The origins of human cancer: molecular mechanisms of carcinogenesis and their implications for cancer prevention and treatment--twenty-seventh G.H.A. Clowes memorial award lecture.
The origins of human cancer: molecular mechanisms of carcinogenesis and their implications for cancer prevention and treatment--twenty-seventh G.H.A. Clowes memorial award lecture.
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人类癌症的起源：致癌的分子机制及其对癌症预防和治疗的影响——G.H.A.第二十七期
作者：
Bernard Weinstein
流行病学研究提供的证据表明，环境因素（外部因素，如化学品，辐射和病毒）在大多数人类肿瘤的病因中起着重要作用。这是一个非常乐观的信息，因为它意味着癌症在很大程度上是一种可预防的疾病。然而，为了应对这一挑战，我们必须在细胞和分子水平上了解癌症病因的机制，并同时努力开发新的实验室方法，用于识别人类的特定致病因子。该方法必须是全面的，因为人类癌症很可能是由于多种因素之间复杂的相互作用造成的，包括化学物质和病毒因子的综合作用。本文回顾了我们实验室的最新研究和其他研究人员对这些主题的研究。研究致癌机制的一个主要原则是，该过程通过多个可识别的阶段进行，包括启动，促进和进展。这些阶段之间的过渡可能是由不同的环境和内源性因素驱动的，并涉及不同的生化机制和遗传因素。有几种化学物质通过产生与细胞DNA共价结合的高活性物质来启动致癌过程。我们的小组已经阐明了这一过程的细节与两组化合物，芳香胺和多环芳烃，强调这些代理如何扭曲DNA的构象和它的功能在DNA复制和转录。这些研究结果的影响与癌基因激活，DNA扩增，基因转位，染色体易位进行了讨论。我们对肿瘤促进的研究集中在有效的肿瘤促进剂12-O-十四酰基佛波醇-13-乙酸酯的作用机制上。几个实验室的研究表明，这种药剂和相关化合物通过激活一种特定的细胞酶，蛋白激酶C（PKC）产生作用。这产生了一系列事件，包括膜相关离子通道和受体功能的改变、基因表达的改变以及最终细胞分化和增殖的变化。最近的研究分离和稳定的过表达的克隆的DNA序列编码PKC的描述。所获得的结果提供了直接的证据，PKC在生长控制中起着关键作用。蛋白激酶C，和其他介质的信号转导途径，在某些人类癌症的起源可能发挥的作用也进行了讨论。（400字处删节）
Epidemiological studies provide evidence that environmental factors (external agents such as chemicals, radiation, and viruses) play a major role in the causation of the majority of human tumors. This is a highly optimistic message, since it implies that cancer is largely a preventable disease. To meet this challenge we must, however, understand the mechanisms of cancer causation at the cellular and molecular levels and, in a parallel effort, develop new laboratory methods that can be used to identify specific causative agents in humans. The approach must be comprehensive since it is likely that human cancers are due to complex interactions between multiple factors, including the combined actions of chemical and viral agents. This paper reviews recent studies from our laboratory and studies by other investigators related to these themes. A major principle in studies on mechanisms of carcinogenesis is that the process proceeds through multiple discernible stages, including initiation, promotion, and progression. It is likely that the transition between these stages is driven by different environmental and endogenous factors and involves different biochemical mechanisms and genetic elements. Several types of chemicals initiate the carcinogenic process by yielding highly reactive species that bind covalently to cellular DNA. Our group has elucidated the details of this process with two groups of compounds, aromatic amines and polycyclic aromatic hydrocarbons, emphasizing how these agents distort the conformation of DNA and its functions during DNA replication and transcription. The implications of these findings with respect to oncogene activation, DNA amplification, gene transposition, and chromosome translocations are discussed. Our studies on tumor promotion have concentrated on the mechanisms of action of the potent tumor promoter 12-O-tetradecanoylphorbol-13-acetate. Studies from several laboratories indicate that this agent and related compounds produce their effects by activating a specific cellular enzyme, protein kinase C (PKC). This produces a cascade of events which include alterations in the function of membrane-associated ion channels and receptors, alterations in gene expression and, ultimately, changes in cellular differentiation and proliferation. Recent studies on the isolation and stable overexpression of a cloned DNA sequence that encodes PKC are described. The results obtained provide direct evidence that PKC plays a critical role in growth control. The possible role of PKC, and other mediators of signal transduction pathways, in the origin of certain human cancers is also discussed.(ABSTRACT TRUNCATED AT 400 WORDS)
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二乙基亚硝胺诱导的大鼠肝肿瘤中逆转录病毒序列和癌基因的表达。
影响因子：
11.2
作者：
Hsieh,LL;Hsiao,WL;Peraino,C;Maronpot,RR;Weinstein,IB
通讯作者：
Weinstein,IB
化学致癌剂对 Z-DNA 构象的稳定作用。
DOI：
--
发表时间：
1985
期刊：
Carcinogenesis; a comprehensive survey
影响因子：
--
作者：
Grunberger,D;Santella,RM;Hanau,LH;Erlanger,BF
通讯作者：
Erlanger,BF
DOI：
10.1073/pnas.83.2.241
发表时间：
1986-01-01
影响因子：
11.1
作者：
JEFFREY, AM;LISKAMP, RMJ
通讯作者：
LISKAMP, RMJ
致癌物诱导的多瘤 DNA 异步复制是由反式作用因子介导的。
影响因子：
4.7
作者：
Lambert,ME;Pellegrini,S;Gattoni-Celli,S;Weinstein,IB
通讯作者：
Weinstein,IB
影响 B6C3 小鼠肝脏内源性逆转录病毒相关序列表达的因素。
影响因子：
11.2
作者：
Dragani,TA;Manenti,G;DellaPorta,G;Weinstein,IB
通讯作者：
Weinstein,IB