| Born: 1940, Israel |
Academic Qualifications:Ph.D. 1971, Hebrew University of Jerusalem
Prof. 1994.
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Academic Positions:
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Research Interests:
The role of vitamin D in mineral homeostasis;Its antiproliferative activity on cancer cells and its regulatory effects on cytokins expression in inflammatory cells;Lipids and lipoproteins as risk factors for cardiovascular diseases.
Lead Toxicity in Children. |
Research Projects:
;The effect of 1,25-dihydroxyvitamin D on Cytokine expression in Peritoneal Macrophages,funding: Ministry of Health.
Molecular actions of vitamin D and analogs on human Prostate cancer cell lines;Combined treatments with NSAID and Deacetylase Drugs.
Lead Toxicity in children. Funding: USAID- MERC. |
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Abstracts of Current Research:- 1,25-DIHYDROXYVITAMIN D3 REGULATES TNFa EXPRESSION IN HUMAN MACROPHAGES. Merav Lahav, Amos Douvdevani, Cidio Chaimovitz and Shraga Shany. Ben Gurion University of the Negev, Beer Sheva,Israel.: Macrophages play an important role in the immune response. Besides their ability to phagocyte antigens and to produce oxidizing radicals, macrophages produce and secrete cytokins which are affecting the immune system and the inflammatory response. Tumor necrosis factor -a (TNF-a) is produced and secreted by macrophages in response to lipopolysacharide (LPS) aggravation. Recent studies have provided evidence for the involvement of 1,25-Dihydroxyvitamin D (1,25(OH)2D3) in the regulation of cytokinsexpression in myelomonocytic cell line; much less is known about human cells in primary cultures. In the present study, the effect of 1,25(OH)2D3 on the expression of TNF-a in human peritoneal macrophages (PM) obtained from uremic patients treated with continuous ambulatory peritoneal dialysis (CAPD) was studied. TNF-a expression was determined on both mRNA and protein levels. PM were obtained from CAPD effluents. Primary cultures of PM in RPMI medium containing 2% FCS were seeded in tubes (1x106 Cells/tube) and incubated with various concentrations of 1,25(OH)2D3 (10-10-10-7M) for 16h. Finally the cells were exposed to various concentrations of LPS (1ng/ml-10mg/ml) for 2.5-6h. The TNF-a protein concentrations produced by PM were determined by ELISA and the mRNA were assayed by reverse transcriptase-PCR procedure, using internal synthetic mRNA standards for quantitative results. Our results demonstrate that LPS enhances significantly TNF-a release by PM. This stimulation was found to be dose dependent, with a maximal stimulation at the highest concentration of LPS (10 mg/ ml). Although 1,25(OH)2D3 alone had no effect on TNF-a expression, even at the high concentration (10-7 M), incubation of PM with 1,25(OH)2D3 prior to the LPS, inhibits the expression of TNF-a. This inhibition was found to be dose dependent. Since PM are capable of converting 25-OH-D3 into 1,25(OH)2D3, the regulating effect of 1,25(OH)2D3 on TNF-a expressi
- The Synthetic Analog 1,24- Dihydroxyvitamin D2 is Equipotent as 1,25-Dihydroxy vitamin D3 in Growth Regulation of Cancer Cell Lines. Yifat Levy, J.C. Knutso n1, C. Bishop1 and S. Shany. Ben Gurion Un: The physiologically active metabolite of the seco-steroid hormonevitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), is a major regulator of mineral homeostasis. Recent evidence suggest also its role in regulating proliferation and differentiation of cells, including cancer cells. Therapeutic application of 1,25(OH)2D3 to hyperpro-liferative diseases, such as cancer, is thwarted by its hypercalcemic activity. To overcome this problem, analogs of 1,25(OH)2D3 have been produced which retain growth regulating properties and exhibit decreased hypercalcemic activity. In the present study the efficacy of the vitamin D2 analog, 1,24S-dihydroxyvitamin D2 (1,24(OH)2D2) in the inhibition ofcancer cells proliferation and in inducing differentiation of cancer cells was compared to that of 1,25(OH)2D3. Using the [3H]-thymidine incorporation procedure, it was demonstrated, that 1,24(OH)2D2 is equipotent as 1,25(OH)2D3 in inhibiting the proliferation of ROS 17/2.8 the rat osteosarcoma cell line, MCF-7 the human breast cancer cell line, HD-11 the chick bone marrow v myc transformed cell line, HT-29 the human colon cancer cell line and of HL-60 the human leukemia cell line. The inhibitory action was found to be dose and time-dependent. It was also demonstrated by the NBT reduction method, that 1,24(OH)2D2 induces the differentiation of human leukemia cells (HL-60) to the same extent as observed with 1,25(OH)2D3. Notwithstanding the vast similarity between 1,24(OH)2D2 and 1,25(OH)2D3 with regard to the above activities, they differ inthat 1,25(OH)2D3 is hypercalcemic, while the analog is not. In conclusion, the present results may encourage the possible use of 1,24(OH)2D2 for the treatment of cancer diseases in vivo. This is inferred both from the high potentialof 1,24(OH)2D2 for regulating growth of cancer cells and the non hypercalcemic activity of this vitamin D analog.
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Publications:- Alon, D.B., Chaimovitz, C., Dvilansky, A., Lugassy, G., Douvdevani, A., Shany, S. & Nathan, I.. Novel role of 1,25(OH)(2)D(3) in induction of erythroid progenitor cell proliferation. Exp. Hematol. 30: 403-409 (2002)
- Henkin, Y., Crystal, E., Goldberg, Y., Friger, M., Lorber, J., Zuili, I. & Shany, S.. Usefulness of lipoprotein changes during acute coronary syndromes for predicting postdischarge lipoprotein levels.
Am. J. Cardiol. 89: 7-11 (2002)
- Shany, S., Levy, Y. & Lahav-Cohen, M.. The effects of 1alpha,24(S)-dihydroxyvitamin D(2) analog on cancer cell proliferation and cytokine expression. Steroids. 66: 319-325 (2001)
- Cohen, M.L., Douvdevani, A., Chaimovitz, C. & Shany, S.. Regulation of TNF-alpha by 1alpha,25-dihydroxyvitamin D3 in human macrophages from CAPD patients. Kidney Int. 59: 69-75 (2001)
- Mokady, E., Schwartz, B., Shany, S. & Lamprecht, S.A.. A protective role of dietary vitamin D3 in rat colon carcinogenesis. Nutr. Cancer. 38: 65-73 (2000)
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| Keywords:Lead Toxicity, Vitamin D, Homocystein, 1,25-Dihydroxyvitamin D, Osteomalacia, Osteoporosis, Cytokins, TNF-a, Cancer, Cholesterol, Triglicerides, Atherosclerosis. |
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Phones:
- Phone: 972-8-6479887
- Fax: 972-8-6281361
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