Ala-Eddin Al Moustafa

Publications (31)107.32 Total impact

• Article: Significant toxic role for single-walled carbon nanotubes during normal embryogenesis.

  Dacian Roman, Amber Yasmeen, Matei Mireuta, Ion Stiharu, Ala-Eddin Al Moustafa
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  ABSTRACT: In order to investigate the effect of SWCNTs in the embryo, we examined the outcome of SWCNTs in avian embryo at an early stage of development. We found that SWCNTs-treatment inhibit the angiogenesis of the chorioallantoic membrane (CAM) and in the chicken embryo. Moreover, we showed that SWCNTs can harm the normal development of the embryo since all SWCNTs-exposed embryos are smaller in comparison with their matched controls. We also found that the majority of SWCNTs-exposed embryos die before 12 days of incubation. Macroscopic examination did not reveal any anomalies in these embryos. However, RT-PCR analysis of eleven genes, which are important regulators of cell proliferation, apoptosis, survival and angiogenesis, shows that these genes are deregulated in brain and liver tissues from SWCNTs-treated embryos in comparison with their matched controls. This study suggests that SWCNTs could have a very toxic effect on the normal development of the embryo.
  Nanomedicine: nanotechnology, biology, and medicine 04/2013; · 5.44 Impact Factor
• Article: Does the Syrian population have to wait for the new generation of human papillomaviruses vaccine?

  Ala-Eddin Al Moustafa, Amber Yasmeen, Lina Ghabreau, Nizar Akil
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  ABSTRACT: We recently conducted several studies regarding the presence of high-risk HPVs in human cervical, colorectal and breast cancers in the Syrian population. Herein, we report that high-risk HPVs type 16, 18, 33, 45, 51, 52 and 58 are frequently present in colorectal cancer in this population. Therefore and based on previous studies and present data, we conclude that the most frequent high-risk HPV types, in the Syrian population, are 16, 18, 33, 35, 45, 51, 52 and 58. Thus, our data suggest that it will be useful to use the new generation of HPV vaccine to protect the Syrian population from high-risk HPVs and their associated cancers.
  Human vaccines & immunotherapeutics. 10/2012; 8(12).
• Article: Current tobacco and water-pipe smoking enhance human cancer invasion and metastasis.

  Etienne Mfoumou, Zhang Li, Ala-Eddin Al Moustafa
  International Journal of Cancer 07/2012; · 5.44 Impact Factor
• Article: A new concept to measure cell proliferation using Fourier transform infrared spectroscopy.

  Etienne Mfoumou, Narayanswami Sivakumar, Amber Yasmeen, Ala-Eddin Al Moustafa, Ion Stiharu
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  ABSTRACT: In our laboratory, we recently developed a new technique to measure cell proliferation that is based on infrared spectro-photometry and the density of cell culture medium. The fluid exchange between intra and extra cellular environments is the key to our method. Using this technique, we found that cell proliferation assessment may be performed much faster than presently existing methods, using two separate pieces of equipment (a cell culture incubator and an interferometer). We confirmed the viability of our method using five different cell lines, breast cancer cells (BT20), mouse normal embryonic fibroblast (NEF) as well as those expressing E6/E7 onco-proteins of human papillomavirus (HPV) type 16, and a human cervical cancer cell line (HeLa). Based on our findings, we propose the design of a mini-incubator allowing cell culture as well as infrared spectra collection of the culture medium, as an accessory to the FTIR work bench, which would become a promising arrangement for continuous cell proliferation monitoring. Moreover, the use of the collected culture medium will be highly efficient in terms of reducing both experimental time and cost.
  Medical Hypotheses 05/2012; 79(2):171-3. · 1.39 Impact Factor
• Article: EGF-receptor signaling and epithelial-mesenchymal transition in human carcinomas.

  Ala-Eddin Al Moustafa, Amal Achkhar, Amber Yasmeen
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  ABSTRACT: The epidermal growth factor receptor (EGF-R) signaling pathway maintains a balance between cell proliferation, differentiation and apoptosis, and thus it is believed that EGF-R signaling pathways play an important role in the development and progression of several human carcinomas. Epithelial-mesenchymal transition (EMT) describes the dedifferentiation switch between polarized epithelial cancer cells and contractile and motile mesenchymal (invasive) cells during cancer progression and metastasis. Activation of EGF-R signaling regulates EMT-associated invasion and migration in normal and malignant epithelial cells. In contrast, blocking EGF-R and consequently its pathways, by a monoclonal antibody (mAb) or a tyrosine kinase inhibitor (TKI), inhibit cellular migration and invasion, suggesting an essential role for EGF-R inhibitors in the control of cancer metastasis. The purpose of this review is to summarize current information regarding the role of EGF-R signaling on EMT during human cancer progression and metastasis.
  Frontiers in bioscience (Scholar edition) 01/2012; 4:671-84.
• Source

  Available from: InTech

  Chapter: Brain Metastases Progression of Breast Cancer

  Ala-Eddin Al Moustafa, Amber Yasmeen, Lina Ghabreau, Ali H. Mohamed, Amal Achkhar
  11/2011; , ISBN: 978-953-307-714-7
• Article: Catechol-O-methyltransferase Val 108/158 Met polymorphism and breast cancer risk: a case control study in Syria.

  Bassam Lajin, Abdul Rezzak Hamzeh, Lina Ghabreau, Ali Mohamed, Ala-Eddin Al Moustafa, Amal Alachkar
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  ABSTRACT: BACKGROUND: Catechol-O-methyltransferase (COMT) inactivates catechol estrogens by methylation and thus may play a protective role against mutations induced by estrogen metabolites. In this study we investigated the relationship between the Vall58Met polymorphism in the COMT gene and breast cancer risk in a population-based case control study in Syria. METHODS: We examined 135 breast cancer patients and 107 healthy controls in North Syria to determine the association between the functional genetic Val158Met polymorphism in the COMT gene and female breast cancer risk. RESULTS: There was no significant overall association between the COMT genotype and individual susceptibility to breast cancer. CONCLUSIONS: Our data suggest that there may be no overall association between the COMT genotype and breast cancer.
  Breast Cancer 11/2011; · 1.36 Impact Factor
• Article: Src inhibitors are promising therapy molecules for human cervical carcinomas.

  Ala-Eddin Al Moustafa, Amber Yasmeen, Amal Alachkar, Amal Achkhar
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  ABSTRACT: Metastatic cervical cancer is a major cause of cancer mortality in women worldwide. In parallel, it is well established that high-risk human papillomaviruses (HPVs) are important factors in the progression of this cancer. Meanwhile, the overall 5 year-survival rate for patients diagnosed with cervical cancer is approximately 50% and has not significantly improved over the past two decades. Therefore, new strategies for the treatment of this cancer, especially the metastatic form, are becoming a major focus of investigation. Alternatively, Src family kinase activities are elevated in several human carcinomas, including cervical, and are often associated with aggressive cancer. Moreover, Src activities are deregulated by E6/E7 onco-proteins of high-risk HPV which are expressed in the majority of human cervical cancers. This raises the question whether Src inhibitors play a significant role in the treatment of human cervical carcinomas. In this paper, we propose the hypothesis that the Src family can be an important target for the treatment of this cancer. Although, we believe that significant studies, using different cells and animal models as well as clinical trails, are necessary to verify this hypothesis.
  Medical Hypotheses 08/2011; 77(5):812-4. · 1.39 Impact Factor
• Source

  Available from: Veronica Martinez Marignac

  Article: The effect of a DNA repair gene on cellular invasiveness: XRCC3 over-expression in breast cancer cells.

  Veronica L Martinez-Marignac, Amélie Rodrigue, David Davidson, Martin Couillard, Ala-Eddin Al-Moustafa, Mark Abramovitz, William D Foulkes, Jean-Yves Masson, Raquel Aloyz
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  ABSTRACT: Over-expression of DNA repair genes has been associated with resistance to radiation and DNA-damage induced by chemotherapeutic agents such as cisplatin. More recently, based on the analysis of genome expression profiling, it was proposed that over-expression of DNA repair genes enhances the invasive behaviour of tumour cells. In this study we present experimental evidence utilizing functional assays to test this hypothesis. We assessed the effect of the DNA repair proteins known as X-ray complementing protein 3 (XRCC3) and RAD51, to the invasive behavior of the MCF-7 luminal epithelial-like and BT20 basal-like triple negative human breast cancer cell lines. We report that stable or transient over-expression of XRCC3 but not RAD51 increased invasiveness in both cell lines in vitro. Moreover, XRCC3 over-expressing MCF-7 cells also showed a higher tumorigenesis in vivo and this phenotype was associated with increased activity of the metalloproteinase MMP-9 and the expression of known modulators of cell-cell adhesion and metastasis such as CD44, ID-1, DDR1 and TFF1. Our results suggest that in addition to its' role in facilitating repair of DNA damage, XRCC3 affects invasiveness of breast cancer cell lines and the expression of genes associated with cell adhesion and invasion.
  PLoS ONE 01/2011; 6(1):e16394. · 4.09 Impact Factor
• Article: Teucrium polium plant extract provokes significant cell death in human lung cancer cells

  Khadidja Haïdara, Amal Alachkar, Ala-Eddin Al Moustafa
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  ABSTRACT: Lung cancer is the first common malignancy worldwide; in view of the limited success of available treatment modalities for this cancer, alternative and complementary strategies need to be developed. On the other hand, Teucrium polium (TP) is a medicinal plant that has been used for more than two thousand years for treating many diseases such as abdominal pain, indigestion and diabetes in the Middle East. However, the effect of TP plant extract on hu-man non-small cell lung cancer (NSCLC) has not been investigated yet. In this study, we exam-ined the effects of TP extract on cell prolifera-tion, cell cycle progression and cell death in H322 and A549 lung cell lines. Our results show that TP plant extract inhibits cell proliferation and deregulates cell cycle progression. More importantly, TP plant extract causes a dramatic cell death in both cell lines in comparison with untreated cells. Our data suggest that this plant extract could have an important therapeutic role in the treatment of human NSCLC.
  01/2011; 3:366-369.
• Article: Identification of deregulated genes by single wall carbon-nanotubes in human normal bronchial epithelial cells.

  Anas Alazzam, Etienne Mfoumou, Ion Stiharu, Amal Kassab, Andrew Darnel, Amber Yasmeen, Narayanswamy Sivakumar, Rama Bhat, Ala-Eddin Al Moustafa
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  ABSTRACT: To identify genes affected by single-walled carbon nanotubes (SWCNTs) in human normal lung cells, we compared the gene expression profiles of untreated human normal bronchial epithelial (HNBE) cells to profiles of HNBE cells treated with SWCNTs. A complementary DNA microarray analysis consisting of 54,675 human genes revealed marked changes in the expression of 14,294 genes, with 7,029 genes being upregulated and 7,265 being downregulated. This comprehensive list of genes included those associated with cell cycle, apoptosis, cell survival, cell adhesion and motility, signal transduction, and transcription regulation. Additional analysis of 19 genes using reverse transcription-polymerase chain reaction confirmed the microarray analysis. More specifically, our study demonstrates to our knowledge for the first time, evidence that 9 of the 19 genes (most of which encode cell apoptotic, signal transduction, and transcription regulator products) are upregulated in the SWCNTs-treated HNBE cells as compared with untreated cells, whereas the remaining 10 of the 19 (involved in cell adhesion and motility, cell proliferation, and cell survival) are downregulated in SWCNTs-treated HNBE cells in comparison with untreated controls. These findings provide a large body of information regarding gene expression profiles associated with SWCNTs exposure in human lung bronchial epithelial cells, and also represent a source to investigate the mechanism of the effect of SWCNTs in human normal lung cells. From the clinical editor: In this study, the gene expression profile of human normal bronchial epithelial cells was compared with single-wall carbon nanotubes-treated cells. A cDNA microarray analysis consisting of 54,675 human genes revealed significant changes in the expression of 14,294 genes, with 7,029 genes being up-regulated and 7,265 being down-regulated. This serves as a first step in clarification of mechanisms of action and to investigate toxicity in this model.
  Nanomedicine: nanotechnology, biology, and medicine 08/2010; 6(4):563-9. · 5.44 Impact Factor
• Article: Reply to the letter to the editor by Chaouachi and Sajid: cancer risks of hookah (shisha, narghile) tobacco use require further independent sound studies

  Ala-Eddin Al Moustafa, Fouad M. Fouad, Samer Rastam
  International Journal of Cancer 01/2010; 127(7):1739 - 1740. · 5.44 Impact Factor
• Article: Reply to the letter to the editor by Chaouachi & Sajid: World available evidence on cancer risk associated with hookah (shisha, narghile) tobacco smoking remains weak.

  Ala-Eddin Al Moustafa, Fouad M Fouad, Samer Rastam
  International Journal of Cancer 01/2010; · 5.44 Impact Factor
• Source

  Available from: PubMed Central

  Article: Locking Src/Abl Tyrosine Kinase Activities Regulate Cell Differentiation and Invasion of Human Cervical Cancer Cells Expressing E6/E7 Oncoproteins of High-Risk HPV.

  Amber Yasmeen, Amal Alachkar, Hafedh Dekhil, Carlo Gambacorti-Passerini, Ala-Eddin Al Moustafa
  [show abstract] [hide abstract]
  ABSTRACT: In this study, we compared the effects of SKI-606 with Iressa, Src/Abl and EGF-R kinase inhibitors, respectively, on selected parameters in HeLa and SiHa cervical cancer cell lines, which express E6/E7 oncoproteins of high-risk HPV types 18 and 16, respectively. Our results show that SKI-606 and Iressa inhibit cell proliferation and provoke G(0)-G(1) cell cycle arrest and reduction of S and G(2)-M phase using 2 and 5 μM concentrations of these inhibitors. In contrast, SKI-606 induces differentiation to an epithelial phenotype "mesenchymal-epithelial transition"; thus SKI-606 causes a dramatic decrease in cell motility and invasion abilities of HeLa and SiHa cancer cells, in comparison to untreated cells and Iressa-treated cells in which these parameters are only slightly affected. These changes are accompanied by a regulation of the expression patterns of E-cadherin and catenins. The molecular pathway analysis of Src/Abl inhibitor revealed that SKI-606 blocks the phosphorylation of β-catenin and consequently converts its role from a transcriptional regulator to a cell-cell adhesion molecule. Our findings indicate that SKI-606 inhibits signaling pathways involved in regulating tumor cell migration and invasion genes via β-catenin alteration, suggesting that Src inhibitor, in comparison to EGF-R, is a promising therapeutic agent for human cervical cancer.
  Journal of Oncology 01/2010; 2010.
• Article: Involvement of water pipe smoking in the development of human pancreatic cancer.

  Fouad M Fouad, Samer Rastam, Ala-Eddin Al Moustafa
  International Journal of Cancer 11/2009; 127(2):497-8. · 5.44 Impact Factor
• Article: Teucrium polium plant extract inhibits cell invasion and motility of human prostate cancer cells via the restoration of the E-cadherin/catenin complex.

  Mustapha Kandouz, Amal Alachkar, Li Zhang, Hafedh Dekhil, Fawaz Chehna, Amber Yasmeen, Ala-Eddin Al Moustafa
  [show abstract] [hide abstract]
  ABSTRACT: Prostate cancer is the first most common malignancy in men worldwide; this cancer is characterized by a marked propensity for invasion and spreading to local lymph nodes. On the other hand, Teucrium polium (TP) is a medicinal plant that has been used for more than two thousand years for treating many diseases such as abdominal pain, indigestion and diabetes in the Middle East. However, the effect of TP plant extract on human metastatic cancer cells especially prostate has not been investigated yet. In this study, we examined the effects of TP extract on selected parameters in PC3 and DU145 prostate cancer cell lines. Our results show that TP plant extract inhibits cell proliferation and provokes S cell cycle arrest and reduction of G0-G1 phase. In parallel, this extract induces differentiation to an epithelial phenotype "mesenchymal-epithelial transition" which is an important event in cell invasion and metastasis; thus TP plant extract causes a dramatic decrease in cell invasion and motility abilities of PC3 and DU145 cancer cells in comparison with untreated cells. These changes are accompanied by a re-localization of the expression patterns of E-cadherin and catenins. The molecular pathway analysis of the TP plant extract revealed that it inhibits the phosphorylation of beta-catenin, via Src dephosphorylation, and consequently converts its role from a transcriptional regulator to a cell-cell adhesion molecule. Our findings indicate that TP plant extract inhibits signaling pathways involved in regulating the E-cadherin/catenin complex and possibly other cell-cell adhesion genes via beta-catenin alteration, suggesting that this plant extract has therapeutic promise in the treatment of human metastatic prostate cancer.
  Journal of ethnopharmacology 11/2009; 129(3):410-5. · 2.32 Impact Factor
• Article: Water pipe smoking and human oral cancers.

  Samer Rastam, Fu-Min Li, Fouad M Fouad, Haysam M Al Kamal, Nizar Akil, Ala-Eddin Al Moustafa
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  ABSTRACT: While cigarette smoking is recognized as an important risk factor in human oral cancers, the effect of water pipe smoking (WPS) on these cancers is not known. WPS is very common in the young adult population, especially in the Middle East, and has been associated with several respiratory problems. However, to date, there have been no studies examining the association between WPS and the progression of human oral cancers. Currently, the role of WPS in human oral cancers remains uncertain because of the limited number of investigations. This raises the question of whether WPS plays a significant role in the development of human oral carcinomas. In this paper, we propose the hypothesis that human oral normal epithelial cells are vulnerable to persistent WPS; moreover, WPS could play an important role in the initiation of a neoplastic transformation of human normal oral epithelial cells. Therefore, we believe that an international collaboration of epidemiological and clinical studies as well as cellular and molecular biology investigations is necessary to answer this important question.
  Medical Hypotheses 11/2009; 74(3):457-9. · 1.39 Impact Factor
• Article: Does the vesicular stomatitis virus really have a selective oncolytic effect in human cancer?

  Amber Yasmeen, Li Zhang, Ala-Eddin Al Moustafa
  International Journal of Cancer 09/2009; 126(10):2509-10. · 5.44 Impact Factor
• Source

  Available from: landesbioscience.com

  Article: Role of E6/E7 onco-proteins of high-risk human papillomaviruses in human colorectal carcinogenesis.

  Riccardo Ricciardi, Lina Ghabreau, Amber Yasmeen, Andrew D Darnel, Nizar Akil, Ala-Eddin Al Moustafa
  Cell cycle (Georgetown, Tex.) 07/2009; 8(12):1964-5. · 5.36 Impact Factor
• Article: Association between human papillomavirus and Epstein-Barr virus infections in human oral carcinogenesis.

  Ala-Eddin Al Moustafa, Dongfeng Chen, Lina Ghabreau, Nizar Akil
  [show abstract] [hide abstract]
  ABSTRACT: Infection by high-risk human papillomaviruses (HPVs) and Epstein-Barr virus (EBV) are very frequent in the adult human population, and have been associated with several human carcinomas, especially oral cancers. However, a small number of studies have examined the association between high-risk HPV and EBV in the progression of human oral cancers. Currently, the role of high-risk HPV and EBV co-infections in human oral cancers, particularly nasopharyngeal carcinomas, remain uncertain because of the limited number of investigations. This raises the question whether high-risk HPV and EBV co-infections play a significant role in the development of human nasopharyngeal carcinomas. In this paper, we propose the hypothesis that human oral normal epithelial cells, especially nasopharyngeal cells, are very susceptible to persistent HPV and EBV co-infections; therefore, high-risk HPV and EBV co-infections play an important role in the initiation of a neoplastic transformation of human oral epithelial cells. We believe that significant studies, using different cells and animal models as well as clinical samples, are necessary to answer these important questions.
  Medical Hypotheses 05/2009; 73(2):184-6. · 1.39 Impact Factor