Suppr超能文献

结束语。

Closing Remarks.

作者信息

Reed E

机构信息

Clinical Pharmacology Branch, Medical Ovarian Cancer Section, National Cancer Institute, Bethesda, Maryland, 20892, USA.

出版信息

Oncologist. 1996;1(4):276-277.

Abstract

About twenty years ago, the leaders of the National Cancer Institute (NCI) decided to start a new branch in the Clinical Oncology Program of the Division of Cancer Treatment. That new entity was named the Clinical Pharmacology Branch (CPB), and its first leader was a brilliant, young, promising investigator named Bruce A. Chabner. Chabner was educated at Yale and Harvard, and appeared to have an extraordinary grasp of novel concepts that were being developed in the emerging area of cancer chemotherapy. What the NCI leaders did not fully appreciate at the time was that they had just given birth to one of the most extraordinary careers in academic medicine. From the early seventies through the early eighties, Bruce Chabner developed a strong laboratory program that was based on scientific discovery and on the development of new talent. The CPB focused on new drug development, elucidation of drug mechanism(s) of action, and the development of new ways to use drugs that were already available. Concurrent with this laboratory effort was active participation in the development of clinical treatment regimens for Hodgkin's disease, non-Hodgkin's lymphoma, and other malignancies. Individuals who trained under Chabner are now cancer center directors, department heads, laboratory chiefs, and hold many other high-profile positions. From 1981 to 1995 Bruce Chabner was Director of the Division of Cancer Treatment (DCT) of the NCI. In that capacity he was Scientific Director of the Intramural Program within DCT, and he had oversight responsibility for the direction of extramural studies that were funded through the NCI, which were focused on the development of new treatments for human malignant disease. The NCI has five divisions for which the NCI Director has ultimate responsibility. While working with one NCI Director from 1981 to 1988, and with another from 1988 to 1995, and during the transition year of 1988, Bruce Chabner provided stability for the DCT while many changes were occurring throughout the five divisions of the NCI. How does one assess the impact of a career on a discipline such as cancer treatment? It's not easy! Each of the articles contributed to this tribute were written by a person who trained directly with Bruce Chabner, or was otherwise directly impacted by Bruce's guidance. As can be seen from the list of contributors to these Proceedings, each individual has made major contributions to the area of cancer treatment in his or her own right. However, Bruce's contribution to cancer treatment goes far beyond the individuals he trained. The many thousands of human lives who have benefited from his efforts cannot be accurately estimated, because his contributions have been so wide-ranging, as indicated below. Being "Scientific Director" is similar in a number of ways to being a football quarterback. One of those ways is that when things go well the quarterback may get a little too much credit, and when things go not-so-well the quarterback may get too much blame. However, it is the quarterback who "calls the plays." With that in mind, a partial list of the accomplishments of the Intramural Program of the DCT while Bruce Chabner was "quarterback" includes the following: * The first human retroviruses, HTLV-1 and HTLV-2, were discovered and shown to be directly linked to the development of specific human malignancies. * Adoptive immunotherapy for human cancer was developed, offering exciting new additions to the anticancer armamentarium. * Paclitaxel (Taxol®) was developed, and shown to be the most important new anticancer agent in the past two decades. * The human genes responsible for the development of several specific malignancies were discovered, such as those for kidney cancer. * Development of blood tests to detect HIV-tainted blood. * Treatment strategies for pediatric AIDS were developed. * The AIDS Drug Development Program within the NIH was established. * New drugs for the treatment of AIDS and AIDS-related conditions were developed. * The only three drugs to date that have been specifically approved for the treatment of AIDS-AZT, DDI, and DDC-were developed under the guidance of the DCT, with Bruce Chabner as Scientific Director. * The first clinical trials conducted with each of these agents-AZT, DDI, and DDC-were performed in the Intramural Program of the DCT. * Concurrently, many of the exciting findings reported by the National Surgical Adjuvant Breast and Bowel Project over the past 10 years (as well as other cooperative groups) were a direct result of the strong support shown by Bruce Chabner during his tenure as Director of the Division of Cancer Treatment. Further, the list above does not include his personal labortory and clinical accomplishments, some of which are: * Development of the principles of use of important antimetabolites, such as methotrexate. * Elucidation of biochemical pathways affected, and the mechanisms of action, of antifols and other antimetabolites. * The conduct of seminal studies in the clinical staging of non-Hodgkin's lymphomas, using laparoscopy as a primary tool. * Important contributions to the development of multiagent regimens in the clinical treatment of lymphomas, and of Hodgkin's disease. * Developed and is editor of the textbook which is considered to be the primary reference source for anticancer chemotherapeutic agents [1]. With all of these accomplishments, his career is long from over. Having just become the Medical Director of the Cancer Center at the Massachusetts General Hospital, Bruce Chabner is uniquely poised to have an even more far-reaching impact on a discipline in which he has played such a strong seminal role. This author was never a postdoctoral fellow in Bruce Chabner's laboratory. However, more than any other single person, he has played a central role in my professional development. I know of many others for whom the same statement would be true. It is a pleasure for me to witness the launching of the second phase of an already tremendous career. From Advances in Cancer Treatment: The Chabner Symposium. Stem Cells 1996;14:64-65.

摘要

大约二十年前,美国国立癌症研究所(NCI)的领导们决定在癌症治疗司的临床肿瘤学项目中设立一个新的分支。这个新机构被命名为临床药理学分支(CPB),其首任负责人是一位才华横溢、年轻有为的研究员,名叫布鲁斯·A·查布纳。查布纳曾在耶鲁大学和哈佛大学接受教育,似乎对癌症化疗这一新兴领域正在发展的新观念有着非凡的理解。当时NCI的领导们并未充分意识到的是,他们刚刚开启了学术医学领域最非凡的职业生涯之一。从20世纪70年代初到80年代初,布鲁斯·查布纳开展了一个强大的实验室项目,该项目基于科学发现和新人才的培养。CPB专注于新药研发、阐明药物作用机制以及开发使用现有药物的新方法。在进行这项实验室工作的同时,还积极参与了霍奇金淋巴瘤、非霍奇金淋巴瘤及其他恶性肿瘤临床治疗方案的制定。在查布纳手下接受培训的人员如今已成为癌症中心主任、系主任、实验室主任,并担任许多其他备受瞩目的职位。1981年至1995年,布鲁斯·查布纳担任NCI癌症治疗司(DCT)司长。在此职位上,他是DCT内部项目的科学主任,并且对由NCI资助的、旨在开发人类恶性疾病新治疗方法的外部研究方向负有监督责任。NCI有五个司,NCI主任对其负最终责任。在1981年至1988年与一位NCI主任共事,以及1988年至1995年与另一位主任共事期间,在1988年这个过渡年里当NCI的五个司都在发生诸多变化时,布鲁斯·查布纳为DCT提供了稳定性。如何评估一个职业生涯对癌症治疗这样的学科所产生的影响呢?这并非易事!为这份致敬文集撰稿的每一篇文章都是由直接在布鲁斯·查布纳手下接受培训的人,或者受到布鲁斯指导直接影响的人撰写的。从这些会议论文集的撰稿人名单可以看出,每个人都在癌症治疗领域凭借自身能力做出了重大贡献。然而,布鲁斯对癌症治疗的贡献远远超出了他所培养的个人。受益于他的努力的成千上万人的生命无法准确估量,因为他的贡献范围如此广泛,如下所示。担任“科学主任”在很多方面类似于担任橄榄球四分卫。其中一点是,当事情进展顺利时,四分卫可能会得到过多赞誉,而当事情进展不顺利时,四分卫可能会受到过多指责。然而,正是四分卫“指挥比赛”。考虑到这一点,在布鲁斯·查布纳担任“四分卫”期间,DCT内部项目的部分成就如下:

  • 发现了首批人类逆转录病毒HTLV - 1和HTLV - 2,并证明它们与特定人类恶性肿瘤的发生直接相关。

  • 开发了针对人类癌症的过继性免疫疗法,为抗癌武器库增添了令人兴奋的新手段。

  • 研发了紫杉醇(泰素®),并证明它是过去二十年来最重要的新型抗癌药物。

  • 发现了导致几种特定恶性肿瘤发生的人类基因,比如肾癌相关基因。

  • 开发了检测受HIV污染血液的血液检测方法。

  • 制定了儿童艾滋病的治疗策略。

  • 在国立卫生研究院内设立了艾滋病药物研发项目。

  • 开发了用于治疗艾滋病及与艾滋病相关病症的新药。

  • 至今仅有的三种专门获批用于治疗艾滋病的药物——齐多夫定、双脱氧肌苷和双脱氧胞苷——是在DCT的指导下研发的,布鲁斯·查布纳担任科学主任。

  • 这些药物——齐多夫定、双脱氧肌苷和双脱氧胞苷——的首批临床试验是在DCT的内部项目中进行的。

  • 与此同时,过去十年里国家外科辅助乳腺和肠道项目(以及其他合作组)所报告的许多令人兴奋的发现,都是布鲁斯·查布纳在担任癌症治疗司司长期间给予大力支持的直接成果。此外,上述列表并未包括他个人的实验室和临床成就,其中一些如下:

  • 确立了使用重要抗代谢物(如甲氨蝶呤)的原则。

  • 阐明了抗叶酸剂和其他抗代谢物所影响的生化途径及其作用机制。

  • 以腹腔镜检查为主要工具,对非霍奇金淋巴瘤的临床分期进行了开创性研究。

  • 在淋巴瘤和霍奇金病的临床治疗中多药联合方案的开发方面做出了重要贡献。

  • 编写并担任了被认为是抗癌化疗药物主要参考资料来源的教科书的编辑[1]。

尽管取得了所有这些成就,他的职业生涯远未结束。布鲁斯·查布纳刚刚成为麻省总医院癌症中心的医学主任,他处于独特的位置,能够对他已发挥如此重要开创性作用的学科产生更深远的影响。本文作者从未在布鲁斯·查布纳的实验室做过博士后研究员。然而,他在我的职业发展中所起的核心作用超过了其他任何人。我知道还有许多其他人也会这样说。我很高兴见证他已经辉煌的职业生涯进入第二阶段。摘自《癌症治疗进展:查布纳研讨会》。《干细胞》1996年;14:64 - 65。

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