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Treatment sequencing in metastatic castrate-resistant prostate cancer

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Asian Journal of Andrology 2014年第3期16卷 426-431页

作者： Oliver Sartor Silke gillessen Department of Medicine and Urology Tulane University School of Medicine New Orleans Louisiana USA Department of Medical Oncology Kantonsspital St. Gallen St. Gallen Switzerland.

Six different treatments have demonstrated improved survival in phase III trials targeted to patients with metastatic castration-resistant prostate cancer （mCRPC）. Front-line therapeutic options for mCRPC include docetaxel, sipuleuceI-T, abiraterone and radium-223. Post-docetaxel options include cabazitaxel, abiraterone, enzalutamide and radium-223. Despite much progress in recent years, much is yet unknown and debates occur over optimal treatment choices and sequences. None of the new agents have been compared to one another, thus physicians in practice today must make choices based on non-randomized comparisons, toxicity considerations and various assumptions. Abiraterone is now moving into the front line mCRPC space given recent regulatory approvals and enzalutamide will follow soon. Both of the hormonal agents have less toxicity when compared to chemotherapeutic options and both of these hormonal agents are expected to be used in a considerable number of mCRPC patients in the years ahead. Little data are available for the post-abiraterone or post-enzalutamide setting. In this review the currently available sequencing data are summarized and interpreted. It is now clear that cross resistance is a potential issue between various treatments, especially those agents that target the androgen axis. This review highlights the need for additional studies to optimize the current treatments for these patients.

关键词： abiraterone cabazitaxel castrate-resistant docetaxel enzalutamide~ radium-223 sipuleuceI-T

Liver tumor infiltrating lymphocytes: Comparison of hepatocellular and cholangiolar carcinoma

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World Journal of Gastroenterology 2009年第40期15卷 5053-5057页

作者： Hans-Udo Kasper Uta Drebber Dirk Ludger Stippel Hans Peter Dienes Anton gillessen Department of Pathology Medical CenterClemenshospital Münster Department of Pathology University of Cologne Department of Visceral and Vascular Surgery University of Cologne Department of Gastroenterology Herz-Jesu-Hospital Hiltrup

AIM: To investigate the role of tumor inf iltrating lym-phocytes (TIL) in primary hepatocellular and cholangio-lar carcinomas of the ***: Immunohistochemical analysis was per-formed including antibodies to CD3, CD4, CD8, CD20, CD56 and TIA-1 in formalin-f ixed and paraff in-embed-ded tissue of 35 liver resection specimens of hepatocel-lular or cholangiocellular carcinomas. Semiquantitative evaluation was performed with emphasis on the area of the tumor itself and of the tumor/liver ***: All hepatocellular carcinomas showed in-filtration of lymphocytes predominantly around the tumor in the tumor/liver interface consisting mainly of CD3+ CD4+ T lymphocytes [164.3/10 high power f ields (HPF)] and in the tumor itself of CD8+ cells (54.9/10 HPF). Cholangiocarcinomas contained a heterogeneous amount of TIL, composed mainly of CD3+ T cells with a predominance of CD8+ cells in the tumor tissue (52.6/10 HPF) and of CD4+ cells in the interface region (223.1/10 HPF). CD56+ cells of the innate immune system were scarce. There was no significant difference between hepatocellular or cholangiolar carcinoma. No correlation with the clinicopathological data was seen. CONCLUSION: Liver TIL consists of intratumoral CD8+ T cells and peritumoral CD4+ T cells indepen-dent of histogenetic origin. Different functions of lym-phocytes in these regions seem possible.

关键词： Liver neoplasms Hepatocellular carcinoma Lymphocytes Immunologic factors Cholangiocarcinoma

Evaluation of Ultrasound-based Surveillance for Hepatocellular Carcinoma in Patients at Risk:Results From a German Multicenter Retrospective Cohort Study

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Journal of Clinical and Translational Hepatology 2023年第3期11卷 626-637页

作者： Johannes gillessen Philipp Reuken Peter-Marton Hunyady Matthias Christian Reichert Lucian Lothschütz Fabian Finkelmeier Matthias Nowka Gabriel Allo Fabian Kütting Martin Bürger Dirk Nierhoff Hans-Michael Steffen Christoph Schramm University Hospital Cologne Department of Gastroenterology and HepatologyCologneGermany University Hospital Jena Department of Internal Medicine IV-GastroenterologyHepatologyInfectious DiseaseJenaGermany University Hospital Frankfurt Department of Internal Medicine 1-Gastroenterology und HepatologyPulmonology und AllergologyEndocrinologyFrankfurtGermany Department of Medicine II Saarland University Medical CenterHomburgGermany Department of Gastroenterology and Hepatology University Hospital of EssenEssenGermany

Background and Aims:Hepatocellular carcinoma(HCC)surveillance in patients at risk is strongly recommended and usually performed by ultrasound(US)semiannually with or without alfa-fetoprotein(AFP)*** pa-rameters except for surveillance intervals have not been strictly *** aimed to evaluate surveillance success and risk factors for surveillance ***:Patients with≥1 US prior to HCC diagnosis performed at four tertiary referral hospitals in Germany between 2008 and 2019 were retrospectively *** success was defined as HCC detection within Milan ***:Only 47%of 156 patients,median age 63(interquartile range:57-70)years,56%male,and 96%with cirrhosis,received recom-mended surveillance modality and *** fail-ure occurred in 29%and was significantly associated with lower median model for end-stage liver disease(MELD)score odds ratio(OR)1.154,95%confidence interval(CI):1.027-1.297,p=0.025)and HCC localization within right liver lobe(OR:6.083,95%CI:1.303-28.407,p=0.022),but not with AFP≥200μg/*** with surveillance failure had sig-nificantly more intermediate/advanced tumor stages(93%vs.6%,p<0.001),fewer curative treatment options(15%vs.75%,p<0.001)and lower survival at 1 year(54%vs.75%,p=0.041),2 years(32%vs.57%,p=0.019)and 5 years(0%vs.16%,p=0.009).Alcoholic and non-alcoholic fatty liver disease(OR:6.1,95%CI:1.7-21.3,p=0.005)and ascites(OR:3.9,95%CI:1.2-12.6,p=0.021)were in-dependently associated with severe visual limitations on ***:US-based HCC surveillance in patients at risk frequently fails and its failure is associated with unfavorable patient-related *** MELD score and HCC lo-calization within right liver lobe were significantly associated with surveillance failure.

关键词： Hepatocellular carcinoma Surveillance success Screening Ultra-sound.

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用荧光原位杂交技术显示染色体易位(英文)

第二军医大学学报 2000年第9期21卷 853-856,F003页

作者：朱冠山 Oliver Bartsch 万谟彬 Gabriele gillessen-Kaesbach Eberhard Passarge 上海长海医院 200433 德累斯顿科技大学临床遗传学研究所埃森大学人类遗传学研究所

目的 :应用荧光原位杂交技术 (fluorescence in situ hybridization,FISH)对 G显带提示有染色体易位的病例进行分析 ,阐明易位本质。方法 :以定位于待研究染色体区段的酵母人工染色体 (yeast artificialchrom osom e,YAC)作为 DNA来源 ... 详细信息

目的 :应用荧光原位杂交技术 (fluorescence in situ hybridization,FISH)对 G显带提示有染色体易位的病例进行分析 ,阐明易位本质。方法 :以定位于待研究染色体区段的酵母人工染色体 (yeast artificialchrom osom e,YAC)作为 DNA来源 ,采用 DOP- PCR(degenerate oligonucleotide- primed,PCR)方法制备荧光标记的位点特异性探针 ,进行染色体原位杂交。结果 :两例经 G显带未能明确显示的染色体结构异常 ,经 FISH证实 ,一例为发生于 11号染色体与 13号染色体之间的平衡易位 ;另一例为发生于 6号染色体与 X染色体之间的不平衡易位。结论 :FISH技术以其高度的灵敏性及特异性 ,成为常规染色体显带技术的一个重要补充 ,特别适用于对微小染色体结构重排以及染色体片段起源的阐明。

关键词：染色体结构异常荧光原位杂交 YAC DOP-PCR

用FISH技术分析一例表型异常的染色体平衡易位

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中华医学遗传学杂志 2001年第2期18卷 96-99页

作者：朱冠山 Oliver Bartsch 万谟彬 Gabriele gillessen-Kaesbach Eberhard Passarge 上海第二军医大学附属长海医院 200433 Institut für Klinische Genetik TU DresdenUniversitatsklinikum Institut für Humangenetik Universitatsklinikum Essen

目的　应用荧光原位杂交技术对 1例染色体结构异常患者进行分析 ,阐明结构异常性质 ,并精细定位断点。方法　对一先天表型异常经细胞遗传学检查有 t(5 ;10 )的病例 ,分别选用 5号染色体探针池以及用酵母人工染色体作为 DNA来源制备的断... 详细信息

目的　应用荧光原位杂交技术对 1例染色体结构异常患者进行分析 ,阐明结构异常性质 ,并精细定位断点。方法　对一先天表型异常经细胞遗传学检查有 t(5 ;10 )的病例 ,分别选用 5号染色体探针池以及用酵母人工染色体作为 DNA来源制备的断点区位点特异性探针 ,进行荧光染色体原位杂交。结果证实患者染色体异常属平衡易位 ,并将 5号和 10号染色体的断点分别定位到 1.5 Mb及约 3Mb的范围。结论　患者的先天性表型异常可能由断点处染色体细微重排或致病基因断裂所致。

关键词：荧光原位杂交染色体结构异常先天性发育不良诊断

用FISH技术分析一例表型异常的染色体平衡易位

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肝脏 2001年第S1期6卷 98-页

作者：朱冠山 Oliver Bartsch 万谟彬 Gabriele gillessen-Kaesbach Eberhard Passarge 上海第二军医大学附属长海医院 Institut fur Klinische Genetik TU DresdenUniversitatsklinikumFescherstrasse7401307 DresdenGermany Institut fur Humangenetik Universitatsklinikum EssenHufelandstrasse5545122 EssenGermany Institut