Author
Michael B. Sporn
Other affiliations: Cornell University, Reata Pharmaceuticals, University of Texas MD Anderson Cancer Center ...read more
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 published on a yearly basis
Papers
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TL;DR: To isolate protein targets using affinity chromatography with immobilized streptavidin as a carrier, C-17 and C-23 biotin conjugates of CDDO (4, 5, and 6) are designed and synthesized on the basis of the established structure-activity relationships.
Abstract: 2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO, 1) and related compounds [for example, CDDO-Me (2) and CDDO-Im (3)] are potential anti-inflammatory, cancer chemopreventive, and chemotherapeutic agents. However, the mechanisms responsible for the multiple effects of CDDO are still unclear. Clarification of these mechanisms and particularly isolation of the protein targets are essential for the development of CDDO and its analogues as clinically useful drugs. Such knowledge would provide superior opportunities for designing new compounds with improved potency and selectivity. Therefore, to isolate protein targets using affinity chromatography with immobilized streptavidin as a carrier, we have designed and synthesized C-17 and C-23 biotin conjugates of CDDO (4, 5, and 6) on the basis of our established structure-activity relationships. For the synthesis of 6, a new important precursor, 23-hydroxy-CDDO-Me (29) was synthesized from 20 by a C-23 oxidation protocol, which involves cyclopalladation of the C-4 methyl group from a 3-one oxime. The inhibitory activity of C-23 conjugate 6 is only about 3 times less potent than the mother compound, CDDO, against the proliferation of MCF-7 breast cancer cells. Consequently, 6 may be a very promising tool for the isolation of the protein targets of CDDO.
81 citations
Journal Article•
TL;DR: The design of new expression vectors carrying growth factor genes will permit further study of the specific effects of constitutive growth factor synthesis in cells expressing receptors for the same growth factors.
Abstract: There is ample evidence for autocrine action of growth factors in malignant transformation and for recognition of growth factor genes as proto-oncogenes. The design of new expression vectors carrying growth factor genes will permit further study of the specific effects of constitutive growth factor synthesis in cells expressing receptors for the same growth factors.
81 citations
TL;DR: In this paper, the expression of TGF-beta s 2, 3, and 4 mRNAs was detected in cultured chondrocytes and myocytes, but not TGF beta 1 mRNA, in vitro and in vivo.
80 citations
TL;DR: A significant level of TGF-beta 2 secretion and receptor binding occur before the decrease in DNA synthesis, suggesting that the inhibition of DNA synthesis associated with differentiation of keratinocytes is mediated through the production and autocrine action of T GF- beta 2.
Abstract: Primary cultures of mouse keratinocytes maintain a basal cell phenotype in 0.05 mm Ca2+ medium, while culture in 1.4 mm Ca2+ results in terminal differentiation and inhibition of DNA synthesis. Induction of differentiation by Ca2+ results in a 10- to 20-fold increase in the expression of transforming growth factor-β2 (TGF-β2) mRNA and peptide, but a decrease in the expression of TGF-β1. In contrast, binding and cross-linking analyses show that the number of available surface 80 kilodalton (kDa) and 65 kDa TGF-β receptor types decrease during differentiation. However, a mild acid wash significantly increases the number of available receptor sites on the differentiated keratinocytes, indicating that the TGF-β receptors are unavailable for binding due to masking by endogenous ligand. A significant level of TGF-β2 secretion and receptor binding occur before the decrease in DNA synthesis, suggesting that the inhibition of DNA synthesis associated with differentiation of keratinocytes is mediated through the pr...
78 citations
TL;DR: It is shown that transforming growth factor-beta 1 is found in mitochondria of rat and mouse cardiac myocytes and rat hepatocytes and the functional role of TGF-beta in the mitochondrion is unknown at present.
Abstract: Using both electron microscopic immunohistochemistry and cell fractionation techniques, we show that transforming growth factor-beta 1 (TGF-beta 1) is found in mitochondria of rat and mouse cardiac myocytes and rat hepatocytes. Four different polyclonal antibodies, raised against various epitopes encompassing the mature portion of the TGF-beta 1 molecule as well as the pro-region of its precursor, were used for the electron microscopy studies. The localization of TGF-beta 1 in mitochondria was confirmed by detection of the native peptide in mitochondria isolated from rat heart and liver; the majority of native TGF-beta 1 found in liver homogenates was recovered in highly pure mitochondrial fractions. The functional role of TGF-beta in the mitochondrion is unknown at present.
78 citations
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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
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
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
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