Mahmoud Romeih

Theodor Bilharz Research Institute

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Mohamed Saber

University of Missouri–Kansas City

Heba Khalil

Theodor Bilharz Research Institute

Tarek S. Abou Shousha

Theodor Bilharz Research Institute

Zhao‐You Tang

Zhongshan Hospital

Mohamed Badawy

Theodor Bilharz Research Institute

Ahmad El-Ray

Theodor Bilharz Research Institute

Hanem Hassan

Theodor Bilharz Research Institute

Xin‐Da Zhou

Ningbo Center for Disease Control and Prevention

Hanem M. Ahmed

Jahangirnagar University

Amr Elkholy

University of Alabama at Birmingham

Cooperative Institutions

Theodor Bilharz Research Institute

Cairo University

Universidade Federal de Minas Gerais

Michigan State University

Children Cancer Hospital

National Water Research Center

National Research Centre

Natural History Museum

Al-Azhar University

Cancer Institute (WIA)

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Injection variceal sclerotherapy and risk of hepatitis C virus transmission

Journal of Hepatology (2000)

Ahmad El-Ray Mahmoud Romeih Magdy Saber

10.1016/s0168-8278(00)80737-0

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COEXPRESSION OF EPITHELIAL-MESENCHYMAL TRANSITION TWIST2 ONCOGENE AND SCHISTOSOMAL ANTIGEN REACTIVITY MARKER IN MUSCLE-INVASIVE UROTHELIAL CARCINOMA OF URINARY BLADDER PERDICT LYMPH NODE METASTASIS AT CYSTECTOMY

Journal of the Egyptian Society of Parasitology (2018)

Mohamed Wishahi HOSSAM ELGANZORY Amr Elkholy Heba Khalil Mohamed Badawy

Bladder cancer is the seventh cancer in males worldwide, approximately 25% of patients with urothelial bladder cancer (BC) present with muscle-invasive tumours, stages T2-T4, while 75% of patients present with non-muscle invasive bladder cancer (NMIBC)T1, Ta.There is a well-established relationship between schistosomiasis and urothelial carcinoma.Epithelial-mesenchymal transition Twist2 is responsible for tumor progression and metastasis when it is overexpressed in tumour tissue and detected by immunohistochemistry (IHC).The study included 123 patients with a urothelial carcinoma of the bladder associated with or without schistosomiasis, patient's data and paraffin embedded tumour tissues were retrieved from different hospitals and archives, inclusion criteria were patients with muscle invasive bladder cancer (MIBC) of transitional cell carcinoma, exclusion criteria were squamous cell carcinoma, adenocarcinoma, and mixed variant histology, clinicopathological characteristics were: 93 patients were stage pT2-T3, No, Mo, 20 patients with NMIBC pT1, and 10 patients had pTa.The study included pre-cystectomy imaging and pathological diagnosis of 93 patients with MIBC, post-operative pathological assessment of lymph node metastasis.IHC detection in tissue samples of Twist2 oncogene and schistosomal antigen reactivity (SAR) marker was done for the 123 patients.The results showed that MIBC harbour high expression of Twist2 indicated strong factor for lymph node metastasis.NMIBC of Ta had low Twist2 expression, while high grade T1 had medium expression.Schistosoma antigen reactivity was over expressed in MIBC associated with schistosomiasis, but was negative in NMIBC group and in non-schistosomal MIBC.Coexpression of Twist2 and SAR with high expression was in 73.8% patients with lymph node metastasis compared to 17.6% patients with negative expression in non-schistosomal MIBC and had negative lymph node metastasis.The results were significant (P=025).Clinical application indicated that detection of expression of twist2 and schistosomal antigen reactivity marker in tissue sample of trans-urethral resection of bladder tumours prior to surgery would indicate a positive lymph node metastasis in cystectomy operation showed extended lymphadenectomy and adjuvant chemotherapy, introducing imunohistochemistry in bladder cancer stratification would be of high impact on planning proper therapeutic regimen..

10.12816/0050450

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Alterations of beta-catenin and Tcf-4 instead of GSK-3beta contribute to activation of Wnt pathway in hepatocellular carcinoma.

PubMed (2003)

Jian Cui Xin‐Da Zhou Yinkun Liu Zhao‐You Tang Mahmoud Romeih

The goal of this study is to investigate the inappropriate activation of Wnt pathway in the hepatocarcinogenesis.We analyzed the alterations of three key components of Wnt pathway, beta-catenin, glycogen synthase kinase 3beta (GSK-3beta) and T cell factor 4 (Tcf-4), in 34 samples of hepatocellular carcinoma (HCC) and paracancerous normal liver by immunohistochemistry, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), direct sequencing, semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization.We found 61.8% (21/34) of all the HCCs examined showed an abnormal beta-catenin protein accumulation in the cytoplasm or nuclei. RT-PCR-SSCP and direct sequencing showed that beta-catenin exon 3 mutations existed in 44.1% (15/34) of the HCCs. No mutations of GSK-3beta or Tcf-4 were detected in HCCs. Moreover, mRNA of beta-catenin and Tcf-4 but not GSK-3beta was found to be over expressed in HCCs. On analyzing the relationship between alterations of beta-catenin or Tcf-4 and C-myc or Cyclin D1 expression, we found that the mutations of beta-catenin as well as over expression of beta-catenin or Tcf-4 gene were independently correlated with C-myc gene over expression in HCCs.Our present findings strongly suggest mutations of beta-catenin as well as over expression of beta-catenin and Tcf-4 gene activate the Wnt pathway in HCC independently with the target gene most likely to be C-myc.

HCCS

Beta-catenin

GSK3B

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Retinoic acid is a negative physiological regulator of N‐cadherin during early avian heart morphogenesis

Development Growth & Differentiation (2009)

Mahmoud Romeih Inese Čakstiņa Maija H. Zile

The vitamin A‐deficient (VAD) early avian embryo has a grossly abnormal cardiovascular system that is rescued by treating the embryo with the vitamin A‐active form, retinoic acid (RA). Here we examine the role of N‐cadherin (N‐cad) in RA‐regulated early cardiovascular morphogenesis. N‐cad mRNA and protein are expressed globally in the presomite through HH14 normal and VAD quail embryos. The expression in VAD embryos prior to HH10 is significantly higher than that in normal embryos. Functional analyses of the N‐cad overproducing VAD embryos reveal N‐cad involvement in the RA‐regulated cardiovascular development and suggest that N‐cad expression may be mediated by Msx1 . We provide evidence that in the early avian embryo, endogenous RA is a negative physiological regulator of N‐cad. We hypothesize that a critical endogenous level of N‐cad is needed for normal early cardiovascular morphogenesis to occur and that this level is ensured by stage‐specific, developmentally regulated RA signaling.

Master regulator

10.1111/j.1440-169x.2009.01134.x

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Wnt signaling in hepatocellular carcinoma: Analysis of mutation and expression of beta‐catenin, T‐cell factor‐4 and glycogen synthase kinase 3‐beta genes

Journal of Gastroenterology and Hepatology (2003)

Jian Cui Xin‐Da Zhou Yinkun Liu Zhao‐You Tang Mahmoud Romeih

Abstract Background and Aims: Hepatocellular carcinoma (HCC) is a common killer cancer in the world. Recently, abnormal activation of the Wnt pathway has been found to be involved in the carcinogenesis of several human cancers including HCC. The goal of the present study was to investigate the mechanism of inappropriate activation of the Wnt pathway in hepatocarcinogenesis. Methods: We analyzed the alterations of three key components of the Wnt pathway: β‐catenin, glycogen synthase kinase (GSK)‐3β and T‐cell factor (Tcf)‐4 in 34 HCC and paracancerous normal liver by immunohistochemistry, polymerase chain reaction (PCR)–single‐strand conformation polymorphism (SSCP), direct sequencing, and quantitative real‐time reverse transcription (RT)–PCR. Results: We found that 61.8% (21/34) of all HCC examined showed an abnormal β‐catenin protein accumulation in the cytoplasm or nuclei. The RT–PCR–SSCP and direct sequencing showed that β‐catenin exon 3 mutations existed in 44.1% (15/34) of the HCC. No mutations of GSK‐3β or Tcf‐4 were detected in HCC. Moreover, messenger RNA of β‐catenin and Tcf‐4, but not GSK‐3β, was found to be overexpressed in HCC. On analyzing the relationship between alterations of β‐catenin or Tcf‐4 and C‐myc or Cyclin D1 expression, we found that mutations of β‐catenin, as well as overexpression of β‐catenin or the Tcf‐4 gene were independently correlated with C‐myc gene overexpression in HCC. Conclusion: Our present findings strongly suggest that mutations of β‐catenin, as well as overexpression of β‐catenin and the Tcf‐4 gene, independently activate the Wnt pathway in HCC, with the target gene most likely to be C‐myc .

Beta-catenin

GSK3B

10.1046/j.1440-1746.2003.02973.x

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Citations (108)

Upregulation of Twist2 in Non-Muscle Invasive Urothelial Carcinoma of the Bladder Correlate with Response to Treatment and Progression

Open Access Macedonian Journal of Medical Sciences (2018)

Mohamed Wishahi Heba Khalil Mohamed Badawy Amr Elkholy Khaled Eseily

Twist2 is a transcription factor and an epithelial-to-mesenchymal transition that plays an important role in cell polarity, cell adhesion, and has a role in tumour invasion and metastases.In this study, we examined the expression of Twist2 in non-muscle invasive bladder carcinoma (NMIBC) and correlated the expression with response to treatment and tumour progression.Data of 305 patients with NMIBC of Ta, T1 were retrieved from hospitals archives. Twist2 expression was examined in tissue samples by immunohistochemistry at initial diagnosis and final follow-up, normal control was 10 normal urothelium, 10 patients with muscle-invasive bladder cancer (MIBC) were a positive control. Treatment of NMIBC was implemented according to the European Association of Urology guidelines on NMIBC. The descriptive statistical analysis included means, standard deviation, p-value; Univariate and multivariate Cox regression analyses.Twist2 expression score was identified as negative, low (1-15%); medium (15-40%); and high (40-100%). Patients who had low or low medium scores at the initial diagnosis had a good response and a favourable prognosis. Expression of a high score of Twist2 in patients having high-grade T1 tumours showed non-responsiveness to repeated courses of intravesical bacillus Calmette Guerin (BCG) therapy and was upstaged to MIBC.Twist2 expression in tissue samples of NMIBC would indicate the tumour response to therapy, upgrading and upstaging in the follow up after intravesical BCG therapy.

Univariate analysis

10.3889/oamjms.2018.165

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Function of RARγ and RARα2 at the initiation of retinoid signaling is essential for avian embryo survival and for distinct events in cardiac morphogenesis

Developmental Dynamics (2003)

Mahmoud Romeih Jian Cui Jean‐Jacques Michaille Weihong Jiang Michael R. Zile

Avian embryogenesis requires retinoid receptor activation by the vitamin A active form, retinoic acid (RA), during neurulation. We conducted loss-of-function analysis in quail embryos by nutritional deprivation of RA and by blocking generation of retinoid receptors. Here we identify a distinct role for RARalpha2 in cardiac inflow tract morphogenesis and for RARgamma in cardiac left/right orientation and looping morphogenesis. Blocking normal embryos with antisense oligonucleotides to RARalpha2 or RXRalpha diminishes GATA-4 transcripts, while blocking RARgamma or RXRalpha diminishes nodal and Pitx2 transcripts; the expression of these genes in the heart forming region resembles that of the vitamin A-deficient embryo. Blocking the function of RARgamma, RARalpha2, and RXRalpha recapitulates the complete vitamin A-deficient phenotype. RARgamma is the most potent mediator of the retinoid signal at this time of development. Our studies provide strong evidence that critical RA-requiring developmental events in the early avian embryo are regulated by means of distinct retinoid receptor signaling pathways.

Retinoid X receptor

10.1002/dvdy.10419

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Citations (27)

Reuse of disposable variceal injection sclerotherapy needles and risk of hepatitis C virus transmission.

PubMed (2001)

Ahmad El-Ray Mahmoud Romeih Mohamed Saber

Source

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Citations (1)

Therapeutic efficacy of Nano-formulation of lactoperoxidase and lactoferrin via promoting immunomodulatory and apoptotic effects

International Journal of Biological Macromolecules (2022)

Esmail M. El-Fakharany Mahmoud Ashry Abd-Elaleem H. Abd-Elaleem Mahmoud Romeih Fatma A. Morsy

Lactoferrin

Lactoperoxidase

10.1016/j.ijbiomac.2022.08.067

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Chromatographic Isolation and Characterization of Certain Bioactive Chemical Ingredients of Phyllanthus emblica Extracts and Assessment of Their Potentials as Antiviral and Anticancer Agents

Egyptian Journal of Chemistry (2021)

Tamer Mohamed Laila A. Refahy Mahmoud Romeih Manal Hamed Hend Okasha

The current study aims to evaluate the antioxidant, anticancer and antiviral activities of Phyllanthus emblica leaves, as well as characterization of bioactive chemical constituents.The total phenolic and flavonoid contents of plant extracts were determined using Folin-Ciocalteu's and aluminium trichloride assays, respectively.The antioxidant activities were evaluated by different methods, the anticancer activity was evaluated via MTT assay, while the antiviral activity was evaluated using cytopathic effect (CPE) inhibition and anti-HCV assays.Moreover, the chemical profiling of extracts was performed using reversed phase high-performance liquid-chromatography method.Our finding revealed that P. emblica is rich in glycosides, flavonoids, phenolics, terpenoids and tannins.The n-butanol fraction exhibited the highest total phenolic and flavonoid contents with values 654.78 mg GAE /g ext and 110.14 mg RE / g ext, respectively.Also, it possessed the most effective antioxidant activities (DPPH; IC50=19.59 µg/mL, RPAA; 0.948 mg AAE /g ext., and TAC; 543.62mgAAE /g ext.) and anticancer activity against HepG-2 and MCF-7 cell lines with an IC50 of 25.63 and 22.80μg/mL, respectively.Moreover, P. emblica extracts exhibited anti-HCV activity.The HPLC finger print results of P. emblica extracts showed 14 peaks superimposed to the standards.Structure elucidation of pure isolates was achieved via IR, UV, 1 H & 13 C-NMR

Phyllanthus emblica

Isolation

Phyllanthus

10.21608/ejchem.2021.79403.3902

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Citations (4)