Benjamín Sredni, Prominente inmunólogo

El Prof. Benjamín Kershenovich Sredni es el Jefe de Científicos del Ministerio Israelí de Salud y Director del Instituto Safdie de Investigación sobre Cancer, Sida e Inmunología en la Universidad Bar-Ilan. Un prominente inmunólogo, el Prof. Sredni fue el primero en desarrollar un método para inducir un gran número de linfocitos de una sola célula. Estos linfocitos juegan un rol determinante en el sistema inmunológico humano. Este desarrollo proclamó el inicio de una nueva era en investigación sobre inmunología, marcando la pauta para que los profesores Sredni y Michael Albeck desarrollaran un nuevo inmunomodulador sintético, el AS101, el cual estimula significativamente las funciones inmunes y que está siendo probado clínicamente en pacientes con tumores y en pacientes con enfermedades neurodegenerativas.

El Prof. Sredni tiene un extenso número de proyectos de investigación con varias instituciones médicas en Israel y otros países, en especial con el National Institute of Health en Maryland.

Originario de México, el Prof. Sredni se graduó de la Universidad Bar-llan, donde completó su Maestría en Ciencias Cum Laude en Química y su doctorado, con altos honores- en Microbiología. Posteriormente trabajó como Científico Visitante en el NIH. Ha recibido numerosos honores, distinciones y premios y publicado más de 160 trabajos de investigación en revistas especializadas. El Dr. Sredni posee más de 20 patentes.

Biunky -como le dicen sus familiares y amigos- está en constante contacto con su país natal, sobre todo en lo que se refiere a sus especialidades. Y como el dice… La distancia jamás borra los recuerdos.

Educación:

• 1965-1969 Licenciatura en Ciencias, Química, Universidad Bar-Ilan, Ramat-Gan, Israel
• 1970-1973 Maestría en Ciencias, Química Orgánica, Universidad Bar-Ilan.
• 1973-1978 Doctorado., Departamento de Ciencias de la Vida, Universidad Bar-Ilan (con altos honores)

Empleos:

• 1970-1973 Asistente de Enseñanza, Departamento de Química Orgánica, Universidad Bar-Ilan
• 1973-1979 Instructor, Departamento de Ciencias de la Vida, Universidad Bar-Ilan
• 1979-1980 Estudiante Visitante, Laboratorio de Inmunología, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, U.S.A.
• 1980-1981 Visitante Asociado, Laboratorio de Inmunología, NIH, Bethesda, MD, U.S.A.
• 1981-1984 Conferencista Senior, Departamento de Ciencias de la Vida, Universidad Bar-Ilan
• 1984-1989 Profesor Asociado, Departamento de Ciencias de la Vida, Universidad Bar-Ilan
• 1985-1987 Científico Visitante, Laboratorio de Inmunología, NEI, NIH, Bethesda, MD, U.S.A.
• 1992-1994 Científico Visitante, Laboratorio de Inmunología, NEI, NIH, Bethesda, MD, U.S.A.
• 1990-presente Profesor, Departamento de Ciencias de la Vida, Universidad Bar-Ilan
• 1989-1991 Director de la Facultad de Ciencias Naturales y Matemáticas,, Universidad Bar-Ilan
• 2000-2001 Científico Visitante,, Laboratorio de Inmunología, NEI, NIH, Bethesda, MD, U.S.A.
• 1988-presente Director del Instituto Safdie de Investigación sobre Cancer, Sida e Inmunología (C.A.I.R. Institute), , Universidad Bar-Ilan
• 1995-presente Científico en Jefe, Bar Ilan Research & Development Company Ltd.

Honores y Otros Reconocimientos:

• 1977 Premio Pinchas Sapir MemorialPrize por Investigación
• 1978 Premio Michael Landau Memorial Prize por Investigación
• 1979 Premio Rothschild Prize por Investigación
• 1981 Beca Yigal Alon (Higher Education Council)
• 1981 Cita de su trabajo en la presentación del Premio Nobel del Profesor Baruj Benacerraf (Science, vol. 212, p. 1229, 1981)
• 1982 A cargo del Isidore Muscovitch – Puesto honorario como Investigador de Cáncer
• 1989 Recibió los Fondos de Dorsha Wallman Research
• 1990 Recibió los Fondos de Frieda Stollman Cancer Research Memorial
• 1990 Recibió los Fondos de Robert Asseraf
• 1991 The Dr. Tovi Comet-Wallerstein -Puesto honorario como Investigador de Cáncer
• 1992 Programa Shiffman Global Research
• 1993 Programa Fetter Cancer Research

Asociaciones Científicas:

• Miembro del Comité Organizador de la Sociedad de Inmunología de Israel.
• Sociedad Israelí de Bioquímica y Biología Molecular
• Asociación Americana de Inmunologistas (AAI)
• Sociedad Americana de Hematología (ASH)
• Asociación Americana de Investigación del Cáncer (AACR)
• Asociación Americana para el Avance de la Ciencia
• Sociedad Internacional de Hematología Experimental(ISEH)
• Sociedad Internacional de Inmunidad Natural
• Sociedad Internacional del Sida (IAS)
• Foro Internacional de Cáncer Microambiental (ICMF) – Miembro Fundador
• FISEB – Federación de Sociedades Israelís de Biología Experimental
• Sociedad Internacional de Células Muertas

Actividades Editoriales:

• 1982-1984 Miembro del Consejo Editorial, Experimental Hematology
• 1987-presente Miembro del Consejo Editorial, Natural Immunity & Cell Growth Regulation
• 1988 Co-editor, Future Trends in Research on AIDS, Cancer and Therapies, Natural Immunity and Cell Growth Regulation, 7(3), 1988.
• 1990-presente Co-editor, International Symposium on AIDS and Cancer, Natural Immunity and Cell Growth Regulation, 9(3), 1990.

Conferencias Científicas Internacionales

• 1984 Co-organizador, 2nd Maimonides Conference on Cancer Research: B Lymphocytes, Israel.
• 1986 Co-organizador, New Developments in Immunology, Venezuela.
• 1987 Organizador, Marilyn Finkler Symposium: Future Trends in Research on AIDS, Cancer and Therapies, Israel.
• 1988 Co-organizador, Simposio Internacional de Atualizacao em AIDS e Cancer, Brasil.
• 1989 Co-organizador, 6th Maimonides Conference on Cancer Research: T Lymphocytes, Israel.
• 1991 Co-organizador, Inernational Conference on Autoimmunity, Cancer and AIDS. Ciudad de México.
• 1992 Organizador, 22nd International Conference of the Israel Immunological Society, Universidad Bar Ilan.
• 1994 Co-organizador, Conferences on Basic and Clinical Immunology, Fifth Conference, Ein Gedi, Israel.
• 1997 Organizador, 27th International Conference of the Israel Immunological Society, Universidad Bar Ilan, Ramat Gan.
• 1998 Co-organizador, 28th International Conference of the Israel Immunological Society, Universidad del Negev, Beer-Sheva.
• 1998 Co-organizador, 2nd Annual Meeting of FISEB (Federación de Sociedades Israelís de Biología Experimental), Eilat.
• 1999 Co-organizador, The Batsheva Seminar on Innate immunity, Zichron Ya’acov
• 2000 Co-organizador, 29th International Conference of the Israel Immunological Society, Centro Médico Hadassah, Jerusalén
• 2001 Co-organizador, 30thInternational Conference of the Israel Immunological Society, Instituto de Ciencias Weizzman, Rehovot.
• 2002 Co-organizador, ILANIT 2002 Congress, Federation of Israel Societies of Experimental Biology, Eilat, Israel
• 2002 Co- organizador, 31th International Conference of the Israel Immunological Society, Universidad de Tel Aviv, Israel
• 2002 Co-organizador, 2nd. International Conference on Tumor Microenvironment, Baden, Austria

Estudiantes de Postgrado y Temas de Tesis:

Maestría en Ciencias

E. Sagiv Mode of action of a viral agent on the immune system as determined by the level of Interleukin-2. (1984)

B. Trink Spontaneous release of lymphokines from lines and clones of T-lymphocytes in culture. (1984)

A. Sterin-Prync Establishment of human T-lymphocyte cell lines which secrete lymphokines. (1985)

L. Kosti The in vivo and in vitro effect of cyclosporin A on the lymphokines’ level in human systems. (1987)

E. Engelsman-Steiner Production of major lymphokines in Grave’s disease: effect of drug therapy. (1987)

H. Ziv Effect of novel chemicals on IL-2 production and IL-2 receptor expression. (1987)

Y. Shamir The effect of Interleukin-3 levels on the immunosuppressed condition of women during pregnancy. (1988)

V. Shtetlander Production of Interleukin 1,2 and 3 by mononuclear cells from women along the menstrual period. (1988)

R. Nedivi Effect of surgery on cytokine production by human mononuclear cells. (1989)

E. Falach Production of cytokines by various body tissues with or without stimulatory effects of synthetic compounds. (1989)

O. Gross Cytokine secretion effected by synergism of the immunomodulator AS101 with the protein kinase-C-inducer – bryostatin. (1989)

M. Oron The protective effects of AS101 against damages caused by whole-body chemotherapy and radiotherapy in mice. (1989)

I. Roth Lymphokine production in auto-immune thyroid-related diseases. (1989)

Z. Rosenthal The effect of AS101 on the reconstitution of the immune system and on the survival rate on MCMV infected mice. (1990)

Z. Roy Synergism between AS101 and protein kinase C activators in stimulating cell proliferation and cytokine production. (1992)

A. Zuloff-Shani Role of endogenous cytokine secretion in radioprotection conferred by the immunomodulator AS101. (1992)

G. Rushkin The protective effect of the immunomodulator AS101 on chemotherapy-induced thrombocytopenia and anemia in mice.(1992)

S. Eliyahu The effect of AS101 on the intercellular signalling pathway. (1996)

J. Silk P53 status in tumor cells inhibited by AS101. (1997)

Sonino T. Differentiation of neuronal cells by AS101. (1997)

A. Peretz Chemotherapy Damages (1999)

M. Bouganim The Synergistic mechanism effect of the immunomodulator AS101 and PMA on HL60 cells differentiation (2000)

D.. Marder-Gilboa Protection of CNS from secondary degeneration by the immunomodulator AS101 and differentiation of PC12 cells by the immunomodulator AS101 and SAS3 (2000)

M. Mizrahi The intracellular mechanism of inhibition of B16 melanoma by AS101 via downregulation of IL-10 (2000)

G. Khomenok The Synergistic mechanism effect of SAS and PMA on HL60 cells differentiation; Regulation of Thioredoxin Reductase in MCF7 and HT29 cells (2000)

Doctorado

P. Fishman In vitro growth of human basophils and mast cells: characterization and isolation of their growth factors. (1987)

T. Mittwoch Hemispheric dominance as an intervening factor between the respondence of the immune system and emotion. (1989)

U. Gafter, M.D. The effect of blood constituents on the immune system (1990)

Y. Kalechman Radio- and chemoprotection of the hemopoietic system by the immunomodulator AS101: Mechanism of action and clinical application (1990)

Z. Rosenthal The in vivo effect of AS101 on MCMV infections (1992)

H. Rosenblatt-Bin Reconstitution of the cellular immune system by AS101 in mice infected with Babesia Rodhaini parasites (1993)

S. Herman Mechanism of stimulation of the immune system by erythrocytes and their components (1994)

Z. Bazak The effect of AS101 in Diabetis (1995)

A. Zuloff-Shani Regulation of IL-10 production by the immunomodulator AS101: Clinical implications and mechanism of action. (1995)

G. Rushkin The effect of the immunomodulator AS101 on macrophages: proliferation, differentiation, function and clinical implications.

S. Eliyahu The effect of AS101 on the intercellular signalling pathway. (1998)

I. Sinuani The influence of the immunomodulator AS101 on Compensatory Renal Growth (CRG) following unilateral nephroctomy (1999)

Post-doctorado

Dr. P. Fishman The inhibitory effect of AS101 on the proliferation and development of tumor cells (1989)

Dr. Xu Renhe Natural immunomodulators (1991)

Dr. M. Malech AS101 and its effects on fertility (1992)

Dr. S. Dovrat Protective effects of AS101 and KGF against alopecia in rats (1996)

Dr. J.P. Da The effect of synergism between PKC activators and AS101(1996)

Dr. Sh. Yu AS101 and PMA synergistically enhance IL-2 production and cell proliferation in spleen cells (1998)

Dr, D. Yan The effect of AS101 in Septic Shock (1999)

Estudiantes de Investigación Médica Básica

Dr. R. Ben Yossef The effect of AS101 in vivo on pluripotent stem cells in mice. (1988)

Dr. S. Zangen The effect of AS101 in vitro on the immune system of children with malignancies. (1989)

Dr. B. Gutman The effects of AS101 on the lymphokine production in Alzheimer patients. (1991)

Dr. Sigal Taitz IL-10 secretion from malignant human tumors and inhibition of its secretion by the immunomodulator AS101. (1997)

Publicaciones:

1 Sredni B. y Braverman S. Different rearrangements of benzylic trichloromethane sulfenates to sulfoxides and chlorides. Israel J. Chem. 8:30, 1970.

2 Sredni B. and Pinchas S. The proton chemical shift of neat H2O. J. Mag. Res. 7:289, 1972.

3 Braverman S. y Sredni B. The rearrangement of benzylic trichlormethane-sulfenates to sulfoxide and chlorides. Tetrahedron 30:2379, 1974.

4 Sredni B., Kalechman I., Michlin H. y Rozenszajn L.A. Development of colonies in vitro of mitogen-stimulated mouse T lymphocytes. Nature 259:130, 1976Æ

5 Sredni B. y Rozenszajn L.A. Inhibitory effect on growth of lymphocyte colonies by an active component derived from monocyte/macrophage cells. Exp. Hemat. 4:33, 1976.

6 Rozenszajn L.A., Michlin H., Kalechman Y. y Sredni B. Colony growth in vitro of mitogen-stimulated mouse B lymphocytes. Immunology 32:319, 1977.

7 Sredni B., Michlin H., Kalechman Y. y Rozenszajn L.A. Colony growth of mouse B lymphocytes induced by polyclonal B cell activators and Lip A component of lipopolysaccharide (LPS). Exp. Hemat. 5:53, 1977.

8 Sredni B., Michlin H., Kalechman Y. y Rozenszajn L.A. Regulatory effects of macrophage-secreted factors on T lymphocyte colony growth. Cell. Immunol. 36:15, 1978.

9 Sredni B. y Rozenszajn L.A. Relation between structure of bacterial lipopolysaccharide and the stimulation of B lymphocytes into colony formation. J. Cell. Physiol. 96:53, 1978.

10 Shahin I., Grossman S. y Sredni, B. Lipoxygenase-like enzyme in rat testes microsomes. Biochem. Biophys. Acta. 529:300, 1978.

11 Sredni B., Michlin H., Kalechman Y. y Rozenszajn L.A. Regulatory effects of macrophage-secreted factors on T lymphocyte colony growth. Israel J. Med. Sci. 4:242; 978Æ

12 Sredni B., Gopas J. y Rozenszajn L.A. Induction of B-lymphocyte colonies in vitro by thymus-derived stimulating factor. Eur. J. Immunol. 8:681, 1978.

13 Rozenszajn L.A., Zeevi A., Gopas J., Radnay J. y Sredni, B. Lymphocyte colony growth in vitro. In: Hematopoietic Cell Differentiation. p. 261, Academic Press,NY, 1978.

14 Sredni B., Gopas J. y Rozenszajn L.A. Murine B lymphocyte colony formation induced in vitro by a thymic factor. Exp. Hemat. 6:3, 1978.

15 Grossman S., Shahin I. y Sredni, B. Rat testes lipoxygenase-like enzyme: characterization of products on linoleic acid. Biochem. Biophys. Acta 572: 293, 1979

16 Sredni B., Tse H.Y. y Schwartz R.H. Cloning of antigen-specific MHC-restricted proliferating T lymphocytes. Fed. Proc. 39:803, 1980.

17 Rozenszajn L.A., Zeevi A., Goldman I. y Sredni, B. Characterization of monocyte and lymphocyte mediators modulating T lymphocyte colony formation. In:Biochemical Characterization of Lymphokines. Eds. A.L. de Weck, F. Kristensen & M. Landy, pp. 261-264, Academic Press, NY, 1980.

18 Rozenszajn L.A. y Sredni B. In vitro growth of colonies of mitogen-stimulated mouse T lymphocytes: I. Conditions affecting colony formation. II. Structure of colonies and component cells. Exp. Hemat. 8:494, 1980.

19 Sredni B., Tse H.Y. y Schwartz, R.H. Direct cloning and extended culture of antigen-specific MHC-restricted, proliferating T lymphocytes. Nature 283:581, 1980.

20 Sredni B. y Schwartz R.H. Alloreactivity of an antigen-specific T cell clone. Nature 287:855, 1980.

21 Sredni B. y Schwartz, R.H. Antigen-specific, proliferating T lymphocytes clones. Metholology, specificity, MHC restriction and alloreactivity. Immunol. Rev. 54:187, 1981.

22 Rozenszajn L.A., Goldman I., Kalechman Y., Michlin H., Sredni B., Zeevi A. y Shoham D. T-lymphocyte colony growth in vitro: factors modulating clonal expansion. Immunol. Rev. 54:157, 1981.

23 Bland C.E., Sredni B. y Metcalfe D.D. Direct cloning and extended culture of basophils from mouse bone marrow: Biochemical characterization of basophil proteoglycan. J. Allergy Clin. Immunol. 67, 1981.

24 Sredni B., Tse H.Y., Chen C. y Schwartz R.H. Antigen-specific clones of proliferating T lymphocytes. I. Methodology, specificity and MHC restriction. J. Immunol. 126:341, 1981.

25 Sredni B., Matis L.A., Lerner E.A., Paul W.E. y Schwartz R.H. Antigen-specific T cell clones restricted to unique F1 major histocompatibility complex determinants. J. Exp. Med. 153:677¨s1981.

26 Sredni B., Volkman D., Schwartz R.H. y Fauci A.S. Antigen-specific human T cell clones: development of clones requiring HLA-DR-compatible-presenting cells for stimulation in the presence of antigen. Proc. Natl. Acad. Sci., U.S.A. 78:1858, 1981.

27 Metcalfe D.D., Bland C.E. y Sredni B. Comparison of proteoglycans synthesized during lymphocyte dependent mast cell and basophil proliferation. Fed. Proc. 40:1023, 1981.

28 Rozenszajn L. A., Goldman I., Kalechman I., Michlin H., Sredni B., Zeevi A. y Shoham D. T-lymphocyte colony growth in vitro: factors modulating clonal expansion. Immunol. Rev. 54:157, 1981.

29 Sredni B. y Schwartz R.H. Antigen-specific clones of proliferating T-lymphocytes. In: Experimental Hematology Today. Eds. S.J. Baum & A. Khan, S. Karger Press, p. 181, 1981.

30 Paul W.E., Sredni B. y Schwartz R.H. Long-term growth and cloning of non-transformed lymphocytes. Review article, Nature 294:697, 1981.

31 Sredni B., Sieckmann D.G., Kumagai S. y Paul W.E. Long-term cloning of nontransformed human B-lymphocytes. Clin. Res. 29:377, 1981.

32 Gorelik E., Kedar E., Sredni B. y Herberman, R. In vivo antitumor effects by local adoptive transfer of mouse and human culture lymphoid cells. Int. J. Cancer 28:157¨1981

33 Sredni B., Sieckmann D.G., Kumagai S., House S., Green I. y Paul W.E. Long-term culture and cloning of nontransformed human B lymphocytes. J. Exp. Med. 154:1500, 1981.

34 Kedar E., Herberman R.B., Gorelik E., Sredni B., Bonnard G.D. y Navarro N. Antitumor reactivity in vitro and in vivo of mouse and human lymphoid cells cultured with T cell growth factor. In: The Potential Role of T Cell Subpopulations in Cancer Therapy, Eds. A. Fefer and A. Goldstein, Raven Press, New York, pp. 173, 1982.

35 Sredni B. Methods for long-term growth and cloning of T cells reactive with soluble antigens. J. Immunol. Methods 49:1, 1982.

36 Kumagi S., Sredni B., House S., Steinberg A.D. y Green I. Defective regulation of B lymphocyte colony formation in patients with systemic lupus erythematosis. J. Immunol. 128:258, 1982.

37 Sredni B., Volkman D., Schwartz R.H. y Fauci A.S. Human T cell clones reactive with soluble antigens: Methodology, specificity and MHC-restriction. In: Isolation, Characterization and Utilization of T Lymphocyte Clones. Eds. F.W. Fitch & G. Fathman. Academic Press, New York, p. 440, 1982.

38 Kedar E., Ikejiri B.L., Sredni B., Bonavida B. y Herberman R.B. Propagation of mouse cytotoxic clones with characteristics of natural killer (NK) cells. Cell. Immunol. 69:305, 1982.

39 Schwartz R.H. and Sredni B. Alloreactivity of antigen-specific T cell clones. In: Isolation, Characterization and Utilization of T Lymphocyte Clones. Eds. F.W. Fitch & G. Fathman, Academic Press, New York, p. 375, 1982.

40 Paul W.E., DeFranco A., Sredni B. y Howard, M. Long term growth of B-lymphocytes. Ann. N.Y. Acad. Sci. 399:105, 1982.

41 Sredni B. Establishment of colonies of antigen reactive human T cells. In: Isolation, Characterization and Utilization of T Lymphocyte Clones. Eds. F.W. Fitch & G. Fathman, Academic Press, New York, p. 535, 1982.

42 Paul W.E., Sredni B. y Howard M. Cell cloning as a tool to analyze the immune response. In: Research Frontiers in Aging and Cancer. National Cancer Institute, Mon. 60:211, 1982.

43 Volkman D.J., Sredni B., Mostowsky H., Fauci A.S. y Schwartz R.H. Demonstration of major histocompatibility complex restriction in man using an antigen-specific proliferating T cell clone. Stem Cells 2:65, 1982.

44 Sredni B., Friedman M., Bland C.E. y Metcalfe D.D. Ultrastructural, biochemical and functional characteristic of histamine-containing cells cloned from mouse bone marrow: Tentative identification as mucosal mast cells. J. Immunol. 131:915, 1983.

45 Michlin H., Kalechman Y. y Sredni B. Normal human T-lymphocyte cell lines producing colony stimulating factor. Exp. Hemat. 11:204¨1983.

46 Fishman P., Sredni B., Hart J. y Djaldeti M. Elemental X-ray microanalysis of mouse peritoneal and bone marrow derived cultured mast cells. Ann. Allergy 53:70, 1984.

47 Rozenszajn L.A., Radnay J., Nussenblatt R. y Sredni B. Human lymphoid cells and their progenitors – isolation, identification and colony growth (CFU-TL, CFU-BL). In: Methods in Hematology: Hematopoiesis. Ed. D.W. Golde, Churchill Livingstone, New York, p. 150, 1984.

48 Roffman E., Sredni B., Smolinsky A. y Wilchek M. Chemical reduction of oxidize human lymphocytes inhibits interleukin 2 production but not induction of responsiveness. Proc. Natl. Acad. Sci. USA 81:5209, 1984.

49 Sredni B. y Rozenszajn L.A. Lymphocyte stem cells. In: Hematopoietic Stem Cells. Eds. D.W. Golde & F. Takaku. New York, Marcel Dekker, p. 148, 1985.

50 Fishman P., Djaldetti M., Hart J. y Sredni B. Growth of human basophil lines derived from chronic myelocytic leukemia cells in vitro; ultrastructure and X-ray microanalyzed studies. Immunology 55(1): 105, 1985.

51 Yehuda S., Sredni B. y Kalechman Y. Effects of DSIP, 5-HTP and serotonin on the lymphokine system: A preliminary study. Intern. J. Neuroscience 33:185, 1987.

52 Sredni B., Caspi R.R., Klein A., Kalechman Y., Danzinger Y., Ben Ya’akov M., Tamari T., Shalit F. y Albeck M. A new immunomodulating compound (AS101) with potential therapeutic application. Nature 330:173-176, 1987.

53 Sredni B. and Albeck M. A new immunomodulating compound (AS101) with potential therapeutic application. Fed. Proc. 46:1354, 1987.

54 Eisenstein Z., Engelsman E., Weiss M., Kalechman Y.y Sredni B. Production of and response to interleukin-2 in Graves’ disease. J. Clin. Immunol. 8: 349-355, 1988.

55 Sredni B., Caspi R.R., Lustig S., Klein A., Kalechman Y., Danziger Y., Ben Ya’akov M., Tamari T., Shalit F. y Albeck M. The biological activity and immunotherapeutic properties of AS101, a synthetic organotellurium compound. Nat. Immun. Cell Growth Regul. 7:163-168, 1988.

56 Albeck M., Tamari T. y Sredni B. A synthesis and properties of ammonium trichloro(dioxyethylene-0,0′)tellurate (AS101). A new immunomodulating compound. Synthesis 8:635-6, 1989.

57 Nyska A., Waner T., Pirak M., Albeck M. y Sredni B. Toxicity study in rats of a tellurium based immunomodulating drug, AS101: a potential drug for AIDS and cancer patients. Archives of Toxicology 63(5):386-93,1989.

58 Alcocer-Varela J., Alarcon-Segovia D., Sredni B. y Albeck M. Effect of the new immunoregulator AS101 on in vitro functions of mononuclear cells from patients with systemic lupus erythematosus. Clin. Exp. Immunol. 77:319, 1989.

59 Kalechman Y., Gafter U., Levi J., Sobelman D. y Sredni B. The effect of a single whole blood transfusion on cytokine secretion. J. Clin. Immunol. 10(2):99-105, 1990.

60 Michlin H., Schlesinger M., Kalechman Y. y Sredni B. Cell lines derived from human autorosette-forming cells with suppressive activity. Nat. Immun. Cell Growth Regul. 9(1):49, 1990.

61 Blank M., Sredni B., Albeck M., Mozes E. y Shoenfeld Y. The effect of the immunomodulator agent AS101 on IL-2 production in SLE disease induced in mice by a pathogenic anti-DNA antibody. Clin. Exp. Immunol. 79:443, 1990.

62 Sredni B., Kalechman Y., Shalit F. y Albeck M. Synergism between AS101 and PMA in lymphokine production. Immunology 69:110-116, 1990.

63 Sredni B., Catane R., Shani A., Gezin A., Levi E., Schlesinger M., Kalechman Y., Michlin H., Shalit F., Rosenzajn L.A., Farbstein H. y Albeck M. Phase I study of AS101 (an organotellurium compound) in patients with advanced malignancies. In: Recent Advances in Chemotherapy. Eds. E. Rubinstein y D. Adam. Jerusalem, E. Lewin-Epstein, 1990, pp. 851.1-851.4.

64 Shani A., Tichler T., Catane, R., Gurwith M., Rozenszajn L.A., Gezin A., Levi E., Schlesinger M., Kalechman Y., Michlin H., Shalit F., Engelsman, E., Farbstein H., Farbstein M., Albeck M. y Sredni B. Immunologic effects of AS101 in the treatment of cancer patients. Nat. Immun. Cell Growth Regul. 9:182-190,1990.

65 Fishman P., Sredni B. y Djaldetti M. Recent advances in Interleukin-3 research: A Review. Israel J. Med. Sci. 26: 414-9, 1990.

66 Kalechman Y., Sredni B., Caspi R.R. y Nussenblatt R.B. Enhancing effect of cyclosporins A and G on bone marrow colony formation. Exp. Hematol. 18(10):1104-7, 1990.

67 Sredni B., Kalechman Y., Albeck M., Gross O., Aurbach D., Sharon P., Sehgal S.N., Gurwith M.J. y Michlin H. Cytokine secretion effected by synergism of the immunomodulator AS101 and the protein kinase-C inducer bryostatin. Immunology, 70(4):473-7, 1990.

68 Kalechman Y., Albeck M., Oron M., Sobelman D., Gurwith M., Sehgal S.N. y Sredni B. The radioprotective effects of the immunomodulator AS101. J. of Immunol. 145:1512-7, 1990.

69 Sredni B., Fishman P., Albeck M. Immunosuppression: New Chemical Immunomodulators. 1991 McGraw-Hill Yearbook of Science and Technology. New York, McGraw-Hill Inc., 1990, pp. 195-197.

70 Djaldetti M., Fishman P., Shtatlender V. y Sredni B. Effect of Dexamethasone on IL-1 and IL-3-LA release by unstimulated human mononuclear cells. Biomed. & Pharmacother. 44:515, 1990.

71 Albeck M., Tamari T., Sredni B. AS101. In: Drugs of the Future. Vol. 15, No. 5, p. 511, 1990.

72 Fishman P., Djaldetti M., Grossman S., Sofer Y. y Sredni B. Spontaneous release of a factor with interleukin-3-like activity by human lymphocytes and monocytes. Nat. Immun. Cell Growth Regul. 9:341-41, 1990.

73 Yron I., Langer A., Weinstein T., Sahar E., Lidor Y., Pardo Y., Katz I., Shohat L., Ovadia J., Kalechman Y., Ovadia J., Witz I.P., y Sredni B. Effect of sex hormones on human T cell activation by Concanvalin A. Nat. Immun. Cell Growth Regul. 10:32-44, 1991.

74 Fishman P., Sredni B. y Djaldetti M. The relationship between interleukin-3-like activity and basophil production in chronic myeloid leukemia patients. Immunology Letters, 28:73-8, 1991.

75 Kalechman Y., Albeck M., Oron M., Sobelman D., Gurwith M., Horwith G., Kirsch T., Maida B., Sehgal S.N., Sredni B. Protective and restorative role of AS101 in combination with chemotherapy. Cancer Res. 51(5):1499-1503, 1991.

76 Kalechman Y., Michlin H., Gafter U. y Sredni B. Generation of cell lines with suppressive activity derived from autorosette forming cells of patients with autoimmune diseases. Annals of the New York Academy of Sciences 628:373-378, 1991.

77 Kalechman Y., Sotnik Barkai I., Albeck M., Horwith G., Sehgal S.N. y Sredni B. Use and mechanism of action of AS101 in protecting bone marrow CFU-GM after purging with ASTA-Z 7557. Cancer Res. 51(20):5614-20, 1991.

78 Gafter U., Kalechman Y., Sobelman D. y Sredni B. Induction of a subpopulation of suppressor cells by a single blood transfusion. Kidney Inter. 41(1):143-148, 1992.

79 Sredni B., Albeck M., Kazimirsky G. y Shalit F. The immunomodulator AS101 administered orally as a chemoprotective and radioprotective agent. Inter. J. of Immunopharmac. 14(4): 613-9, 1992.

80 Kozenitzki L., David M., Sredni B., Albeck M. y Shohat B. Immunomodulatory effects of AS101 on Interleukin-2 production and T lymphocyte function of lymphocytes treated with psoralens and ultraviolet A. Photodermatol Photoimmunol. Photomed. 9: 24-28¨†1992

81 Bakimer R., Fishman P., Blank M., Sredni B., Djaldetti M. y Shoenfeld Y. Induction of Primary Anti-Phospholipid Syndrome in Mice by Immunization with a Human Monoclonal Anti-Cardiolipin Antibody (H-3): J. Clin. Invest. 89: 1558-1563, 1992.

82 Vonsover A., Sredni B., Loya S., Horwith G., Kirsch T.M., Albeck M., Gotlieb-Stematsky T. y Hizi A. Inhibition of the reverse transcriptase activity and replication of human immunodeficiency virus type 1 by AS101 in vitro. AIDS Res. & Human Retro. 8®5©?613-23¨1992

83 Kalechman Y., Albeck M. y Sredni B. In vivo synergistic effect of the immunomodulator AS101 and the PKC inducer Bryostatin. Cellular Immunol. 143(1):143-53, 1992.

84 Kalechman Y., Sotnik-Barkai I., Albeck M. y Sredni B. The Effect of AS101 on the Reconstitution of T cell Reactivity following Irradiation or Cyclophosphamide Treatment. Exp. Hematol. 20:1302-8, 1992.

85 Fishman P., Sredni B., Reznick R., Zigelman R., Djaldetti M. y Hart J. Cultured human cord blood cells spontaneously produce a factor with basophil-promoting activity. Immunol Lett 30(3): 189-193, 1992.

86 Albeck M. y Sredni B. AS101 [Ammonium trichloro(dioxoethylene-0,0′)tellurate] a new immunomodulator for use in treatment of malignancies and AIDS. In: Trends in Medicinal Chemistry, IUPAC, Blackwell Scientific Publications, Oxford, 90: 329-332, 1992

87 Kalechman Y., Gafter U., Sotnik Barkai I., Albeck M., Gurwith M., Horwith G., Kirsch T., Maida B., Sehgal S.N. y Sredni B. Mechanism of radioprotection conferred by the immunomodulator AS101. Exp. Hematol. 21:150-5, 1993.

88 Gafter U., Kalechman Y., Zevin D., Korzets A., Livni E., Klein T., Sredni B. y Levi J. Tubulo-Interstitial Nephritis y Uveitis: Association with suppressed cellular immunity. Nephrol Dial and Transplant 8:821-826, 1993.

89 Kalechman Y., Sotnik-Barkai I., Albeck M. y Sredni B. Protection of bone marrow stromal cells from the toxic effects of Cyclophosphamide in vivo and of ASTA-Z 7557 and Etoposide in vitro by Ammonium trichloro(dioxyethylene-0-0′)tellurate (AS101). Cancer Res. 53(8): 1838-1844, 1993.

90 Fishman P., Shoenfeld Y., Azizi E., Sredni B., Yecheskel G., Zigelman R., Floro S. y Djaldetti M. Vitiligo antibodies are effective against melanoma cells. Cancer. 72: 2365-2389, 1993.

91 Kalechman K., Herman S., Gafter U. y Sredni B. Enhancing effects of autologous erythrocytes on human or mouse cytokine secretion and IL-2R expression. Cell. Immunol. 148: 114-129, 1993.

92 Kalechman Y., Sotnik-Barkai I., Albeck M. y Sredni B. Increased DNA repair ability following irradiation after treatment with the immunomodulator AS101. Rad. Res. 136: 197-204¨†1993

93 Shohat B., Kozenitzki L., David M., Albeck M. y Sredni B. Effect of UVB and AS101 on Interleukin-2 production and helper activity in psoriatic patients. Nat. Immun. 12: 50-55, 1993.

94 Fishman P., Falach-Vaknine E., Zigelman R., Bakiner R., Sredni B, Djaldetti M. y Shoenfeld Y. Prevention of fetal loss in experimental antiphospholipid syndrome by in vivo administration of RIL-3. J. Clin. Invest. 91: 1834-1837, 1993.

95 Fishman P., Nedivi R., Djaldetti M., Sredni B., Kayzer S. y Chiamoff C. Kinetics of cortisol, IL-2 and IL-3-Like activity levels following surgical intervention. Nat. Immun. 12: 35-40, 1993.

96 Kalechman Y., Shani A., Sotnik-Barkai I., Albeck M. y Sredni B. The protective role of Ammonium Trichloro(dioxoethylene-0,0′)tellurate in combination with several cytotoxic drugs acting by different mechanisms of action. Cancer Res. 53: 5962-5969, 1993

97 Huberman M., Shalit F., Roth Deri I., Gutman B., Kott E. y Sredni B. Decreased IL-3 production by peripheral blood mononuclear cells in patients with multiple sclerosis. J. Neurological Sciences 118: 79-82, 1993.

98 Sredni B., Albeck M. y Kalechman Y. Immunomodulation by AS101: mode of action and clinical applications in cancer therapy. In: The negative regulation of hematopoiesis. Ed. M. Guigon et al. Colloque INSERM/John Libbey Eurotext Ltd., 229, pp. 477-484¨†1993.

99 Gafter U., Kalechman Y., Orlin J.B. y Levi J., Sredni B. Anemia of uremia is associated with reduced cytokine secretion: immunopotentiating activity of red bood cells. Kidney International 45: 224-231, 1994.

100 Eisenstein Z., Engelsman E., Weiss M., Kalechman Y. y Sredni B. Modulation of the Interleukin-2 production defect in vitro in Graves’ Disease. Clin. Exp. Immunol. 96: 323-328, 1994.

101 Shalit F., Sredni B., Stern L., Kott E. y Huberman M. Elevated Interleukin-6 secretion levels by mononuclear cells of Alzheimer patients. Neuroscience Lett. 174: 130-132, 1994.

102 Huberman M., Shalit F., Roth-Deri I., Gutman B., Brodie C., Kott E. y Sredni B. Correlation of cytokine secretion by mononuclear cells of Alzheimer patients and their disease stage. J. Neuroimmunol. 52: 147-152, 1994.

103 Dastgheib K., Hikita N., Sredni B., Albeck M., Sredni D., Nussenblatt R. B. y Chan C. Ocular inflammation stimulated by the immunomodulator AS101 [ammonium trichloro(dioxyethylene-O-O’) tellurate]. Curr. Eye Res. 13: 603-610, 1994.

104 Sredni B., Rosenthal Z., Michlin H., Sobelman D., Segev Y., Blagerman S., Albeck M., Kalechman Y. y Rager-Zisman B. Restoration of murine cytomegalovirus (MCMV) induced myelosuppression by AS101. Immun Letters 43(3): 159-165, 1994.

105 Sredni B., Albeck M. y Kalechman Y. The immunomodulating and therapeutic properties of AS101. In: Forum on Immunomodulators. M. Guenounou (Ed.) John Libbey Eurotext, Paris, 1995, pp.123-146.

106 Kalechman Y., Shani A., Albeck M. y Sredni B. Induction of acute phase proteins in mice and humans by treatment with AS101, an immunomodulator with radioprotective properties. Immunopharmacology 29:149-158, 1995.

107 Kalechman Y., Zuloff A., Albeck M. y Sredni B. Role of Endogenous cytokine secretion in radioprotection conferred by the immunomodulator AS101. Blood 85:1555-1561,1995

108 Fishman P., Falach-Vaknin E., Sredni B., Meroni L. y Shoenfeld Y. Aspirin Modulates Interleukin-3 Production: Additional explanation for the preventive effects of Aspirin in anti-phospholipid syndrome. J. Rheumat.

109 Sredni B., Albeck M., Tichler T., Shani A., Shapira J., Bruderman I., Catane R., Kaufman B., Kalechamn Y. Bone marrow sparing and prevention of alopecia by AS101 in NSCL cancer patients treated with carboplatin and etoposide. J. Clin. Oncol. 13:2342-2353, 1995.

110 Xu R., Kalechman Y., Albeck M. y Sredni B. The cytoprotective effect of the immunomodulator AS101 against hydrochloride induced gastric lesions. Research Communications in Molecular Pathology & Pharmacology, 87: 4-20, 1995.

111 Kalechman Y., Lederer G., Nerubay J., Albeck M. y Sredni B. Effect of the immunomodulator AS101 on chemotherapy-induced multilineage myelosuppression, thrombocytopenia and erythropenia in mice. Exp. Hematol. 23:1358-66, 1995.

112 Shalit F., Sredni B., Brodie C., Kott E., y Huberman M. T lymphocyte subpopulations and activation as a marker for severity of Alzheimer’s disease. Clinical Immunology and Immunopathology 75: 246-250, 1995.

113 Huberman M., Sredni B., Stern L., Kott, E. y Shalit F. IL-2 and IL-6 secretion in dementia: correlation with type and severity of disease. J. of Neurological Sciences 130: 161-164, 1995.

114 Mittwoch-Jaffe T., Shalit F., Sredni B. y Yehuda S. Modification of cytokine secretion following mild emotional stimuli. Neuro Report. 6:789-792, 1995.

115 Sredni B., Xu R.H., Albeck M., Gafter U., Gal R., Shani A., Tichler T., Shapira J., Bruderman I., Catane R., Kaufman B., Whisnant J.K., Mettinger K.L. y Kalechman Y. The protective role of the immunomodulator AS101 against chemotherapy-induced alopecia. Studies on human and animal models. International J of Cancer 65:97-103, 1996.

116 Herman S., Kalechman Y., Gafter U., Sredni B. y Malik A. Photofrin II induces cytokine secretion by mouse spleen cells and human peripheral mononuclear cells. Immunopharmacology, 31: 195-204, 1996.

117 Kalechman Y., Shani A., Dovrat S., Whisnant J.C., Mettinger K., Albeck M., y Sredni B. The antitumoral effect of the immunomodulator AS101 and Paclitaxel (Taxol) in a murine model of lung adenocarcinoma. J Immunol 156: 1101-1109, 1996

118 Xu, R.H., Kalechamn Y., Albeck M., Kung H.F., and Sredni B. Inhibition of B16 melanoma metastasis by the immunomodulator AS101. International J of Oncology, 9: 319-325, 1996.

119 Rosenblatt-Bin H., Klein A. y Sredni B. The effect of the immunomodulalor AS101 on mice infected with Babesia Rodhaini. Parasite Immunology 18:297-306, 1996.

120 Sredni B., Tichler T., Shani A., Catane R., Kaufman B., Strassmann G., Albeck M. y Kalechman Y. Predominance of TH1 response in tumor bearing mice and cancer patients treated with AS101. JNCI (Journal of the National Cancer Institute) 88(18):1276-1284, 1996.

121 Kalechman Y., y Sredni B. Differential Effect of the immunomodulator AS101 on B7-1 and B7-2 Costimulatory Molecules: Role in the Antitumoral Effects of AS101. J Immunol 157:589-597, 1996.

122 Gafter U., Kalechman Y., y Sredni B. Blood transfusion enhances production of T-helper-2 cytokines and transforming growth factor b in humans. Clinical Science, 91:519-523, 1996.

123 Gafter U., Sredni B., Segal J., y Kalechamn Y . Suppressed cell-mediated immunity, monocyte and Natural Killer cell activity following allogeneic immunization of women with spontaneous recurrent abortions. Journal of Clinical Immunology, 17:408-419, 1997.

124 Kalechman Y., Gafter U., Da J.P., Albeck M., Alarcon-Segovia D., y Sredni B. Delay in the onset of Systemic Lupus Erythematosus following treatment with the immunomodulator AS101. J Immunol 159:2658-2667, 1997.

125 Shalit F., Sredni B., Rosenblatt-Bin H., Brodie C., Huberman M. Beta amyloid peptide induces tumor necrosis factor-a and nitric oxide production in murine macrophage cultures. NeuroReport, 8(16), 1997.

126 Rosenblatt-Bin H., Kalechman Y., Vonsover A., Xu R-H., Da J-P., Shalit F., Klein A., Albeck M., y Sredni B. The immunomodulator AS101 restores Th1 type of response suppressed by Babesia Rodhaini in BALB/c mice. Cell Immunol, 184:12-25, 1998.

127 Kalechman Y., Strassmann G., Albeck M. y Sredni B. Up-regulation by Ammonium Trichloro(Dioxoethylene-0,0′)Tellurate (AS101) of Fas/Apo-1 expression on B16 melanoma cells: implications for the antitumor effects of AS101. The Journal of Immunology, 161:3536-3542, 1998.

128 Albeck A., Weitman H., Sredni B. y Albeck M. Tellurium compounds: selective inhibition of Cysteine proteases and model reaction with Thiols. Inorg. Chem. 37: 1704-1712, 1998.

129 Kalechman Y., Longo D.L., Catane R., Shani A., Albeck M. y Sredni B. Synergistic antitumoral effect of Paclitaxel (Taxol) + AS101 in a murine model of B16 melanoma: association with ras-dependent signal transduction pathways. International J of Cancer 86:281-288, 2000.

130. Dagon Y., Dovrat S., Vilchick S., Hacohen D., Shlomo G., Sredni B., Salzberg S y Nir U. Double-stranded RNA-dependent protein kinase, PKR, down-regulates CDC2/cyclin B1 and induces apoptosis in non-transformed but not in v-mos transformed cells. Oncogene, 6; 20: 8045-56, 2001.

131. Kalechman Y., Gafter U., Gal R., Rushkin G., Yan D., Albeck M. y Sredni B. Anti IL-10 therapeutic strategy using the immunomodulator AS101 in Protecting mice from sepsis-induced death: dependence on timing of immunomodulating intervention The Journal of Immunology,:384-392, 2002.

132. Sinnuani I., Averbukh Z., kalechman Y.M Rapoport M., Albeck M., Sredni B. y Weissgarten J. Inhibition of compensatory tubular cell hypertrophy by the immunomodulator AS101 via decreased Interleukin-10 activity.

133. Sredni B., Geffen R., Duan W., Albeck M., Shalit F., Longo D.L., Sonino T., Kalechman Y., Mattson M.P. y Yadid G. Anti-Apoptotic Immunomodulating Tellurium Compound (AS101) as a Potential Treatment of Parkinson’s Disease.

134. Sredni B., Eliahu S., Gal R., Gafter U., Motro B., Albeck M., Lander H., Cohen I., y Kalechman Y. The tellurium immunomodulator AS101 induces hair-growth in mice and humans by delaying terminal differentiation of keratinocytes via a ras-dependent upregulation of KGF expression.

135. Kalechman Y.,Sredni B., Weinstein T.,Freidkin I., Tobar A., Albeck M. y Gafter U. Production of the novel mesangial autocrine growth factors GDNF and IL-10 is regulated by the immunomodulator AS101: role in experimental mesangial proliferative glomerulonephritis.

136. Rosenblatt-Bin H., Kalechman Y., Shalit F., Klein A., y Sredni B. The immunomodulator AS101 enhances effector functions of macrophages in vivo otherwise subverted by Babesia Rodhaini parasites. Cellular Immunology.

Patentes Registradas:

1 Djaldetti M., Sredni B., Fishman P. y Grossman S: Extraction of Lymphokines – Isolation of Natural Human Interleukin-3. Patente Israel No. 04469 I-1051, 1986.

2 Djaldetti M., Sredni B., Fishman P. y Grossman S: Receptors – Characterization and Isolation of Receptors of Human Interleukin-3. Patente Israel No. 04528 I-1051, 1986.

3 Albeck M. y Sredni B: Pharmaceutical compositions of Tellurium and Selenium compounds for the induction of in vivo and in vitro production of Cytokines. Patente No. 4,752,614. Patente EE.UU., Junio 21 de1988.

4 Albeck M. y Sredni B: Organic derivatives of Tellurium and Selenium and their use to stimulate Cytokine production. Patent No. 4,761,490. Patente EE.UU., Agosto 2 de 1988.

5 Albeck M. y Sredni B: Tellurium and Selenium compounds for the induction of in vivo and in vitro production of Cytokines. Patente No. 4,764,461. Patente EE.UU., Agosto 16 de 1988.

6 Djaldetti M., Sredni B., Fishman P. y Grossman S: Isolation of Lymphokines. Patente EE.UU. No. 05984 I-1077, 1988.

7 Djaldetti M., Sredni B., Fishman P. y Grossman S: Anti-Metastatic Factor Derived from Muscle Cultures. Patente Israel No. 08597 I-1072, 1989.

8 Sredni B., Pavliv L. Albeck M: Complexes of Tellurium and Selenium derivatives. Patente EE.UU. No. 4,929,739, Mayo 29 de 1990.

9 Sredni B. y Albeck M: Method for the stimulation of bone marrow cells. Patente EE.UU. No. 4,946,437, Agosto 7 de 1990.

10 Albeck M. y Sredni B: Organic derivatives of Tellurium and Selenium. Patente EE.UU. No. 4,962,207, Octubre 9 de 1990.

11 Albeck M. y Sredni B: Compounds for the induction of in vivo and in vitro production of cytokines. Patente EE.UU. No. 5,093,135, Marzo 3 de 1992.

12 Sredni B. y Albeck M: Method of inducing the production of cytokines. Patente EE.UU. No. 5,126,149, Junio 30 de 1992.

13 Sredni B. y Albeck M: Method of treating or preventing alopecia. Patente No. 5,262,149. Patente EE.UU., Noviembre 16 de 1993.

14 Sredni B., Huberman M., y Shalit F. Diagnosis of Alzheimer disease stage by mononuclear cell cytokine secretions. 081257,740. Estados Unidos, 1994.