Tumor necrosis factor (TNF) is a highly potent pleiotropic response modifier in inflammatory and immunologic host defense reactions. It can also be toxic to cells and elicit toxic systemic reactions, as evinced by certain pathophysiologic conditions that are initiated or aggravated by an excess of TNF. The cellular mechanisms for transducing TNF signals are complex. There are two forms of TNF, alpha and beta, and two distinct TNF receptors. Many cells express both receptor types simultaneously, even though neither membrane receptor can distinguish between TNF-alpha and TNF-beta. The effects of TNF are inhibited by binding proteins that are truncated fragments of the extracellular domains of the TNF receptors. The mechanisms by which these components of the TNF signal transmission pathways interact to mediate the pleiotropic effects of TNF remain unclear.
{"title":"Tumor necrosis factor: receptors and inhibitors.","authors":"H Loetscher, M Steinmetz, W Lesslauer","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Tumor necrosis factor (TNF) is a highly potent pleiotropic response modifier in inflammatory and immunologic host defense reactions. It can also be toxic to cells and elicit toxic systemic reactions, as evinced by certain pathophysiologic conditions that are initiated or aggravated by an excess of TNF. The cellular mechanisms for transducing TNF signals are complex. There are two forms of TNF, alpha and beta, and two distinct TNF receptors. Many cells express both receptor types simultaneously, even though neither membrane receptor can distinguish between TNF-alpha and TNF-beta. The effects of TNF are inhibited by binding proteins that are truncated fragments of the extracellular domains of the TNF receptors. The mechanisms by which these components of the TNF signal transmission pathways interact to mediate the pleiotropic effects of TNF remain unclear.</p>","PeriodicalId":77504,"journal":{"name":"Cancer cells (Cold Spring Harbor, N.Y. : 1989)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1991-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12820852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Taxol: the supply issue.","authors":"G M Cragg, K M Snader","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77504,"journal":{"name":"Cancer cells (Cold Spring Harbor, N.Y. : 1989)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1991-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12845286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recognition of malignant cells by antibodies to the T-cell antigen receptor: potential for diagnosis.","authors":"A W Boylston, F C Lancaster","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77504,"journal":{"name":"Cancer cells (Cold Spring Harbor, N.Y. : 1989)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1991-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13070441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acute promyelocytic leukemia (APL) is a particularly virulent subtype of acute myeloid leukemia that is associated with a specific chromosomal translocation, t(15;17). Patients with APL are currently being managed with cytolytic chemotherapy (usually an anthracycline in combination with arabinosylcytosine), a treatment that can induce complete remissions in 65% or more of patients and probably cure 15% or more. Exciting new clinical observations have shown that patients with APL also respond extremely well to treatment with all-trans retinoic acid, an agent which induces the leukemic promyelocytes to undergo maturation and lose their ability to proliferate. Retinoic acid by itself is not curative, but by combining it with cytolytic chemotherapy, it may be possible to cure the majority of patients with this previously fatal leukemia. Interestingly, independent molecular studies have recently revealed that the breakpoint of t(15;17) lies within the gene encoding the retinoic acid receptor-alpha (RAR-alpha) on chromosome 17q21, and that patients with APL express aberrant forms of the RAR-alpha transcript. This convergence of clinical and molecular observations, though fortuitous, is extremely important because it represents the first example of a selective form of treatment for a human leukemia that is related to a specific genetic abnormality.
{"title":"Retinoic acid in acute promyelocytic leukemia: the promise and the paradox.","authors":"B Clarkson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Acute promyelocytic leukemia (APL) is a particularly virulent subtype of acute myeloid leukemia that is associated with a specific chromosomal translocation, t(15;17). Patients with APL are currently being managed with cytolytic chemotherapy (usually an anthracycline in combination with arabinosylcytosine), a treatment that can induce complete remissions in 65% or more of patients and probably cure 15% or more. Exciting new clinical observations have shown that patients with APL also respond extremely well to treatment with all-trans retinoic acid, an agent which induces the leukemic promyelocytes to undergo maturation and lose their ability to proliferate. Retinoic acid by itself is not curative, but by combining it with cytolytic chemotherapy, it may be possible to cure the majority of patients with this previously fatal leukemia. Interestingly, independent molecular studies have recently revealed that the breakpoint of t(15;17) lies within the gene encoding the retinoic acid receptor-alpha (RAR-alpha) on chromosome 17q21, and that patients with APL express aberrant forms of the RAR-alpha transcript. This convergence of clinical and molecular observations, though fortuitous, is extremely important because it represents the first example of a selective form of treatment for a human leukemia that is related to a specific genetic abnormality.</p>","PeriodicalId":77504,"journal":{"name":"Cancer cells (Cold Spring Harbor, N.Y. : 1989)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1991-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13070440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biological response modifiers in the treatment of cancer and infectious diseases.","authors":"J J Rusthoven","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77504,"journal":{"name":"Cancer cells (Cold Spring Harbor, N.Y. : 1989)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1991-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13070443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The different but distinctly related lines of investigation discussed during this workshop are likely to provide important insights into the molecular events that initiate and mediate the oncogenic process. Pediatric embryonal tumors were the first malignancies in which chemotherapeutic responses were recognized, and they have been singularly important clinical models for the development of many important principles of cancer treatment. Judging from the emerging insights into the pathogenesis of these tumors, it seems likely that they will also serve as important models for designing novel approaches to cancer treatment.
{"title":"Molecular origins of pediatric embryonal tumors.","authors":"M A Israel","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The different but distinctly related lines of investigation discussed during this workshop are likely to provide important insights into the molecular events that initiate and mediate the oncogenic process. Pediatric embryonal tumors were the first malignancies in which chemotherapeutic responses were recognized, and they have been singularly important clinical models for the development of many important principles of cancer treatment. Judging from the emerging insights into the pathogenesis of these tumors, it seems likely that they will also serve as important models for designing novel approaches to cancer treatment.</p>","PeriodicalId":77504,"journal":{"name":"Cancer cells (Cold Spring Harbor, N.Y. : 1989)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1991-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12844917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The role of stromal cells in tumor metastasis: a new link.","authors":"A van den Hooff","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77504,"journal":{"name":"Cancer cells (Cold Spring Harbor, N.Y. : 1989)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1991-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12845046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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