Browsing by Author "Mamdouh, Samah"

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Elevated expression patterns of P-element Induced Wimpy Testis (PIWI) transcripts are potential candidate markers for Hepatocellular Carcinoma
(IOS Press, 2023-12) Hammada, Gehan; Mamdouh, Samah; Seoudi, Dina Mohamed; Seleem, Mohamed Ismail; Safwat, Gehan; Mohamed, Rania Hassan
BACKGROUND: P-Element-induced wimpy testis (PIWI) proteins, when in combination with PIWI-interacting RNA (piRNA), are engaged in the epigenetic regulation of gene expression in germline cells. Different types of tumour cells have been found to exhibit abnormal expression of piRNA, PIWIL-mRNAs, and proteins. We aimed to determine the mRNA expression profiles of PIWIL1, PIWIL2, PIWIL3, & PIWIL4, in hepatocellular carcinoma patients, and to associate their expression patterns with clinicopathological features. METHODS: The expression patterns of PIWIL1, PIWIL2, PIWIL3, PIWIL4 mRNA, was assessed via real-time quantitative polymerase chain reaction (RT-QPCR), on tissue and serum samples from HCC patients, their impact for diagnosis was evaluated by ROC curves, prognostic utility was determined, and In Silico analysis was conducted for predicted variant detection, association with HCC microRNAs and Network Analysis. RESULTS: Expression levels were significantly higher in both HCC tissue and serum samples than in their respective controls (p < 0.001). Additionally, the diagnostic performance was assessed, Risk determination was found to be statistically significant. CONCLUSION: PIWIL mRNAs are overexpressed in HCC tissue and serum samples, the expression patterns could be valuable molecular markers for HCC, due to their association with age, tumour grade and pattern. To the best of our knowledge, our study is the first to report the expression levels of all PIWIL mRNA and to suggest their remarkable values as diagnostic and prognostic biomarkers, in addition to their correlation to HCC development. Additionally, a therapeutic opportunity might be also suggested through in silico miRNA prediction for HCC and PIWIL genes through DDX4 and miR-124-3p.
HEPPAR1 and PIWIL2 as Panel Markers for Hepatocellular Carcinoma
(Asian Pacific Organization for Cancer Prevention : APJCP, 2024-06) Hammad, Gehan; Magdy, Mona; Aboushousha, Tarek; Abdelraouf, Amr; Mamdouh, Samah
OBJECTIVE: The aim of this study was to evaluate the expression profiles of PIWI-like protein- 2 (PIWIL2), and HepPar1 and their immunohistochemical (IHC) characteristics in Hepatocellular Carcinoma (HCC), and determine their correlation with clinicopathological parameters of this type of cancer to determine their diagnostic value in combination. METHODS: Seventy-five patients with HCC were assessed for the expression of PIWIL2 in serum and tissue using real-time polymerase chain reaction (RT-PCR) and IHC was performed for PIWIL2 and HepPar1 was performed on all patients. RESULTS: A statistically significantly higher level of PIWIL2 was found in HCC compared to controls (p≤0.001). Both HepPar1 and PIWIL2 were detected in 84% of HCC cases, the diagnostic and prognostic factors for PIWIL2 were found to be significant in liver tumour tissue samples and non-tumorous sections p<0.001, and the same was observed for serum samples and results of healthy serum controls (p<0.001) when compared to AFP. CONCLUSION: Our results affirm the hypothesis that reactivation of PIWI expression in various caner types is crucial for cancer development, and that a possible panel maybe used for these markers HCC diagnosis.
Molecular Detection of Genetic Susceptibility to Bladder Cancer in Egyptian Patients
(Asia Pacific Organization for Cancer Prevention (APOCP), 2022-01) Mamdouh, Samah; Khorshed, Fatma; Hammad, Gehan; Elesaily, Khaled; Safwat, Gehan; Hammam, Olfat; Aboushousha, Tarek
Objective: Genome-wide association studies (GWAS) have identified a number of genetic variants associated with the susceptibility of bladder cancer (BC) in European and Chinese populations. Here, we assessed the association of two of these variants, rs9642880 and rs710521 in an Egyptian patients and also examined the expression of c-Myc.The basis was due to the absence of studies on Egyptian patients to determine the association between rs9642880& rs710521 and bladder cancer risk, particularly due to the known role of the variant (rs9642880) in the Progression and development of bladder cancer. Methods: Urine samples were collected from onehundred and fiftybladder cancer patients under particular standards and fifty healthy controls. Genomic DNA was extracted, rs9642880 G>T and rs710521 A>G polymorphisms were amplified, assessed via restriction fragment length polymorphism(RFLP) and sequenced. Urine retrieved results were compared to the histopathological diagnosis of tissue biopsies and to the results of C-Myc immunohistochemistry. Data were statistically analyzed using Microsoft Excel 2016, association between significant genotypes of the two studied variables and bladder cancer risk was performed. Results: We found that the TT genotype of rs9642880 G>T was strongly associated with the risk of bladder cancer, andfor rs710521 A>G, AG genotype was also identified to has an association with bladder cancer risk.All 150 tumor sections showed positive immunoreactivity for c-Myc in the nucleus and the cytoplasm. Conclusion: Identifying the association to risk of bladder cancer using genetic analysis will help in the early detection of the disease.
P- element Induced Wimpy Testis (PIWI), a Novel Powerful Candidate Diagnostic Marker for Hepatocellular Carcinoma
(Springer, 2022-08) Hammad, Gehan; Mamdouh, Samah; Seoudi, Dina Mohamed; Seleem, Mohamed Ismail; Safwat, Gehan; Mohamed, Rania Hassan
P-Element-induced wimpy testis (PIWI) proteins are engaged in epigenetic regulation of gene expression in germline cells when they are in combination with PIWI-interacting RNA (piRNA). Different types of tumour cells have been found to exhibit abnormal expression of piRNA and PIWI proteins. HCC is majorly diagnosed in later stages, which is associated with lower survival rates. There is an urgent need for improved, more specific and less invasive diagnostic methods that can detect earlier stages of the disease. Purpose: The aim of this study was to assess the diagnostic potential by determining the expression profiles of PIWI-like protein-1, -2, -3, & -4 (PIWIL1, PIWIL2, PIWIL3, & PIWIL4) in hepatocellular carcinoma, and determine its association with clinicopathological features. Methods: Samples from patients comprising serum and frozen fragments of paired tissue specimens (tumour and adjacent non- malignant liver tissue) were employed for molecular analyses. Real-time polymerase chain reaction was performed on 50 tissue and serum samples from HCC patients and 25 serum samples from healthy controls. Results: The PIWIL1, PIWIL2, PIWIL3, & PIWIL4 levels were significantly (<0.001) higher in both HCC tissue and serum samples than in the controls. Additionally, the diagnostic performance was assessed by ROC curves, the PIWIL1-4 levels in serum showed better potential and sensitivity to screen HCC patients than their levels in tissues. Moreover, some PIWIL elements were found here to be significantly correlated with the HCC profile. Conclusion: PIWI expression is considered as a powerful non- invasive diagnostic tool for HCC. Our findings also support the theory that PIWIL expression is critical for cancer progression.
RNA Interference based Midkine Gene Therapy for Hepatocellular Carcinoma
(Asian Pacific Organization for Cancer Prevention, 2024-07) Mamdouh, Samah; Khorshed, Fatma EL-Zahraa Mohamed; Hammad, Gehan; Magdy, Mona; Abdelraouf, Amr; Hemida, Eman; Shemis, Mohamed
BACKGROUND: Hepatocellular carcinoma (HCC) arises from hepatocytes and accounts for 90% of primary liver cancer. Reasons for HCC prognosis remaining dismal are that HCC is asymptomatic in its early stages, leading to late diagnosis, and it is markedly resistant to conventional chemo- and radiotherapy. In this study, we investigated RNA interference (RNAi)-based treatment for HCC by targeting MDK. AIM: The present study aimed to evaluate MDK serum levels as a diagnostic biomarker for HCC detection and the effect of MDK silencing by RNAi on HCC. SUBJECTS AND METHODS: A total of 140 participants, including 120 patients diagnosed with HCC and 20 healthy volunteers were enrolled in this study, all patients who underwent liver resection were sampled for tumor and adjacent non-tumor liver tissues, in addition to 5 ml of blood sample. Midkine expression levels were evaluated by ELISA and by qRT-PCR. The in vitro transfection and gene knockdown efficiency of midkine by MDK-siRNA was detected by qRT-PCR and ELISA. Gene knockdown effect at the molecule level on the proliferation of HepG2 in vitro was determined by cell counting. RESULTS: The results showed that the expression of MDK was significantly increased in the serum of HCC patients compared to control serum samples with P<0.001 and significant elevated expression levels of MDK in tumor tissues compared to non-tumor ones with P<0.001. It also showed that down-regulation of MDK using RNAi can significantly inhibit HepG2 cells. CONCLUSION: Molecular targeting of MDK using RNAi interference decreases proliferation and could be a therapeutic target.
TP53 Mutation for Prediction of Tumor Recurrence and Metastasis in Bladder Cancer Patients
(Springer nature, 2022-03) Mamdouh, Samah; Khorshed, Fatma; Aboushousha, Tarek; Safwat, Gehan; Elesaily, Khaled
Background: Bladder cancer (BC) is one of the most commonly diagnosed malignancies worldwide. Its complex etiopathogenesis is dependent on numerous risk factors that can be divided into three distinct categories: genetic and molecular abnormalities, chemical or environmental exposure and previous genitourinary disorders and family history of different malignancies. This study highlights the genetic and molecular abnormalities that considered to be part of bladder carcinogenesis such as genetic mutations of TP53. To date, cystoscopy remains the gold standard for diagnosis, butit is invasive and uncomfortable. Hence, many efforts are focusing on the development of accuratenon-invasive diagnostic tests for BC, consequently, this study aims to develop a new non-invasive and reliable test to accurately detect TP53 mutations in urine sediments of Egyptian BC patients and to evaluate the influence of their genetic status on tumor metastasis and recurrence as they are the main problems during the disease. Methods: A total of 150 BC patients and 50 healthy volunteers as controls were enrolled in this study, urine samples were obtained from all participants. DNA was extracted and TP53 mutations were examinedin exons (2+3), 4 and 5 by polymerase chain reaction (PCR). All PCR products were subjected to bidirectional sequencing. Results: Fifty four (36.0%) patients of 150 were mutated in exon (2+3) with statistically higher significant in patients when compared to controls (P = 0.001),while 96 patients(64.0%) in Exon 4, and 111 patients(74.0%) in Exon 5 with the same (P = 0.001).Moreover, a significant association was observed between TP53 status with tumor stage and grade, being alterations more common in high-stage and high-grade tumors. Conclusion: We conclude that TP53genetic mutations are independent prognostic factors for tumor metastasis and recurrence and the genetic alternation of TP53 could be used for prediction of bladder tumorigenesis.