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Abstracts of Talks
Georges Al Makdessi
Advisor: Dr Malek Tabbal, Physics, FAS.
Development and characterization of a low-pressure
plasma system for surface modification of materials.
Abstract :
Low pressure plasmas (below 1 Torr) are extensively investigated because of their broad range of applications
in high-impact technological fields. For example, such plasmas are used for improving adhesion between
surfaces by enhancing bondability on substrates such as glass or polymers through the control of surface
energies. Oxygen plasmas are among the most attractive for these applications. They are used for surface
cleaning of biomaterials that come in contact with blood or proteins and require special surface treatments to
induce biocompatibility. Oxygen plasmas are also utilized in the growth of oxide materials that play a central
role in the semiconductor and opto-electronic industry. Remote plasma processing allows for the possibility of
oxidizing a material by exposing it to an oxygen reactive species generated by the plasma. A remote plasma is
formed when the excited species of the plasma diffuse and expand at low pressure beyond the plasma volume
thereby making the process scalable and applicable to large surfaces. One of the most important type of species
present in the remote plasmas are the free radicals that have a high chemical reactivity and promote compound
formation at temperatures much lower than those required by purely thermal reactions. In addition, remote
plasmas have a low thermal budget since they induce little heating of the treated material; this factor is very
important because it allows independent control of plasma conditions and substrate temperature. Another
important property of remote plasma processing is that it allows surface specific oxidation of materials.
The aim of this work is to characterize the oxygen plasma generated by a microwave source that is being used
for thin film growth and oxidation. The study consists in evaluating the oxygen atomic density by optical
emission spectroscopy and determining the electron density and electron temperature in the remote plasma
using Langmuir probes.
Tests of oxidation of pure metallic films through thermal treatment in the oxygen remote plasma have also been
performed. A parametric study as a function operating conditions, namely microwave power, flow rate,
chamber pressure, plasma source-substrate distance, and substrate temperature, has been achieved in order to
optimize the oxidation process and correlate it to plasma operating conditions.
Wassim Kassem
Advisor: Dr Malek Tabbal, Physics, FAS.
Pulsed Laser Deposition of Tungsten Thin Films for Magnetic Fusion Applications.
Abstract:
The ASDEX upgrade utilized Tungsten as a first wall material for its plasma facing components in fusion
reactors. Coatings of Tungsten on CFC tiles were done by several techniques and evaluated at the Max-PlanckInstitut für Plasmaphysik. The investigation of these coatings is of prime importance for the efficiency of the
plasma generated inside the reactors and more so for the case of Tungsten, so improvement in the production of
these wall materials is an ongoing process. PLD is one such technique that has yet to be fully tried out.
Thin coatings of Tungsten were deposited on Graphite by ablating a 99.99% Tungsten target using a 20 ns KrF
excimer laser (λ=248nm). Two types of substrates were used. The main body of work so far was done on
substrates fabricated by pre-depositing Graphite on Si(100) substrates. The other substrate used is a Graphite
(CFC) pucks donated by the Max-Planck institute matching specifically those already used in fusion reactors.
The two substrates have different properties in terms of crystalline structure, roughness, thickness, as well as
other physical properties.
The effect of background gas pressure, substrate temperature, laser fluency, and substrate properties is studied
using several techniques including x-ray diffraction, AFM, surface profileometry, and RBS. The key goal is to
assess the quality of the Tungsten thin films in terms of adherence, coverage, and overall quality.
Early results show films ranging in thickness between 360 and 10 nm. A sputtering effect has been detected
during deposition of the thin films due to highly energetic species in the nascent plume hindering film growth.
However, all samples show excellent coverage with a mirror-like finish under the naked eye. Even the very
rough donated CFC substrate with very tall features in the µm range show very good coverage. All samples tested- exhibited a crystal structure of varying quality vis-à-vis deposition conditions.
Maya Saade
Advisor: Dr Elie Barbour, Animal and Veterinary Sciences, FAFS
Optimization of Sperm Separation and Gene Characterization in Animals.
Abstract
In intensive farming systems, there is a desire to control the sex ratio of animals; furthermore, recent trends
emphasize the use of specific marker genes in selection for better animals. The research objectives are to
optimize a flowcytometric method to separate goat male and female spermatozoa, and to standardize different
Polymerase Chain Reaction (PCR) methods to detect genes of selection interest, namely those responsible for
production, immunity and disease resistance. The work was performed on semen of Lebanese local low
production goats and imported high production Saanen goats. Optimization of sperm sexing was done using
flowcytometry using increasing amounts of fluorophore labelling, incubation time, and number of sperm
washings. The PCR was adopted to verify sperm sorting, and to optimize detection protocols for genes of
interest with varying primers concentrations. Successfully amplified αS1-Casein and MHC-class IIDRB were
subjected to restriction endonucleases. Optimized Flowcytometry showed 2 distinct peaks relative to X and Y
spermatozoa at 22.4µM fluorophore concentration, 30 minutes incubation time and 3 times sperm-washing.
Growth Hormone, α-Lactalbumin, αS1-Casein, MHC-classIIDRB, Scrapie prion were successfully amplified at
4µl (5pmol/µl), 1.2µl (100pmol/µl), 0.5µl (100pmol/µl), 4µl (5pmol/µl) and 4µl (5pmol/µl) primers level
respectively. PCR for selected genes revealed similarity between local and imported Saanen sperms, in relation
to amplicons of each of Growth Hormone gene (435.4 and 110bp), α-Lactalbumin (190.5bp), αS1-Casein
(230.6bp) and MHC-classIIDRB (285bp). Various banding patterns were obtained following the endonucleases
activity on amplicons, patterns that could be related in the future to targeted traits for selection. As for the prion
gene, a common 811bp band was obtained in most sperms; the sequencing of the prion amplicon will help in
future selection of goats that are resistant to scrapie disease, causing variant-CJD in humans. In conclusion,
Lebanese local goats showed a genetic potential for selection for the studied traits; however, further trials
should be done to finalize sperm sexing protocols. Future research will target genes responsible for higher
prolificacy in animals.
Dr Hala Gali-Muhtasib, Biology, FAS.
Thymoquinone: a promising plant derived anticancer drug.
Abstract:
There has been growing interest in naturally occurring compounds with anti-cancer potential. Black seed is one
of the most extensively studied plants. This annual herb grows in countries bordering the Mediterranean Sea
and India. Thymoquinone (TQ) is the bioactive constituent of the volatile oil of black seed. It has been shown to
exert anti-neoplastic and anti-inflammatory effects. The molecular pathways of TQ action are not fully
understood. Nevertheless, TQ is known to induce apoptosis by p53-dependent and p53-independent pathways in
cancer cell lines. Growth inhibition is associated with induction of cell cycle arrest. TQ also acts on the immune
system by modulating the levels of inflammatory mediators. To date, the chemotherapeutic potential of TQ in
the clinic has not been tested, but numerous studies have shown its promising anti-cancer effects in animal
models. The combination of TQ with clinically used anti-cancer drugs has led to improvements in their
therapeutic index, and prevents non-tumor tissues from sustaining chemotherapy-induced damage.
Eileen Dergarabetian
Advisor: Dr Hala Gali-Muhtasib, Biology, FAS.
Thymoquinone induces cell death in T cell leukemia through caspase-dependent mechanisms.
Thymoquinone induces cell death in T cell leukemia through caspase-dependent mechanisms.
Abstract:
HTLV-I associated adult T-cell leukemia (ATL) and HTLV-I-negative peripheral T-cell lymphomas are
associated with poor prognosis. Using increasing concentrations of Thymoquinone (TQ); a black seed extract,
we demonstrate inhibition of cell proliferation and induction of apoptosis in HTLV-I transformed and HTLV-I
negative malignant T cells, while normal resting or activated T lymphocytes were resistant. TQ-induced
apoptosis was associated with the dissipation of mitochondrial membrane potential in both HTLV-I negative
and positive malignant T cells and the subsequent release of cytchrome c and decrease in the protein expression
levels of Bcl-2. Such loss of mitochondrial membrane integrity was associated with caspases-3, -8 and -9
activation. Treatment of cells with caspase inhibitors suppressed TQ-induced cell death, suggesting that
caspases are partially involved in cell death mechanisms by TQ. Our data suggest that TQ treatment affects
multiple pathways critical for the survival of HTLV-I positive and negative malignant T cells supporting a
potential role for TQ in the treatment of ATL and HTLV-I-negative T-cell leukemias.
Khaled Ghattass
Advisor: Dr Hala Gali-Muhtasib, Biology, FAS.
Cell death by the quinoxaline dioxide DCQ in human colon cancer cells is enhanced under hypoxia and is
independent of p53 and p21.
Abstract:
The radio sensitizer DCQ has been shown by our group to enhance sensitivity of HCT116 human colon cancer
cells to hypoxia. Here we used HCT116 that are either wildtype for p53 and p21, null for p53 or null for p21 to
understand the role of these genes in cellular response to DCQ under normoxia or hypoxia. DCQ decreased
colony forming ability and viability of all HCT116 cells to a greater extent under hypoxia than normoxia and
the p21-/-cell line was most sensitive. Cells had different HIF-1α responses to hypoxia and/or drug treatment.
Higher DCQ doses induced PreG1-phase increase and apoptosis, however, lower doses caused mitotic
catastrophe. In p53+/+ cells, apoptosis correlated with the increased expression of the pro-apoptotic caspase-2
and inhibition of the pro-survival protein PIDD-C. Exposure of p53+/+ cells to 5 or 10μM DCQ induced single
strand breaks and triggered the activation of the nuclear kinase ATM by phosphorylation at Ser1981 in all
phases of the cell cycle. On the other hand, no drug toxicity to normal FHs74 Int human intestinal cell line was
observed. The ability of DCQ to induce apoptosis independently of p53 or p21 and in more than one colon
cancer cell line makes it an interesting molecule with potential anticancer activities.
Chirine El-Baba
Advisor: Dr Hala Gali-Muhtasib, Biology, FAS.
The sage components linalyl acetate and α-terpeniol enhance cell death through inhibition of nuclear factor
kappa-B signaling.
Abstract:
Linalyl acetate (Ly) and α-terpineol (Te), two monoterpenes derived from Lebanese sage, exhibit synergistic
anti-proliferative effects when combined together through mechanisms that are not fully understood. Here, we
investigated the effect of Ly and Te on the NF-κB signaling pathway in HCT-116 human colon cancer cells.
The drug combination dose-dependently inhibited the proliferation of HCT-116 at non-cytotoxic concentrations.
Treatment with Ly+Te at 0.6mM or 1mM induced 30% and 60% respective increases in the PreG1 population
and the mechanism was found to be due to apoptosis and necrosis. DNA binding assays revealed that Ly and Te
combinations suppressed both basal and TNFα-induced NF-κB activation. The suppression of NF-κB activation
correlated with the inhibition of p65 nuclear translocation and IκBα degradation. Ly and Te combination also
downregulated the expression of NF-κB-regulated antiapoptotic (cIAP1, cIAP2, Bcl-2, Bcl-iixL) and
proliferative (cyclin D1, c-Myc) gene products. Separate treatments and drug combinations significantly
decreased the DNA binding activity of NF-κB as early as 3hrs. Overall, our results indicate that the anticancer
activities of Ly and Te are mediated in part through the suppression of NF-κB activation, suggesting that these
sage components may be used in combination with chemotherapeutic agents to induce apoptosis.
Akram Ghantous
Advisor: Dr Nadine Darwiche, Biology, FAS
Chemopreventive Properties of Parthenolide in Epidermal Carcinogenesis: Role of NF-KB Signaling.
Abstract:
Parthenolide, the major sesquiterpene lactone and bioactive molecule from the medicinal plant feverfew
(Tanacetum parthenium), demonstrates
specificity towards tumor cells and is currently in clinical trials.
It is among the most promising anticancer drugs and the only small molecule, to date, that kills cancer stem
cells while sparing normal ones. We investigated the chemopreventive properties of parthenolide
in skin cancer using an in vitro model of epidermal carcinogenesis.
This model is suited for chemoprevention studies and depicts the multistep process of cancer. Skin cancer
incidence is on the rise, and it has been increasing in Lebanon as evidenced from the American University of
Beirut Medical Center Tumor Registry in 2006.
At low micromolar concentrations, parthenolide selectively inhibited the growth of neoplastic keratinocytes
while sparing normal ones. At these concentrations, promoter-induced cell proliferation was inhibited, and cells
were blocked in the S and G2/M phases. Cyclin proteins were reduced while key differentiation markers were
upregulated. Elevated NF-?B signaling is essential for keratinocyte malignant transformation. Importantly,
parthenolide prevented promoter-induced anchorage-independent growth, a hallmark of transformation, and
inhibited promoter-induced NF-?B DNA binding and transcriptional activities.
Our studies highlight chemopreventive and therapeutic properties of parthenolide in skin cancer. Since tumor
promotion is epigenetically regulated, we are currently testing for the ability of parthenolide to epigenetically
inhibit epidermal carcinogenesis by modulating NF-?B target genes.
Gilbert Rahme
Advisor: Dr Rabih Talhouk, Biology, FAS
Connexin-43 Expression Reduces the Tumor Phenotype of Breast Adenocarcinoma Cell Lines in a Pathway
Dependent on β-Catenin Signaling.
.
Abstract:
Gap junction intercellular communication (GJIC) is crucial for tissue homeostasis, differentiation and
development. Connexins (Cx), the gap junction proteins, are tumor suppressors, and Cx43 expression is often
down regulated in breast tumors. Furthermore, Cx43, among others, regulates mammary tissue differentiation.
We sought to study the effect of exogenous Cx43 fused to eGFP in the construct P-eGFP-N1 when transfected
into the human breast adenocarcinoma cells, MDA-MB-231 cells, exhibiting a high invasive phenotype, and
MCF-7 cells, exhibiting a less invasive phenotype. MCF-7 cells transfected with Cx43-eGFP showed a 56%
decrease in total cell number by day 6 in culture, when grown in 2D on plastic, in comparison to a sham
transfected (empty plasmid), and to untransfected cells which showed comparable total cell numbers. Similarly,
MCF-7 Cx43 transfected cells showed an 80% reduction in total cell number at day 8 when grown in 3D
cultures (on reconstituted basement membrane), and demonstrated a significantly higher amount of small sized
spherical clusters. Exogenous Cx43-eGFP expression decreased the extravasative ability and cellular motility of
MCF-7 cells by 60% and 70% respectively. On the other hand, MDA-MB-231 cells did not show any difference
in total cell number when grown in 2D cultures on plastic, but exhibited a 35% reduction in proliferation when
grown in 3D cultures. Remarkably, MDA-MB-231 cells showed stellate growth cluster morphology in 3D. This
phenotype was decreased by 20% in cells transfected with exogenous Cx43-eGFP, and showed spherical
clusters instead of stellate ones. The association of Cx43-eGFP with α-,β-catenin and ZO-2 was noted in MCF-7
cells in both 2D and 3D cultures, in contrast to no complex assembly in MDA-MB-231 cells in 2D cultures.
Interestingly, nuclear levels of β-catenin were shown to decrease in 2D and 3D cultures of MCF-7 cells in
conjunction with gap junction assembly and tumor suppression, in contrast to decreased nuclear β-catenin only
in 3D cultures of MDA-MB-231 cells, where tumor suppressive effects are only noted. This comparative study
suggested that the assembly of the gap junction complex with α-,β-catenin and ZO-2 may be partly involved in
reduced growth rate, invasiveness, and change in morphology of MCF-7 in 2D and 3D cultures, and MDA-MB231 cells in 3D cultures. In conclusion, and in addition to having a crucial role in mammary differentiation
(Talhouk et al. 2008), the assembly of the GJ complex could possibly have a role in reverting mammary
tumorigenesis, to a state of partial re-differentiation. Lastly, 3D studies suggest that Cx43 expression exerts a
context dependent effect, particularly in the higher invasive cell line, MDA-MB-231. Moreover, our laboratory
has initiated a study aiming to elucidate the significance of Cx43 gap junction complexes, particularly with βcatenin, in maintaining the “normal” phenotype of MCF-10A cells.
Hassan Yassine
Advisor: Dr Mike Osta, Biology, FAS
Two C-Type Lectins Cooperate to Defend Anopheles Gambiae Against Gram-Negative Bacteria.
Abstract:
Insect C-type lectins (CTLs) have been shown to mediate immune effector responses in vitro, however, the
relative contribution of these CTLs to immune defenses in vivo is still poorly understood. Here, we report that
two C-type lectin-like molecules, CTL4 and CTLMA2, which were shown previously to inhibit Plasmodium
berghei ookinete melanization in the malaria vector Anopheles gambiae, are required for the clearance of
Escherichia coli, but not Staphylococcus aureus, from adult female mosquitoes. Silencing either CTL by RNA
interference dramatically reduces mosquito survival to Gram-negative but not to Gram-positive bacterial
infections, suggesting a role in defense against Gram-negative bacteria. Further, molecular characterization
reveals that both CTLs are secreted into the mosquito hemolymph mainly in the form of a disulfide-linked
heterodimer. This association explains the similar roles of these CTLs in bacterial defense as well as in the
melanization response to P. berghei ookinetes. Apparently, CTL4 and CTLMA2 serve pleiotropic functions in
the innate immune response of A. gambiae.
Myriam Khawand
Advisor: Dr Colin Smith, Biology, FAS
The Microbial Biodiversity of Jeita Grotto: A Unique Lebanese Habitat.
Abstract:
Subterranean microbial ecologies are important and poorly understood. The identification and characterization
of microbes in these ecologies are interesting because they reside in starved environments with no sunlight and
limited organic input. They participate in elemental cycles, including the carbon cycle, and they pass to drinking
water. The most accessible subterranean habitats are caves, yet very few have been studied worldwide, and
none have been described in Lebanon. This study aims to identify the diverse bacteria residing in Jeita Grotto at
two different seasons: high flow during spring and low flow in autumn. 16S rDNA analysis identified bacteria
belonging to the phyla Proteobacteria, Bacteroidetes, Actinobacteria, and Acidobacteria. Of these,
Proteobacteria is the most abundant phylum with Beta Proteobacteria most common. Preliminary results suggest
the presence of a complex metabolic network consisting of heterotrophs, such as Flavobacteria and
Acidobacteria, and chemoautotrophs, such as Variovorax sp. and nitrite-oxidizing bacteria. That heterotrophs
outnumber the autotrophs suggests that there is organic input. The identification of five coliform bacteria
suggests sewage could be a source of organic input.
Mohamed Bilal Fares
Advisor: Dr Rabih Talhouk, Biology, FAS
An Anti-Inflammatory Component in the Popular Folk Medicinal Plant Chamomile Exhibits Parthenolide
Analogous Anti-Proliferative Activities and Predicted Binding.
Abstract:
A Lebanese endemic plant commonly known as “Chamomile”, has been a popular folk medicinal remedy for
centuries, having various claimed therapeutic effects. Using bioactive guided fractionation and spectroscopic
techniques, an anti-inflammatory agent in the water extract of the plant, that is capable of suppressing IL-6
production by endotoxin treated SCp2 mammary epithelial cells, was identified by our lab. The structure of the
identified molecule “K100” appeared to be analogous to that of parthenolide (PT), the major sesquiterpene
lactone extracted from the plant Tanacetum parthenium (feverfew), which has been extensively studied and
reported to be capable of inhibiting the proliferation of several cancerous cell lines. Interestingly, recent
literature reports have shown that di-methyl-amino-parthenolide (DMAPT), a more soluble PT analogue, has
similar effects to those of PT in vitro as well as in vivo and is currently under clinical trials. Molecular docking
in silico of K100, DMAPT and Salograviolide A (a sesquiterpene lactone isolated by our lab from the plant
Centaurea ainetensis) against 10 known target proteins of PT, predicted that K100 can bind to all tested targets
at similar positions as PT, and that its affinity of binding is either higher than that of PT or second best to it. In
vitro, K100 showed less cytotoxicity than PT, and inhibited the growth of two mammary epithelial tumor cell
lines (MDA-MB-231 and MCF-7) in a dose dependent manner, at concentrations tolerable by the normal human
mammary epithelial cell line MCF10-A. Moreover, when compared to PT, K100 exhibited a larger difference
between concentrations affecting cancerous but not normal cells.
Ola El Zein
Advisor: Dr Sawsan Kreydiyyeh, Biology, FAS
Pine Bark Extract inhibits glucose uptake by down regulating SGLT1 and GLUT2
Abstract:
Diabetes is considered one of the chronic metabolic disorders that continue to present a major worldwide health
problem. Folk medicine relies significantly on some plants in the treatment of diabetes and mainly on the
presence therein of some active ingredients. Pine bark extract (PBE) has been claimed to have various beneficial
and therapeutic effects including hypoglycemic effects. The aim of this work was to investigate the effect of PBE
on intestinal glucose uptake using Caco-2 cells as a model and [14C] 3-O-methyl-D-glucose as a tracer.
Differentiated Caco-2 cells were starved overnight and treated next day with an ethanolic extract of the bark of
Pinus pinea (PBE) and the change in radioactivity of the incubation medium was taken as a measure of glucose
uptake. The extract reduced significantly glucose uptake, an effect that may be due to a decrease in the activity
and/or the number of glucose transporters present in the brush border membrane. Western blot analysis of a crude
membrane fraction confirmed the suspected decrease in the number of both Sodium-dependent Glucose
Transporter 1 (SGLT1) and Facilitated-Diffusion Glucose Transporter 2 (GLUT2) transporters. To determine the
mechanism of action of the extract, different signaling mediators known to be involved in glucose transport were
inactivated by specific inhibitors. The results showed that PBE activates SGLT1 transporters by activating p38
Mitogen-activated protein (MAP) kinase. SGLT, in turn, modulates the activity of two different pathways that
target GLUT2: a stimulatory one involving MAP/Extracellular signal-regulated kinase and an inhibitory one
involving Phosphatidylinositol-3 kinase. Supported by URB.
Dr Antoine Ghauch, Chemistry, FAS
Reaction of Pharmaceuticals with Micrometric Iron Particles (MIP) and Amended MIP: Application to
Diclofenac (Voltaren’s Active Ingredient)
Abstract:
The elimination of Voltaren’s active ingredient diclofenac (DF) from water by micrometric iron particles (MIP)
and amended MIP (AMIP) under oxic and anoxic conditions was investigated. Tested catalysts were Pd, Ni, Cu,
Sn, Ir, Co plated on the surface of MIP in bimetallic and trimetallic systems. Results confirmed the superiority
of plated iron particles for aqueous DF removal. Among tested catalysts Pd was the most efficient in increasing
DF removal rate followed by Cu and Ni either in bimetallic (PdFe, NiFe, CuFe) or trimetallic (PdNiFe, NiPdFe,
PdCuFe, CuPdFe) systems. Anoxic degradation experiments undertaken with PdFe, IrFe (bimetallics) and all
trimetallics clearly showed DF transformation products. Under oxic conditions, those were only observed in the
CuPdFe trimetallic system. This was ascribed to the plating order of transition metals on the surface of iron
particles and consequently to the formation of iron corrosion products (ICP) changing the physicochemical
properties of catalyst’s surface thereby enhancing the removal rate. Rapid DF elimination was mainly attributed
to the capacity of metallic catalysts to corrode faster iron atoms then collecting more atomic hydrogen within
the iron oxide film. This promoted catalytic hydrodehalogenation especially for systems showing
transformation products. However, absence of transformation product intended DF removal via adsorption,
sequestration or co-precipitation within in-situ formed ICP.
Raghida Bou Zerdan
Advisor: Dr makhlouf Haddadin, Chemistry, FAS
Synthesis of novel quinnolines, quinolino[2,3-c]cinnolines, and indoloquinolines.
Abstract:
Functionalized quinolines and their hetero-fused analogues represent an important class of organic molecules
that have attracted a great deal of attention from organic as well as medicinal chemists, because of the wide
spectrum of physiological activities displayed by these compounds. Among the various routes available for the
synthesis of functionalized quinolines is the “Friedländer reaction”, an extension of which involves a reaction
between o-amino arylcarbaldehydes and o-nitroaryl acetonitriles, and which is employed by this work for the
synthesis of a number of unknown 3-(2-nitrophenyl)quinolin-2-amines. The cycloannulation of substituted 2aminoquinolines affords the corresponding quinolino[2,3-c]cinnoline 5-oxide, which upon deoxygenation
yielded the corresponding quinolino[2,3-c]cinnoline, both heterocycles are unknown in the literature. Reduction
of the substituted 2-aminoquinolines was attempted in the context of a new approach for the preparation of the
naturally occurring and biologically active 6H-indolo [2,3-b]quinoline through ring-cyclization of the
corresponding unidentified 3-(2-amino-phenyl)-quinolin-2-amine. Methylation of the 6H-indolo [2,3b]quinoline leads to neocreptolepine derivatives some of which had been shown to be active against malaria and
cancer.
Tharallah Shoker
Advisor: Dr Makhlouf Haddadin, Chemistry, FAS
Synthesis and reactions of Some Quinoxalines and Quinoxalinocinnoline 5-oxides
Abstract:
It is well-documented that nitrogen-containing heterocycles possess various pharmacological activities and
there is a growing interest in preparing such novel compounds.
In this work, the synthesis of the unknown 2-Amino-3-(2-nitrophenyl)quinoxaline derivatives from
benzofurazan oxide (BFO) derivatives and 2-nitrobenzylcyanide will be illustrated (Beirut Reaction).
Furthermore, the treatment of the former with hot methanolic base resulted in an intramolecular cyclization led
to quinoxalinocinnoline 5-N-oxide.
However, the attempt to cyclize 6(7)-methyl-2-Amino-3-(2-nitrophenyl) quinoxaline and 2-Amino-3-(5-methyl2-nitrophenyl) quinoxaline resulted in an interesting result which illustrated the ability to activate these benzylic
methyl groups.
This activation resulted in products which involved an unprecedented nucleophilic attack of a methoxy anion,
on the
benzylic carbon of these methyl groups.
Fadi Jradi
Advisor: Dr Bilal Kaafarani, Chemistry, FAS
Synthesis and investigation of a library of pyrene derivatives as potential cationic sensors.
Abstract:
Abstracts of Posters
p21Waf1/Cip1 antagonizes apoptosis and causes senescence in response to Gallotannin in human colon cancer cells
Racha Al-Halabi, Hind Zahr, Aida Habib, and Hala Gali-Muhtasib
Departments of Biology and Biochemistry.
Abstract:
The polyphenolic hydrolysable tannin, Gallotannin (GT), is known to possess anti-carcinogenic properties
against colon cancer. Our recent findings indicate that GT significantly decreases the growth of human colon
cancer xenografts in NOD/SCID mice and this anti-tumor activity may be mediated in part through the
suppression of the NF-ĸB activation pathway (unpublished data). In this study, we show that GT causes S-phase
arrest in human colon cancer HCT116 p21+/+cells and significant apoptosis in HCT116 p21-/- cells. GT
induced senescence in HCT116 p21+/+ and not in HCT116 p21-/- cells. The colony forming ability of both cell
lines was significantly decreased by GT. Apoptosis in HCT116 p21-/- cells was shown to be independent of
p53 and Puma. The DNA damage sensor and checkpoint kinase ATM was activated in both cell lines in
response to GT, although more so in p21-/- cells. Transfection of HCT116 p21-/- cells with the p21 plasmid
rescued the cells from apoptosis and induced S-phase arrest upon GT treatment. The fact that the GT-induced
cell cycle arrest is not reversible makes it an interesting anticancer drug. Our results suggest that GT may be
used for colon cancers that harbor p53 mutations and in which the expression of the p21 protein is low.
Anti-Cancer and Chemopreventive Properties of Sesquiterpene Lactones, Isolated from Indigenous Lebanese
plants, in Epidermal Carcinogenesis
Melody Saikali, Akram Ghantous, Najat Saliba, and Nadine Darwiche.
Departments of Biology and Chemisrty.
Abstract:
Most cancers are of epithelial origin of which skin cancer is the most frequent. Numerous naturally occurring
compounds have been identified as skin chemopreventive agents, and many of the best-selling anticancer drugs
are plant-derived. While screening for anti-cancer activities of Middle Eastern plant extracts used in folk
medicine, we identified the Lebanese indigenous plants, Centaurea ainetensis and Achillea falcata, to possess
potent and selective activities against skin cancer cells. Bioassay-guided fractionation of these plants’ crude
extracts led to the isolation of the sesquiterpene lactones, Salogravolide A (Sal A) from Centaurea ainetensis
and 3-β-methoxy-iso-seco-tanapartholide (β-tan) from Achillea falcata.
Using well established in vitro models of human and mouse epidermal carcinogenesis, we have shown that
purified sesquiterpene lactones preferentially inhibited the proliferation of papilloma and malignant skin cells
without affecting the growth of normal cells. Sal-A caused G0/G1 arrest and reduced cyclin D1 proteins while βtan induced G2/M arrest and decreased cyclin B1 proteins. Furthermore, both Sal A and β-tan, at concentrations
not toxic to primary keratinocytes, show promising anti-promoting properties and inhibit promoter-induced cell
proliferation and anchorage-independent growth in soft agar. These results highlight the potential
chemopreventive and therapeutic properties of Sal A and β-tan in skin cancer. We are currently in the phase of
testing their chemopreventive properties using an established in vivo mouse epidermal carcinogenesis model.
Aqueous removal of diclofenac by plated elemental iron: bimetallic systems.
Hala Abou Assi, Habib Baydoun and Antoine Ghauch.
Department of Chemistry.
Abstract:
The aqueous removal of diclofenac (DF) by micrometric iron particles (Fe0) and amended Fe0 (Me 0 ( Fe 0 )) under
oxic and anoxic conditions was investigated. Bimetallic systems were obtained by plating the surface of Fe with
Co, Cu, Ir, Ni, Pd and Sn. Experimental results confirmed the superiority of (Me 0 ( Fe 0 )) for DF removal except
for IrFe (oxic) and SnFe (anoxic). Under anoxic conditions, Pd was by far the most efficient plating element
followed by Ir, Ni, Cu, Co and Sn. However, under oxic conditions, Pd and Cu showed almost the same
efficiency in removing DF followed by Ni, Co, Sn and Ir. Oxidative and reductive DF transformation products
were identified under oxic and anoxic conditions respectively. In some systems (e.g. CoFe and SnFe
oxic/anoxic; PdFe oxic; NiFe anoxic), no transformation product could be detected. This was ascribed to the
nature of the plating element and its impact on the process of the formation of metal corrosion products
(MCPs). MCPs are known for their high potential to strongly adsorb, bond, sequestrate and enmesh both the
original contaminant and its reaction products. Obtained results corroborate the universal validity of the view,
that aqueous contaminants are basically removed by adsorption and co-precipitation.
Keywords: Diclofenac, emerging contaminants, Fe0/H2O systems, bimetallics, HPLC/MS.
Advanced Oxidation Processes: Catalytic Use of ZVI Powder for the Degradation of Carbamazepine in the
Presence of Hydrogen Peroxide at Low Sonication Frequency. Habib Baydoun, Hala Abou Assi and Antoine
Ghauch.
Department of Chemistry.
Abstract:
The Fe0-assisted ultrasonic/hydrogen peroxide (Fe0-US/H2O2) process for the oxidation of persistent antieliptic
carbamazepine (CBZ) was studied in the aim to develop an improved Fenton’s process more efficient for the
treatment of non-halogenated pharmaceuticals in water. H2O2 is a powerful oxidant to degrade CBZ at low US
frequency (40 kHz), room temperature and moderate pH in the presence of small amount of zero valent iron
(ZVI) powder as Fe2+ catalyst precursor. Almost com
2O2 additive. Many factors are found to be
influencing CBZ elimination (e.g. pH, iron load, US power, H2O2 and MeOH content). There is no CBZ
degradation in alkaline solution and in the presence of MeOH as hydroxyl radical scavenger even under acidic
conditions. The degradation process yields the formation of CBZ hydroxylated intermediates most of them
identified by LC/MS. As the treatment goes forward, intermediates disappeared as well toward probable full
mineralization. Results showed that such technique should also be effective in removing other pharmaceuticals
under moderate experimental conditions.
Keywords: Carbamazepine, sonication, H2O2, zero valent iron
Highly Porous Cobalt Ferrite Aerogels: Efficient Catalysts for the Hydrolysis of 4-nitrophenyl phosphate.
Joelle Akl, Tarek Ghaddar, Aline Ghanem, and Houssam El-Rassy.
Department of Chemistry.
Abstract:
Cobalt ferrite aerogels were synthesized for the first time by sol-gel processing of cobalt and iron salts solutions
with propylene oxide, followed by a supercritical carbon dioxide drying at low temperature. Aerogels are
known to be low density and high porosity sol-gel solid materials consisting of nanoparticle building blocks
networked together. The prepared cobalt ferrite aerogels show a porous structure with a surface area exceeding
550 m2/g and a very high porosity and low density. The chemical nature of these solids was confirmed by
infrared spectroscopy and their crystalline structure by x-ray diffraction. The as-prepared cobalt ferrite XRD
pattern did not show any diffraction peak reflecting the amorphous nature of these aerogels. Heat treating these
aerogels at different temperatures up to 800oC revealed a change in their crystalline nature without affecting
their chemical nature. In the other hand, increasing the temperature improved the
Discrimination of Viable and Dead Fecal Enterococcus Bacteria in Recreational Waters Using Quantitative
PCR with Propidium Monoazide.
Khaled Salam, and Pascal E. Saikaly.
Department of Civil and Environmental Engineering.
Abstract:
The contamination of marine recreational waters with fecal matter due to the discharge of untreated wastewater
is a major environmental and public health problem, present mainly in developing countries, causing the spread
of waterborne diseases among recreational water users. Real-time PCR is an important DNA-based quantitative
method for monitoring the microbiological quality of marine recreation waters. However, real-time PCR does
differentiate between the DNA of viable and dead cells in marine waters, producing false-positive results and an
overestimation of the potential health risk. In 2006, Nocker et al. integrated propidium monoazide (PMA) with
real-time PCR for the detection and quantification of viable bacterial cells. PMA is a live/dead discriminating
dye that selectively enters the comprised membranes of dead cells and intercalates in the DNA. Upon exposure
to the blue light of LEDs, PMA covalently binds to the DNA of dead cells and the modified DNA can no longer
be detected nor amplified by real-time PCR. The aim of our study is to optimize PMA treatment to achieve an
efficient discrimination of 11 to 15 Ct cycles between viable and dead Enterococcus cells. Three parameters in
PMA treatment were optimized: PMA concentration and incubation period and light exposure period. A signal
reduction of 13 cycles was achieved for a PMA concentration and incubation period of 15 µM and 5 minutes
respectively and a light exposure period of 30 minutes. The optimization of PMA treatment showed the
potential of the PMA-QPCR method in accurately assessing the water quality in marine recreational waters.
Arsenic trioxide and interferon-a synergize to inhibit proliferation and induce apoptosis in chronic myeloid
leukemia cell lines.
Jessica Saliba, Ahmad Iskandarani, Ahmad Kurdi, Hugues de Thé, Ali Bazarbachi, and Rihab Nasr.
Department of Internal Medicine.
Abstract:
Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative disorder resulting from the neoplastic
transformation of a hematopoietic stem cell. Pathogenesis of CML usually involves the Philadelphia
chromosome
(Ph) generated by a reciprocal translocation that fuses the Abelson kinase gene (ABL) with the breakpoint
cluster region (BCR) gene that results in BCR-ABL fusion gene which encodes a constitutively active tyrosine
kinase. BCR-ABL activates multiple signal transduction cascades that enhance cell survival and proliferation.
The specific BCR-ABL tyrosine kinase inhibitor, imatinib, is currently the standard of care in the treatment of
CML patients. Imatinib induces a high rate of complete hematological and cytogenetic responses. However,
imatinib is not curative since most patients who discontinue therapy will rapidly relapse. Interferon alpha (IFN)
alone induces hematologic and cytogenetic remissions in a small percentage of CML patients and interestingly,
prior exposure to IFN allowed imatinib discontinuation in CML patients who achieved long-term complete
molecular response.
Arsenic trioxide was previously shown to exhibit inhibitory effect on proliferation of BCR-ABL-expressing
cells. Since both arsenic and IFN were reported to inhibit CML cell proliferation, we have investigated the
effects of the combination of arsenic and IFN on cell proliferation and apoptosis in CML-derived cell lines. We
found that IFN alone had minimal effect on the three tested CML cell lines.
Arsenic alone significantly decreased their proliferation in a time and dose-dependent manner. Interestingly, the
addition of IFN to arsenic was synergistic in one CML cell line (AR230) at any time and dose used and additive
in K562 but not in LAMA. This synergistic effect between IFN and arsenic on the inhibition of CML cells
proliferation