Liver Cancer Stem Cell Induction from Induced Pluripotent Stem Cells

( Said M Afify ),( Ghmkin Hassan ),( Hend M Nawara ),( Hager M Mansour ),( Amira Osman ),( Sadia Monzur ),( Hagar Ali Abu Quora ),( Maram H Zahra ),( Akimasa Seno ),( Yoshiaki Iwasaki ),( Masaharu Sen 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Liver cancer stem cells represent a small fraction of cells in liver cancer tissues so that studying these cells is very hard. Generation of liver cancer stem cells considered as one of the most important issue in cancer biology research. For this reason, we tried to generate liver cancer stem cells from induced pluripotent stem (iPSCs). Methods: First of all, CM was collected from confluent culture of Huh7 cells. Then, mouse iPSCs cells without MEF feeder cells were cultured in the presence of 50% CM for 4 weeks. The medium was changed every day with fresh medium containing 50% of CM. Mouse iPSCs cultured is the complete medium with LIF were used as a control. The survived cells (5x105 cells) were suspended in HBSS and injected into the liver of BALB/ c nude mice. After 25 days malignant tumor was formed in the liver while benign teratoma was formed by the injection of iPSCs. Tumors were then excised and partly fixed in 10% neutral formalin buffer solution for HE staining and immunohistochemical analysis. The rest of tumors were subjected to rt-qPCR anaylsis and primary culture. Results: Immunohistochemical analysis with liver cancer associated markers and cancer stem cell marker showed that malignant liver tumor was developed. These results indicate that the primary cells from the malignant tumor are rich in CSCs. Conclusions: This model will be very important and useful to assess the significant molecular mechanisms necessary to maintain liver cancer stem cells, which will help in defat liver cancer.

Synergistic Activity of Paclitaxel and Sorafenib Against Liver Cancer Stem Cells

( Hend M. Nawara ),( Said M. Afify ),( Ghmkin Hassan ),( Maram H. Zahra ),( Marwa N. Atallah ),( Hager Mansour ),( Hagar A. Abu Quora ),( Amira Osman ),( Hiroki Kakuta ),( Hiroki Hamada ),( Akimasa Se 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), are suggested to be responsible for drug resistance and cancer recurrence. Current treatments with conventional chemotherapy are not highly efficient against the cancer stem cells (CSCs). The combination of anticancer drugs, of which functions are different from the other, enhances efficiency compared to the mono-therapy because it targets cancer cells in a synergistic or an additive manner. In this study, the effect of paclitaxel and sorafenib on cancer stem cells (CSCs) developed from mouse iPSCs in very low concentration was evaluated. Methods: To investigate the effect of combination therapy, CSCs were exposed to paclitaxel and/or sorafenib at different concentrations of 1, 2 and 4 nM, respectively. Cell viability was assessed with 3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide (MTT). The same concentrations of the agents were assessed for the effect on the self-renewal potential of CSCs subpopulation by sphere formation ability. Results: As a result, a combination of sorafenib and paclitaxel significantly reduced the resistance while the CSCs exhibited drug resistance against paclitaxel alone. Also, combination of these agents reduces the self-renewal potential of CSCs when compared to single treatment. Simultaneously, combination significantly suppressed not only the colony formation but also the tube formation of the Cancer stem cells. Conclusions: These results suggest the combination therapy of paclitaxel and sorafenib in low doses be an attractive approach to target cancer stem cells in the future.

Antitumor Activity of Novel Pyridine, Thiophene and Thiazole Derivatives

Mostafa M. Ghorab,Mansour S. Al-Said 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.6

2-Cyano-N'-[1-(2,5-dimethoxyphenyl)]ethylideneacetohydrazide 1 was obtained via reaction of cyanoacetic acid hydrazide with 2,5-dimethoxyacetophenone. A number of novel pyridines 2aj, 3, 4, thiophenes 5-9 and thiazoles 10-12 were prepared by using the hydrazide-hydrazone derivative 1 as a starting material. The structure of the newly synthesized compounds was characterized by elemental analyses, IR, 1H-NMR, 13C-NMR and mass spectral data. All the target compounds were subjected to in vitro antitumor activity against Ehrlich Ascites Carcinoma (EAC) cells. Compounds 2j and 6 showed a higher activity with IC50 values (54.54, 61.57 μM), 8 when compared with a reference drug IC50 value (68.99 μM), while compound 5 is nearly as active as Doxorubicin (CAS 23214-92-8).

Anticancer Activity of Novel Indenopyridine Derivatives

Mostafa M. Ghorab,Mansour S. Al-Said 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.6

Eighteen new 4-[2-amino-3-cyano-5-oxo-4-substitutedaryl-4H-indeno[1,2-b]pyridin-1-(5H)-yl]benzenesulfonamide derivatives 6a-q were synthesized via a reaction of aromatic aldehydes, enaminone 3 and malononitrile in one-pot reaction. Also, compounds 6a-q were obtained, via another route by reaction of enaminone 3 with arylidenemalononitriles 4a-q. The structure of the synthesized compounds was characterized by microanalysis, IR, 1H-NMR, 13C-NMR and mass spectral data. All the target compounds were subjected to in vitro anticancer activity against breast cancer cell line (MCF7). Compound 6d showed a higher potency with IC50 value (4.34 μM) than that of the Doxorubicin (5.40 μM), as the reference drug, while compound 6n with IC50 value (6.84 μM) is nearly as active as Doxorubicin. Also, compounds 6a-c, 6e, 6f, 6h and 6p exhibited a moderate activity, while compounds 3, 6g, 6i-m, 6o and 6q showed weak activity.

Elaboration and characterization of fiber-reinforced self-consolidating repair mortar containing natural perlite powder

Benyahia, A.,Ghrici, M.,Mansour, M. Said,Omran, A. Techno-Press 2017 Advances in concrete construction Vol.5 No.1

This research project aimed at evaluating experimentally the effect of natural perlite powder as an alternative supplementary cementing material (SCM) on the performance of fiber reinforced self-consolidating repair mortars (FR-SCRMs). For this purpose, four FR-SCRMs mixes incorporating 0%, 10%, 20%, and 30% of natural perlite powder as cement replacements were prepared. The evaluation was based on fresh (slump flow, flow time, and unit weight), hardened (air-dry unit weight, compressive and flexural strengths, dynamic modulus of elasticity), and durability (water absorption test) performances. The results reveal that structural repair mortars confronting the performance requirements of class R4 materials (European Standard EN 1504-3) could be designed using 10%, 20%, and 30% of perlite powder as cement substitutions. Bonding results between repair mortars containing perlite powder and old concrete substrate investigated by the slant shear test showed good interlocking justifying the effectiveness of these produced mortars.

Static analysis of the FGM plate with porosities

R. Benferhat,T. Hassaine Daouadji,L. Hadji,M. Said Mansour 국제구조공학회 2016 Steel and Composite Structures, An International J Vol.21 No.1

This work focuses on the behavior of the static analysis of functionally graded plates materials (FGMs) with porosities that may possibly occur inside the functionally graded materials (FGMs) during their fabrication. For this purpose a new refined plate theory is used in this work, it contains only four unknowns, unlike five unknowns for other theories. This new model meets the nullity of the transverse shear stress at the upper and lower surfaces of the plate. The parabolic distribution of transverse shear stresses along the thickness of the plate is taken into account in this analysis; the material properties of the FGM plate vary a power law distribution in terms of volume fraction of the constituents. The rule of mixture is modified to describe and approximate material properties of the FG plates with porosity phases. The validity of this theory is studied by comparing some of the present results with other higher-order theories reported in the literature, the influence of material parameter, the volume fraction of porosity and the thickness ratio on the behavior mechanical P-FGM plate are represented by numerical examples.

Proanthocyanidin-Rich Date Seed Extract Protects Against Chemically Induced Hepatorenal Toxicity

Atallah F. Ahmed,Jawaher H. Al-Qahtani,Hanan M. Al-Yousef,Mansour S. Al-Said,AbdelKader E. Ashour,Mohammed Al-Sohaibani,Syed Rafatullah 한국식품영양과학회 2015 Journal of medicinal food Vol.18 No.3

A hydroacetone extract was prepared from seeds of Phoenix dactylifera L. var. Khalas, which is an industrial by-product of date processing. The proanthocyanidin nature of the extract (coded as DTX) was characterized by phytochemical and nuclear magnetic resonance (NMR) analyses. The total phenol/proanthocyanidin content and antioxidant activity of DTX were estimated by Folin–Ciocalteu, vanillin-sulfuric acid, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays, respectively. The hepatorenal protective activity of DTX was evaluated using CCl4-induced toxicity model in rats, in comparison with silymarin (SYL). Results of the histopathological examination and measurements of various hepatorenal serum indices and tissue biochemical markers demonstrated that DTX displayed marked protective potential against CCl4-induced liver and kidney injury at 100 mg/kg/rat. Relative to the control CCl4-intoxicated group, pretreatment with DTX significantly (P<.001) suppressed the elevated serum levels of alanine aminotransferase and aspartate aminotransferase (ALT and AST), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), bilirubin, creatinine, and calcium, whereas it significantly (P<.001) increased the diminished serum levels of high-density lipoprotein cholesterol (HDL-C) and total protein (TP). Moreover, DTX significantly decreased malondialdehyde (MDA) formation and increased TP synthesis in hepatorenal tissues compared with the intoxicated control. The improvement in biochemical parameters by DTX was observed in a dose-dependent manner and confirmed by restoration of normal histological features. The acute toxicity test of DTX in rats revealed safety of the extract. This study reveals that DTX enhances the recovery from xenobiotics-induced toxicity initiated by free radicals.