BIOLOGY Publication Record Araj, G. F., R. S. Talhouk, L. Y. Itani, W. Jaber, G.
Jamaledin. 2000. Comparative performance of PCR-based assay vs. microscopy
and culture for the direct detection of Mycbacteria tuberculosis in clinical
respiratory specimens in Lebanon. The International Journal of
Tuberculosis and Lung Disease. Azar, S. T., S. C. Major, and B. Safieh-Garabedian. 1999.
Altered plasma levels of nerve growth factor and transforming growth factor
beta2 in type-1 diabetes mellitus. Brain Behavior and Immunity
13:361366. Barbour, E. K., M. Bouljihad, B. Hamdar, W. Sakr, A. Eid, and
B. Safieh-Garabedian. 1999. Dynamics of protein 27 of avian leukosis and
transforming growth factor beta2 in lymphoid leukosis-susceptible and
resistent broiler chicken breeders. Veterinary Research Communications 23:191200. Barbour, E. K., L. H. Jurdi, R. S. Talhouk, M. Qatanani, A.
Eid, and W. Sakr. 1999. Emergence of Salmonella enteritidis outbreaks in
broiler chickens of Lebanon: Epidemiologic markers and competitive exclusion
control. Revue scientifique et techniqueOffice international des
ιpizooties. Baydoun, E., R. Abdel-Massih, D. Dani, S. Rizk, and C. T. Brett. 2001.Galactosyl-and fucosyltransferases in etiolated pea epicotyls:Product identification and sub-cellular localisation.Journal of Plant Physiology 158:145150. Baydoun, E., S. Rizk, and C. T. Brett. 1999.Localisation of methyltransferases involved in glucouronoxylan and pectin methylation in the Golgi apparatus in etiolated pea epicotyls.Journal of Plant Physiology 155:24044. Dardenne, M., B. Safieh-Garabedian, and J. M. Pleau. 1999.
Pain and Neuroimmune Interactions. Thymic peptides: Transmitters between the
neuroendocrine and immune system. New York: Kluwer Academic/Plenum
Publishers. Darwiche, N., L. Freeman, and A. Strunnikov. 1999.
Characterization of the components of the putative mammalian sister chromatid
cohesion complex. Gene 233 (1-2):3947. Darwiche, N., M. El-Sabban, R. Bazzi, R. Nasr, S. Al-Hashimi,
and A. Bazarbachi. 2001. Retinoic acid dramatically enhances the arsenic
trioxide induced cell cycle arrest and apoptosis in retinoic acid receptor
alpha- positive human T-cell leukemia virus type-I transformed cells. The
Hematology Journal 2:127135. Farhat, G., N. Affara, and H. Gali-Muhtasib. 2001. Seasonal
changes in the composition of the essential oil extract of East Mediterranean
Sage (Salvia libanotica) and its toxicity in mice. Toxicon. Gali-Muhtasib, H., and N. Affara. 2000. Chemopreventive
effects of sage oil on skin papillomas in mice. Phytomedicine 7
(2):129136. Gali-Muhtasib, H., H. Christo, and C. Khater. 2000. Traditional uses of Salvia libanotica (East Mediterranean Sage) and the effects of its essential oils. Journal of Ethnopharmacology 71 (3):513520. Gali-Muhtasib, H., M. Haddadin, D. Rahhal, and I. Younes.
2001. Quinoxaline 1,4-dioxides as anticancer and hypoxia-selective drugs. Oncology
Reports. Gali-Muhtasib, H., S. Yamout, and M. Sidani. 2000. Tannins
protect against skin tumor promotion induced by ultraviolet B radiation in
hairless mice. Nutrition and Cancer 37 (1):7377. Gali-Muhtasib, H., S. Yamut, and M. Sidani. 1999. M. Plant
tannins as inhibitors of hydroperoxide production and tumor promotion induced
by ultraviolet B radiation in mouse skin in vivo. Oncology Reports 6
(4):847853. Gali-Muhtasib, H., I. Younis, J. Karchesy, and M. El-Sabban.
2001. Plant tannins inhibit the induction of aberrant crypt foci and colonic
tumors by 1,2-dimethylhydrazine in mice. Nutrition and Cancer. Haddad, J. J., S. C. Land, N. E. Saade, and B.
Safieh-Garabedian. 2000. Immunomodulatory potential of thymulin-Zn in the
alveolar epithelium: Amelioration of endotoxin-induced cytokine release and
partial amplification of a cytoprotective IL-10 sensitive pathway. Biochemical
and Biophysical Research CommunicationsBiochem. Haddad, J. J., R. Lauterbach, N. E. Saade, B.
Safieh-Garabedian, and S. C. Land. 2001. Alpha-melanocyte-related tripeptide
lys-D-pro-val ameliorates endotoxin-induced NF-kappaB translocation and
activation: Evidence for involvement of an interleukin-beta 193-195 receptor
antagonism in the alveolar epithelium. Biochemical Journal 355:2938. Haddad, J. J., B. Safieh-Garabedian, N. E. Saade, S. A.
Kanaan, and S. C. Land. 2001.
Chemioxyexcitation dependent release of Il-1beta, Il-6 and TNF-alpha:
Evidence of cytokines as oxygen-sensitive mediators in the alveolar
epithelium. Cytokine 13:13847. Haddad, J. J., B. Safieh-Garabedian, N. E. Saade, and S. C.
Land. 2001. The novel biphasic pattern of pyrimidylpiperazine (Y-40138)
abrogation of endotoxin-induced pro-inflammatory cytokine biosynthesis is
IL-10 sensitive and requires NF-kappaB targeting in the alveolar epithelium. British
Journal of Pharmacology 133:4960. . 2001. Thiol regulation of pro-inflammatory cytokines
revealed by a novel immunopharmacological potential of glutathione in the
alveolar epithelium. Journal of Pharmacology and Experimental Therapeutics
296:9961005. Hajjar, L., R. Abou-Gergi, N. Saadeh, and B.
Safeih-Garabedian. 2000. Functional interplay between gelatinases and
Hyperalgesia in an endotoxin induced localized inflammatory pain. Pain. Ibarra-Perez, F. J., D. Barnhart, B. Ehdaie, K. M. Knio, and
J. G. Waines. 1999. Effects of insect
tripping on seed yield of common bean. Crop Science. Knio, K., E. Baydoun, R. Tawk, and N. Nuwayri-Salti. 2001.
Isoenzyme characterization of Leishmania isolates from Lebanon and Syria.
American Journal of Tropical Medicine and Hygiene. Knio, K., R. Goeden, and D. Headrick. 2001. Resource
utilization in the sibling species T. nigricornis, a polyphage, and the
nearly monophagous, T. bisetosa (Diptera:Tephritidae) in Southern California.
Proceedings of the Entomological Society of Washington. Knio, K., and S. Kalash. 2001. White, I. Flower-head infesting
fruit flies (Tephritidae) on Asteraceae plants in Lebanon. Journal of
Natural History. Knio, K. M., A. Saad, and S. Dagher. 2000. The fate and
persistence of zineb, maneb, and ethylenethiourea on fresh and processed
tomatoes. Food Additives and Contaminants 17:39398. Kreydiyyeh, S. 2000. Cyclic AMP and furosemide stimulate the
Na+-K+ ATPase in isolated rat jejunal cells. Pharmacological
Research 41:179185. . 2000. Epinephrine stimulates the Na+-K+ATPase
in isolated rat jejunal crypt cells. Life Sciences 67:12751283. Kreydiyyeh, S., J. Usta, and R. Copti. 2000. Effect of
cinnamon, clove and some of their constituents on the Na+-K+ATPase
activity in the rat jejunum. Food and Chemical Toxicology 38:755762. Nuwayri-Salti, N., E. Baydoun, R. El-Tawk, M. Fakhoury, and K.
Knio. 2000. The epidemiology of leishmaniases in Lebanon. Transactions of
the Royal Society of Tropical Medicine and Hygiene 94:164166. Rizk, S., R. Abdel-Masih, E. Baydoun, and C. T. Brett.
2000.Protien and pH-dependent binding of nascent pectin and
glucuronoarabinoxylan to xyloglucan in pea. Planta 211:42329. Safieh-Garabedian, B., S. A. Kanaan, S. F. Atweh, S. J.
Jabbur, and N. E. Saade. 2000. Prostaglandin-E2 dependent cytokine
upregulation and hyperalgesia induced by thymulin. Neuropharmacology
39:16521660. . 2000. Thymulin and inflammatory pain: A possible
substrate for PGE2 dependent neuroimmune loop. Pain and Neuroimmune
Interaction, 13947. New York: Kluwer Academic/Plenum Publishers. Shbaro, C., C. Tarraf, R. Talhouk, S. Shamat, E. Kastoun, and
M. Sabeh. 2000. Life Science for Secondary Education. Educational
Center for Research and Development. . 2000. Teacher's Guide for Life Science for Secondary Education. Educational Center for Research and Development. Abstracts, Conferences, and Proceedings Abdel-Massih, R., E. Baydoun,
and C. T. Brett. November 2000. Galactan synthesis in
Peas. 14th Science Meeting of the Lebanese Association for the Advancement of
Science, Beirut, Lebanon. . April 2001.
In vitro biosynthesis of 1,4-B-galactan attached to a pectin-xyloglucan
complex in Pea. 11th Scottish Cell Wall Meeting, Stirling, U.K. Affara, N., and H. Gali-Muhtasib. November 1999. Chemopreventive effects of sage oil on skin
papillomas in mice. 13th Science Meeting, Beirut, Lebanon. Al-Maalouf, S., M. El-Sabban,
N. Darwiche, and H. Gali-Muhtasib. November 1999. The effect of vitamin E on UVB-induced
apoptosis in murine keratinocytes. 13th Science Meeting, Beirut, Lebanon. Al-Sadi, R., I. Kaouk,
and S. Kreydiyyeh. November 2000. Parsley inhibits net
fluid absorption from the rat colon. 14th Science Meeting, Beirut, Lebanon. Assaf-Diab, M., M. Haddadin,
and H. Gali-Muhtasib. April 2001. Quinoxaline 1,4-dioxides
alter epithelial cell proliferation via changes in transforming growth
factors expression. 5th Middle East Oncology Congress, Beirut, Lebanon. . April 2001.
Quinoxaline 1,4-dioxides: A new class of hypoxia-selective drugs. 5th Middle
East Oncology Congress, Beirut, Lebanon. Ayoub, G. M., P. Saikaly,
E. Baydoun, and M. El-Fadel. November 2000. The impact of step
feeding on rotating biological contactors. 14th Science Meeting of the
Lebanese Association for the Advancement of Science, Beirut, Lebanon. Baydoun, E., S. Rizk,
R. Abdel-Massih, and C. T. Brett. April 2000. Assemblins: Proteins
which mediate pH-dependent binding between cell-wall matrix polysaccharides.
10th Scottish Cell Wall Meeting, Edinburgh, Scotland. Bazzi, H., S. Al-Maalouf, E. Hatoum, H. Gali-Muhtasib, and N. Darwiche. November 2000. Retinoic acid inhibits early vitamin A deficiency induced by ultraviolet irradiation of primary mouse keratinocytes. Proceedings of the 14th Science Meeting, Beirut, Lebanon. Bazzi, R., R. Nasr,
M. El-Sabban, A. Bazarbachi, and N. Darwiche. November
1999. Retinoic acid receptor alpha status determines the apoptotic
response of HTLV-I transformed cells to the synergistic combination of
retinoic acid and arsenic trioxide treatment. Proceedings of the 13th Science
Meeting, Beirut, Lebanon. Copti, R., J. Usta,
and S. Kreydiyyeh. November 1999. Effect of commonly
used spices on the activity of the Na+-K+ATPase and alanine absorption. Thirteenth
Science Meeting, Beirut, Lebanon. Darwiche, N., M. El-Sabban,
R. Bazzi, R. Nasr, H. De The, and A. Bazarbachi. January
2000. Retinoic acid
dramatically enhances the arsenic trioxide induced cell cycle arrest and
apoptosis in retinoic acid receptor alpha positive Human T-cell leukemia
virus type-I transformed cells. Cell and Molecular Biology Keystone
Symposium: Cancer, Cell Cycle and Therapeutics, Steamboat Springs,
Colorado, USA. Darwiche, N., M. El-Sabban,
H. De The, R. Nasr, and A. Bazarbachi. December
2000. Retinoic acid and
arsenic trioxide combination induces cell cycle arrest and apoptosis and
down-regulates tax in retinoic acid receptor alpha positive human HTLV-I
transformed cells. 42nd Annual Meeting of the American Society of Hematology,
San Francisco, California, USA. Darwiche, N., E. Hatoum, J. Khoury, and M. El-Sabban. January 2001. Introduction of retinoic acid receptors alpha and gamma into epidermal cell lines causes retinoic acid-induced growth arrest. Cell and Molecular Biology Keystone Symposium, The Molecular Basis of Cancer: Signaling to Cell Growth and Death, Taos, New Mexico, USA. El-Sabban, M., M. Daher,
A. Sfeir, R. Bassam, H. Abou-Haidar, and R.
Talhouk. December 2000.
Interplay between cell/ECM interaction and Gap Junctional Intercellular
Communication (GJIC) modulates differentiation of mammary epithelial cells in
culture. American Society of Cell Biology, San Francisco, California, USA. Gali-Muhtasib, H., S. Al-Maalouf,
M. Tabbal, and M. El-Sabban. September 2000. Vitamin E protects
against UVB-induced damage in murine keratinocytes. 7th International
Conference on Antimutagenesis and Anticarcinogenesis, Michigan, USA. Gali-Muhtasib, H., M. Haddadin,
D. Rahhal, and I. Younes. November 2000. Quinoxaline 1,4-dioxides as anticancer and
hypoxia-selective drugs. 14th Science Meeting, Beirut, Lebanon. Gali-Muhtasib, H., I. Younes,
M. Abou-Karam, and M. El-Sabban. September 2000. Gallotannin induces cell
cycle arrest and apoptosis in human colon cancer cell lines. 7th
International Conference on Antimutagenesis and Anticarcinogenesis, Michigan,
USA. Gali-Muhtasib, H., I. Younis,
J. Karchesy, and M. El-Sabban. October 2000. Plant tannins as
chemopreventive agents against colon cancer: Mechanistic aspects of action in
human colon cancer cell lines. 5th World Congress on Advances in Oncology,
Crete, Greece. Hatoum, E., J. Khoury,
and M. El-Sabban. January 2001. Introduction of retinoic
acid receptors alpha and gamma into epidermal cell lines causes retinoic
acid-induced growth arrest. Cell and Molecular Biology Keystone Symposium,
The Molecular Basis of Cancer: Signaling to Cell Growth and Death, Taos,
New Mexico, USA. Hatoum, E., J. Khoury,
M. El-Sabban, and N. Darwiche. November 2000. Introduction of
retinoic acid receptors alpha and gamma into epidermal cell lines causes
retinoic acid-induced growth arrest. Proceedings of the 14th Science Meeting,
Beirut, Lebanon. Nakkash, H., K. Bajakian,
S. Kreydiyyeh, and J. Usta. November 1999. Effect of cinnamon and clove extracts on
Na+-K+ATPase, Cu++ATPase, and F0F1ATPase: A comparative study. Thirteenth
Science Meeting, Beirut, Lebanon. Nasr, R., R. Bazzi,
M. El-Sabban, A. Bazarbachi, and N. Darwiche. November
1999. Mechanism of action of the synergistic apoptotic effect of
retinoic acid and arsenic trioxide in the HTLV-I transformed HUT-102 cells.
Proceedings of the 13th Science Meeting, Beirut, Lebanon. Nasr, R., N. Darwiche,
H. De The, and A. Bazarbachi. December 2000. Retinoic acid
increases retinoid X receptor DNA binding activity despite the degradation of
retinoid receptor proteins in HTLV-I transformed cells. 42nd Annual Meeting
of the American Society of Hematology, San Francisco, California, USA. Rizk, S., R. Abdel-Massih,
E. Baydoun, and C. T. Brett. April 2001. Mechanisms of cell-wall
assembly in pea and maize. 11th Scottish Cell Wall Meeting, Stirling, U.K. Rizk, S., E. Baydoun,
and C. T. Brett. November 1999. Characterization of
nascent EDTA -soluble polysaccharides and their pH-dependent binding to
Xyloglucan. The 13th Science Meeting of the Lebanese Association for the
Advancement of Science, Beirut, Lebanon. Rizk, S., E. Baydoun,
and C. T. Brett. November 2000. Assemblins: Proteins
involved in interactions between cell-wall matrix polysaccharides. 14th
Science Meeting of the Lebanese Association for the Advancement of Science,
Beirut, Lebanon. Safieh-Garabedian, B., M.
Dardenne, S. A. Kanaan, F. Haour, S. F. Atweh, and N. E.
Saade. September 1999. Endotoxin
(ET) induced alterations in thymulin levels through capsaicin sensitive
neuro-immune loop. International Society of Neuroimmunomodulation, Lugano,
Switzerland. Safieh-Garabedian, B., M.
Dardenne, I. Ochoa-Chaar,
C. A. Masaad, S. F. Atweh, S. J.
Jabbur, and N. E. Saade. September 2000. Intracerebroventricular
(ICV) injection of thymulin modulates cytokine and nerve growth factor levels
in different areas of the rat brain. Federation of European Neuroscientists,
Brighton, UK. Safieh-Garabedian, B., S.
A. Kanaan, S. F. Atweh, S. J. Jabbur, and N. E. Saade. August
1999. Time course of changes in glial derived neurotrophic factor
(GDNF), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in
endotoxin(ET)-induced localized hyperalgesia. 9th World Congress on
Pain, Vienna, Austria. Safieh-Garabedian, B., S.
A. Kanaan, S. J. Jabbur, and N. E. Saade. October 1999. Chemical sympathectomy
modulates hyperalgesia and cytokine levels in th endotoxin (ET) of localized
inflammatory hyperalgesia. 29th Society for Neuroscience Meeting, Miami
Beach, Florida, USA. Safieh-Garabedian, B., I.
Ochoa-Chaar, S. F. Atweh,
S. J. Jabbur, and N. E. Saade. November 2000. Intracerebroventricular (ICV) injections of
endotoxin (ET) induce hyperalgesia (HA) and cytokine upregulation which are
modulated by thymulin. 30th Society for Neuroscience Meeting, New Orleans,
Louisiana, USA. Talhouk, R., N. Kalaany,
R. Shami, A. Shaayto, R. Bassam, and M.
El-Sabban. December 1999. Gap
junctional protein expression and function in CID-9 mammary cells is
modulated by extracellular matrix. American Society of Cell Biology, San
Francisco, California, USA. Talhouk, R., G. Mouneimne,
M. Beirouty, and B. Safieh-Garabedian. August 2000. The effect of endotoxin
on functional and morphological parameters of mammary CID-9 cells. Sixth
International Endotoxin Society Meeting, Paris, France. Tarraf, C., M. Beyrouthy,
J. Chamoun, I. El-Hajj, and R. Talhouk. November
2000. Effect of organochlorine mixtures on reproduction in rats. 14th
Meeting of the Lebanese Association for the Advancement of Science, Beirut,
Lebanon. Tarraf, C. G., R. S. Talhouk,
A. A. Shaito, and M. E. El-Sabban. December 2000. The effect of the
extracellular matrix on dofferentiation and gap junctional intercellular
communication in rat granulosa cells. The American Society for Cell Biology
40th Annual Meeting, San Francisco, California, USA. . October 1999. Gallotannin
induces cell cycle arrest and apoptosis in a human colon cancer cell line.
4th World Congress on Advances in Oncology, Athens, Greece. Tarraf, C., R. Talhouk,
A. A. Shaito, J. Kogan, and M. E. El-Sabban. November 2000. Characterization and
modulation of gap junctional intercellular communication in rodent granulosa
cells. 14th Meeting of the Lebanese Association for the Advancment of
Science, Beirut, Lebanon. Younis, I., M. El-Sabban,
and H. Gali-Muhtasib. November 1999. In vitro effects of
gallotannin on a human colon cancer cell line. 13th Science Meeting, Beirut,
Lebanon. Miscellaneous Safieh-Garabedian, B. September 2000. The role of thymulin in the cross-talk between the immune and the nervous system. The Molecular Neuropharmacology Laboratory, Neuroscience Research Center, Guy's, King's and St. Thomas' School of Biomedical Sciences, University of London, London, UK. . November 2000. The
role of thymulin in the cross-talk between the immune and the nervous system.
Department of Physiology, Northwestern University Medical School,
Chicago, Illinois, USA. . May 2001. Interactions
between the immune and the nervous system during pain states: A possible
target for intervention. The XXXVI Middle East Medical Assembly, AUB, Beirut,
Lebanon. Graduate Theses and Projects Al-Maalouf, S. October 1999. The effect of vitamin E on
UVB-induced apoptosis in a papilloma-derived keratinocyte cell line. H.
Gali-Muhtasib, M. El-Sabban, and N. Darwiche. Bassam, R. A. February 2001. Developmental regulation of
mammary gland gap junction proteins and effect of dieldrin on mammary gland
function in vivo and in vitro. R. Talhouk, M. El-Sabban, and H.
Gali-Muhtasib. Chaar, C. I. O. June 2000. Hyperalgesia and alterations of
pro-inflammatory cytokines and neurotrophin levels by intracerebroventricular
injection of thymulin. N. E. Saade, and B. Safieh-Garabedian. Daher, M. July 2000. Correlation between gap junctional
intercellular communication and differentiation of mammary cells in vitro.
R. Talhouk, M. El-Sabban, N. Darwiche, and S. Kreydiyyeh. Kalaany, N. Y. July 1999. Effect of ECM and oMDGF-1 on
functional parameters of mammary cells in vitro. R. Talhouk, M.
El-Sabban, N. Darwiche, and H. Gali-Muhtasib. Markarian, N. July
1999. Mosquito Species of Lebanon. Kh. Knio. Shaito, A. June 2000. Characterization and modulation of gap
junctional intercellular communication in rodent granulosa cells. C. Tarraf,
M. El-Sabban, and R. Talhouk. Younis, I. H. September 1999. Inhibition of
1,2-dinethylhydrazine-induced colon cancer in balb-c mice by hydrolyzable and
consensed tannins. H. Gali-Muhtsib, M. El-Sabban, and Kh. Knio. Research Projects Control of phenolic cross-linking in cell walls of food
plants Diferulate phenolic cross-links between cell-wall
polysaccharides control plant growth and food texture. This project will
investigate factors controlling the amounts and types of diferulate
cross-links in sugar beet. Effects of different ferulate isomers, different
peroxidase iso-enzymes, and availability of cross-linking
agents,"dirigent proteins," source of pectin, and ferulate
availability will be investigated. Baydoun, E. Supported by LNCSR Localization of enzymes involved in the synthesis of
cell-wall matrix polysaccharides within the Golgi apparatus Our results showed that the enzymes glucuronyl-, xylosyl-,
fucosyl-, and methyl-transferases involved in the biosynthesis of
cell-wall-matrix polysaccharides are located principally in the Golgi
apparatus. The glycosyltransferases and methyltransferases involved in
polysaccharide and glycoprotein synthesis are differentially located between
the different membrane vesicles in the Golgi. Each enzyme has a
characteristic distribution, which does not always correspond to the site at
which the enzyme's product has been observed to accumulate by
immunocytochemistry. Thus, it is likely that sites of synthesis and
accumulation within the Golgi may be different for some, or all, of these
macromolecular products. Baydoun, E. Supported by URB Purification and significance of Assemblins, proteins
controlling plant-cell-wall assembly Plant cell walls contain several different polysaccharides
in a complex, supramolecular structure. Assemblins are proteins which mediate
polysaccharide-polysaccharide binding during cell-wall assembly. The project
aims at purifying assemblins, determine their size and discover how
widespread they are in plants. Assemblins attached to nascent pectin and
xylan in pea Golgi membranes and cell walls will be purified, their size
determined by SDS-PAGE and amino-acid sequence information obtained. The
presence of assemblins attached to other wall polysaccharides (xyloglucan and
mixed-linked glucan) and in other species and tissues will be investigated.
Baydoun, E. Supported by URB and The Third World Academy of Sciences The mechanism of action of and development of novel
therapies for HTLV-I associated adult T-cell leukemia/lymphoma (ATL) ATL is a malignancy of activated T cells resistant to
chemotherapy. The viral transactivator protein, Tax, plays a critical role in
HTLV-I-induced transformation and apoptosis resistance by inducing IkB-Kinase
(IKK)-mediated IkB-alpha phosphorylation and proteasomal degradation,
resulting in sustained activation of the NF-kB pathway. We recently showed
that As/IFN synergies induce cell cycle arrest and apoptosis in ATL cells. We
demonstrated that As/IFN induces the degradation of Tax, associated with an
upregulation of IkB-alpha resulting in cytoplasmic retention of RelA subunit
of NF-kB and a sharp decrease in RelA DNA binding NF-kB complexes. Due to the
pivotal role Tax plays in HTLV-I-induced transformation, its down-regulation
by As/IFN may account for cell death through inactivation of the NF-kB
pathway. We also showed that ATRA synergize with As induce cell cycle arrest
and apoptosis in RAR-alpha-positive ATL cells. In this proposal, we aim to
decipher the mechanism of action of As/IFN and ATRA therapies in ATL-derived
cells. Bazarbachi, A. (PL), M. El-Sabban, G. Dbaibo, and N. Darwiche. The role of retinoic acid receptor alpha in the
combined retinoic acid and arsenic treatment of adult T-cell leukemic (ATL)
cells Adult T-cell leukemia (ATL) is an aggressive malignancy of
mature activated T cells that is caused by human T-cell leukemia virus type I
(HTLV-I). Recently, we investigated the combined effects of retinoic
acid (RA) and arsenic (As) treatments on the growth of HTLV-I transformed
cells (HuT-102 and MT-2). We showed that, while both cell lines were
resistant to RA treatment, the combination RA/As induced a highly synergistic
effect only on HuT-102 cells. The combination treatment resulted in a
dramatic inhibition of cell proliferation and induction of massive apoptosis
in HuT-102 cells. Retinoid receptor protein analysis showed that both cell
lines express RXRalpha proteins; RARalpha protein levels are undetectable in
MT-2 cells but highly expressed in HuT-102 cells. We would like to test
our hypothesis linking the successful combination treatment of RA and As in
ATL to the presence of RARalpha using retroviral-mediated gene transfer
methods. Darwiche, N. (PL). Supported by URB Combined retinoic acid and arsenic treatment of adult
T-Cell leukemic (ATL) cells: Effects on cell cycle control and apoptosis
Regulation of neoplastic keratinocyte proliferation and cell cycle control by
retinoid receptors Adult T-cell leukemia (ATL) is an aggressive peripheral
T-cell neoplasm caused by human T-cell leukemia virus type I (HTLV-I).
Multiple chemotherapy combinations are used for the treatment of ATL
patients. Unfortunately, the results are disappointing with a mean
survival time of less than 8 months, mainly due to acquired resistance.
We will investigate the effects of retinoic acid (RA) and arsenic (As) on
different cellular parameters, namely cytotoxicity, proliferation, cell cycle
analysis, and apoptosis. If RA and As combination treatment results in
the induction of apoptosis in ATL derived cells, we will also study the
induction of the different apoptotic pathways and their relationship to
retinoid receptor signaling. We will determine the retinoid receptor
profile in RA and As treated cells in an attempt to understand whether the
different treatments enhance retinoid responsiveness in these cells. Darwiche,
N. (PL), A. Bazarbachi, and M. El-Sabban. Supported by URB and LNCSR Effect of ultraviolet irradiation on retinoid receptors
expression in primary keratinocytes and modulation by retinoic acid Retinoic acid (RA) is an essential regulator of cell
growth and differentiation in mammalian skin. It exerts its effects by
activating two families of nuclear receptors, namely, the retinoic acid
receptors (RARs) and the retinoid X receptors (RXRs). Alterations in
nuclear retinoid receptors are observed in many types of cancer.
Ultraviolet (UV) irradiation is known to be the chief cause of premature
photoaging and skin cancer. In a recent study on human skin, UV
irradiation caused a significant reduction in expression and function of
epidermal RARs and RXRs. Interestingly, RA pretreatment of skin could
partially protect against this loss of retinoid receptors. We aim to
investigate the deleterious effects of UV on the retinoid signaling pathways
and its possible prevention by RA pretreatment in primary mouse
keratinocytes. In addition, we will test the effects of different RA
derivatives on UV-induced retinoid signaling damage that may contribute to
skin premature aging and carcinogenesis.
Darwiche, N. (PL), and H. Bazzi. Completed or in progress at AUB Regulation of neoplastic keratinocyte proliferation and
cell cycle control by retinoid receptors Retinoids are essential for normal epidermal cell growth
and differentiation. They are widely used in the prevention, as well as
treatment, of several skin disorders and cancers in humans. Most of the
effects of retinoids are mediated by two families of nuclear retinoid
receptors RARs and RXRs, each consisting of the receptor types alpha, beta,
and gamma. Our studies indicate that retinoic acid receptors RARalpha
and RARgamma are lost during skin tumor progression. Furthermore,
during transformation, decreased expression of RARalpha is closely linked to
malignant conversion of skin tumors. Using combined in vitro and in vivo
strategies, we will explore the relationship between RARs and neoplastic
keratinocyte proliferation and cell cycle regulation. This will include
the use of RAR and RXR selective ligands and retroviral constructs, harboring
normal RARalpha, RARgamma, and RAR dominant-negative mutants. Darwiche, N.
(PL), and I. F. Durr. Supported by Terry Fox Cancer Research Funds, Diana Tamari
Sabbagh Fund, AUB Medical Practice Plan, and URB Overexpression of retinoic acid receptors alpha and
gamma in neoplastic epidermal cells causes retinoic acid-induced growth
arrest and apoptosis Retinoids, essential for normal epidermal differentiation, are used for the prevention and treatment of skin disorders and cancers in humans. Previously we have shown that retinoic acid receptors (RARs) -alpha and -gamma are down-regulated during skin tumor progression. Our primary objective is to investigate the roles that RARalpha and RARgamma play in keratinocyte tumor cell proliferation. Through retroviral gene transduction we overexpressed RARalpha or RARgamma in neoplastic mouse epidermal cells. Following retinoic acid (RA) treatment, RARalpha- and RARgamma-transduced cell lines exhibit a progressive, dose-dependent growth inhibition relative to the control LXSN cell lines. Chromatin condensation, PARP cleavage, and a late upregulation and apparent cleavage of the squamous differentiation marker PKCeta are observed in both RARalpha- and RARgamma-transduced cells. These results suggest that RARalpha and RARgamma enhance growth suppression and apoptosis of neoplastic epidermal keratinocytes. We showed that this growth inhibitory effect of both retinoid receptors in neoplastic keratinocytes may be achieved through distinct as well as overlapping mechanisms of cell cycle control. Submitted for publication. Darwiche, N. (PL), E. Hatoum, M. El-Sabban, J. Khoury, and S. H. Yuspa. Supported by Terry Fox Cancer Research Funds, Diana Tamari
Sabbagh Fund, AUB Medical Practice Plan, and URB Effect of extracellular matrix and lactational hormones
on the expression of gap junction proteins in a mammary epithelial cell
strain (CID-9): Relation to functional differentiation In continuation of our work from a previous URB grant, we
are studying the regulation of expression of gap junctional proteins
(connexins, Cx) in mammary epithelial cells under a different extracellular
matrix (ECM) and hormonal conditions. For that purpose, we have
established the culture conditions of a functional mammary epithelial cell
strain, CID-9, responsive both to matrix and lactational hormones. We
have shown that this cell strain mimics in vivo mammary morphology and
function under proper hormonal and ECM conditions. Furthermore we have
established immuno-staining techniques for Cx 26, 32, and 43, and have
initiated efforts for detection of mRNA transcripts by RT-PCR and northern
blot analysis. The preliminary data suggest that function of gap junctional
proteins is regulated by matrix and hormones. Further studies are
needed to confirm our preliminary observations and to show a cause and effect
relationship between differentiation of mammary epithelial cells and
modulation of gap junctions. Gaining insight into the regulation of gap
junctions and how they relate to cell differentiation will allow us to
address future questions relating to the role that gap junctions play in the
processes of cell transformation. El-Sabban, M. Supported by URB The effect of heterocellular communication, via gap
junction proteins, on mammary epithelial cell differentiation In this project, we propose to study the regulation of gap
junction proteins (connexins) in mammary epithelial cells. The effect
of hetero-cellular communication on expression of connexins and assembly of
functional "Gap Junction Intracellular Communication" (GJIC) will
be assessed. For that purpose, a mammary epithelial cell strain responsive
both to matrix and lactational hormones will be used. This cell strain,
known as CID-9, mimics in vivo mammary function and morphology under proper
hormonal and ECM conditions. It is composed of multiple cell types,
namely epithelial cells, fibroblast, and myoepithelial cells. In this
proposal, and based on previous data, we will attempt to define what cell
type expresses the gap junction proteins, and under what culture
conditions. Gaining insight into the regulation of gap junctions and
how they relate to cell differentiation will allow us to address questions in
the future relating to the role that gap junctions play in the processes of
cell transformation. El-Sabban, M. Supported by URB 2000-2001-1. Molecular mechanisms of colon cancer
chemoprevention by gallotannins The main goal of our study is to identify potential
phytochemicals that can inhibit colon carcinogenesis and, in turn, elucidate
their mechanism(s) of action at the cellular and molecular levels. We have
recently shown that naturally occurring gallotannin (GT) is a potent
chemopreventive agent against 1,2-dimethylhydrazine (DMH)-induced colon
cancer in Balb/c mice. In this project, will study the effect of GT on cell
cycle and molecules that are involved in the signal transudation pathway of
cell growth, such as RAS, JNK, and MAPK. We will also investigate the
effect of GT on biomarkers of apoptosis, such as members of the Bcl-2 family
of proteins. Elucidating the mechanism(s) of action of GT will provide
insights into the potential use of this drug as a natural chemopreventive
agent against colon cancer.
Gali-Muhtasib, H. (PL). Supported by Third World Academy of Science (TWAS)
Research Grants, Trieste, Italy Inhibitory effect of plant tannins on
colon cancer cell lines
We have recently studied the ability of a hydrolyzable
tannin, gallotannin (GT), and a condensed tannin, red alder (RA) bark
extract, to inhibit 1,2-dimethylhydrazine (DMH)-induced colonic aberrant
crypt foci (ACF) and tumors in Balb-c mice. The multiplicity, size and
distribution of ACF, and tumors were significantly inhibited by both tannins,
even when these compounds were administered for only two weeks prior to a
24-week treatment with the carcinogen DMH. The most effective treatments at
inhibiting colon cancer included GT given by gavage, RA bark extract injected
i.p., and either tannin dissolved in drinking water, suggesting a potential
role for these drugs as preventive agents against colon cancer. This project
aims at determining the cellular and molecular mechanisms by which tannins
exert their cancer preventive effects using human colon cancer cell lines. To
achieve this goal, the effects of tannins on the growth and proliferation of
cancer cell lines and their ability to induce apoptosis, affect cell cycle
phase distribution, and modulate connexin expression will be investigated.
Gali-Muhtasib, H. (PL), and M. El-Sabban. Supported by URB and AUB Medical Practice Plan Quinoxaline 1,4-di-N-oxides as
anticancer and hypoxia-selective drugs
A problem that confronts clinicians in the treatment of
cancer is the resistance of hypoxic tumors to chemotherapy and radiation
therapy. Thus, the development of new drugs that are selectively toxic to
hypoxic cells found in solid tumors is an important objective for effective
anticancer chemotherapy. We have recently shown that the heterocyclic
aromatic N-oxides, quinoxaline 1,4-dioxides (QdNOs), are cytotoxic to tumor
cells cultured under hypoxia. In this study, we will evaluate the
hypoxia-selective toxicity of four differently-substituted quinoxaline
1,4-dioxides (QdNOs) and determine their effect on the expression of the
hypoxia inducible factor-1alpha (HIF-1alpha) in the human colon cancer cell
line (T-84). Gali-Muhtasib, H. (PL), M. Haddadin, and M. Diab-Assaf. Supported by LNCSR Effect of Awassi sheep mammary derived oMDGF-1 and
oMDGF-2 on mammary epithelial cell differentiation Developmental regulation of growth-promoting activities in mammary secretions of pregnant Awassi ewes was defined, and growth factors contained in these secretions were partially purified and characterized. Mammary secretions from pregnant ewes enhanced fibroblast cell (AKR-2B) and mammary cell (CID-9) proliferation to levels comparable to those induced by 100% fetal calf serum. Major milk proteins in mammary secretions collected from pregnant ewes from one month prior to lambing up to one week after lambing were resolved by SDS-PAGE while gelatinases were resolved by zymography. Gelatinase activity was noted prior to P134 and decreased thereafter to reach a minimum during lactation. This decrease was concomitant with the onset of casein production. It is during this critical developmental period that highest growth-promoting activity in mammary secretions was detected.
Isolation and preliminary characterization of new
temperature-sensitive (Ts) ftsZ alleles in Escherichia coli Mutant strains of Escherichia coli defective in their
ability to divide at the non-permissive temperature of 42’ͺC will be isolated
using P1-mediated localized mutagenesis. Genes in the division and cell wall
synthesis cluster (dcw) at 2 minutes on the physical map of the E. coli
chromosome will be targeted with the aim of isolating temperature-sensitive
mutations in the cell division gene ftsZ that encodes the essential cell
division protein FtsZ, the initiator of cell division. Confirmation of the
success of the localized mutagenesis will be carried out using
plasmid-mediated complementation of the newly-isolated strains. The
availability of the new ftsZ(Ts) alleles will allow us to test for potential
interactions between FtsZ and other Fts (division proteins) using
plasmid-mediated suppression. An exciting, long-term outcome of this genetic
approach is the mapping of sites within FtsZ that are interactive with other
division proteins in a manner that is essential for Z-ring formation and
function. Khattar, M. (PL). Supported by URB Survey of the flower-head infesting fruit flies
(Tephritidae) on Asteraceae plants in Lebanon A survey of the flower-head infesting tephritids associated with thistles in Lebanon was started in 1995. Out of 23 thistle species belonging to the Asteraceae, 19 yielded fruit flies. The reared fruit flies belonged to 18 species, 16 of which are reported for the first time to occur in Lebanon. Ten new and unusual host records for those paleartic tephritids are also reported for the first time. Knio, K. (PL), S. Kalash, and I. White. Supported by URB Mosquito species of Lebanon Mosquitoes are of great economic importance because they
are vectors for a number of diseases. With the changing environment,
the epidemiology of many vector-borne diseases is also changing. Recent
malaria outbreaks have occured in many countries, where the disease was
thought to have been eradicated. Several Anopheles species have been
unexpectedly found in the neighboring countries of Lebanon. This study
updates and re-evaluates the status of mosquitoes in Lebanon and determines
their distribution and breeding sites. Knio, K. (PL), N. Markarian, A. Kassis,
and N. Nuwayri-Salti. Supported by URB A study of the mechanism underlying
IL-1 beta-induced diarrhea in the rat
Interleukin-1 beta was shown to reduce water absorption
from the rat colon by down-regulating the Na+-K+ pump and stimulating the
NaKCl2 transporter. The involvement of PGE2 in the response is also
investigated. Kreydiyyeh, S. (PL). Supported by URB Effect and mechanism of action of interleukin-1 beta on the Na+-K+ ATPase in inner medullary collecting duct cells We have demonstrated an inibition of the Na+-K+ATPase
by IL-1 beta. The involvement of the MAP kinase pathway and NF-KB
is investigated. Kreydiyyeh, S. (PL). Supported by LNCSR The mechanism underlying the laxative
properties of parsley extract
Parsley extract was shown to reduce water absorption from
the rat colon by inhibiting the Na+-K+ pump and stimulating the NaKCl2
transporter supporting the claimed laxative effect attributed to parsley in
herbal medicine. Kreydiyyeh, S. (PL), J. Usta, I. Kaouk, and R. Al-Sadi. Supported by URB The study of neural immune interactions Supported by LNCSR Effect of organochlorines on function of normal mouse
mammary gland cells (CID-9), normal human breast cell line (MCF-10A) and
human carcinoma breast cell line (MCF-7) Numerous synthetic chemicals released into the environment
and found to persist and travel through the food chain can cause cancers in
laboratory rodents. Many of these chemicals have accumulated in animals and
humans through several routes of exposure. Results of previous research
showed that treatment of female rats with dieldrin had a negative effect on
the number of offspring delivered as well as on their body weight gain.
Histological studies of mammary gland tissue from lactating rats treated with
organochlorines (dieldrin/toxaphene) also showed delayed development, and
necrotic lesions were noted in their livers. The objective of the proposed study is to further investigate the influence of organochlorines (dieldrin/toxaphene) at the culture level on the function of normal mammary cells, such as mouse (CID-9) cell strain, as well as of normal human breast cell line (MCF-10A) and human carcinoma breast cell line (MCF-7). We have designed experiments to determine the effect of the environmental chemicals, dieldrin and toxaphene, on the growth, rate, differentiation, and apoptosis of CID-9, MCF-10A, and MCF-7. All results will be compared with appropriate matching controls. Talhouk, R., and J. Kogan. Supported by LNCSR Bioprospection: An alternative for
sustainable agricultural development in Lebanon
This project aims at identifying and investigating the medicinal/agricultural potential of selected plant species with potential medicinal, bioactive, and/or ornamental value to diversify the national agricultural portfolio and promote sustainable agro-industrial growth in rural communities. It also aims at assessing the market potentials for selected plant species to initiate production of plants with market potential. Talhouk, S. (PL), H. Gali-Muhtasib, R. Talhouk, E. Abou Fakhr, R. Baalbacki, E. Barbour, and others. Supported by Mercy Corps, Lebanon Program Changes in gap junctions of rat granulosa cells maintained
on extracellular matrix In this study we propose to probe the effects of extracellular matrix (ECM), in the form of a reconstituted basement membrane (EHS), on granulose cell (GC) function. The parameters studied include progesterone and cytokine production by RIA and ELISA, respectively, cell morphology, and possible modulation of gap junctional intracellular communication (GJIC). Changes in GJIC will be assessed by scrape loading and microinjection of the fluorescent dye lucifer yellow (LY). Western blotting, immunocytochemistry, and northern blotting will be used for assaying the expression of gap junction protein connexin43 (Cx43), the connexin expressed in GC. Effects of a function blocking integrin antibody and gap junction inhibitors on progesterone production and cell morphology will also be studied. Tarraf, C. (PL), R. Talhouk, and M. El-Sabban. Supported by Third World Academy of Science Expression of gap junction proteins and gap junctional intercellular
communication in rat granulosa cells maintained on extracellular matrix Gap junctions are specialized membrane structures that
connect the plasma membrane of adjacent cells. They may play a role
both in maintaining homeostasis and in exchange of regulatory molecules
involved in normal cellular growth and development. These associations
are thought to be important in follicular development. Soluble
mediators, cell-cell, and cell-extracellular matrix (ECM) interactions
constitute major means of regulating granulosa cell (GC) function.
During development of ovarian follicles, GCs undergo different processes of
proliferation and differentiation accompanied by changes in their
micro-environment. The surrounding basement membrane undergoes remodeling;
the granulosa cell layer becomes vascularized; and there is down-regulation
in the expression of gap junction proteins connexins (Cx) upon
vascularization and basement membrane disruption, suggesting that gap
junctions in GCs are under direct hormonal and ECM regulation. In this
study, we propose to probe the effects of ECM, in the form of a reconstituted
basement membrane (EHS), on the expression of gap junction proteins and
possible modulation of gap junctional intercellular communication. Tarraf, C.
(PL), R. Talhouk, and M. El-Sabban. Supported by AUB |