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Michael B. Sporn

Bio: Michael B. Sporn is an academic researcher from Dartmouth College. The author has contributed to research in topics: Transforming growth factor & Transforming growth factor beta. The author has an hindex of 157, co-authored 559 publications receiving 94605 citations. Previous affiliations of Michael B. Sporn include Cornell University & Reata Pharmaceuticals.


Papers
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Journal ArticleDOI
TL;DR: The data suggest that TGF-beta s 2 and 3 may play a role in regulation of neuronal migration and differentiation, as well as in glial cell proliferation and differentiation.
Abstract: We present evidence for unique localization and specific biological activities for transforming growth factor-beta s (TGF-beta s) 2 and 3, as compared to TGF-beta 1, in the nervous system of the 12–18 day mouse embryo. Each TGF-beta isoform was localized immunohistochemically by specific antibodies raised to peptides corresponding to unique sequences in the respective TGF-beta proteins. Staining for TGF-beta 1 was principally in the meninges, while TGF-beta s 2 and 3 co-localized in neuronal perikarya and axons, as well as in radial glial cells. In the central nervous system, staining was most prominent in zones where neuronal differentiation occurs and less intense in zones of active proliferation, while in the peripheral nervous system, many nerve fibers as well as their cell bodies were strongly immunoreactive for TGF-beta s 2 and 3. Functionally, we have also found that in the presence of an extract of chick eye tissue, TGF-beta s 2 and 3 inhibit survival of cultured embryonic chick ciliary ganglionic neurons in a dose-dependent fashion; TGF-beta 1 shows no inhibitory effects. Our data suggest that TGF-beta s 2 and 3 may play a role in regulation of neuronal migration and differentiation, as well as in glial cell proliferation and differentiation.

368 citations

Journal Article
TL;DR: Inhibitory effects of TP-69 or TP-72 on iNOS formation were not blocked by the glucocorticoid receptor antagonist RU-486, indicating that these triterpenoids do not act through the glucopreventive receptor, nor does TP- 72 act as an iN OS or COX-2 enzyme inhibitor when added to RAW cells in which synthesis of these two enzymes in response to LPS has already been induced.
Abstract: We have synthesized more than 80 novel triterpenoids, all derivatives of oleanolic and ursolic acid, as potential anti-inflammatory and chemopreventive agents. These triterpenoids have been tested for their ability to suppress the de novo formation of two enzymes, inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2), using IFN-γ-stimulated primary mouse macrophages or lipopolysaccharide (LPS)-activated RAW 264.7 macrophages as assay systems. Two synthetic oleananes, 3,12-dioxoolean-1-en-28-oic acid (TP-69) and 3,11-dioxoolean-1,12-dien-28-oic acid (TP-72), were highly active inhibitors of de novo formation of both iNOS and COX-2. Both TP-69 and TP-72 blocked the increase in iNOS or COX-2 mRNA induced by IFN-γ or LPS. In addition, TP-72 suppressed NF-κB activation in primary macrophages treated with the combination of IFN-γ and LPS or IFN-γ and tumor necrosis factor. The 3-α(axial)-epimer of ursolic acid suppressed de novo formation of COX-2, in contrast to naturally occurring 3-β(equatorial)-ursolic acid. Inhibitory effects of TP-69 or TP-72 on iNOS formation were not blocked by the glucocorticoid receptor antagonist RU-486, indicating that these triterpenoids do not act through the glucocorticoid receptor, nor does TP-72 act as an iNOS or COX-2 enzyme inhibitor when added to RAW cells in which synthesis of these two enzymes in response to LPS has already been induced. It may be possible to develop triterpenoids as useful agents for chemoprevention of cancer or other chronic diseases with an inflammatory component.

368 citations

Journal Article
TL;DR: In vivo evidence is found that 3 months of tamoxifen treatment causes a consistent induction of extracellular TGF-beta 1 in breast cancer biopsies, compared with matched pretreatment samples from the same patient.
Abstract: We have investigated the ability of tamoxifen to regulate members of the transforming growth factor beta (TGF-beta) family in human breast cancers in vivo. Using immunohistochemical techniques, we find that 3 months of tamoxifen treatment causes a consistent induction of extracellular TGF-beta 1 in breast cancer biopsies, compared with matched pretreatment samples from the same patient. The induced TGF-beta is localized between and around stromal fibroblasts and appears to be derived from these cells. Lower levels of TGF-beta 1,-beta 2, and -beta 3 seen in epithelial cells were not altered by tamoxifen treatment. The increased stromal staining of TGF-beta 1 occurred in estrogen receptor-negative as well as estrogen receptor-positive tumors. These results provide in vivo evidence for a novel, estrogen receptor-independent mechanism of action for tamoxifen, involving the stromal induction of a potent growth inhibitor for epithelial cells.

366 citations

Journal ArticleDOI
TL;DR: Overall mortality statistics are unlikely to change in a fundamental way until there has been a re-orientation of emphasis in cancer research that will direct greater resources towards prevention of new disease, rather than treatment of end-stage disease.
Abstract: Mortality that results from the common forms of cancer is still unacceptably high. Despite immense advances in the understanding of the mechanisms of carcinogenesis, in bringing potent new drugs to the clinic and in treating several relatively rare forms of cancer, overall mortality statistics are unlikely to change in a fundamental way until there has been a re-orientation of emphasis in cancer research that will direct greater resources towards prevention of new disease, rather than treatment of end-stage disease.

364 citations

Journal ArticleDOI
TL;DR: Results from RIA and ELISAs indicate that anti-LC(1-30) and anti-CC(1 -30) recognize different epitopes of this peptide and of TGF-beta 1 itself, suggesting that T GF-beta synthesis sites may be bound to matrix proteins.
Abstract: We have localized transforming growth factor-beta (TGF-beta) in many cells and tissues with immunohistochemical methods, using two polyclonal antisera raised to different synthetic preparations of a peptide corresponding to the amino-terminal 30 amino acids of TGF-beta 1. These two antibodies give distinct staining patterns; the staining by anti-CC(1-30) is intracellular. This differential staining pattern is consistently observed in several systems, including cultured tumor cells; mouse embryonic, neonatal, and adult tissues; bovine fibropapillomas; and human colon carcinomas. The extracellular staining by anti-CC(1-30) partially resembles that seen with an antibody to fibronectin, suggesting that extracellular TGF-beta may be bound to matrix proteins. The intracellular staining by anti-LC(1-30) is similar to that seen with two other antibodies raised to peptides corresponding to either amino acids 266-278 of the TGF-beta 1 precursor sequence or to amino acids 50-75 of mature TGF-beta 1, suggesting that anti-LC(1-30) stains sites of TGF-beta synthesis. Results from RIA and ELISAs indicate that anti-LC(1-30) and anti-CC(1-30) recognize different epitopes of this peptide and of TGF-beta 1 itself.

361 citations


Cited by
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Journal ArticleDOI
07 Jan 2000-Cell
TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.

28,811 citations

28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
29 Apr 1993-Nature
TL;DR: The ability to control the expression of genes encoding these molecules and to target specific cell types provides opportunities to develop new diagnostic and therapeutic agents to induce the regression of the lesions and, possibly, to prevent their formation.
Abstract: Atherosclerosis, the principal cause of heart attack, stroke and gangrene of the extremities, is responsible for 50% of all mortality in the USA, Europe and Japan. The lesions result from an excessive, inflammatory-fibroproliferative response to various forms of insult to the endothelium and smooth muscle of the artery wall. A large number of growth factors, cytokines and vasoregulatory molecules participate in this process. Our ability to control the expression of genes encoding these molecules and to target specific cell types provides opportunities to develop new diagnostic and therapeutic agents to induce the regression of the lesions and, possibly, to prevent their formation.

10,861 citations

Journal ArticleDOI
19 Mar 2010-Cell
TL;DR: The principal mechanisms that govern the effects of inflammation and immunity on tumor development are outlined and attractive new targets for cancer therapy and prevention are discussed.

8,664 citations

Journal ArticleDOI
TL;DR: The transforming growth factor beta (TGF-beta) family of growth factors control the development and homeostasis of most tissues in metazoan organisms and mutations in these pathways are the cause of various forms of human cancer and developmental disorders.
Abstract: The transforming growth factor beta (TGF-beta) family of growth factors control the development and homeostasis of most tissues in metazoan organisms. Work over the past few years has led to the elucidation of a TGF-beta signal transduction network. This network involves receptor serine/threonine kinases at the cell surface and their substrates, the SMAD proteins, which move into the nucleus, where they activate target gene transcription in association with DNA-binding partners. Distinct repertoires of receptors, SMAD proteins, and DNA-binding partners seemingly underlie, in a cell-specific manner, the multifunctional nature of TGF-beta and related factors. Mutations in these pathways are the cause of various forms of human cancer and developmental disorders.

7,710 citations