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Biological and molecular studies on specific immune cells treated with checkpoint inhibitors for the thera-personal approach of breast cancer patients(ex-vivo study)

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Oncology Research 2021年第5期29卷 319-330页

作者： MOTAWA E.EL-hOUSEINI MOSTAFA S.ARAFAT AhMED M.EL-hUSSEINY ISLAM M.KASEM MAhMOUD M.KAMEL AhMED h.EL-hABAShY MEDhAT M.KhAFAGY ENAS M.RADWAN maha h.hELAL MONA S.ABDELLATEIF Medical Biochemistry and Molecular Biology Cancer Biology DepartmentNational Cancer InstituteCairo UniversityCairo11976Egypt Biotechnology Department Faculty of ScienceCairo UniversityGiza12613Egypt Zoology department Faculty of ScienceCairo UniversityGiza12613Egypt Clinical Pathology Department National Cancer InstituteCairo UniversityCairo11976Egypt Department of Pathology National Cancer InstituteCairo UniversityCairo11976Egypt Surgical Oncology Department National Cancer InstituteCairo UniversityCairo11976Egypt Radio-Diagnosis Department National Cancer InstituteCairo UniversityCairo11976Egypt

Immunotherapy becomes a promising line of treatment for breast cancer(BC)however,its success rate is still ***:The study was designed to optimize the condition for producing an effective dendritic cell(DCs)based immunotherapy by using DCs and T lymphocytes together with tumor-inﬁltrating lymphocytes(TILs)and tumor-inﬁltrating DCs(TIDCs),treated with anti-PD1 and anti-CTLA4 monoclonal *** mixture of immune cells was co-cultured with autologous breast cancer cells(BCCs)isolated from 26 BC ***:There was a signiﬁcant upregulation of CD86 and CD83 on DCs(p=0.001 and 0.017,respectively),similarly upregulation of CD8,CD4 and CD103 on T cells(p=0.031,0.027,and 0.011,respectively).While there was a signiﬁcant downregulation of FOXP3 and combined ***8 expression on regulatory T cells(p=0.014 for both).Increased CD8/Foxp3 ratio(phere was a signiﬁcant increase in interferon-γ(IFN-γ,phydrogenase(LDh,p=0.02),and a signiﬁcant decrease in vascular endothelial growth factor(VEGF,ph ligand 1(PDL-1)were downregulated in BCCs(ph),similarly cytotoxic T lymphocyte antigen-4(CTLA4,p=0.02),Programmed cell death 1(PD-1,ph immune checkpoint inhibitors could produce a potent and effective BC ***,these data should be validated on an experimental animal model to be transferred to the clinical setting.

关键词： Immunotherapy breast cancer PD1 CTLA4 TIDCs TILs

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Phytochemical and anti-neuropathic investigations of Crocus sativus via alleviating inflammation, oxidative stress and pancreatic beta-cells regeneration

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Chinese herbal Medicines 2020年第1期12卷 47-55页

作者： Karim Raafat maha Aboul-Ela Abdalla El-Lakany Department of Pharmaceutical Sciences Faculty of PharmacyBeirut Arab UniversityBeirut 115020Lebanon

Objective:The aim of this study is to investigate the phytochemical and the long-term anti-neuropathic potentials of Crocus sativus cultivated in the University botanical garden,and explore its most bioactive compounds and their underlying mechanisms of ***:Phytochemical analysis and bio-guided isolation-procedures including RP-hPLC and1 h and13 C NMR utilizing biological models of diabetes,inflammation,and diabetic-neuropathy were *** saffron(S-RCED)and Spanish-saffron stigma(S-SP)alone or in combination with Camellia sinus(CS)were ***:The RP-hPLC analyses showed the presence of picrocrocin,crocin I,crocin II,crocin I’,crocin II’,and safranal(SAF)in both S-SP and S-RCED extracts with *** had been shown that SAF was the most bioactive-compound in Crocus *** S-SP and S-RCED possessed significant(Ph),subchronic(8 d)and chronic(8 weeks)models.S-RCED had been proven with more hypoglycemic potentials when compared to S-SP and SAF.S-SP,S-RCED,and SAF produced significant anti-inflammatory and anti-nociceptive activities against carrageenan-induced inflammatory,hyperalgesic and tactile diabetic-neuropathy models,respectively.S-SP,S-RCED,and SAF elevated serum catalase,reduced glutathione,and insulin serum levels,ameliorated lipid peroxidation and hb A1 c levels,and histopathologically regenerated the pancreatic *** with CS showed more significant efficacy than the single ***:The oxidative stress reduction,insulin secretagogue,and pancreatic beta-cells regeneration potentials might be responsible for the mechanism underlying the anti-diabetic,anti-inflammatory and anti-diabetic neuropathy ***,the cultivated Crocus sativus might be clinically useful for protecting against many serious-disorders.

关键词： Crocus sativus L neuropathy pancreatic histopathology phytochemical investigation university botanical garden

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Measuring Radiotherapy Setup Errors in IMRT Treated head and Neck Cancer Patients Requiring Bilateral Neck Irradiation, NCI-Egypt Experience

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Journal of Cancer Therapy 2017年第13期8卷 1160-1168页

作者： May G. Ashour Tarek h. Shouman Ashraf h. hassouna Reem M. Emad El Din maha h. Mokhtar Mohamed A. Khalil Radiation Oncology Department National Cancer Institute Cairo University Cairo Egypt Physics Unit Radiation Oncology Department National Cancer Institute Cairo University Cairo Egypt

Objective: We aim to quantify the magnitude of setup errors in intensity-modulated radiotherapy (IMRT) treated head and Neck cancer patients and recommend appropriate PTV margin. Methods: 60 patients with head and neck cancer required bilateral neck irradiation were planned and treated by simultaneous integrated boost IMRT technique either treated radically or postoperative. Patients undergoing image-guided radiotherapy (IGRT) each with once weekly scheduled cone beam computed tomography (CBCT). The 3D displacements, systematic and random errors were calculated. The appropriate PTV expansion was determined using Van herk’s formula. Results: Mean 3D displacement was 0.16 cm in the vertical direction, 0.14 cm in the horizontal direction and 0.16 cm in the longitudinal direction. Conclusion: Use of weekly CBCT allows the planning target volume (PTV) expansion to be reduced according to our setup. The appropriate clinical target volume (CTV)-PTV margin for our institute is 0.30 cm, 0.38 cm, and 0.33 cm in the horizontal, vertical, and longitudinal directions, respectively.

关键词： IMRT CBCT Setup Errors head and Neck

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Flow cytometric detection of hepatitis C virus antigens in infected peripheral blood leukocytes: Binding and entry

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World Journal of Gastroenterology 2005年第33期11卷 5203-5208页

作者： Mostafa K El-Awady Ashraf A Tabll El-Rashdy M Redwan Samar Youssef Moataza h Omran Fouad Thakeb maha El-Demellawy Department of Biomedical Technology National Research Center Tahrir Street Dokki Cairo Egypt Genetic Engineering and Biotechnology Research Institute New Borg El-Arab City Alexandria Egypt Department of Gastroenterology-hepatology Faculty of Medicine Cairo University Egypt Genetic Engineering and Biotechnology Research Institute New Borg El-Arab City Alexandria Egypt

AIM: We designed two synthetic-core-specific peptides core 1 (C1) and core 2 (C2), and an E1-specific peptide (E1). We produced specific polyclonal antibodies againstthese peptides and used the antibodies for detection of hCV antigens on surface and within infected peripheral blood ***: Peripheral blood from a healthy individual who tested negative for hCV RNA was incubated with hCV type 4 infected serum for 1 h and 24 h at 37 ℃. Cells were stained by direct and indirect immunofluorescence and measured by flow ***: After 1 h of incubation, antibodies against C1,C2, and E1 detected hCV antigens on the surface of 27%,26% and 73% of monocytes respectively, while 10%, 5% and 9% of lymphocytes were positive with anti-C1, anti-C2 and anti-E1 respectively. Only 1-3% of granulocytes showed positive staining with anti-C1, anti-C2 and anti E1 antibodies. After 24 h of incubation, we found no surface staining with anti-C1, anti-C2 or anti-E1. Direct immunostaining using anti-C2 could not detect intracellular hCV antigens, after 1 h of incubation with the virus, while after 24 h of incubation, 28% of infected cells showed positive staining. Only plus strand RNA was detectable intracellularly as early as 1 h after incubation, and remained detectable throughout 48 h ***, minus RNA strand could not be detected after 1 h, but became strongly detectable intracellularly after 24 h ***: Monocytes and lymphocytes are the preferred target cells for hCV infection in peripheral blood leukocytes. Our specific anti-core and anti-E1 antibodies are valuable reagents for demonstration of hCV cell ***, hCV is capable of infecting and replicating in peripheral blood mononuclear cells as confirmed by detection of minus strand hCV RNA as well as intracellular staining of core hCV antigen.

关键词：丙型肝炎病毒病毒感染外周血白细胞

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Improvement of hematopoietic and Immunologic Findings in Sublethal Gamma Irradiated Rats Treated with Bone Marrow Transplantation and Wheat Germ Oil

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Journal of Immune Based Therapies, Vaccines and Antimicrobials 2015年第2期4卷 9-18页

作者： maha G. Soliman Omaima M. Ashry Mervat A. E. Ahmed Yasmine h. Abd El-Naby Zoology Department Faculty of Science Al-Azhar University for Girls Cairo Egypt Radiation Biology Department National Center for Radiation Research and Technology (NCRRT) Cairo Egypt

The objective of this study was to evaluate the efficacy of the wheat germ oil (WGO) and bone marrow transplantation (BMT) in boosting the immuno response and protecting from oxidative stress in irradiated rats. BM was given by intravenous injection to male rats, one hour post gamma irradiation at the dose level of 5 Gy. Rats were orally administrated with 54 mg/Kg body wt of wheat germ oil daily for 2 weeks before irradiation. After 14 days, results revealed that total body irradiation induced significant decreases in RBCs, WBCs and lymphocytes, as well as Glutathione (GSh) and zinc superoxide dismutase (Zn/SOD), splenocyte count, bone marrow lymphocyte count and viability. Tumor necrosis factor alpha (TNF-α) and interleukin 2 (IL-2) also recorded significant decrease while interleukin 6 (IL-6) and lipid peroxidation marker malondialdehde (MDA) in serum and spleen were conversely elevated. In irradiated animals receiving BMT and WGO, values of MDA in serum and tissue were significantly depressed as compared with the irradiated group, while lymphocytes, bone marrow viability percentage, splenocytes percentage, IL-2, IL-6 and GSh were significantly elevated. The curative action of WGO enforcing significant innate response could trigger and augment adaptive immune response by BMT, thus protecting immune system from radiation induced damage as well as oxidative stress.

关键词： BMT Gamma Irradiation WGO Immune Response

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Amyloid-beta-dependent phosphorylation of collapsin response mediator protein-2 dissociates kinesin in Alzheimer＇s disease

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Neural Regeneration Research 2018年第6期13卷 1066-1080页

作者： Sara h.Mokhtar Min Joung Kim Kylie A.Magee Pei Mun Aui Speros Thomas maha M.Bakhuraysah Amani A.Alrehaili Jae Young Lee David L.Steer Rachel Kenny Catriona Mc Lean Michael F.Azari Antonis Birpanagos Ewlina Lipiec Philip heraud Bayden Wood Steven Petratos Department of Neuroscience Central Clinical School Monash University Prahran Victoria Australia Department of Biochemistry and Molecular Biology Monash Universityl Clayton Victoria Australia Department of Anatomy & Developmental Biology Monash University Clayton Victoria Australia Department of Anatomical Pathology Alfred Hospital Prahran Victoria Australia School of health and Biomedical Sciences RMIT University Bundoora Victoria Australia Division of Animal and human Physiology Department of Biology National and Kapodistrian University of Athens Ilisia Athens Greece The henryk Niewodniczanski Institute of Nuclear Physics Polish Academy of Sciences Department of Applied Spectroscopy RadzikowskiegoKrakow Poland Centre for Biospectroscopy and Department of Microbiology Monash University Clayton Victoria Australia

Alzheimer’s disease（AD）is a neurodegenerative disorder characterized by accumulation of amyloid plaques and neurofibrillary *** to the development of these characteristic pathological hallmarks of AD,anterograde axonal transport is ***,the key proteins that initiate these intracellular impairments remain *** collapsin response mediator protein-2（CRMP-2）plays an integral role in kinesin-1-dependent axonal transport and there is evidence that phosphorylation of CRMP-2releases ***,we tested the hypothesis that amyloid-beta（Aβ）-dependent phosphorylation of CRMP-2 disrupts its association with the kinesin-1（an anterograde axonal motor transport protein）in *** found that brain sections and lysates from AD patients demonstrated elevated phosphorylation of CRMP-2 at the T555 ***,in the transgenic Tg2576 mouse model of familial AD（FAD）that exhibits Aβaccumulation in the brain with age,we found substantial co-localization of p T555CRMP-2and dystrophic *** Sh-SY5Y differentiated neuronal cultures,Aβ-dependent phosphorylation of CRMP-2 at the T555 site was also elevated and this reduced the CRMP-2 association with *** overexpression of an unphosphorylatable form of CRMP-2 in neurons promoted the re-establishment of CRMP-2-kinesin association and axon *** data suggest that Aβ-dependent phosphorylation of CRMP-2 at the T555 site may directly impair anterograde axonal transport protein function,leading to neuronal defects.

关键词： amyloid-beta protein kinases collapsin response mediator protein microtubules kinesin tubulin

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helicobacter pylori may be an initiating factor in newly diagnosed ulcerative colitis patients: A pilot study

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World Journal of Clinical Cases 2018年第13期6卷 641-649页

作者： Loai Mansour Ferial El-Kalla Abdelrahman Kobtan Sherief Abd-Elsalam Mohamed Yousef Samah Soliman Lobna Abo Ali Walaa Elkhalawany Ibrahim Amer heba harras maha M hagras Mohamed Elhendawy Tropical Medicine and Infectious Diseases Department Faculty of Medicine Tanta University hepatology and Gastroenterology Department Faculty of Medicine Kafr El-Sheikh University Pathology Department Faculty of Medicine Tanta University Clinical Pathology Department Faculty of Medicine Tanta University

AIM To directly visualize helicobacter pylori(h. pylori) by the highly sensitive and specific technique of immunohistochemical staining in colonic tissue from patients newly diagnosed with ulcerative colitis(UC).METhODS Colonoscopic biopsies from thirty patients with newly diagnosed UC and thirty controls were stained with Giemsa stain and immunohistochemical stain for detection of h. pylori in the colonic tissue. Results were confirmed by testing h. pylori Ag in the stool then infected patients were randomized to receive either anti h. pylori treatment or *** Twelve/30(40%) of the UC patients were positive for h. pylori by Giemsa, and 17/30(56.6%) by immunohistochemistry stain. Among the control group 4/30(13.3%) and 6/30(20 %) were positive for h. pylori by Giemsa and immunohistochemistry staining respectively. h. pylori was significantly higher in UC than in controls(P = 0.04 and 0.007). All Giemsa positive patients and controls were positive by immunohistochemical stain. Four cases of the control group positive for h. pylori also showed microscopic features consistent with early *** h. pylori can be detected in colonic mucosa of patients with UC and patients with histological superficial ulcerations and mild infiltration consistent with early UC. There seems to be an association between UC and presence of h. pylori in the colonic tissue. Whether this is a causal relationship or not remains to be discovered.

关键词： Ulcerative colitis Immunohistochemical staining Inflammatory bowel disease helicobacter pylori Giemsa stain

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Trends of Pediatric Outpatients Prescribing in Umm Al Quwain, United Arab Emirates

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Pharmacology & Pharmacy 2015年第1期6卷 9-16页

作者： Suleiman I. Sharif Aseel h. Nassar Fatima K. Al-hamami maha M. hassanein Ashkur h. Elmi Rubian S. Sharif Department of Pharmacy Practice & Pharmacotherapeutics College of Pharmacy University of SharjahSharjah United Arab Emirates

Background: Data with regard to local drug prescribing in pediatric population is scarce. This study was carried out to investigate the patterns of drug prescribing for pediatric outpatient in a general hospital in the United Arab Emirates. Methods: A total of 707 prescriptions were collected from a governmental hospital in Umm Al Quwain, United Arab Emirates covering the months of June and July, 2014. Encounters issued for patients older than 12 years were rejected. A total of 520 prescriptions for age groups ranging from 1 week to 12 years were studied. Prescriptions were analyzed using WhO drug use indicators. Results: All prescriptions were electronic and head lettered by the name of the hospital. Average number of drugs per prescriptions was 2.6 and all drugs were generics. Name of patient, age and gender and prescriber’s name and E-signature were present in 100%. Patient’s address, allergy and diagnosis were present in 21.15%, 83.26% and 64.42% of prescriptions respectively. Complete dosage regimen was present in all encounters. Patients were prescribed one, two, three, four or more than four drugs per prescription in 23.84%, 27.88%, 26.53%, 12.69%, and 8.65% respectively. The most commonly prescribed therapeutic classes of drugs were antibiotics (44.60%), antihistamines (43.65%), and analgesics/antipyretics (32.30%). The most commonly prescribed drugs among each class were amoxicillin (40%), xylometazoline (61.23%), and paracetamol (87.5%). Conclusion: Present results indicate that prescribing trends for pediatric population seems to be rational. however, there is over use of antibiotics and there are some areas that warrant further attention by the prescribers for a more significantly rational prescribing.

关键词： Prescriptions Trends Pediatrics Outpatients Drug Use Indicators

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Evaluation of the Antitumor and Radiosynthetizing Activity of a Novel Quinoline Sulfonamide Derivative (PIQSA) as a histone Deacetylase Inhibitor

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Journal of Cancer Therapy 2011年第4期2卷 567-578页

作者： Eman Noaman Nadia Fahmy Raafat Yousri Omama El Shawi maha Ghazy 不详

Inhibition of histone deacetylases (hDACs) is emerging as a new strategy in cancer therapy. In the present work a novel pyrimido-quinoline benzene sulfonamide (PIQSA compound) was designed and synthesized postulating its ability to inhibit hDAC enzyme in cancer cells. This study was designed to examine the in vitro anti-tumor efficacy of PIQSA against Ehrlich Ascite carcinoma cells (EAC) and three of the human cancer cell lines (h460), brain (U251) and liver (hepG2). The results of Cytotoxic assays showed that PIQSA exhibited in vitro antitumor activity in a dose dependant manner. The tumor growth delay studies indicating that PIQSA resulted in significant regression in tumor growth, which was more pronounced when PIQSA treatment accompanied with radiation exposure. Also, the efficacy of PIQSA to influence radiation response in Ehrlich solid carcinoma (ESC) tumors was estimated. The results suggest that PIQSA exhibited antitumor activities and strong radioenhancing properties associated with inhibition of hDAC activity, DNA fragmentation followed by apoptotic cell death, preferential cell loss of cells particularly in G1/G0 phase through an apoptotic pathway.

关键词： Antitumor Radiosynthetization Quinoline Derivative Sulfonamide Moiety hDACI Apoptosis Cell Cycle DNA Fragmentation

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The common pentanucleotide polymorphism of the 3’-untranslated region of the leptin receptor gene is associated with obesity in Saudi females

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health 2013年第2期5卷 285-291页

作者： maha h. Daghestani Mazin h. Daghestani Pinar T. Ozand Ahmed R. Al-himaidi Mamoon h. Daghestani Nadia A. Aleisa hana h. hakami Abdelmoneim Eldali Ali N. Al-odaib Biostatistics Epidemiology & Scientific Computing (MBC-03) King Faisal Specialist Hospital and Research Center Riyadh KSA Department of Genetics King Faisal Specialist Hospital and Research Center Riyadh KSA Department of Obstetrics & Gynecology Umm-Al-Qura University Makkah KSA Department of Surgery King Abdulaziz Medical City National Guard Health Affairs Jeddah KSA Department of Zoology Center for Scientific and Medical Female Colleges King Saud University Riyadh KSA Department of Zoology Science College King Saud University Riyadh KSA Duzen Laboratories Istanbul Turkey

Obesity is due to the combined effects of genes, environment, lifestyle, and the interactions of these factors. Leptin receptor (LEPR) gene has been intensively evaluated in the search of variants that could be related to obesity. The results of most of these studies have been controversial. We investigated the effects of leptin receptor gene 3’-untranslated region (3’-UTR) polymorphism on phenotype, metabolic parameters and anthropometric measurements of obese Saudi females. 122 healthy women aged 19 to 36 years. The subjects were divided into 3 groups according to their body mass index BMI;lean (BMI 18 - 24), overweight (BMI 25 - 29) and obese (BMI ≥ 30). There were 13 homozygotes and 34 heterozygotes for the 3’-UTR insertion allele amongst all 122 women. The results of this study show that the allele frequency of the insertion allele (I) of 3’UTR was significantly higher in overweight (35.3) and obese females (32.2) compared to the frequency in lean females (15.6). The insertion allele was associated with increased BMI in obese groups. The results obtained from this study indicated that in the obese subjects most variable values increased in I/I homozygote but the significant high value recorded among BMI (40.9 ± 7.11 kg/m2, P = 0.042). Our findings indicated that, the obesity in Saudi females is influenced by alteration in the leptin receptor gene 3’-UTR polymorphism.

关键词： Pentanucleotide Polymorphism Leptin Obesity Saudi Females

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