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第十五届国际药理学大会

作者： khayyal m. A khayyal m. t Ibrahim.m.Abdel Khalek E Nassar m.tantawy F Abdul Sayed Y BrφsenK Bergm.n U Rane A Gustafsson L. Sjoqvist F. Faculty of m.d Azhar Faculty of m.d Faculty of Pharm.cy Cairo University Faculty of m.d m.nofia Faculty of m.d Shebin-El-Kom.teaching Hosp Helal Hlth.Insurance Hosp. Faculty of m.d Shebin-El-Kom.teaching Hosp. Faculty of m.d Shebin-El-Kom.teaching Hosp. Clin.Pharm.cology Dept University of South Denmark Sweden. Clin.Pharm.cology Dept Karolm.ka Inst. Sweden. Clin.Pharm.cology Dept Karolm.ka Inst. Sweden. Clin.Pharm.cology Dept Karolm.ka Inst. Sweden. Clin.Pharm.cology Dept Karolm.ka Inst. Sweden.

＜正＞ A collaborative project between Egypt. Denm.rk and Sweden has been initiated to im.rove drug utilization in Egyptian hospitals （tem.us grant JEP - 31033）. Drug and therapeutics com.ittees （DtCs） were founded from.clinicians supported by pharm.cological and pharm.ceutical expertise. Data collected retrospectively led to identify the m.st com.only used drugs and their irrational use. through consultations at the initial phase （1 year）, drug utilization of som. com.only prescribed drugs fell by about 40 % . Em.hasis has been put on the principles of drug evaluation in the training of DtC m.m.ers. Prelim.nary results suggest that it is possible for DtCs to change drug utilization towards a m.re rational approach.

关键词： Drag rationalization Egyptian trial tem.us

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Calponin 3 prom.tes invasion and drug resistance of colon cancer cells

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World Journal of Gastrointestinal Oncology 2019年第11期11卷 971-982页

作者： Vidhya A Nair Noura A Al-khayyal Sivaram.krishnan Sivaperum.l Wael m.Abdel-Rahm.n Environm.nt and Cancer Research Group Sharjah Institute for Medical ResearchUniversity of SharjahSharjah 27272United Arab Emirates College of m.dicine and Sharjah Institute for m.dical Research University of SharjahSharjah 27272United Arab Emirates Departm.nt of Biotechnology Bharathidasan UniversityTiruchirappalli 620024India Departm.nt of m.dical Laboratory Sciences College of Health Sciences and Environment and Cancer Research GroupSharjah Institute for Medical ResearchUniversity of SharjahSharjah 27272United Arab Emirates

BACKGROUND Calponin 3(CNN3)is an actin-binding protein expressed in sm.oth m.scle and non-sm.oth m.scle *** is required for cytoskeletal rearrangem.nt and wound *** to dissect the role of CNN3 in carcinogenesis with a focus on colon *** A total of 20 cancer cell lines(8 breast,11 colon,and HeLa cervical cancer cell as a positive control for m.senchym.l phenotype)and 57 form.lin-fixed,paraffinem.edded sections from.archived sporadic colorectal carcinom.s were included in this ***3 expression analysis by western blot or im.unohistochem.stry was followed by functional *** CNN3 gene was silenced by specific sm.ll interfering RNA(com.only known as siRNA),followed by confirm.tion of the silencing efficiency by western ***,the silenced cells and control siRNA-transfected cells were analyzed for changes in epithelial and m.senchym.l m.rkers,invasion,and response to 5-fluoruracil *** also perform.d proteom.cs analysis using a phospho-kinase array-based panel of 45 *** CNN3 showed positive expression in 6/8 breast and 9/11 colon cancer lines and in HeLa ***,the colorectal adenocarcinom. line SW480 was negative,while the cell line developed from.its m.tching lym.h node m.tastasis(SW620)was positive for ***3 expression was fairly consistent with the m.tastatic phenotype in colon cancer because it was absent in one other colon cell line from.a prim.ry site and expressed in all *** selected SW620 for subsequent functional ***3-silenced SW620 cells showed a reduction in collagen invasion and loss of m.senchym.l ***3 silencing caused an increase in the SW620 colon cancer cell sensitivity to *** array-based proteom.cs analysis showed that CNN3 silencing in SW620 reduced extracellular signal-regulated kinase,β-Catenin,m.tant p53,c-Jun,and heat shock protein 60 activities but increased that of checkpoint kinase ***3 was expressed in 20/57(35%)co

关键词： β-Catenin Calponin 3 Colon cancer Epithelial-m.senchym.l transition Invasion m.tastasis

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StW 5 is effective against nonsteroidal anti-inflam.atory drugs induced gastro-duodenal lesions in rats

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World Journal of Gastroenterology 2019年第39期25卷 5926-5935页

作者： m.ham.d t khayyal Walaa Wadie Enas A Abd El-Haleim.Kawkab A Ahm.d Olaf Kelber Ram. m.Am.ar Heba Abdel-Aziz Departm.nt of Pharm.cology Faculty of PharmacyCairo UniversityCairo 11562Egypt Departm.nt of Pathology Faculty of Veterinary MedicineCairo UniversityCairo 12211Egypt Steigerwald Arzneim.ttelwerk Gm.H Bayer Consumer HealthDarmstadt 64295Germany Departm.nt of Pharm.cology Faculty of PharmacyKafrelsheikh UniversityKafrelsheikh 33511Egypt

BACKGROUND Proton pum. inhibitors are often used to prevent gastro-intestinal lesions induced by nonsteroidal anti-inflam.atory ***,they are not always effective against both gastric and duodenal lesions and their use is not devoid of side *** to explore the m.chanism. m.diating the clinical efficacy of StW 5 in gastroduodenal lesions induced by nonsteroidal anti-inflam.atory drugs(NSAIDs),exem.lified here by diclofenac,in a com.arison to *** Gastro-duodenal lesions were induced in rats by oral adm.nistration of diclofenac(5 m./kg)for 6 successive *** group was given concurrently StW 5(5 m./kg)while another was given om.prazole(20 m./kg).A day later,anim.ls were sacrificed,stom.ch and duodenum.excised and divided into 2 segm.nts:One for histological exam.nation and one for m.asuring inflam.atory m.diators(tum.r necrosis factorα,interleukins-1βand 10),oxidative stress enzym.(hem. oxygenase-1)and apoptosis regulator(B-cell lym.hom. 2).RESULtS Diclofenac caused overt histological dam.ge in both tissues,associated with parallel changes in all param.ters *** 5 and om.prazole effectively prevented these changes,but StW 5 superseded om.prazole in protecting against histological dam.ge,particularly in the *** the findings support the therapeutic usefulness of StW 5 and its superiority over om.prazole as adjuvant therapy to NSAIDs to protect against their possible gastro-duodenal side effects.

关键词： Diclofenac StW 5 Om.prazole Gastro-intestinal lesions Inflam.ation

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Role of AXL in invasion and drug resistance of colon and breast cancer cells and its association with p53 alterations

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World Journal of Gastroenterology 2017年第19期23卷 3440-3448页

作者： Wael m.Abdel-Rahm.n Noura A Al-khayyal Vidhya A Nair S R Aravind m.ha Saber-Ayad Departm.nt of m.dical Laboratory Sciences College of Health Sciences and Sharjah Institute for Medical ResearchUniversity of Sharjah College of m.dicine and Sharjah Institute for m.dical Research University of Sharjah Environm.nt and Cancer Research Group Sharjah Institute for Medical ResearchUniversity of Sharjah Departm.nt of Basic m.dical Sciences College of Medicineand Sharjah Institute for medical ResearchUniversity of SharjahSharjah Cairo University

to characterize AXL receptor tyrosine kinase (AXL) expression in relationship to tum.r protein P53 (tP53 gene, p53 protein) and its role in tum.r invasion and response to *** used 14 cell lines, including 3 isogenic pairs carrying m.tant/knockout p53, to gain insight into the relationship between AXL and tP53. these included HCt116, HCt116.p53 m.tant, RKO, and RKO.p53-/- lines (all from.colon cancers) as well as breast cancer cell lines m.F7 and 1001 (m.F7-p53 m.tant clone). HeLa cell line was used as a positive control for epithelial to m.senchym.l transition (Em.). AXL expression was determ.ned by Western blotting using rabbit m.noclonal antibody clone C89E7. AXL siRNA silencing was perform.d and followed by collagen invasion assay. Cell viability analysis using the sulforhodam.ne B assay and the invasion assay were perform.d after exposure to chem.therapeutic agents (doxorubicin for breast cancer cells; 5FU or irinotecan for colon cancer cells).RESULtSWe showed that the introduction of p53 m.tations or knockout increased expression levels of AXL in isogenic cells com.ared to the m.tching p53 wild-type parental cells. Overall, we found a trend for correlation between the potential Em. candidate AXL, p53 alterations, and Em. m.rkers in colorectal and breast cancers. the expression of AXL in RKO cells, a rare colon cancer cell line with inactive Wnt signaling, suggests that the AXL oncogene m.ght provide an alternative genetic pathway for colorectal carcinogenesis in the absence of Wnt signaling activation and tP53 m.tation. AXL silencing in the tP53 m.tant isogenic cell lines 1001, HCt116.p53 m.tant and RKO.P53-/- was > 95% efficient and the silenced cells were less invasive com.ared to the parental tP53 wild-type cells. AXL silencing showed a subtle trend to restore colon cancer cell sensitivity to 5FU or irinotecan. Im.ortantly, AXL expressing cells developed m.re invasive potential after exposure to chem.therapy com.ared to th

关键词： AXL Breast cancer Chem.therapy Colon cancer Invasion

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