AIM: To compare the effects of bevacizumab and pazopanib with corticosteroids on wound healing after trabeculectomy. METHODS: In the study, 35 New Zealand white rabbits were randomly divided into five groups. Apart fr...AIM: To compare the effects of bevacizumab and pazopanib with corticosteroids on wound healing after trabeculectomy. METHODS: In the study, 35 New Zealand white rabbits were randomly divided into five groups. Apart from the first group, limbus-based trabeculectomy was performed for the eyes of rabbits. No postoperative treatment was administered for group Ⅰ. Topically administered saline, prednisolone acetate(1%), bevacizumab 5 mg/mL, pazopanib 5 mg/mL for group Ⅱ, Ⅲ, Ⅳ and Ⅴ respectively were applied for groups 6 h daily for 28 d. On day 28 of the experiment, eyes were enucleated and histologically and immunohistochemically analyzed.RESULTS: The fibroblast counts of groups Ⅳ and Ⅴ were determined to be lower than those of groups Ⅱ and Ⅲ(P<0.05). In the mononuclear cell(MNC) count evaluation, no statistically significant difference was determined between the treatment groups(P>0.05). The immunohistochemical staining intensity of fibroblast growth factor β(FGF-β) and vascular endothelial growth factor(VEGF) was determined to be lower in groups Ⅳ and Ⅴ than in groups Ⅱ and Ⅲ(P<0.05). No statistically significant difference was determined between groups Ⅳ and Ⅴ in respect of fibroblast count, MNC count, FGF-β and VEGF staining intensity(P>0.05). The platelet derived growth factor β(PDGF-β) intensity was lower in group Ⅴ than in groups Ⅱ, Ⅲ and Ⅳ(P<0.05). While the PDGF-β staining intensity was significantly lower in group Ⅳ thanin group Ⅱ, the difference compared with group Ⅲ was not statistically significant(P>0.05). CONCLUSION: Bevacizumab and pazopanib might be good alternatives of corticosteroid treatment on delaying wound healing in glaucoma surgery.展开更多
Purpose: The aim of the study is to reveal associations between NF-κB, HIF-1alpha, VEGF expres-sions, proteasome and calpain activities with tumor progression in patients with kidney cancers and to find molecular par...Purpose: The aim of the study is to reveal associations between NF-κB, HIF-1alpha, VEGF expres-sions, proteasome and calpain activities with tumor progression in patients with kidney cancers and to find molecular parameters, associated with the effective pazopanib therapy. 93 patients with clear cell kidney cancers are included in investigation. 26 patients with disseminated kidney cancer have the pazopanib therapy. Methods: Transcription factors, VEGF, VEGFR2 and p-m-TOR expression are measured by ELISA kits. Proteasome and calpain activity are determined using specific fluorogenic substrate. Results: It is found the increase of NF-κB, HIF-1 expression in cancer tissues followed the hematogenic metastasis development. Coefficient NF-κB р65/р50 and VEGF expression are increased in cancer tissues with single metastasis and are decreased in cancer tissues with multiple ones. It is observed in the low proteasome activity in metastatic cancer tissues. The partial cancer regression is revealed in 29.6% of patients treated with pazopanib, cancer stabilization—in 61.5% of patients and cancer progression—in 11.5% of patients. The increased level of transcription factors NF-κB, HIF-1, growth factor VEGF and high proteasome activity in cancer tissues before targeted therapy are associated with the effective treatment. It is obtained the significant decrease of investigated markers after pazopanib application in metastatic kidney cancer patients. Conclusion: Coefficient NF-κB р65/р50, VEGF expression and proteases activities are the potential prognostic molecular markers of hematogenic metastasis development in kidney cancers. NF-κB, HIF-1 and VEGF levels can be considered as additional molecular markers predicting the effective pazopanib therapy.展开更多
BACKGROUND Non-clear cell(ncc)metastatic renal-cell carcinoma(RCC)has dismal results with standard systemic therapies and a generally worse prognosis when compared to its clear-cell counterpart.New systemic combinatio...BACKGROUND Non-clear cell(ncc)metastatic renal-cell carcinoma(RCC)has dismal results with standard systemic therapies and a generally worse prognosis when compared to its clear-cell counterpart.New systemic combination therapies have emerged for metastatic RCC(mRCC),but the pivotal phase III trials excluded patients with nccRCC,which constitute about 30%of metastatic RCC cases.AIM To provide a piece of real-life evidence on the use of pazopanib in this patient subgroup.METHODS The present study is a multicenter retrospective observational analysis aiming to assess the activity,efficacy,and safety of pazopanib as first-line therapy for advanced nccRCC patients treated in a real-life setting.RESULTS Overall,48 patients were included.At the median follow-up of 40.6 mo,the objective response rate was 27.1%,the disease control rate was 83.3%,and the median progression-free survival and overall survival were 12.3(95%confidence interval[CI]:3.6-20.9)and 27.7(95%CI:18.2-37.1)mo,respectively.Grade 3 adverse events occurred in 20%of patients,and no grade 4 or 5 toxicities were found.CONCLUSION Pazopanib should be considered as a good first-line option for metastatic RCC with variant histology.展开更多
Posterior reversible encephalopathy syndrome (PRES), a rare disease is characterized by multiple neurological complications. It has been reported to be associated with the use of angiogenesis inhibitors such as sorafe...Posterior reversible encephalopathy syndrome (PRES), a rare disease is characterized by multiple neurological complications. It has been reported to be associated with the use of angiogenesis inhibitors such as sorafenib, sunitinib, pazopanib, regorafenib, and lenvatinib. We reported a case of 76-year-old woman with history of stage III hepatocellular carcinoma (HCC), who developed adverse drug reactions related to pazopanib induced PRES. Pazopanib, an angiogenesis inhibitor which inhibits the vascular endothelial growth factor (VEGF) pathway may lead to vascular endothelial damage, and these pathophysiological changes may lead to vascular leaks and brain edema. Medical staff must be aware of the possible association between angiogenesis inhibitors and the development of PRES. In patients with retroperitoneal soft-tissue sarcoma undergoing treatment with pazopanib, regular monitoring of their blood pressure and following-up brain magnetic resonance imaging (MRI) should be encouraged.展开更多
Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysesthesia, is a skin toxicity that could be observed during target therapies such as with tyrosine-kinase inhibitors (TKI). It usually develops within th...Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysesthesia, is a skin toxicity that could be observed during target therapies such as with tyrosine-kinase inhibitors (TKI). It usually develops within the first 2 - 4 weeks of drug administration. We present a case of HFS induced by Pazopanib after 2 months of treatment, in patients previously treated with Sunitinib, suggesting a possible cumulative toxicity of two drugs. The clinical and therapeutic management of skin adverse reactions during TKI therapy usually requires 25% dose reduction and adequate local treatment. It is important for the clinicians to recognize clinical signs and symptoms of such skin toxicities. Attention should be paid especially when two or more drugs from the same class are used in combined treatment.展开更多
Thrombotic thrombocytopenic purpura(TTP)is a rare and life-threatening form of thrombotic microangiopathy,primarily caused by a deficiency of ADAMTS-13 activity.Immune-related adverse events(irAEs)are autoimmune toxic...Thrombotic thrombocytopenic purpura(TTP)is a rare and life-threatening form of thrombotic microangiopathy,primarily caused by a deficiency of ADAMTS-13 activity.Immune-related adverse events(irAEs)are autoimmune toxicities mediated by the use of immune checkpoint inhibitors(ICIs).Here,the study reports a case of thrombotic thrombocytopenic purpura that developed in a patient with renal cell carcinoma and vertebral metastasis following combined treatment with Toripalimab and Pazopanib.The patient received Toripalimab in combination with Pazopanib after undergoing radical nephrectomy for right renal cell carcinoma.Five days later,a generalized erythematous rash appeared,partly confluent,accompanied by congestion and swelling of both palpebral and bulbar conjunctiva.Based on the clinical presentation and laboratory results showing thrombocytopenia and hemolytic anemia,the diagnosis of TTP was established.The condition was considered an adverse effect associated with the combination therapy of Toripalimab and Pazopanib.Plasma exchange and high-dose intravenous immunoglobulin therapy were promptly initiated.The treatment regimen was subsequently modified to Axitinib combined with radiotherapy,leading to a gradual recovery of platelet counts.This report highlights the potential risk of TTP associated with combined ICI and TKI therapy,and underscores the importance of early recognition and timely management of this potentially fatal complication.展开更多
目的:探讨紫杉醇联合帕唑帕尼治疗铂耐药复发性卵巢癌的有效性和安全性。方法:检索PubMed、Web of Science、Cochrane Library、EMbase、Ovid Medline、ScienceDirect、Scopus、中国知网(CNKI)、万方和维普等数据库,检索时限均为建库至2...目的:探讨紫杉醇联合帕唑帕尼治疗铂耐药复发性卵巢癌的有效性和安全性。方法:检索PubMed、Web of Science、Cochrane Library、EMbase、Ovid Medline、ScienceDirect、Scopus、中国知网(CNKI)、万方和维普等数据库,检索时限均为建库至2023年11月24日,纳入紫杉醇联合帕唑帕尼或不联合帕唑帕尼治疗铂耐药复发性卵巢癌的文献。运用Revman5.4软件进行meta分析。结果:最终纳入3篇文献,共295例患者,其中紫杉醇+帕唑帕尼组168例,紫杉醇组127例。Meta分析结果显示,相比紫杉醇组,紫杉醇联合帕唑帕尼组的完全缓解(CR)(RR=1.47,95%CI为0.44~4.94)、无进展生存时间(PFS)(HR=0.68,95%CI为0.40~1.15)、总生存期(OS)(HR=0.87,95%CI为0.63~1.20)表现出有利的倾向。两组的客观缓解率(ORR)、疾病控制率(DCR)、部分缓解(PR)、病情稳定(SD)比较,差异均无统计学意义。与紫杉醇组相比,紫杉醇+帕唑帕尼组的生存优势随着生存时间延长而增加,但安全性较差,发病率前五的不良事件包括贫血、疲劳、中性粒细胞减少、恶心、高血压。结论:对于铂耐药复发性卵巢癌,紫杉醇+帕唑帕尼组相比紫杉醇组在治疗疗效上表现出有利的倾向,但需避免不良事件。展开更多
文摘AIM: To compare the effects of bevacizumab and pazopanib with corticosteroids on wound healing after trabeculectomy. METHODS: In the study, 35 New Zealand white rabbits were randomly divided into five groups. Apart from the first group, limbus-based trabeculectomy was performed for the eyes of rabbits. No postoperative treatment was administered for group Ⅰ. Topically administered saline, prednisolone acetate(1%), bevacizumab 5 mg/mL, pazopanib 5 mg/mL for group Ⅱ, Ⅲ, Ⅳ and Ⅴ respectively were applied for groups 6 h daily for 28 d. On day 28 of the experiment, eyes were enucleated and histologically and immunohistochemically analyzed.RESULTS: The fibroblast counts of groups Ⅳ and Ⅴ were determined to be lower than those of groups Ⅱ and Ⅲ(P<0.05). In the mononuclear cell(MNC) count evaluation, no statistically significant difference was determined between the treatment groups(P>0.05). The immunohistochemical staining intensity of fibroblast growth factor β(FGF-β) and vascular endothelial growth factor(VEGF) was determined to be lower in groups Ⅳ and Ⅴ than in groups Ⅱ and Ⅲ(P<0.05). No statistically significant difference was determined between groups Ⅳ and Ⅴ in respect of fibroblast count, MNC count, FGF-β and VEGF staining intensity(P>0.05). The platelet derived growth factor β(PDGF-β) intensity was lower in group Ⅴ than in groups Ⅱ, Ⅲ and Ⅳ(P<0.05). While the PDGF-β staining intensity was significantly lower in group Ⅳ thanin group Ⅱ, the difference compared with group Ⅲ was not statistically significant(P>0.05). CONCLUSION: Bevacizumab and pazopanib might be good alternatives of corticosteroid treatment on delaying wound healing in glaucoma surgery.
文摘Purpose: The aim of the study is to reveal associations between NF-κB, HIF-1alpha, VEGF expres-sions, proteasome and calpain activities with tumor progression in patients with kidney cancers and to find molecular parameters, associated with the effective pazopanib therapy. 93 patients with clear cell kidney cancers are included in investigation. 26 patients with disseminated kidney cancer have the pazopanib therapy. Methods: Transcription factors, VEGF, VEGFR2 and p-m-TOR expression are measured by ELISA kits. Proteasome and calpain activity are determined using specific fluorogenic substrate. Results: It is found the increase of NF-κB, HIF-1 expression in cancer tissues followed the hematogenic metastasis development. Coefficient NF-κB р65/р50 and VEGF expression are increased in cancer tissues with single metastasis and are decreased in cancer tissues with multiple ones. It is observed in the low proteasome activity in metastatic cancer tissues. The partial cancer regression is revealed in 29.6% of patients treated with pazopanib, cancer stabilization—in 61.5% of patients and cancer progression—in 11.5% of patients. The increased level of transcription factors NF-κB, HIF-1, growth factor VEGF and high proteasome activity in cancer tissues before targeted therapy are associated with the effective treatment. It is obtained the significant decrease of investigated markers after pazopanib application in metastatic kidney cancer patients. Conclusion: Coefficient NF-κB р65/р50, VEGF expression and proteases activities are the potential prognostic molecular markers of hematogenic metastasis development in kidney cancers. NF-κB, HIF-1 and VEGF levels can be considered as additional molecular markers predicting the effective pazopanib therapy.
文摘BACKGROUND Non-clear cell(ncc)metastatic renal-cell carcinoma(RCC)has dismal results with standard systemic therapies and a generally worse prognosis when compared to its clear-cell counterpart.New systemic combination therapies have emerged for metastatic RCC(mRCC),but the pivotal phase III trials excluded patients with nccRCC,which constitute about 30%of metastatic RCC cases.AIM To provide a piece of real-life evidence on the use of pazopanib in this patient subgroup.METHODS The present study is a multicenter retrospective observational analysis aiming to assess the activity,efficacy,and safety of pazopanib as first-line therapy for advanced nccRCC patients treated in a real-life setting.RESULTS Overall,48 patients were included.At the median follow-up of 40.6 mo,the objective response rate was 27.1%,the disease control rate was 83.3%,and the median progression-free survival and overall survival were 12.3(95%confidence interval[CI]:3.6-20.9)and 27.7(95%CI:18.2-37.1)mo,respectively.Grade 3 adverse events occurred in 20%of patients,and no grade 4 or 5 toxicities were found.CONCLUSION Pazopanib should be considered as a good first-line option for metastatic RCC with variant histology.
文摘Posterior reversible encephalopathy syndrome (PRES), a rare disease is characterized by multiple neurological complications. It has been reported to be associated with the use of angiogenesis inhibitors such as sorafenib, sunitinib, pazopanib, regorafenib, and lenvatinib. We reported a case of 76-year-old woman with history of stage III hepatocellular carcinoma (HCC), who developed adverse drug reactions related to pazopanib induced PRES. Pazopanib, an angiogenesis inhibitor which inhibits the vascular endothelial growth factor (VEGF) pathway may lead to vascular endothelial damage, and these pathophysiological changes may lead to vascular leaks and brain edema. Medical staff must be aware of the possible association between angiogenesis inhibitors and the development of PRES. In patients with retroperitoneal soft-tissue sarcoma undergoing treatment with pazopanib, regular monitoring of their blood pressure and following-up brain magnetic resonance imaging (MRI) should be encouraged.
文摘Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysesthesia, is a skin toxicity that could be observed during target therapies such as with tyrosine-kinase inhibitors (TKI). It usually develops within the first 2 - 4 weeks of drug administration. We present a case of HFS induced by Pazopanib after 2 months of treatment, in patients previously treated with Sunitinib, suggesting a possible cumulative toxicity of two drugs. The clinical and therapeutic management of skin adverse reactions during TKI therapy usually requires 25% dose reduction and adequate local treatment. It is important for the clinicians to recognize clinical signs and symptoms of such skin toxicities. Attention should be paid especially when two or more drugs from the same class are used in combined treatment.
基金Natural Science Foundation of Gansu Province(Project No.:24JRRA615)Outstanding Talent Recruitment Program and the Doctoral Start-up Fund of Gansu Provincial Central Hospital(Project No.:GMCCH2024-2-6)。
文摘Thrombotic thrombocytopenic purpura(TTP)is a rare and life-threatening form of thrombotic microangiopathy,primarily caused by a deficiency of ADAMTS-13 activity.Immune-related adverse events(irAEs)are autoimmune toxicities mediated by the use of immune checkpoint inhibitors(ICIs).Here,the study reports a case of thrombotic thrombocytopenic purpura that developed in a patient with renal cell carcinoma and vertebral metastasis following combined treatment with Toripalimab and Pazopanib.The patient received Toripalimab in combination with Pazopanib after undergoing radical nephrectomy for right renal cell carcinoma.Five days later,a generalized erythematous rash appeared,partly confluent,accompanied by congestion and swelling of both palpebral and bulbar conjunctiva.Based on the clinical presentation and laboratory results showing thrombocytopenia and hemolytic anemia,the diagnosis of TTP was established.The condition was considered an adverse effect associated with the combination therapy of Toripalimab and Pazopanib.Plasma exchange and high-dose intravenous immunoglobulin therapy were promptly initiated.The treatment regimen was subsequently modified to Axitinib combined with radiotherapy,leading to a gradual recovery of platelet counts.This report highlights the potential risk of TTP associated with combined ICI and TKI therapy,and underscores the importance of early recognition and timely management of this potentially fatal complication.
文摘目的:探讨紫杉醇联合帕唑帕尼治疗铂耐药复发性卵巢癌的有效性和安全性。方法:检索PubMed、Web of Science、Cochrane Library、EMbase、Ovid Medline、ScienceDirect、Scopus、中国知网(CNKI)、万方和维普等数据库,检索时限均为建库至2023年11月24日,纳入紫杉醇联合帕唑帕尼或不联合帕唑帕尼治疗铂耐药复发性卵巢癌的文献。运用Revman5.4软件进行meta分析。结果:最终纳入3篇文献,共295例患者,其中紫杉醇+帕唑帕尼组168例,紫杉醇组127例。Meta分析结果显示,相比紫杉醇组,紫杉醇联合帕唑帕尼组的完全缓解(CR)(RR=1.47,95%CI为0.44~4.94)、无进展生存时间(PFS)(HR=0.68,95%CI为0.40~1.15)、总生存期(OS)(HR=0.87,95%CI为0.63~1.20)表现出有利的倾向。两组的客观缓解率(ORR)、疾病控制率(DCR)、部分缓解(PR)、病情稳定(SD)比较,差异均无统计学意义。与紫杉醇组相比,紫杉醇+帕唑帕尼组的生存优势随着生存时间延长而增加,但安全性较差,发病率前五的不良事件包括贫血、疲劳、中性粒细胞减少、恶心、高血压。结论:对于铂耐药复发性卵巢癌,紫杉醇+帕唑帕尼组相比紫杉醇组在治疗疗效上表现出有利的倾向,但需避免不良事件。
