排序方式: 共有117条查询结果,搜索用时 15 毫秒
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Suraj Konnath George Deeksha Vishwamitra Roxsan Manshouri Ping Shi Hesham M. Amin 《Oncotarget》2014,5(14):5750-5763
NPM-ALK+ T-cell anaplastic large-cell lymphoma (ALCL) is an aggressive type of cancer. Standard treatment of NPM-ALK+ ALCL is CHOP polychemotherapy. Although patients initially respond favorably to CHOP, resistance, relapse, and death frequently occur. Recently, selective targeting of ALK has emerged as an alternative therapeutic strategy. ASP3026 is a second-generation ALK inhibitor that can overcome crizotinib resistance in non-small cell lung cancer, and is currently being evaluated in clinical trials of patients with ALK+ solid tumors. However, NPM-ALK+ ALCL patients are not included in these trials. We studied the effects of ASP3026 on NPM-ALK+ ALCL cell lines in vitro and on systemic lymphoma growth in vivo. ASP3026 decreased the viability, proliferation, and colony formation, as well as induced apoptotic cell death of NPM-ALK+ ALCL cells. In addition, ASP3026 significantly reduced the proliferation of 293T cells transfected with NPM-ALK mutants that are resistant to crizotinib and downregulated tyrosine phosphorylation of these mutants. Moreover, ASP3026 abrogated systemic NPM-ALK+ ALCL growth in mice. Importantly, the survival of ASP3026-treated mice was superior to that of control and CHOP-treated mice. Our data suggest that ASP3026 is an effective treatment for NPM-ALK+ ALCL, and support the enrollment of patients with this lymphoma in the ongoing clinical trials. 相似文献
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《Expert opinion on investigational drugs》2013,22(6):793-807
Introduction: Pancreatic adenocarcinoma (PDAC) has the worst prognosis of any major malignancy, with 5-year survival painfully inadequate at under 5%. Investigators have struggled to target and exploit PDAC unique biology, failing to bring meaningful results from bench to bedside. Nonetheless, in recent years, several promising targets have emerged. Areas covered: This review will discuss novel drug approaches in development for use in PDAC. The authors examine the continued efforts to target Kirsten rat sarcoma viral oncogene homolog (KRas), which have recently been successfully abated using novel small interfering RNA (siRNA) eluting devices. The authors also discuss other targets relevant to PDAC including those downstream of mutated KRas, such as MAPK kinase and phosphatidylinositol 3-kinase. Expert opinion: Although studies into novel biomarkers and advanced imaging have highlighted the potential new avenues toward discovering localized tumors earlier, the current therapeutic options highlight the fact that PDAC is a highly metastatic and chemoresistant cancer that often must be fought with virulent, systemic therapies. Several newer approaches, including siRNA targeting of mutated KRas and enzymatic depletion of hyaluronan with PEGylated hyaluronidase are particularly exciting given their early stage results. Further research should help in elucidating their potential impact as therapeutic options. 相似文献
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《Expert review of anticancer therapy》2013,13(2):225-233
Crizotinib (XALKORI?, Pfizer) is a tyrosine kinase inhibitor targeting ALK, MET and ROS1, currently approved for the treatment of adults with ALK-rearranged non-small-cell lung cancer. Optimizing the management of frequent crizotinib-related adverse events is crucial to ensure its continuous administration and reproduce the response and survival rates reported in clinical trials. Here, we propose some practical measures, which are mostly derived from the recommendations given to the investigators of the PROFILE 1001, 1005, 1007 and 1014 trials and are based on experience and scientific findings regarding the management of these disorders. While visual disturbances or bradycardia are frequent but benign, the severity of the cardiac and hepatic adverse events requires special attention potential to QT interval prolongations and to the monitoring of electrolyte levels and liver function, taking into account potential drug–drug interactions. 相似文献
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目的 探讨克唑替尼联合PC方案治疗非小细胞肺癌的临床疗效。方法 选择2016年1月—2018年12月新疆喀什地区第二人民医院治疗的64例非小细胞肺癌患者作为研究对象。用抽签法随机将患者分为对照组和观察组,每组各32例。对照组每天静脉滴入注射用培美曲塞二钠,500 mg/m2,静滴时间超过10 min,并静脉滴入卡铂注射液,AUC5静滴时间超过30 min。观察组在对照组的基础上口服克唑替尼胶囊,250 mg/次,2次/d。1个周期为21 d,两组共治疗2个周期。观察两组患者的临床疗效,同时比较两组患者治疗前后的血清癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)、人鳞状细胞癌相关抗原(SCCAg)以及细胞角蛋白19片段(Cyfra21-1)水平和Karnofsky功能状态评分量表(KPS)评分情况。结果 治疗后,观察组总有效率为81.25%,明显高于对照组的59.37%(P<0.05)。两组治疗后的NSE、CEA、SCCAg和CYFRA21-1水平均明显降低(P<0.05),且观察组上述肿瘤标志物水平明显低于对照组(P<0.05)。治疗后,观察组的生活质量好转率明显高于对照组,恶化率明显低于对照组(P<0.05)。结论 克唑替尼联合PC方案治疗非小细胞肺癌患者的疗效显著,能明显降低肿瘤标志物水平,提高生活质量。 相似文献
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Qiuyu Liu Yunzhen Kan Yuewu Zhao Hui He Lingfei Kong 《International journal of clinical and experimental pathology》2015,8(11):15328-15332
Epithelioid inflammatory myofibroblastic sarcoma is extremely rare and belongs to a variant of inflammatory myofibrobalstic tumor with aggressive clinical course. We describe a case of a 22 years old man presented with an abdominal huge tumor. Microscopically, the neoplasm cells were rounded and epithelioid in shape. Abundant interstitial edema and less myxoid stroma were also present together with an inflammatory infiltrate. Fluorescence in situ hybridization revealed that ALK gene presented mutation. After surgery the patient received chemotherapy with an anaplastic lymphoma kinase (ALK) inhibitor, crizotinib. The patient continues to be alive with disease for 16 months and has no recurrence. Although EIMS has a poor prognosis, this is the few successful case with sustained response of targeted therapy. 相似文献
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Quan Zhang Jinghui Wang Shucai Zhang 《International journal of clinical and experimental pathology》2015,8(2):2195-2198
ALK rearrangement is a very rare subset of squamous cell cancer of lung and the efficacy of crizotinib treatment for these patients is lack of data. Here we report a case with squamous cell cancer of lung that harbored the ALK rearrangement was given crizotinib in the second-line therapy. A 55-year-old female patient was diagnosed with squamous cell carcinoma of lung by bronchoscopy biopsy with stage IV. The patient was given two cycles of chemotherapy and the response was progressive disease. After failure to chemotherapy, genotype testing showed wild-type EGFR/KRAS and ALK rearrangement positive. The patient was administered with crizotinib and had a partial response, and the progression-free survival was 6 months. The side effects were tolerable. 相似文献
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Alicia M. Blessing MD PhD Janice M. Santiago-O'Farrill MD PhD Weiqun Mao BS MD Lan Pang BS MD Jing Ning MD PhD Daewoo Pak MD PhD Lakshmi Reddy Bollu MD PhD Philip Rask BS MD LaKesla Iles BS MD Hailing Yang PhD MD Samantha Tran BS MD Ezzeddine Elmir BS MD Geoffrey Bartholomeusz MD PhD Robert Langley MD PhD Zhen Lu MD Robert C. Bast Jr MD 《Cancer》2020,126(15):3579-3592