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Name : Tawfik Mustafa Alhussainy

Academic Rank: Professor

Administrative Position : Faculty Academic Member

Office 8208       Ext No 8300

Email :

Specialization: Pharmacology

Graduate Of: University of New York at Buffalo






    Baghdad University
    University of Kansas Medical Center
    United States of America
    University of New York at Buffalo
    United States of America

  • Book

      Alhussainy T.M., Al-Sakit M. Arab center for student services (publisher), 1998

      Al-Jawad F,Fahmi H.H, Hameed K.A, Alhussainy T.M., Bashir, A.,Hassan L.M., Ezzat A.,Al-Hachim G. Publisher: Baghdad University

      Alhussainy T.M., Zalzala K.A. Published by Iraqi Ministry of Health 1986

  • Journal Paper

      Al-Hanbali M, Ali D,, " Epicatechin suppresses IL-6,IL-8 and enhances IL-10 production with NF-KB nuclear translocation in whole blood stimulated system " , "Neuroendocrinol Lett ",Vol.30,No.1, , , 02/02/2009 Abstract:
      Al-Hanbali M,Ali D, Bustami M,Abdel-Malek S,Al-Hanbali R, Alhussainy T, Qadan F, Matalka KZ Neuroendocrinol.lett.30(1):2009 Download

      Muhi-Eldeen Z,Al-Shamma,KJ,Alhussainy TM, Al-Kaissi EN, Al-Daraji A. European J.Sceitific research 22, 494-500

      Alhussainy,TM Annals college of Medicine,Mosul , Iraq 18,123 (1992).

      Hindi AJ, Al-Shamma G, Al-jadri AM, Zaidan Z, Alhussainy TM Medical Sci.research 17,155, 1989

      Al-Kafaji SH, Al-Shamma KJ, Alhussainy TM,Al-Ghrary NG, Eldeen ZM J.Community Medicine 2,36,1989

      Al-Jalil B.H., Al-Shamma K.J., Alhussainy T.M. Iraqi J.Pharm.sciences 2(1), 13,1989

      Eldeen Z.M., Al-Shamma K.J., Alhussainy T.M., Al-Jubouri I. Iraqi J.Pharm.sciences 1,24,1981

      Alhussainy, T.M., Salman S.D. Bull. of Biological center, Baghdad,12,87,1980

      Alhussainy T.M., Al-Dahan M.I., Abbou Y.Z., Al-Zubaidi A. Pharmacologic Res.Communication 11,199,1979

      Al-Hachim G.M., Al-Katib H., Abbou Y.Z., Al-Kadhi K., Alhussainy T.M. Confidential report submitted to Iraqi foundation of scietific reaeach, Baghdad, 1978

      Y.Rustum, Tawfik Alhussainy, Enrico Mihich, " Antiproliferative effects of N6-benzyladenosine(BAR) in rats " , "",Vol.,No., , , 04/04/1973 Abstract:
      Rustum Y.M.,Alhussainy T.M., Mihich E. Proc.Amer.Assoc.cancer research 14, 135,1973

      Matalka KZ, Attallah, " Dopamine selectively modulates lipopolysaccharide-induced TNF-α, IFN-γ and IL-10 within mice tissues " , "Neuroendocrinology Letters",Vol.32,No.2, , , 03/31/2011

      matalka KZ,Alsaadi M, " Enhancing Doxorubicin-induced MCA-fibrosarcoma cytotoxicity by an Eriobotrya japonica hydrophilic butanol-treated extract through natural killer cells activation " , "J Cancer Sci Ther",Vol.S18-003,No.special issue 18, , , 12/31/2012 Abstract:
      Special Issue 18 • 2012 J Cancer Sci Ther ISSN:1948-5956 JCST, an open access journal Open Access Research Article Cancer Science & Therapy Matalka et al., J Cancer Sci Ther 2012, S18 S18-003 Keywords : Eriobotrya japonica; NK cells; Cytotoxicity Introduction Despite recent advances in cancer therapy, treating solid cancer is still very difficult. This difficulty can be explained by the heterogeneity of cancer cells within the tumor microenvironment, the down regulation of the patient’s immune system and the timing of diagnosis is usually late [1]. Thus a single-treatment modality is usually insufficient for the complete elimination of cancer cells and new therapeutic strategies from various aspects are needed. Doxorubicin (Dox) is a potent chemotherapeutic drug and is widely used as a treatment of choice for solid tumors as well as lymphomas and some leukemias. Dox is known to interact with DNA by intercalation and thus inhibits macromolecular biosynthesis [2,3]. In addition, Dox was found to inhibit the progression of the enzyme topoisomerase and thus inhibiting DNA replication, and transcription [2-4]. Later, it has been proposed that Dox exerts an immunomodulatory activity since it has been shown that spleen cells and/or macrophages from Dox- treated mice have higher cell-mediated toxicity to tumor cell lines [5,6]. Furthermore, Dox administration resulted in increasing TNF, IL-1 and IFN-γ production in association with higher antitumor activity of peritoneal cells [7]. Recently, injection of Dox with plasmid-containing IL-12 gene enhanced the accumulation of IFN-γ in solid tumors [8]. In addition, Dox was found to inhibit TGF-β signaling in human lung carcinoma cell line [9]. The treatment of cancer patients with Dox, however, has several acute and chronic side effects. The acute effects are mainly myelosuppression, nausea, vomiting, weight loss, and arrhythmias, whereas the main chronic effect of Dox is severe cardiomyopathy with high risk of congestive heart failure [2-4]. Furthermore, Dox treated lymphoma and myeloma cell lines produces higher levels of IL-6 and IL-10 which were thought to induce chemoresistant [10]. Eriobotrya japonica (LINDL is a member of Rosaceae family and found in many countries. It has shown to have antimutagenic and antitumor effects in mouse tumor models and human oral tumor cell lines [11]. In addition, Eriobotrya japonica hydrophilic extract has been shown to induce in vitro and in vivo proinflammatory (IL-12, IFN-γ, TNF-α) cytokines production more than anti-inflammatory cytokines (IL-10) [12]. Moreover, the latter extract has been modified by butanol treatment to further modulate inflammatory and anti-inflammatory cytokines within tumor microenvironment, and shown to prolong survival of mouse bearing subcutaneous fibrosarcoma [12,13]. The induction of IFN-γ in the tumor microenvironment and spleen of MCA fibrosarcoma (MCA FS)-bearing mice by triple i.p. injection of such extract enhanced the activity of antitumor effectors cells [13]. In the present work, we evaluated the combination of Eriobotrya japonica hydrophilic butanol-treated extract (EJWR) with Dox on MCA FS cytotoxicity in the absence and presence of spleen cells or Natural Killer (NK) lymphocytes from tumor bearing mice. In addition, the latter effects were studied in association with the ability to modulate cytokines production such as IFN-γ and TNF-α. B y *Corresponding author: Khalid Z Matalka, Department of Pharmacology and Biomedical Sciences, Petra University, Amman, Jordan, Tel: (00962-6) 5715546- 5715549; Fax: 5715561-5715570; E-mail: Received November 05, 2012; Accepted December 12, 2012; Published December 14 , 2012 Citation: Matalka KZ , Alsaadi MT , Qinna N , Mallah E , Awad R , et al. (2012) Enhancing Doxorubicin-Induced MCA-Fibrosarcoma Cytotoxicity by an Eriobotrya japonica Hydrophilic Butanol-Treated Extract through Natural Killer Cells Activation . J Cancer Sci Ther S18: 003. doi: 10.4172/1948-5956.S18-00 3 Copyright: © 2012 Matalka KZ , et al . This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract The combination of cytotoxic drugs with immunotherapy should be more effective than monotherapy alone since both therapeutic modalities may target different mechanisms. In addition, combination therapy may reduce adverse events associated with cytotoxic drugs. Eriobotrya japonica hydrophilic butanol-treated extract (EJWR) was found to modulate cytokines by enhancing IL-12, IFN-γ and TNF-α in vitro and in vivo and within tumor microenvironment. This was associated with enhancing survival time of mice bearing intra-peritoneal MCA fibrosarcoma (MCA FS). In the present work, we evaluated the combination of EJWR with doxorubicin (Dox) on MCA FS cytotoxicity using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay in the absence and presence of spleen cells or Natural Killer (NK) lymphocytes from tumor bearing mice. The results showed that Dox exhibited mild cytotoxicity to healthy spleen cells and EJWR reversed such cytotoxicity. In addition, increasing concentrations of Dox induced 40% (p<0.01) MCA FS cytotoxicity. This percent increased significantly to 60% at Dox 5 μM when co-cultured with NK cells from tumor bearing mice and increased further to 80% (p<0.01) when Dox was combined with EJWR. The latter increase in cytotoxicity was significantly (p<0.01) higher than each agent alone. This enhancement was associated with significant production of TNF-α and retaining IFN-γ levels from NK cells lysates. This concluded that the immunomodulator, EJWR, mediates NK activation and enhances Dox- induced MCA FS cytotoxicity. Enhancing Doxorubicin-Induced MCA-Fibrosarcoma Cytotoxicity by an Eriobotrya japonica Hydrophilic Butanol-Treated Extract through Natural Killer Cells Activation Khalid Z Matalka 1 *, Marwa T Alsaadi 1 , Nidal Qinna 1 , Eyad Mallah 2 , Riad Awad 2 , Wael Abu Dayyih 2 , Tawfiq Alhussainy 1 and Fadi Qadan 2 1 Department of Pharmacology and Biomedical Sciences Petra University, Amman, Jordan 2 Department of Pharmaceutical Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy and Medical Sciences, Petra University, Amman, Jordan Citation: Matalka KZ , Alsaadi MT , Qinna N , Mallah E , Awad R , et al. (2012) Enhancing Doxorubicin-Induced MCA-Fibrosarcoma Cytotoxicity by an Eriobotrya japonica Hydrophilic Butanol-Treated Extract through Natural Killer Cells Activation . J Cancer Sci Ther S18: 003. doi: 10.4172/1948- 5956.S18-00 3 Special Issue 18 • 2012 J Cancer Sci Ther ISSN:1948-5956 JCST, an open access journal Page 2 of 6 utilizing both, the long term goal is to enhance the therapeutic activity of Dox via enhancing the immune system mainly the tumor infiltrating lymphocytes within the tumor microenvironment of solid tumors, and thus reducing Dox-induced adverse events and cancer cell resistance. Materials and Methods Materials RPMI-1640, Fetal Bovine Serum (FBS), penicillin-streptomycin, and endotoxin-free Dulbecco’s PBS without calcium and magnesium were purchased from Euroclone (Siziano, Italy). Igepal CA-630, Meth-A 3-methylcholanthrene (MCA; 98%) and Dox hydrochloride were products of Sigma (St.Louis, MO, USA). Trypsin and HEPES buffer were purchased from PAA Laboratories Gmbh (Linz, Austria) and T75 flasks were obtained from Costar (Cambridge, MA, USA). Mouse erythrocytes lysing kit and MagCellect mouse NK cell biotinylated antibody cocktail were products of R and D systems (UK). 3-(4,5-di- methylthiazolyl)-2,5 diphenyl-tetrazolium bromide (MTT reagent) and sodium dodecyl sulfate (MTT detergent) were purchased from Trevigen. Bovine serum albumin (BSA) was purchased from Research Organics (Cleveland, OH, USA). Tissue culture and Maxisorb 96-well flat plates were products of Nunc International (Denmark). Plant material and extraction Fresh leaves of EJ LINDL (Rosaceae) were collected, washed, grounded, and identified as described elsewhere [12,13]. Similarly, the extraction procedure is described in details elsewhere [12,13]. Before utilization in cell culture, EJWR was dissolved in endotoxin-free Phosphate Buffered Saline (PBS) and sterilized by filtration with 0.2 μm sterile filters and used fresh for each experiment. It has been noted that bacterial endotoxin levels from processed plants are variable but those plants that were cleaned have very low levels of endotoxins [12- 14]. Furthermore, further extraction with two-phase partitioning such as in butanol, reduces endotoxin levels [15]. Animals BALB/c males and females mice were utilized throughout the experiments as indicated. BALB/c mice were purchased from Yarmouk University (Irbid, Jordan). All mice were housed in a pathogen free environment at 22°C with 12 hours light/dark cycle with food and tap water ad libitum . All animal experiments were performed in compliance with FELASA guidelines (Federation of European Laboratory Animal Science Association) and the study protocol was approved by the Deanship of Scientific Research at Petra University. MCA-induced tumors and cell culture MCA fibrosarcoma (MCA FS) was induced in mice by injecting mice subcutaneously with 0.1 mg MCA/mouse dissolved in olive oil [13]. After 10-12 weeks, when the tumor size reached 1-2 cm in diameter it was removed aseptically, cut in small pieces, minced and cultured in T75 flask with RPMI-1640 and incubated at 37°C in humidified atmosphere and 5% CO 2 . Media was changed every two days, and cells were split when they reached confluency. Spleen and NK cells isolation Mice were sacrificed by cervical dislocation and spleen tissues were collected, squeezed between two slides to generate a single cell suspension. Red blood cells were lysed using M-lyse buffer and then the cells were washed with washing buffer and centrifuged for 10 mins and the supernatant was discarded. The spleen cells were counted and added to a 96-well plate at density of 10 5 /100 μl/well, incubated at 37°C in a humidified atmosphere with 5% CO 2 . For NK cells isolation, spleen cells as prepared above were re- suspended with 0.5 ml of cold MagCellect plus buffer and transferred to a polystyrene tube. MagCellect Mouse NK Cell biotinylated antibody cocktail was added mixed and then incubated for 15 minutes at 2-8°C. After the incubation, 100 μL of MagCellect streptavidin ferrofluid was added, mixed, and incubated for another 15 minutes at 2-8°C. The tube was put in the MagCellect Magnet for 6 minutes at room temperature, the unwanted cells migrated toward the magnet, and the desired cells were left in the suspension, removed by sterile Pasteur pipette into another polystyrene tube and repeated again. The purity of NK cells ranges between 80-90%. NK cells were counted, diluted to the proper concentration, and added to the 96 wells culture plate. Cytotoxicity assay MTT assay was performed to test the cytotoxicity of the Dox, EJWR, or their combination to cultured spleen cells or MCA FS tumor cells in 96-well plate at density of 10 5 /100 μl/well incubated at 37°C in a humidified atmosphere with 5% CO 2 . Spleen cells were cultured for 2 hrs whereas MCA FS cells were cultured for 24 hrs before Dox, EJWR, or their combination in a 100 μl volume/well was added and incubated for 48 hrs. Then MTT reagent was added to form a purple precipitate followed 4 hrs later with the addition of MTT detergent. When spleen or NK cells were co-cultured with the adherent MCA FS and before adding the MTT reagent, the supernatant content of each well was removed carefully leaving the adherent MCA FS in the wells. The absorbance was read at 490 nm by Microplate Reader SCO GmbH (Dingelsadt, Germany). Spleen or NK cells culture for cytokine analysis Spleen cells from healthy or tumor-bearing mice were treated as above and incubated with Dox, EJWR or their combination. In case of MCA FS stimulation, MCA FS cells were seeded into 96 well plates at a density of 10 5 /well for 24 hrs, followed by the addition of spleen cells or NK cells at a similar density followed by the addition of Dox, EJWR, or both for another 24 hrs. After the second incubation, the content of the wells was harvested and added to a tube containing 50 μl of 0.1 % igepal CA-630 nonionic detergent diluted in endotoxin-free PBS for ten minutes at 4°C. The tubes were stored at -30°C for cytokine analysis. Cytokines analysis Measurement of NK cell-extracted IFN-γ and TNF-α level were performed using sandwich ELISA according to the manufacturer instructions (mouse Duoset cytokines; R& D Systems, UK). Data analysis The cytotoxicity data are presented as percent of survival of the target cells. The percent survival was calculated based on the control absorbance. The control setup (i.e. without or with spleen cells of NK cells) depends on each experiment. As for the cytokines analysis, the data are presented as pg/10 5 NK cells and control or the zero concentration was applied for each cytokine assay for each condition. All the data in the figures are depicted as the mean ± standard error of the mean and assessed by using one way ANOVA analysis followed by a Tukey’s test (95% confidence) for multiple comparisons (SPSS version 17). P value of <0.05 is considered statistically significant.

      Qinna NA,Muhi-eldeen, " Non-selective inhibition of cyclooxygenase enzymes by aminoacetylenic isoindoline 1,3-diones " , "Inflamm Allergy Drug Target",Vol.11,No., , , 08/31/2012

      Qinna NA, Kamona BS,, " Effects of Prickly Pear dried leaves, Artichoke leaves, Turmeric and Garlic extracts and their combinations on preventing dyslipidemia in rats, " , "ISRN Pharmacol",Vol.2012:167979,No., , , 05/10/2012 Abstract:
      The successful use of herbal combinations in managing diseases or conditions over a single herb has lead us to evaluate the anti- dyslipidemic properties of the combination of the artichoke leaves extract, turmeric extract, prickly pear dried leaves (PPL) and garlic extract versus each one alone in two di ff erent hyperlipidemic animal models. A two-week treatment of each of the natural extracts, combination 1 (artichoke, turmeric and PPL) or combination 2 (artichoke, turmeric, PPL and garlic) prior to a single intraperitoneal injection of Pluronic F-127 resulted in decreasing significantly serum LDL levels by garlic and PPL extracts and serum LDL/HDL ratios by turmeric, PPL, combination 1 and 2. In a 10-day high fat diet model, only the combination 1 and 2 lowered serum cholesterol, LDL by 8–12%, decreased significantly triglycerides, LDL/HDL ratio; and increased significantly HDL ( P< 0 . 0001). However, a long term treatment of each natural product for 7 weeks resulted in decreasing significantly serum LDL levels and LDL/HDL ratio ( P< 0 . 05–0 . 0001). Furthermore, only artichoke and PPL inhibited significantly HMG-CoA reductase activity ( P< 0 . 05). In conclusion, short term, as well as long term, treatment using the combination of artichoke, turmeric, PPL and garlic extract prevents dyslipidemia; partially through inhibiting HMG-CoA reductase

      Nidal A.Qinna,Obbei , " Evidence of reduced oral bioavailability of paracetamol in rats following multiple ingestion of grapefruit juice " , "The European Journal of drug metabolism and pharmacokinetics",Vol.,No., Springer, , 12/01/2014

      Nidal Qinna, Qutaiba, " Influence of molecular weight and degree of deacytlation of low molecular weight chitosan on the bioactivity of oral insulin oreoarations " , "marindrugs",Vol.,No., MDPI, Basil, Switzerland, 12/10/2014

  • Conference paper

      Alhussainy TM, Alwan AG, Farid YZ Proceeding of third congress of Saddam medical college

      Alhussainy TM, Yunis HA, Farid YZ. Proceedings of third congress of Saddam medical college

      Alhussainy TM, Mosa SO J. Community Med. 4,1 ,1991

      Alhussainy T.M., Al-Badr A.H. Proc. 67th annual meeting of Federation of American Soc.for Experm.Biology (FASEB), Chicago , USA, 1983

      Alhussainy T.M., Al-Shamma K.J.,Eldeen Z.M., Al-Jubouri I. Proc.8th international congress of Pharmacology, Tokyo, Japan,1981

      Alhussainy T.M., Salman S.D. Proc. second International congress on Toxicology, Brussels, Belgium,1980

      Alhussainy T.M. Proc. 35th International congress of Pharmaceutical sciences (FIP), Dublin, Ireland, 1975

      Alhussainy T.M. Proc.fourth congress of Arab Pharmacists Union , Cairo, Egypt 1974

      Tawfik Alhussainy, Enrico Mihich, S.Simpson, " Preclinical toxicology study of N6-benzyladenosine(BAR) " , "",Vol.,No., , , 05/05/1972 Abstract:
      Alhussainy T.M., Simpson C.I., Mihich E. Confidential report submitted to the National Cancer Institute, Bethesda, USA,1972

      Lama J.Attallah,Tawfiq Alhussainy,Nidal Quinna, Khalid Matalka
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