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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: It is indicated that SO are a new class of immunomodulatory drugs and support further studies investigating this class of agents as potential adjunctive therapy for severe malaria.
Abstract: Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection associated with high mortality and neurocognitive impairment in survivors. New anti-malarials and host-based adjunctive therapy may improve clinical outcome in CM. Synthetic oleanane triterpenoid (SO) compounds have shown efficacy in the treatment of diseases where inflammation and oxidative stress contribute to pathogenesis. A derivative of the SO 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), CDDO-ethyl amide (CDDO-EA) was investigated for the treatment of severe malaria in a pre-clinical model. CDDO-EA was evaluated in vivo as a monotherapy as well as adjunctive therapy with parenteral artesunate in the Plasmodium berghei strain ANKA experimental cerebral malaria (ECM) model. CDDO-EA alone improved outcome in ECM and, given as adjunctive therapy in combination with artesunate, it significantly improved outcome over artesunate alone (p = 0.009). Improved survival was associated with reduced inflammation, enhanced endothelial stability and blood–brain barrier integrity. Survival was improved even when administered late in the disease course after the onset of neurological symptoms. These results indicate that SO are a new class of immunomodulatory drugs and support further studies investigating this class of agents as potential adjunctive therapy for severe malaria.

17 citations

Journal ArticleDOI
TL;DR: 3-Amino-3′-deoxythymidine 5′-phosphate and 5-amino-5′- deoxymidine 3′-Phosphate were prepared as analogues of the corresponding naturally occurring nucleotides.
Abstract: 3′-Amino-3′-deoxythymidine 5′-phosphate (6) and 5′-amino-5′-deoxythymidine 3′-phosphate (10) were prepared as analogues of the corresponding naturally occurring nucleotides.

17 citations

Journal ArticleDOI
TL;DR: It is determined that the 350 nucleotide RNA band may be composed of multiple species of RNA which are related to the anti-sense DNA strand that is opposite to the strand that codes for the 4800 nucleotide TGF alpha mRNA.
Abstract: Human transforming growth factor α (TGFα) is coded for by an mRNA of about 4800 nucleotides. The cDNA sequence demonstrates that the 50 amino acid TGFα is embedded in a larger 160 amino acid precursor protein. We report here that in addition to the 4800 nucleotide TGFα mRNA, there is a novel second RNA species of about 350 nucleotides that hybridizes to a human TGFα cDNA probe. This small RNA species has been found in the RNA of several human tumor cells including HT1080, A549, A431, A2058, and A673. We have demonstrated an inverse relationship between the amounts of the 4800 nucleotide TGFα mRNA and the 350 nucleotide novel RNA in these human cells. Restriction enzyme cleavage of a human TGFα cDNA probe into three separate domains consisting of a processed coding region and 5′- and 3′-preprocessed coding and untranslated regions showed that only the 3′-untranslated region hybridized to the 350 nucleotide RNA. Using sense and anti-sense single-stranded 3′-untranslated region probes, we determined that the...

17 citations

Journal ArticleDOI
TL;DR: The development of a new system for quantitating the process of prostatic carcinogenesis in an experimental animal is described and this system is used to demonstrate that the retinoid, 4-hydroxyphenylretinamide, the deltanoid, Ro24-5531, and the estrogen analog, tamoxifen, all are effective agents for prevention of experimental prostate cancer.

17 citations

Journal ArticleDOI
TL;DR: Topical application of TP-225 to the backs of mice that were previously subjected to low-level chronic UVB radiation led to 50% reduction in multiplicity of skin tumors and the total tumor burden of squamous cell carcinomas was reduced by 5.5-fold.

16 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