fathia El Sharkawi | Helwan University (original) (raw)

Papers by fathia El Sharkawi

Molecular Biology Reports

Background Bladder cancer (BC) is recorded as the fifth most common cancer worldwide with high mo... more Background Bladder cancer (BC) is recorded as the fifth most common cancer worldwide with high morbidity and mortality. The most urgent problem in BCs is the high recurrence rate as two-thirds of non-muscle-invasive bladder cancer (NMIBC) will develop into muscle-invasive bladder cancer (MIBC), which retains a feature of rapid progress and metastasis. In addition, only a limited number of biomarkers are available for diagnosing BC compared to other cancers. Hence, finding sensitive and specific biomarkers for predicting the diagnosis and prognosis of patients with BC is critically needed. Therefore, this study aimed to determine the expression and clinical significance of urinary lncRNA BLACAT1 as a non-invasively diagnostic and prognostic biomarker to detect and differentiate BCs stages. Methods and results The expression levels of urinary BLACAT1 were detected by qRT-PCR assay in seventy (70) BC patients with different TNM grades (T0-T3) and twelve (12) healthy subjects as control...

Zenodo (CERN European Organization for Nuclear Research), Nov 23, 2022

International Journal of Advanced Research

Circular RNAs (circRNAs) are a class of non-coding RNAs with a circular, covalent structure, whic... more Circular RNAs (circRNAs) are a class of non-coding RNAs with a circular, covalent structure, which are highly conserved, stable unique molecules found in eukaryotic cells. The most notable character of circRNAs is their high stability in biological systems which is a key factor in their potential for use in a variety of RNA-focused medical applications. Despite the fact that circRNAs have a wide range of biological roles and regulatory functions, their circular structure and sequence overlap with their linear mRNA counterparts make it difficult to research them in depth. Furthermore, little is known about their function in viral infections and in immune responses.Since circRNAs have been found to be involved in a number of viral infections (including hepatitis B virus infection and human papilloma virus infection), their significance in viral infections is being more recognized in the last years.In this review, we aimed to provide a broad basis and overview on the biogenesis, signif...

International Journal of Advanced Research

Back ground: Cystoscopic examination and histological evaluation of bladder tissues are considere... more Back ground: Cystoscopic examination and histological evaluation of bladder tissues are considered the gold standard for initial diagnosis of bladder cancer. For decades, researchers explore novel, non-invasive, specific and sensitive biomarkers for preliminary diagnosis and surveillance of bladder carcinoma. Exosomes are nano-sized vesicles present in various biological fluids and encapsulate huge number of biomarkers such as proteins, mRNAs and miRNAs. Caveolin-1(Cav-1) is a major protein of caveolae structure that expressed in a variety of cells and has a fundamental regulatory role in cancer development. Therefore, determination ofexosomal Cav-1 expression in different stages of bladder cancer is a critical concern for clinical diagnosis and prognosis. Methods: Exosomes Cav-1 was isolated and extracted from urine and serum samples of 79 patients of bladder cancer at different stages (T0:T3) and 12 healthy controls.Exosomal Cav-1 expression levels were determined by using Rt-qPCR...

Asian Pacific Journal of Cancer Prevention, 2019

tumor progression over recent decades (Gangoda et al., 2015). Also they have ability to protect t... more tumor progression over recent decades (Gangoda et al., 2015). Also they have ability to protect their components from degradation by enzymes present in extracellular space (Katsuda et al., 2014). Exosomes are nano-sized

Indian Journal of Clinical Biochemistry, 2017

Urine is a proven source of metabolite biomarkers and has the potential to be a rapid, noninvasiv... more Urine is a proven source of metabolite biomarkers and has the potential to be a rapid, noninvasive, inexpensive, and efficient diagnostic tool for various human diseases. Despite these advantages, urine is an under-investigated source of biomarkers for multiple sclerosis (MS). The objective was to investigate the level of some urinary metabolites (urea, uric acid and hippuric acid) in patients with MS and correlate their levels to the severity of the disease, MS subtypes and MS treatment. The urine samples were collected from 73 MS patients-48 with RRMS and 25 with SPMS-and age matched 75 healthy controls. The values of urinary urea, uric acid and hippuric acid in MS patients were significantly decreased, and these metabolites in SPMS pattern showed significantly decrease than RRMS pattern. Also showed significant inverse correlation with expanded disability status scale and number of relapses. Accordingly, they may act as a potential urinary biomarkers for MS, and correlate to disease progression.

Meta Gene, 2017

Despite major efforts by the scientific community over the years, our understanding of the pathog... more Despite major efforts by the scientific community over the years, our understanding of the pathogenesis or the mechanisms of injury of multiple sclerosis is still limited. Multiple lines of evidence implicate that T cells play a central role in both mediating and regulating MS pathophysiology, and efforts to develop rational therapeutic strategies for MS have focused on understanding factors which control T cell function. So, aim of this study is to determine the association between the polymorphic features located within the IL-17F gene and susceptibility to MS in Egyptian patients. In this study, single nucleotide polymorphism (SNP) (rs763780; T7488C; His161Arg) of IL-17 F gene was genotyped in 178 Egyptians divided into 83 MS patients and 95 healthy controls with matched age and sex by using Genotyping Taqman assay. All genotypic and allelic frequencies of the tested IL-17 F polymorphism were in Hardy-Weinberg equilibrium. A significantly increased frequency of rs763780 CT + CC genotypes (p = 0.009, odds ratio = 2.56 (95% CI: 1.4-4.7) and C allele (P = 0.005, odds ratio = 2.05 (95% CI: 1.24-3.39) was detected in MS patients compared to controls. Additionally, we elucidated a significantly high risk for susceptibility of the disease incidence in female cohort only (P = 0.006, odds ratio = 3.3 (95% CI: 1.53-7.12). IL-17 F CT genotype and C allele may be associated with a susceptibility to MS by a gender-dependent mechanism that contributes to unique predisposition in females. So this rs763780 can be considered risk factor for the development of MS in Egyptian population.

Journal of Biomedical Science, 2014

Background: Matrix metalloproteinases (MMPs) have long been associated with cancer-cell invasion ... more Background: Matrix metalloproteinases (MMPs) have long been associated with cancer-cell invasion and metastasis. Few studies are available that describe this association with bladder cancer either related or unrelated to schistosoma infection. Evaluating the urinary levels of MMP3 and MMP9 as diagnostic and prognostic biomarkers in different stages of schistosomal and non schistosomal bladder cancer was the aim of the present study. Urine samples were collected from 70 patients with schistosomal and non schistosomal bladder cancer at early and advanced stages and also from12 healthy volunteers as controls. Urinary levels of MMP-3 and MMP-9 was measured by ELISA technique. Sensitivity and specificity of both markers were determined. Results: Urinary levels of both MMP-3 and MMP-9 were significantly elevated in all bladder cancer patients compared with controls. MMP-3 started to elevate in early stages of schistosomal bladder cancer (0.173 ng/ml) and non-schistosomal bladder cancer patients (0.308 ng/ml) compared to control (0.016 ng/ml) and remained elevated in advanced stages (0.166, 0.235 ng/ml) of both types of bladder cancer patients. In contrast, MMP-9 showed a significant elevation in advanced stages only of both schistosomal and non schistosomal bladder cancer patients (10.33, 21.22 ng/ml) compared to control (0.409 ng/ml) and this elevation of both markers was much higher in non schistosomal bladder cancer. Both Metalloproteinases were specific for the diagnosis of the disease but MMP-3 was more sensitive and this sensitivity was evident in the early stage (84.85% for MMP3, 27.28% for MMP9). Conclusions: MMP3 may be the recommended urinary metalloproteinases as early diagnostic biomarker in the early stages of both types of bladder cancer although both MMP9 and MMP3 can be used in the diagnosis of advanced stages. Further studies are required on large number of urine samples to confirm these results.

International Journal of Advanced Research, 2016

Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spre... more Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. The most common types of cancer in males are lung, liver, prostate, colorectal and stomach and in females, breast, colorectal, stomach and liver cancers worldwide (WHO, 2014).

Frontiers in Microbiology, 2011

The apoptosis-associated speck-like protein containing a caspase recruitment domain (Asc) is an a... more The apoptosis-associated speck-like protein containing a caspase recruitment domain (Asc) is an adaptor molecule that mediates inflammatory and apoptotic signals. Legionella pneumophila is an intracellular bacterium and the causative agent of Legionnaire's pneumonia. L. pneumophila is able to cause pneumonia in immuno-compromised humans but not in most inbred mice. Murine macrophages that lack the ability to activate caspase-1, such as caspase-1 −/− and Nlrc4 −/− allow L. pneumophila infection. This permissiveness is attributed mainly to the lack of active caspase-1 and the absence of its down stream substrates such as caspase-7. However, the role of Asc in control of L. pneumophila infection in mice is unclear. Here we show that caspase-1 is moderately activated in Asc −/− macrophages and that this limited activation is required and sufficient to restrict L. pneumophila growth. Moreover, Asc-independent activation of caspase-1 requires bacterial flagellin and is mainly detected in cellular extracts but not in culture supernatants. We also demonstrate that the depletion of Asc from permissive macrophages enhances bacterial growth by promoting L. pneumophila-mediated activation of the NF-κB pathway and decreasing caspase-3 activation. Taken together, our data demonstrate that L. pneumophila infection in murine macrophages is controlled by several mechanisms: Asc-independent activation of caspase-1 and Asc-dependent regulation of NF-κB and caspase-3 activation.

Gastroenterología y Hepatología, 2022

Lisinopril, propranolol and nifedipine are three commercial drugs used clinically for the managem... more Lisinopril, propranolol and nifedipine are three commercial drugs used clinically for the management of hypertension, angina pectoris, and cardiac arrhythmias. It has been reported that these drugs have inhibitory effects on some cancer cells. In the current study the cytotoxicity of these drugs was evaluated against HeLa, HepG2, MCF- 7 and EACC transformed cell lines using Neutral Red and Trypan Blue assay methods. The three drugs showed a cytotoxicity against HeLa, HepG2 and MCF-7 cells with different potentiality. Lisinopril was the most potent cytotoxic drug against HepG2 cells with IC50 = 33.8±88.4 µg/ml at the concentration of 300ug/ml; while Nifedipine was the most active one against HeLa cells with IC50 =130±58.4ug/ml at a concentration of 300ug/ml. Propranolol was the most active against MCF7 cells IC50 of 78.0± 121.4 µg/ml at a concentration of 3000ug/ml. The three used drugs inhibited the growth of EACC cells and propranolol showed highest inhibitory activity; it inhibite...

The aim of the present study was to examine the effect of Molokhia soup (prepared from the leaves... more The aim of the present study was to examine the effect of Molokhia soup (prepared from the leaves of Corchorus olitorius L.) on fasting blood glucose level (FBG), lipid profile and hepatic oxidative status of streptozotocin (STZ)-induced diabetic rats. The study was carried on 28 male albino rats weighing 100-150 g classified into four groups: control group (group 1) and other three groups (from 2 to 4). Experimentally induced diabetes was developed in rats of groups 3 and 4 by single intraperitoneal injection of STZ (at a dose of 65mg/Kg body weight). One week after injection of STZ, diabetes was well established in these groups and blood samples were collected from all groups for determination of serum FBG levels. Then Molokhia soup (4.80 g/Kg BW) was given by gastric tube for 14 days to groups 2 and 4. At the end of the experimental period, blood samples were collected from all groups for the determination of serum FBG, total cholesterol (TC), high-density lipoprotein cholesterol...

The present study aimed to evaluate the antitumor efficacy of Snake venom (SV), bee venom (BV), c... more The present study aimed to evaluate the antitumor efficacy of Snake venom (SV), bee venom (BV), combinations of their components and their apoptotic, cell death mechanisms in liver (HepG2) and breast (MCF7) cell lines. Cytotoxic effects of venoms, L-Amino acid oxidase (svLAAO), phospholipase A2(svPLA2), Melittin ( MEL) were tested against HepG2 and MCF-7 cell lines and IC50 was calculated . mRNA expression of p53, Bax and Bcl-2 was carried out. All the tested compounds had anti proliferative effects on the tumor cell lines with different potency. BV had a higher cytotoxicity against liver and breast cells (IC50=1.26 and 2.85 μg/ml) than SV (IC50=5.86, 13.05μg /ml). The cytotoxicity of svLAAO was much higher than SV with IC50 = 3.65 and 0.48 μg /ml. MEL showed a higher cytotoxic effect than BV against MCF7 cells (IC50=1.14 μg /ml). MEL when combined with svPLA2 gave a synergistic effect on the expression of P53 and Bax in the two cancer cells. Venoms combination had the least synergi...

Circular RNAs (circRNAs) play critical roles in the development and progression of diseases, espe... more Circular RNAs (circRNAs) play critical roles in the development and progression of diseases, especially in cancer. Thus, expanding our understanding of circRNAs will enrich knowledge of cancer and give new opportunities for cancer therapy. In this review, we discuss the genesis of circular RNAs, their types and epigenetic aspects in tumorigenesis of abnormal cellular proliferation. The possible applications of individual circRNAs as biological markers in laboratory diagnosis of cancer received considerable attention recently.

Gene

Levels of CCL20 and its CCR6 receptor are elevated in many autoimmune diseases which help in the ... more Levels of CCL20 and its CCR6 receptor are elevated in many autoimmune diseases which help in the recruitment of T helper (Th17) cells to site of inflammation. Determine the value of single nucleotide polymorphism of CCL20 (rs6749704) and IL-17F (rs763780) genes and their concomitant effect on the serum CCL20 level and susceptibility to MS in Egyptian patients. Blood samples were collected from 83 patients and 95 healthy subjects. Serum levels of CCL20 were measured by ELISA. The DNA was analyzed for rs6749704 and rs763780 using Genotyping Taqman assay. The mean serum levels of CCL20 in the MS group were significantly higher than healthy group (P &amp;lt; 0.001). Frequencies of CT genotype of rs6749704 in CCL20 gene and C allele in MS patients were significantly higher compared to controls. Also significant increase of rs763780 in IL-17F gene was detected in MS patients. Concomitant polymorphism in both genes in MS patients showed an increase risk to MS rather than individual locus. CCL20 may play an important role in the pathogenesis of MS. Both allelic variation of (rs6749704) within CCL20 gene and (rs763780) within IL-17F gene can be considered risk factor for development of MS in Egyptian patients.

Asian Pacific Journal of Cancer Prevention

Objective: Hepatocellular carcinoma (HCC) is considered the highest recorded malignancy in Egypt.... more Objective: Hepatocellular carcinoma (HCC) is considered the highest recorded malignancy in Egypt. The shortage of appropriate biomarkers for early detection often results in the late diagnosis of the HCC. Circular RNAs (CircRNAs) are presented as long stranded non-coding RNA that combine covalently to make a sealed circular form which make them very stable. CircRNAs are known to have interpretative role in cancer development and metastasis. Aim: To examine the dysregulation of two new CircRNAs obtained from Circbase database (hsa_circ_0064286 and hsa_circ_0000475) in the serum of HCC patients as predictable diagnostic biomarkers of HCC and their correlation with some liver biochemical parameters. Methods: Sixty clinically diagnosed HCC Egyptian patients and 25 healthy volunteers were enrolled in the study. Expression levels of the selected CircRNAs was evaluated in subjects' serum. Moreover, correlation with liver biochemical parameters, sensitivity, and specificity of studied CircRNAs were estimated. Results: Both circular RNAs were significantly down regulated in HCC patients, which was negatively correlated with ALP, ALT, AST, AFP, and bilirubin levels. Circ_0064286 showed more sensitivity and specificity (88.3% and 96%, respectively). Conclusion: As far as we know, this is the first study that shed light on the expression levels of both circRNAs in Egyptian HCC patients. They may serve as potential biomarkers for HCC diagnosis. Moreover, those circRNAs draw attention as therapeutic targets for HCC through targeting their sponge miRNAs.

Journal of Drug Targeting, 2017

Gene therapy is one of the recent approaches in treatment of hepatocellular carcinoma (HCC). Deve... more Gene therapy is one of the recent approaches in treatment of hepatocellular carcinoma (HCC). Development of a vector or vehicle that can selectively and efficiently deliver the gene to target cells with minimal toxicity is an urgent demand. In the present study, Phosphatase and Tensin homolog (PTEN) and Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) genes were loaded to Zein nanoparticles (ZNPs). The formulated PTEN and TRAIL-loaded ZNPs were tested for their in-vitro and in-vivo potential antitumor efficacy using liver tumor cells (HepG2) and HCC-induced rats as animal model. Also, mRNA expression of p53, VGEF and MMP-2 were carried out as markers of apoptosis, angiogenesis and metastasis in animal liver tissues. The results of the study showed that both PTEN and TRAIL- loaded ZNPs proved anti-proliferative activity against HepG2 cell lines with IC50 values of 0.09, 0.25 µg/ml, respectively. In-vivo assay confirmed decrease in mRNA expression of both VEGF and MMP-2 with increased in P53 expression level in liver tissues of the treated animals. Therefore, authors introduced new integration between gene therapy and nanotechnology in the form of PTEN and TRAIL- loaded ZNPs that proved potential to be used in gene therapy for treatment of HCC.

Life Science Journal, 2013

Lisinopril, propranolol and nifedipine are three commercial drugs used clinically for the managem... more Lisinopril, propranolol and nifedipine are three commercial drugs used clinically for the management of hypertension, angina pectoris, and cardiac arrhythmias. It has been reported that these drugs have inhibitory effects on some cancer cells. In the current study the cytotoxicity of these drugs was evaluated against HeLa, HepG2, MCF-7 and EACC transformed cell lines using Neutral Red and Trypan Blue assay methods. The three drugs showed a cytotoxicity against HeLa, HepG2 and MCF-7 cells with different potentiality. Lisinopril was the most potent cytotoxic drug against HepG2 cells with IC 50 = 33.8±88.4 µg/ml at the concentration of 300ug/ml; while Nifedipine was the most active one against HeLa cells with IC 50 =130±58.4ug/ml at a concentration of 300ug/ml. Propranolol was the most active against MCF7 cells IC 50 of 78.0± 121.4 µg/ml at a concentration of 3000ug/ml. The three used drugs inhibited the growth of EACC cells and propranolol showed highest inhibitory activity; it inhibited 97.7% of cell growth at a concentration of 300 ug/ml and 100% inhibition at a concentration of 3000 ug/ml . Lisinopril and nifedipine showed a lower rate of growth inhibition of 18.28% and 11.40% respectively at a concentration of 3000ug/ml. In conclusion: At these high concentrations, the three tested drugs are lethal in vitro to cancer cells of endometrial, cervical, hepatic, and breast origin. Further animal studies are required to confirm this conclusion.

Gene, 2015

Breast cancer (BC) is the most notorious cancer between females with high rates of morbidity and ... more Breast cancer (BC) is the most notorious cancer between females with high rates of morbidity and mortality. The aim of this study was to determine the differential expression of breast tissues microRNA-221 (miR-221) and assess its prognostic and biological significance in breast cancer (BC). A quantitative reverse transcription PCR (qPCR) assay was performed to detect the expression of breast tissue miR-221 in different subtypes of BC (n=76) and controls (n=36) and its correlations with clinicopathological factors of patients. Univariate and multivariate analyses using the Cox proportional hazards model were performed to analyze the prognostic significance of miR-221 expression. Our data indicated that the relative level of miR-221 expression in BC tissues was significantly higher than that in noncancerous breast tissues (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01). Of 76 BC patients, 62 (81.6%) were positive cases. By statistical analyses, high miR-221 expression was observed to be closely correlated with advanced clinical stage (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01). Moreover, patients with high miR-221 expression had worse 5-year relapse free survival (p=0.0124). Univariate and multivariate analyses indicated that high miR-221 expression was an independent poor prognostic factor for BC patients. miR-221 is a potential biomarker for predicting the survival of BC patients and may be a molecular therapeutic target for BC.

Molecular Biology Reports

Zenodo (CERN European Organization for Nuclear Research), Nov 23, 2022

International Journal of Advanced Research

Asian Pacific Journal of Cancer Prevention, 2019

Indian Journal of Clinical Biochemistry, 2017

Meta Gene, 2017

Journal of Biomedical Science, 2014

International Journal of Advanced Research, 2016

Frontiers in Microbiology, 2011

Gastroenterología y Hepatología, 2022

Gene

Asian Pacific Journal of Cancer Prevention

Journal of Drug Targeting, 2017

Life Science Journal, 2013

Lisinopril, propranolol and nifedipine are three commercial drugs used clinically for the managem... more Lisinopril, propranolol and nifedipine are three commercial drugs used clinically for the management of hypertension, angina pectoris, and cardiac arrhythmias. It has been reported that these drugs have inhibitory effects on some cancer cells. In the current study the cytotoxicity of these drugs was evaluated against HeLa, HepG2, MCF-7 and EACC transformed cell lines using Neutral Red and Trypan Blue assay methods. The three drugs showed a cytotoxicity against HeLa, HepG2 and MCF-7 cells with different potentiality. Lisinopril was the most potent cytotoxic drug against HepG2 cells with IC 50 = 33.8±88.4 µg/ml at the concentration of 300ug/ml; while Nifedipine was the most active one against HeLa cells with IC 50 =130±58.4ug/ml at a concentration of 300ug/ml. Propranolol was the most active against MCF7 cells IC 50 of 78.0± 121.4 µg/ml at a concentration of 3000ug/ml. The three used drugs inhibited the growth of EACC cells and propranolol showed highest inhibitory activity; it inhibited 97.7% of cell growth at a concentration of 300 ug/ml and 100% inhibition at a concentration of 3000 ug/ml . Lisinopril and nifedipine showed a lower rate of growth inhibition of 18.28% and 11.40% respectively at a concentration of 3000ug/ml. In conclusion: At these high concentrations, the three tested drugs are lethal in vitro to cancer cells of endometrial, cervical, hepatic, and breast origin. Further animal studies are required to confirm this conclusion.

Gene, 2015