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Targeting chronic lymphocytic leukemia cells in the tumor microenviroment: A review of the in vitro and clinical trials to date

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World Journal of Clinical Cases 2015年第8期3卷 694-704页

作者： Kyle Crassini Stephen P Mulligan o giles best Northern Blood Research Centre and CLL Australian Research Consortium Kolling Institute of Medical Research Royal North Shore Hospital

Chronic lymphocytic leukemia(CLL) is the most common leukemia in the western world. Despite significantadvances in therapy over the last decade CLL remains incurable. Current front-line therapy often consists of chemoimmunotherapy-based regimens, most commonly the fludarabine, cyclophosphamide plus rituximab combination, but rates of relapse and refractory disease are high among these patients. Several key signaling pathways are now known to mediate the survival and proliferation of CLL cells in vivo, the most notable of which are the pathways mediated by the B-cell receptor(BCR) and cytokine receptors. A better understanding of the pathogenesis of the disease, the underlying biology of the CLL-cell and the roles of the tumour microenvironment has provided the rationale for trials of a range of novel, more targeted therapeutic agents. In particular, clinical trials of ibrutinib and idelalisib, which target the Brutons tyrosine kinase and the delta isoform of phosphoinositol-3 kinase components of the BCR signaling pathway respectively, have shown extremely promising results. Here we review the current literature on the key signaling pathways and interactions of CLL cells that mediate the survival and proliferation of the leukemic cells. For each we describe the results of the recent clinical trials and in vitro studies of novel therapeutic agents.

关键词： Chronic lymphocytic leukemia Therapy Microenvironment Leukemia Novel

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Therapeutic approaches and drug-resistance in chronic lymphocytic leukaemia

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Cancer Drug Resistance 2020年第3期3卷 532-549页

作者： Narjis Fatima Kyle R.Crassini Lauren Thurgood Yandong Shen Richard I.Christopherson Bryone Kuss Stephen P.Mulligan oliver giles best Kolling Institute of Medical Research University of SydneyRoyal North Shore HospitalSydneyNSW 2065Australia. School of Life and Environmental Sciences University of SydneySydney NSW 2008Australia. College of Medicine and Public Health Flinders UniversityBedford ParkAdelaideSA 5042Australia.

The treatment of chronic lymphocytic leukaemia has been revolutionised in recent years,first by the introduction of chemoimmunotherapy regimens and subsequently by the development of drugs,including ibrutinib,idelalisib and venetoclax,that target components of the B-cell receptor signalling pathway or B-cell lymphoma 2 family of *** high initial response rates in patients treated with chemoimmunotherapy or targeted agents,a significant proportion of patients relapse with progressive and refractory *** a subset of these patients,drug resistance has been associated with specific genetic lesions or activation of alternate pro-survival ***,the mechanisms that confer drug resistance in the remainder of the patients with refractory disease have yet to be fully *** this review,we discuss our current understanding of the mechanics of drug resistance in chronic lymphocytic leukaemia and describe how this knowledge may aid in rationalising future treatment strategies to prevent the development of refractory or aggressive transformation of the disease.

关键词： Chronic lymphocytic leukaemia drug resistance targeted cancer therapy

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Urachal Cancer: Experience of a High-Volume Bladder Cancer Center

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open Journal of Urology 2023年第7期13卷 201-213页

作者： Abdulla Uthman Christopher C. Khoo Jiten Jaipuria Ahmed Abdel-Aziz Nathan Taylor Norma Gibbons David Hrouda giles Hellawell Eva Bolton Imperial College Healthcare NHS Trust London UK Portsmouth Hospitals University NHS Trust Portsmouth UK Tanta University Hospital Tanta Egypt

Introduction: Primary urachal cancer (UrCa) is rare, with an estimated incidence of 0.2% - 0.5% of all bladder tumors. Although the preferred treatment is surgical, there is no consensus on the best approach. We present our experience managing 14 cases of primary UrCa. Methods: A retrospective analysis was conducted on the clinical records of a high-volume bladder cancer center in the UK to identify patients diagnosed with UrCa between May 2013 and June 2022. Results: 9 males and 6 females, aged between 30 and 85 years, were included. The diagnosis was most commonly made via flexible cystoscopy and CT for haematuria. 3 patients had metastasis at presentation, and while radiologically no patients showed positive lymph nodes, 2 patients were found to have positive lymph nodes on histopathology. 13 patients underwent partial cystectomy, with 1 undergoing radical cystoprostatectomy. 8 patients underwent concurrent umbilectomy and/or lymphadenectomy. The most common histological subtype was mucinous adenocarcinoma. 2 patients experienced local recurrence and underwent transurethral resection, while 6 patients experienced metastasis. Metastasis-free survival rate was 74.1% and 55.6% at 12 and 24 months, respectively. Umbilectomy and lymphadenectomy did not decrease rates of positive surgical margin, local recurrence, metastasis, or mortality. Conclusions: UrCa is a rare and aggressive malignancy that can occur at any age and may be advanced upon presentation. Bladder-sparing surgery is becoming more prevalent, with chemotherapy being reserved for recurrence or metastasis. In our series, routine umbilectomy and lymphadenectomy did not improve oncologic outcomes. However, lymphadenectomy may have a role in cancer staging.

关键词： Urachal Cancer Urachus Bladder Cancer

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肥胖与早期动脉粥样硬化性心血管疾病识别的关系

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中国慢性病预防与控制 2009年第3期17卷 258-260页

作者：王朝霞木尼热.吾不力马依彤 Jean-Louis Megnien GillesChironi 新疆医科大学第一附属医院心脏中心新疆乌鲁木齐830054 Preventive Cardiology Department Center of Medicine Preventive Cardiovascular Hospital of European Georges Pompidoufranceparis75015

目的评价人体脂肪测量指标[体质指数(BMI)、腰围(WC)、腰臀比(WHR)和体脂量(BFM)]与早期动脉粥样硬化性心血管疾病识别的关系。方法共分析649名研究对象,平均年龄(55±11)岁,均行人体脂肪测量4个指标的评价。同时进行形态学和血生化两... 详细信息

目的评价人体脂肪测量指标[体质指数(BMI)、腰围(WC)、腰臀比(WHR)和体脂量(BFM)]与早期动脉粥样硬化性心血管疾病识别的关系。方法共分析649名研究对象,平均年龄(55±11)岁,均行人体脂肪测量4个指标的评价。同时进行形态学和血生化两个方面的早期动脉粥样硬化性心血管疾病识别的评价。结果脂肪测量的4个评价指标与收缩压、舒张压、血糖、甘油三酯和载脂蛋白B呈正相关(r>0),与高密度脂蛋白胆固醇和载脂蛋白A1呈负相关(roR>1)。在与颈动脉内膜中层厚度的相关性分析中,BFM的作用最强(oR值和95%CI分别为1.98和1.44～2.57)。在与轻度炎症的相关性中,WHR的作用最强(oR和95%CI分别为1.74和1.43～2.10)。结论BFM与早期动脉粥样硬化的关系最为密切。提示BFM可以作为预测成人心血管事件的参考指标。

关键词：体质指数腰围腰臀比体脂量早期动脉粥样硬化

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Naturally acidic and metalliferous waters at unmined volcanogenic massive sulfide deposits in the Bonnifield mining district, Alaska Range, east-central Alaska

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Chinese Journal of Geochemistry 2006年第B8期25卷 232-232页

作者： Robert G. Eppinger Paul H. Briggs Cynthia Dusel-Bacon Stuart A. giles Larry P. Gough Jane M.Hammarstrom Bernard E. Hubbard U.S. Geological Survey Central Mineral Resources Team Denver Colorado USA U.S. Geological Survey Western Mineral Resources Team Menlo Park California USA U.S. Geological Survey Eastern Mineral Resources Team Reston Virginia USA

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