular, the concentration of BV increased of 3.96 ± 0.69 folds in serum of responsive patients after 3 more cycles of therapy compared to those with stable or progressive disease with a 0.72 ± 0.25 and 2.10 ± 0.13 fold increase, respectively. The determination of free and total VEGF demonstrated that the ratio between the two values, evaluated immediately before the 2^(nd) and the 5^(th) cycle of therapy, decreased from 26.65% ± 1.33% to 15.50% ± 3.47% in responsive patients and from 53.41% ± 4.75 to 34.95% ± 2.88% in those with stable disease. Conversely, in those with progression of disease, the ratio showed the opposite behavior coming up from 25.99% ± 5.23% to 51.71% ± 5.28%. The Ang-2 levels did not show any relationship. CONCLUSION: Our data show that the ratio of not BV-bound VEGF to total VEGF serum and BV plasma concentrations for predicting the response to BV plus oxaliplatin-based chemotherapy could be a promising biomarker of response to BV.展开更多
AIM： To evaluate the effects of gliadin on the oxidative environment in the “in vivo-like”model of a three-dimensional cell culture system. METHODS： LoVo cell line （intestinal adenocarcinoma） multicellular spher...AIM： To evaluate the effects of gliadin on the oxidative environment in the “in vivo-like”model of a three-dimensional cell culture system. METHODS： LoVo cell line （intestinal adenocarcinoma） multicellular spheroids were treated with digested gliadin （with albumin used as a control）. Spheroid volumes, cell viability and morphology, lactate dehydrogenase （LDH） release, content of reduced glutathione （GSH） and activity of GSH-related enzymes were examined. The data were statistically analyzed using the Student＇s t-test （P〈0.05）. was considered statistically significant. RESULTS： Gliadin reduced cell viability （from 20% to 60%） and led to morphological alterations characterized by apoptotic findings and cytoskeletal injuries. LDH activity increased. The content of GSH reduced （-20% vscontrols）, and activity of GSH-related enzymes was significantly inhibited. CONCLUSION： Gliadin treatment induces an imbalance in the antioxidative mechanism of cells cultured by the three-dimensional technique. This alteration may explain cell damage directly caused by gliadin and the subsequentmorphological abnormalities.展开更多
Lapatinib ditosylate (Tyverb?) is a potent and selective oral dual receptor tyrosine kinase inhibitor (TKI), preventing autophosphorylation of epidermal growth factor receptor (EGFR/ErbB1) and human epidermal growth f...Lapatinib ditosylate (Tyverb?) is a potent and selective oral dual receptor tyrosine kinase inhibitor (TKI), preventing autophosphorylation of epidermal growth factor receptor (EGFR/ErbB1) and human epidermal growth factor receptor 2 (HER2/ErbB2) intracellular domain. This interference blocks the Ras/Raf MAPKs and PI3K/Akt pathways, that lead to uncontrolled cellular proliferation and survival. After the demonstration of its effectiveness and safety in HER2-overexpressed breast cancer, in 2007 the US Food and Drug Administration (FDA) approved this molecule in combination with capecitabine, in patients with locally advanced or metastatic disease, that progressed after previous treatment with anthracyclines, taxanes and trastuzumab. In 2010, Lapatinib received approval for the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer in combination with letrozole. The most common adverse events (AE) are: anorexia, insomnia, diarrhea and skin rash and mild cardiovascular toxicity. This paper reviews the most important studies on Lapatinib in advanced breast cancer. However, promising results were recently reported on this drug, also in adjuvant setting and in combination with other target drugs, which warrant further investigation for the future.展开更多
文摘Objective: Radical cystectomy(RC)is a standard treatment for localized muscle invasive bladder cancer and high-risk or very high-risk non-muscle invasive bladder cancer not responding to adequate endovesical therapy.In women,traditionally RC is performed with hystero-adnexectomy and resection of the anterior vaginal wall,often resulting in sexual disorders.Vaginal-sparing techniques have been developed to improve functional outcomes.The present study explores the safety and the functional outcome of vaginal-sparing techniques.Methods: We retrospectively analyzed all consecutive female patients undergoing robot-assisted RC(RARC)with neobladder diversion between October 2017 and February 2022.The indications for vaginal-sparing RC were absence of tumor on bladder neck or urethra and no sign of infiltration of posterior bladder wall at the preoperative MRI.Functional results were evaluated with the aid of five questions out of the Bladder Cancer Index questionnaire.Complications were reported according to the Clavien–Dindo classification and cancer control was evaluated by recurrence-free and cancer-specific survival.Results: A total of 22 female patients underwent RARC with neobladder diversion.Neoadjuvant chemotherapy was given in 17(77%)cases.Clavien–Dindo grades III–IV complications occurred in four(18%)cases.After a mean follow-up of 29(interquartile range 16–44)months,six(27.3%)patients developed distant metastases,and one(4.5%)woman loco-regional relapse.Sexual-sparing surgery was performed in 19(86%)patients,and in the others the anterior vaginal wall was resected,but neobladder was still performed.During daytime,no patients reported total incontinence and 73%(11/15)reported total continence or only occasional leaks.Sexual results showed that seven of 15(47%)women regained sexual activity after surgery,with a quality reported as“good”or“very good”in 40%of all 19 cases.Conclusion: RARC in female with anterior vaginal wall preservation is feasible.The approach showed a good safety profile,with satisfying results on continence and sexual activity.Sexual-sparing approaches should be carried out after correct patient selection.
文摘Hepatocellular carcinoma(HCC)is the fifth most common cause of cancer in the world.According to Barcelona Clinic Liver Cancer modified criteria,patients with early stage disease are candidate to radiofrequency ablation(RFA),while patients with intermediate stage HCC are usually treated by transarterial chemoembolization(TACE).TACE and RFA induce a transient devascularisation effect followed by strong neoangiogenic stimulus.In fact,after these procedures,it has been demonstrated an up-regulation of pro-angiogenic and growth factors such as vascular endothelial growth factor-A,which might contribute to accelerated progression in patients with incomplete response.Several studies have demonstrated that MAP-kinase and AKT pathways,in addition to neo-angiogenesis,have an important role in the development of HCC.In advanced HCC,anti-angiogenic therapy and tyrosine kinases inhibitors showed potential clinical benefit.Actually,a number of clinical studies are ongoing testing these agents in combination with TACE or RFA.In this paper,we have reviewed the most recent preclinical and clinical results of such trials.
文摘AIM: To identify suitable biomarkers of response to bevacizumab(BV)- it remains an open question. The measurement of serum vascular endothelial growth factor(VEGF) has been proposed as a predictive factor for this drug, even if literature data are contradictory. METHODS: We prospectively evaluated the role of BV, total and not BV-bound VEGF and angiopoietin-2(Ang-2) serum levels as potential predictive factors of response for BV in combination with an oxaliplatinbased chemotherapy. BV, Ang-2, total and not BVbound VEGF levels were measured at baseline, before 2^(nd) and 5^(th) cycle of oxaliplatin-based chemotherapy in 20 consecutive metastatic colorectal cancer patients. RESULTS: Results were correlated to response to treatment. Variability in BV levels have been found, with decreased level in less responding patients. In particular, the concentration of BV increased of 3.96 ± 0.69 folds in serum of responsive patients after 3 more cycles of therapy compared to those with stable or progressive disease with a 0.72 ± 0.25 and 2.10 ± 0.13 fold increase, respectively. The determination of free and total VEGF demonstrated that the ratio between the two values, evaluated immediately before the 2^(nd) and the 5^(th) cycle of therapy, decreased from 26.65% ± 1.33% to 15.50% ± 3.47% in responsive patients and from 53.41% ± 4.75 to 34.95% ± 2.88% in those with stable disease. Conversely, in those with progression of disease, the ratio showed the opposite behavior coming up from 25.99% ± 5.23% to 51.71% ± 5.28%. The Ang-2 levels did not show any relationship. CONCLUSION: Our data show that the ratio of not BV-bound VEGF to total VEGF serum and BV plasma concentrations for predicting the response to BV plus oxaliplatin-based chemotherapy could be a promising biomarker of response to BV.
基金Supported by the San Paolo Foundation grant to "Centro per lo Studio della Celiachia"
文摘AIM： To evaluate the effects of gliadin on the oxidative environment in the “in vivo-like”model of a three-dimensional cell culture system. METHODS： LoVo cell line （intestinal adenocarcinoma） multicellular spheroids were treated with digested gliadin （with albumin used as a control）. Spheroid volumes, cell viability and morphology, lactate dehydrogenase （LDH） release, content of reduced glutathione （GSH） and activity of GSH-related enzymes were examined. The data were statistically analyzed using the Student＇s t-test （P〈0.05）. was considered statistically significant. RESULTS： Gliadin reduced cell viability （from 20% to 60%） and led to morphological alterations characterized by apoptotic findings and cytoskeletal injuries. LDH activity increased. The content of GSH reduced （-20% vscontrols）, and activity of GSH-related enzymes was significantly inhibited. CONCLUSION： Gliadin treatment induces an imbalance in the antioxidative mechanism of cells cultured by the three-dimensional technique. This alteration may explain cell damage directly caused by gliadin and the subsequentmorphological abnormalities.
文摘Lapatinib ditosylate (Tyverb?) is a potent and selective oral dual receptor tyrosine kinase inhibitor (TKI), preventing autophosphorylation of epidermal growth factor receptor (EGFR/ErbB1) and human epidermal growth factor receptor 2 (HER2/ErbB2) intracellular domain. This interference blocks the Ras/Raf MAPKs and PI3K/Akt pathways, that lead to uncontrolled cellular proliferation and survival. After the demonstration of its effectiveness and safety in HER2-overexpressed breast cancer, in 2007 the US Food and Drug Administration (FDA) approved this molecule in combination with capecitabine, in patients with locally advanced or metastatic disease, that progressed after previous treatment with anthracyclines, taxanes and trastuzumab. In 2010, Lapatinib received approval for the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer in combination with letrozole. The most common adverse events (AE) are: anorexia, insomnia, diarrhea and skin rash and mild cardiovascular toxicity. This paper reviews the most important studies on Lapatinib in advanced breast cancer. However, promising results were recently reported on this drug, also in adjuvant setting and in combination with other target drugs, which warrant further investigation for the future.
