Distribution of Glutathione S-Transferase Omega Gene Polymorphism with Different Stages of HBV Infection Including Hepatocellular Carcinoma in the Egyptian Population

Shaban, Nadia Z,Salem, Halima H,Elsadany, Mohamed A,Ali, Bahy A,Hassona, Ehab M,Mogahed, Fayed AK Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.4

Background: Infection with hepatitis B virus (HBV) is a major global public health problem, with a wide spectrum of clinical manifestations. Human cytosolic glutathione-S-transferases (GSTs) include several classes such as alpha (A), mu (M), pi (P), sigma (S), zeta (Z), omega (O) and theta (T). The present study aimed to investigate the role of GST omega genes (GSTO1 and GSTO2) in different groups of patients infected with HBV. Materials and Methods: HBV groups were classified according to clinical history, serological tests and histological analysis into normal carriers (N), acute (A), chronic (CH), cirrhosis (CI) and hepatocellular carcinoma (HCC) cases. The study focused on determination of the genotypes of GST omega genes (GSTO1 and GSTO2) and GST activity and liver function tests. Results: The results showed that GSTO1 (A/A) was decreased in N, A, CH, CI and HCC groups compared to the C-group, while, GSTO1 (C/A) and GSTO1(C/C) genotypes were increased significantly in N, A, CH, CI and HCC groups. GSTO2 (A/A) was decreased in all studied groups as compared to the C-group but GSTO2(A/G) and GSTO2(G/G) genotypes were increased significantly. In addition, GST activities, albumin and TP levels were decreased in all studied groups compared to the C-group, while the activities of transaminases were increased to differing degrees. Conclusions: The results indicate that GSTO genetic polymorphisms may be considered as biomarkers for determining and predicting the progression of HBV infection.

Anticancer and Radiosensitization Efficacy of Nanocomposite Withania somnifera Extract in Mice Bearing Tumor Cells

Abdallah, Nadia M,Noaman, Eman,Eltahawy, Noaman A,Badawi, Abdelfattah M,Kandil, Eman,Mansour, NA,Mohamed, Hebatallah E Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.9

The objective of the present study was to evaluate the anticancer and radio-sensitizing efficacy of a Withania somnifera extract/Gadolinium III oxide nanocomposite (WSGNC) in mice. WSGNC was injected to solid Ehrlich carcinoma-bearing mice via i.p. (227 mg/kg body weight) 3 times/week during 3 weeks. Irradiation was performed by whole body fractionated exposure to 6Gy, applied in 3 doses of 2 Gy/week over 3 weeks. Biochemical analyses as well as DNA fragmentation were performed. Treatment of solid Ehrlich carcinoma bearing mice with WSGNC combined with ${\gamma}$-radiation led to a significant decrease in the tumor size and weight associated with a significant decrease in mitochondrial enzyme activities, GSH content and SOD activity as well as a significant increase in caspase-3 activity, MDA concentration and DNA fragmentation in cancer tissues. Combined treatment of WSGNC and low dose of ${\gamma}$-radiation showed great amelioration in lipid peroxidation and antioxidant status (GSH content and SOD activity) in liver tissues in animals bearing tumors. It is concluded that WSGNC can be considered as a radio-sensitizer and anticancer modulator, suggesting a possible role in reducing the radiation exposure dose during radiotherapy.

Anti-proliferative Activities of Metallic Nanoparticles in an in Vitro Breast Cancer Model

Loutfy, Samah A,Al-Ansary, Nadia A,Abdel-Ghani, Nour T,Hamed, Ahmed R,Mohamed, Mona B,Craik, James D,Eldin, Taher A. Salah,Abdellah, Ahmed M,Hussein, Yassmein,Hasanin, MTM,Elbehairi, Serag Eldin I Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.14

Aims: To investigate effect of metallic nanoparticles, silver (AgNPs) and gold nanoparticles (AuNPs) as antitumor treatment in vitro against human breast cancer cells (MCF-7) and their associated mechanisms. This could provide new class of engineered nanoparticles with desired physicochemical properties and may present newer approaches for therapeutic modalities to breast cancer in women. Materials and Methods: A human breast cancer cell line (MCF-7) was used as a model of cells. Metallic nanoparticles were characterized using UV-visible spectra and transmission electron microscopy (TEM). Cytotoxic effects of metallic nanoparticles on MCF-7 cells were followed by colorimetric SRB cell viability assays, microscopy, and cellular uptake. Nature of cell death was further investigated by DNA analysis and flow cytometry. Results: Treatment of MCF-7 with different concentrations of 5-10nm diameter of AgNPs inhibited cell viability in a dose-dependent manner, with IC50 value of $6.28{\mu}M$, whereas treatment of MCF-7 with different concentrations of 13-15nm diameter of AuNPs inhibited cell viability in a dose-dependent manner, with IC50 value of $14.48{\mu}M$. Treatment of cells with a IC50 concentration of AgNPs generated progressive accumulation of cells in the S phase of the cell cycle and prevented entry into the M phase. The treatment of cells with IC50 concentrations of AuNPs similarly generated progressive accumulation of cells in sub-G1 and S phase, and inhibited the entrance of cells into the M phase of the cell cycle. DNA fragmentation, as demonstrated by electrophoresis, indicated induction of apoptosis. Conclusions: Our engineered silver nanoparticles effectively inhibit the proliferation of human breast carcinoma cell line MCF-7 in vitro at high concentration ($1000{\mu}M$) through apoptotic mechanisms, and may be a beneficial agent against human carcinoma but further detailed study is still needed.

Citric Acid Effects on Brain and Liver Oxidative Stress in Lipopolysaccharide-Treated Mice

Omar M.E. Abdel-Salam,Eman R. Youness,Nadia A. Mohammed,Safaa M. Youssef Morsy,Enayat A. Omara,Amany A. Sleem 한국식품영양과학회 2014 Journal of medicinal food Vol.17 No.5

Citric acid is a weak organic acid found in the greatest amounts in citrus fruits. This study examined the effect of citric acid on endotoxin-induced oxidative stress of the brain and liver. Mice were challenged with a single intraperitoneal dose of lipopolysaccharide (LPS; 200 lg/kg). Citric acid was given orally at 1, 2, or 4 g/kg at time of endotoxin injection and mice were euthanized 4 h later. LPS induced oxidative stress in the brain and liver tissue, resulting in marked increase in lipid peroxidation (malondialdehyde [MDA]) and nitrite, while significantly decreasing reduced glutathione, glutathione peroxidase (GPx), and paraoxonase 1 (PON1) activity. Tumor necrosis factor-alpha (TNF-a) showed a pronounced increase in brain tissue after endotoxin injection. The administration of citric acid (1–2 g/kg) attenuated LPS-induced elevations in brain MDA, nitrite, TNF-a, GPx, and PON1 activity. In the liver, nitrite was decreased by 1 g/kg citric acid. GPx activity was increased, while PON1 activity was decreased by citric acid. The LPS-induced liver injury, DNA fragmentation, serum transaminase elevations, caspase-3, and inducible nitric oxide synthase expression were attenuated by 1–2 g/kg citric acid. DNA fragmentation, however, increased after 4 g/kg citric acid. Thus in this model of systemic inflammation, citric acid (1–2 g/kg) decreased brain lipid peroxidation and inflammation, liver damage, and DNA fragmentation.

Synthesis and Three-dimensional Qualitative Structure Selectivity Relationship of 3,5- Disubstituted-2,4-Thiazolidinedione Derivatives As COX2 Inhibitors

Ahmed M. Ali,Gamal E. Saber,Nadia M. Mahfouz,Mahmoud A. El-Gendy,Awwad A. Radwan,Mohamed A.-El. Hamid 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.10

In our effort for synthesis of selective COX2 inhibitors, certain new 2,4-thiazolidinedione derivatives were synthesized. It necessitates preparation of potassium salt of 2,4-thiazolidinedione 2, which condensed with intermediate 4a. The resulting 3-[2-(4-methylphenyl)-2-oxo-1-phenylethyl]- 2,4-thiazolidinedione 8 was condensed with appropriate aldehyde to afford compounds 10a, 10i-l, 10o and 10p. Compounds (9a-l, 10a-n, 10p, 11 and 12) were obtained through the preparation of 5-arylmethylidene-2,4-thiazolidinediones 6a-p and reaction of its potassium salt 7a-p with compounds 4a, 4b, and 5. Some compounds displayed significant analgesic activity as compared to reference standards. The anti-inflammatory activity of the synthesized compounds revealed that intermediate 8 and compounds 9c, 10c and 10d showed good results. Compound 10c produced no significant mucosal injury. HipHop methodology of Catalyst program was used to build up hypothetical model of selective COX2 inhibitors followed by fitting the synthesized compounds to this model. Compounds 10c and 10d were suspected to be promising selective COX2 inhibitors. Also, compounds (6c, 8, 9a,c,d,k, 10a,c,d,k, 11 and 12) were docked into COX1 and COX2 X-ray structures, using DOCK6 program. Docking results suggested that several of these derivatives are active COX inhibitors with a significant preference for COX2.

Synthesis and Three-dimensional Qualitative Structure Selectivity Relationship of 3,5-Disubstituted-2,4- Thiazolidinedione Derivatives As COX2 Inhibitors

Ali, Ahmed M.,Saber, Gamal E.,Mahfouz, Nadia M.,EI-Gendy, Mahmoud A.,Radwan, Awwad A.,Hamid, Mohamed A.-EI. 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.10

In our effort for synthesis of selective COX2 inhibitors, certain new 2,4-thiazolidinedione derivatives were synthesized. It necessitates preparation of potassium salt of 2,4-thiazolidinedione 2, which condensed with intermediate 4a. The resulting 3-[2-(4-methylphenyl)-2-oxo-1-phenylethyl]-2,4-thiazolidinedione 8 was condensed with appropriate aldehyde to afford compounds 10a, 10i-I, 10o and 10p. Compounds (9a-I, 10a-n, 10p, 11 and 12) were obtained through the preparation of 5-arylmethylidene-2,4-thiazolidinediones 6a-p and reaction of its potassium salt 7a-p with compounds 4a, 4b, and 5. Some compounds displayed significant analgesic activity as compared to reference standards. The anti-inflammatory activity of the synthesized compounds revealed that intermediate 8 and compounds 9c, 10c and 10d showed good results. Compound 10c produced no significant mucosal injury. HipHop methodology of Catalyst program was used to build up hypothetical model of selective COX2 inhibitors followed by fitting the synthesized compounds to this model. Compounds 10c and 10d were suspected to be promising selective COX2 inhibitors. Also, compounds (6c, 8, 9a,c,d,k, 10a,c,d,k, 11 and 12) were docked into COX1 and COX2 X-ray structures, using DOCK6 program. Docking results suggested that several of these derivatives are active COX inhibitors with a significant preference for COX2.

Effect of Punica Granatum (Pomegranate) Juice Extract on Healthy Liver and Hepatotoxicity Induced by Diethylnitrosamine and Phenobarbital in Male Rats

Nadia Z. Shaban,Mohamed A.R. El-Kersh,Mohamed M. Bader-Eldin,Sosan Amin Kato,Asmaa F. Hamoda 한국식품영양과학회 2014 Journal of medicinal food Vol.17 No.3

The effect of pomegranate juice (PJ) on hepatic antioxidant enzyme activities, lipid peroxidation, DNA fragmentation (DNAF), and caspase-3 activity in rats both treated and not treated with diethylnitrosamine (DEN) and phenobarbital (PB) was studied. Administration of rats with DEN and PB caused an elevation in the levels of malondialdehyde (MDA), DNAF, and activities of glutathione reductase (GSR) and caspase-3, while the activities of superoxide dismutase, glutathione S-transferase, total glutathione peroxidase (t-GPx), and glutathione (GSH) level were decreased in hepatocytes compared to the control. Treatment of rats with PJ pre, during, and post DEN and PB administration improved liver function and decreased the levels of MDA, DNAF, t-GPx, GSR, and caspase-3 activities, but the GSH level did not change compared to the D–P group. This indicates that PJ reduced the oxidative stress and apoptosis induced by DEN and PB. Administration of healthy rats with PJ only for a long period induced oxidative stress and apoptosis for hepatocytes.

Leukemia propagating cells in Philadelphia chromosome-positive ALL: a resistant phenotype with an adverse prognosis

Nadia El-Menshawy,Sherin M. Abd-Aziz,Enas M. Elkhamisy,Mohammed A. Ebrahim 대한혈액학회 2018 Blood Research Vol.53 No.2

Background Targeted therapy has revolutionized the management of Philadelphia chromo-some-positive (Ph+) acute lymphoblastic leukemia (ALL); however, relapse still occurs because of the presence of quiescent stem cells, termed leukemia propagating cells (LPCs). This study aimed to assess the phenotypic diversity of LPCs in adult patients with Ph+ B-Acute ALL (B-ALL) and to assess its prognostic impact. Methods Seventy adults with newly diagnosed Ph+ B-ALL were recruited at the Mansoura Oncology Center. Multiparameter flow cytometry studies of mononuclear blast cells for cluster of differentiation (CD)34, CD38, and CD58 were performed. Results Seventeen patients had blasts with the pattern of LPCs (CD34+CD38-CD58-), while 53 cases had other diverse phenotypic patterns. The rate of complete response was significantly lower in patients with the LPC phenotype (47% vs. 81%, P=0.006). The median time to achieve a complete response was prolonged in patients with the CD34+ CD38-CD58- phenotype (48 vs. 32 days, P=0.016). The three-year overall survival was significantly lower in patients with the CD34+CD38-CD58- phenotype (37% vs. 55% respectively, P=0.028). Multivariate analysis showed that the CD34+CD38- CD58- phenotype was an independent risk factor for overall survival. Conclusion The presence of CD34+CD38-CD58- LPCs at diagnosis allows rapid identification of higher risk patients. Risk stratification of these patients is needed to further guide therapy and develop effective LPCs-targeted therapy to improve treatment outcome.

3-[(6-Arylamino)pyridazinylamino]benzoic acids: design, synthesis and in vitro evaluation of anticancer activity

KhaledA.M.Abouzid,Nadia A. Khalil,Eman M. Ahmed,Khaled Omar Mohamed 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.1

A series of novel substituted 3,6-disubstitutedpyridazines based on the structure of vatalanib (PTK787)were designed and synthesized. The cytotoxicity of thefinal compounds was tested in vitro on HT-29 colon cancercell line. Compounds 2a and 2b with 4-chlorophenylaminomoiety, exerted the highest cytotoxic activity with IC50values equal to 15.3 and 3.9 lM respectively. The mostpromising compound, 2b, was found to be about fivefoldmore active than vatalanib against HT-29 colon cancer cellline.

Leukemia propagating cells in Philadelphia chromosome-positive ALL: a resistant phenotype with an adverse prognosis

Nadia El-Menshawy,Sherin M. Abd-Aziz,Enas M. Elkhamisy,Mohammed A. Ebrahim 대한혈액학회 2018 Blood Research Vol.53 No.2

Background Targeted therapy has revolutionized the management of Philadelphia chromo-some-positive (Ph+) acute lymphoblastic leukemia (ALL); however, relapse still occurs because of the presence of quiescent stem cells, termed leukemia propagating cells (LPCs). This study aimed to assess the phenotypic diversity of LPCs in adult patients with Ph+ B-Acute ALL (B-ALL) and to assess its prognostic impact. Methods Seventy adults with newly diagnosed Ph+ B-ALL were recruited at the Mansoura Oncology Center. Multiparameter flow cytometry studies of mononuclear blast cells for cluster of differentiation (CD)34, CD38, and CD58 were performed. Results Seventeen patients had blasts with the pattern of LPCs (CD34+CD38-CD58-), while 53 cases had other diverse phenotypic patterns. The rate of complete response was significantly lower in patients with the LPC phenotype (47% vs. 81%, P=0.006). The median time to achieve a complete response was prolonged in patients with the CD34+ CD38-CD58- phenotype (48 vs. 32 days, P=0.016). The three-year overall survival was significantly lower in patients with the CD34+CD38-CD58- phenotype (37% vs. 55% respectively, P=0.028). Multivariate analysis showed that the CD34+CD38- CD58- phenotype was an independent risk factor for overall survival. Conclusion The presence of CD34+CD38-CD58- LPCs at diagnosis allows rapid identification of higher risk patients. Risk stratification of these patients is needed to further guide therapy and develop effective LPCs-targeted therapy to improve treatment outcome.