Background: Circulating tumor cells (CTCs) are cancer cells in the circulation that are derived from the original tumor or metastatic foci.Chemokines and their receptors have major roles in hepatocellular carcinoma (HCC) metastasis.They also represent a very promising group of markers to detect CTCs in HCC patients.The CCL20-CCR6 axis promotes cancer proliferation, migration, and tumor remodeling through immune cell control.Objective: This study aimed to identify the role of CTC and CCR6 in hepatocellular carcinoma patients. Patients and methods:The study included 91 subjects; 71 HCC patients and 20 normal individuals.Routine laboratory investigations included CBC, PT and INR, ALT, AST, bilirubin, albumin, alpha fetoprotein, and creatinine in addition to detection of chemokine receptor 6 (CCR6) RNA by real time PCR and CTCs by flow cytometry as CD45 ¯CK19 + cells were performed for all subjects enrolled in this study.Results: There was significant difference between the studied groups as regards liver function tests.Also, high significant difference was recorded regarding CCR6 RNA expression, CTCs count and hepatic focal lesion detection by ultra sound.No significant difference between both groups regarding kidney function tests.Correlation studies between CTCs and other variables showed positive correlations with liver function tests (ALT, AST, BIL, Alb, AFP, and INR) and negative correlations with albumin and platelets.Conclusion: CCR6 mRNA concentration was significantly increased in HCC patients and its elevation was correlated with CTCs percentage.Therefore, it can be concluded that the combined assessment of CTCs and CCR6 could be considered as noninvasive biomarkers for HCC patients.

Identification

10.21608/ejhm.2021.175732

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Influence of defatted flaxseed diet on insulin sensitivity, vascular permeability and lipid profile in a rat model of type 2 diabetes mellitus

Journal of Medicinal Plants Research (2012)

Mohamed F. Elshal

The impact of flaxseed (FSD) intake, a rich source of alpha linolenic acid (ALA), fiber and lignans, on the cardiovascular system is well documented. However, mechanisms by which flaxseed improve cardiovascular health are not clear. The aim of this study was to investigate the effects of dietary flaxseed on vascular permeability and endothelial function in streptozotocin-induced type 2 diabetes in rats. Type 2 diabetes mellitus (T2DM) was induced in male Sprague-Dawley rats by intraperitoneal injection of streptozotocin (35 mg/kg body weight) after short term feeding of high fructose diet. Diabetic rats were divided into three groups, one group fed standard diet, second group fed standard diet supplemented with defatted flaxseed powder (FSD), and third group received Metformin (200 mg/kg BW (body weight)) for 8 weeks. Fasting serum concentrations of glucose (FPG), insulin, vascular endothelial growth factor (VEGF), nitric oxide (NO), uric acid (UA) and lipid profile were measured. Vascular permeability index (VPI) was assessed at the end of experiment by quantifying the extravasation of albumin-bound Evans blue (EB) dye in the heart. Dietary FSD supplementation is comparable to Metformin in modulating blood lipid profiles, insulin and FPG levels. FSD intake was associated with significant reductions in serum insulin (-66%), glucose (-68%), VEGF levels (-66.8%) and UA (-63%), and NO (-37.5%) as compared to diabetic group without FSD supplementation. There were also improvements in lipid profile, vascular permeability index (VPI), insulin resistance and atherogenic indices in diabetic rats supplemented with flaxseed. These results suggest that dietary FSD supplementation may reduce the incidence of diabetic vascular complications through improvement of insulin sensitivity, vascular permeability and lipid profile. Key words: Diabetes mellitus, cardiovascular diseases, vascular permeability, endothelial dysfunction, insulin resistance, vascular endothelial growth factor, nitric oxide.

Lipid Profile

10.5897/jmpr11.1705

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Citations (8)

L-Asparaginase Isolated from Phaseolus vulgaris Seeds Exhibited Potent Anti-Acute Lymphoblastic Leukemia Effects In-Vitro and Low Immunogenic Properties In-Vivo

International Journal of Environmental Research and Public Health (2016)

Saleh A. Mohamed Mohamed F. Elshal Taha Kumosani Alia Aldahlawi Tasneem Basbrain

Escherichia coli-derived L-asparaginases have been used in the treatment of acute lymphoblastic leukemia (ALL), however, clinical hypersensitivity reactions and silent inactivation due to antibodies against E. coli-asparaginase, lead to inactivation of these preparations in most cases.Therefore, this study was aimed to investigate the cytotoxicity and antitumor effects ofa novel L-asparaginaseenzyme, isolated from Phaseolus vulgaris seeds (P-Asp) on the ALL cell line (Jurkat). The immunogenicity of the enzyme was also evaluated in-vivo and results were compared to commercially available enzymes of microbial sources. The data demonstrated that P-Asp has an enhanced anti-proliferative effect on ALL cells as detected by the WST-8 cell viability assay kit. Cells treated with P-Asp also exhibited a higher degree of early apoptosis compared with asparaginase from Escherichia coli (L-Asp) or its pegylated form Pegasparagas (PEG-ASP) that induced higher rates of late apoptosis and necrosis as detected by an Annexin V/Propidium iodide binding assay. In-vivo experiments indicated that mice treated with P-Asp had less distinct allergenic responses than other bacterial enzyme preparations as indicated by lower serum concentrations of IgG, IgE, IgM and mMCP-1 compared with other treated groups. In conclusion, P-Asp can be considered as a promising candidate for use in the treatment of ALL.

Propidium iodide

Asparaginase

Jurkat cells

Ex vivo

10.3390/ijerph13101008

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Citations (16)

Loperamide potentiates doxorubicin sensitivity in triple‐negative breast cancer cells by targeting MDR1 and JNK and suppressing mTOR and Bcl‐2: In vitro and molecular docking study

Journal of Biochemical and Molecular Toxicology (2021)

Shenouda G. Elia Ahmed A. Al‐Karmalawy Mohamed Nasr Mohamed F. Elshal

Multidrug resistance (MDR) is the leading cause of treatment failure in triple-negative breast cancer (TNBC) patients treated with doxorubicin (DXR). We aimed to investigate the potential of the antidiarrheal drug Loperamide (LPR) in sensitizing TNBC cells to DXR and elucidate the underlying molecular mechanisms. Therefore, we examined the effects of DXR alone or in combination with LPR on MDA-MD-231 cells viability using MTT assay, cell cycle, and apoptosis by flow cytometry, and the expression of the MDR-related genes (MDR1 and JNK1) and cell cycle/survival genes (p21, mTOR, and Bcl-2) by quantitative reverse transcription polymerase chain reaction. Results showed that adding LPR to DXR potentiated its antiproliferation effect and reduced its IC50 by twofolds compared with DXR alone. The value of the combination index of LPR/DXR was <1 indicating a synergistic effect. Combined DXR/LPR treatment also caused G1 arrest and potentiated apoptosis more than DXR-single treatment. At the molecular levels, LPR/DXR treatment downregulated the mRNA of MDR1 (1.35-folds), JNK1 (2.5-folds), mTOR (6.6-folds), Bcl-2 (9.5-folds); while upregulated p21 gene (8-folds) compared with DXR alone. Molecular docking analyses found LPR antagonizes MDR1 and JNK1 proteins, and hence supports the in vitro studies. In conclusion, the results confirmed the potential of LPR in sensitizing TNBCs to DXR by targeting MDR1 and JNK1 and suppressing Bcl-2 and mTOR genes, while upregulating the cell cycle inhibitor gene p21. Additionally, LPR could be repurposed to reduce the therapeutic doses of DXR as indicated by the dose reduction index (DRI) and subsequently decrease its side effects.

Triple-negative breast cancer

MTT assay

Viability assay

10.1002/jbt.22938

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Citations (34)

AMPK expression patterns are significantly associated with poor prognosis in breast cancer patients

Annals of Diagnostic Pathology (2017)

Jaudah Al‐Maghrabi Kaltoom Al‐Sakkaf Imtiaz Ahmad Qureshi Nadeem Shafique Butt Lila Damnhory

Immunostaining

Tissue microarray

10.1016/j.anndiagpath.2017.05.012

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Citations (15)

Sitagliptin synergizes 5‐fluorouracil efficacy in colon cancer cells through MDR1‐mediated flux impairment and down regulation of NFκB2 and p‐AKT survival proteins

Journal of Biochemical and Molecular Toxicology (2024)

Asmaa Eisa Shaden Muawia Hanafy Hany Khalil Mohamed F. Elshal

Abstract 5‐fluorouracil (5‐FU) is an inexpensive treatment for colon cancer; however, its efficacy is limited by chemoresistance. This study investigates the combination therapy approach of 5‐FU with Sitagliptin (Sita), a diabetic drug with potential cancer‐modulating effects. The combination was evaluated in vitro and in silico, focusing on the effects of Sita and 5‐FU on colon cancer cells. The results showed that the addition of Sita significantly decreased the IC50 of 5‐FU compared to 5‐Fu monotherapy. The study also found that Sita and 5‐FU interact synergistically, with a combination index below 1. Sita successfully lowered the 5‐FU dosage reduction index, decreasing the expression of MDR1 mRNA and p‐AKT and NFκB2 subunits p100/p52 protein. Molecular docking analyses confirmed Sita's antagonistic action on MDR1 and thymidylate synthase proteins. The study concludes that sitagliptin can target MDR1, increase apoptosis, and significantly reduce the expression of p‐AKT and NFκB2 cell‐survival proteins. These effects sensitize colon cancer cells to 5‐FU. Repurposing sitagliptin may enhance the anticancer effects of 5‐FU at lower dosages.

10.1002/jbt.23796

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Citations (1)

Correlation between endoscopy, histopathology, and DNA flow cytometry in patients with gastric dyspepsia.

PubMed (1996)

Mohamed Abdel Wahab Abdelfattah M. Attallah Mohamed F. Elshal I Eldousoky K. Zalata

Gastric cancer has a poor prognosis, this is partly due to the advanced stage in which the tumor is diagnosed. The objective of this study is to elucidate the clinical significance of DNA flow cytometry and study its impact on monitoring the progression of gastric precancerous lesions in patients with gastric dyspepsia, and to correlate between endoscopic and histopathological findings with results of DNA flow cytometry.A total of 92 cases underwent upper gastrointestinal endoscopy, 69 males with mean age 44.0 years and 23 females with mean age 38.7 years. Based on the endoscopic appearance, patients under study were classified into: 15 cases with endoscopic normal mucosa (EN), 26 cases with endoscopic gastritis (EG), 43 cases with duodenal ulcer (DU), and 8 cases with gastric ulcer (GU). Two antral biopsies were taken for histopathology and DNA flow cytometry.Chronic gastritis (CG) was present in 12 (80%) of EN cases. In DU patients, CG was present in 42 (97.7%) of cases, and it was associated with intestinal metaplasia (IM) in 11 (25.6%), and with dysplasia in 9 (20.9%) of these cases. While in GU patients, CG was present in all cases. Two (13.3%) of endoscopic normal cases revealed DNA aneuploidy in specimens with CG. The incidence of aneuploidy increases as the endoscopic findings changes from EG (15.4%), DU (16.3%) to GU (37.5%), and as the histopathological changes progresses from chronic atrophic gastritis (CAG) (18.2%), IM (21.7%) to dysplasia (33.3%).DNA aneuploidy is a useful marker for recognizing the presence of abnormal cells in epithelial lesions of the stomach, and for monitoring the progression of gastric lesions. Patients with gastric dyspepsia should not only be subjected to endoscopy but also to biopsy and DNA flow cytometry to allow the early detection of malignant transformations in gastric precancerous lesions.

Histopathology

Atrophic gastritis

Intestinal metaplasia

Chronic gastritis

Source

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Citations (10)

Preclinical biochemical studies using a novel 5-aminolevulinic acid ester derivative with superior properties for photodynamic therapy of tumors

International Journal of Medicine and Medical Sciences (2009)

Mohamed El‐Far Mohamed F. Elshal Samir Bondock Manar Refaat

We have synthesized a novel 5-aminolevulinic acid (ALA) ester derivative from reacting ALA with β-citronellol and tested its potential for treatment of tumors by photodynamic therapy (PDT) in comparison to the widely used agents, ALA and Me-ALA (the methyl ester of ALA). The β-citronellol-ALA ester derivative was far superior to ALA in causing complete destruction of solid skin tumors after PDT treatment. Ex vivo PDT treatment of Ehrlich as cites carcinoma (EAC) cells indicated that the novel ester was effective in causing cell death and inhibition of cell growth, while flow cytometry studies revealed G0/G1 cell cycle arrest during the PDT-mediated response. Inoculation of healthy animals with EAC cell preparations extracted from tumor-bearing animals treated with various agents and then subjected to PDT treatment ex vivo revealed that the novel ester derivative was a significantly better agent than either ALA or Me-ALA at preventing or inhibiting growth of tumors in the inoculated animals. The findings suggest that the novel β-citronellol-ALA ester derivative offers a promising therapy for the treatment of apoptosis-reluctant tumors such as malignant tumors and may be superior to ALA or Me-ALA in PDT applications. Key words: Cancer, PDT, ALA, β-citronellol-ALA ester derivative, flow cytometry, tumor apoptosis, ALA-PDT.

Citronellol

Derivative (finance)

Ex vivo

10.5897/ijmms.9000178

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Assessment of cardiovascular dysfunction in Egyptian women with diminished ovarian reserve: A single-center study

Gene Reports (2021)

Omnia Abdullah N.M. Elsorogy Mohamed F. Elshal

Ovarian Reserve

Cut-off

Anti-Müllerian hormone

10.1016/j.genrep.2021.101364

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Citations (1)