Introduction
The obesity epidemic has been linked to a wide range of health and nutritional probl... more Introduction The obesity epidemic has been linked to a wide range of health and nutritional problems, including anemia, which is often caused by impaired iron metabolism. The World Health Organization considers anemia and obesity to be global health issues among adolescent girls and women experiencing menstruation. This study aims to examine the association between iron deficiency anemia and obesity/overweight among female medical students. Methodology This cross-sectional descriptive study conducted as an online self-administered questionnaire. Furthermore, blood samples were collected from 206 students to evaluate the complete blood count, iron and lipid profile. Results The convenience sampling technique was used and a total of 206 students were enrolled in the study. The average body mass index (BMI) was 22.51 ± 3.25, with 83.5% (n = 172) falling within the normal weight range, 12.6% (n = 26) as overweight, and 3.9% (n = 8) as obese. Anemia was present in 16.0% (n = 33) of the participants overall. Higher prevalence of anemia was observed among overweight participants with 10 out of 26 (38.5%) subjects compared to obese with two out of eight (25.0%) and normal weight 21 out of 172 (12.2%); this difference was highly significant (P = 0.005). Individuals with anemia exhibited a significant association with those experiencing a diet full of unhealthy fats and carbohydrates (P = 0.05) and a diet containing all essential nutrients (P = 0.01). There is no statistically significant correlation between anemia prevalence and participants' response to the presence of signs of anemia, physical activity or other dietary habits. Obese participants had a significantly higher mean value of triglycerides (129.5 ± 20.5) compared to normal weight and overweight participants (74.5 ± 12.02 and 51.2 ± 15.04), respectively (P = 0.001). Conclusion A dependable assembly exists between obesity and overweight in cases of iron deficient anemia. The prevalence of iron deficiency anemia was substantially higher among overweight/obese females, highlighting that overweight/obesity signifies both quantitative and qualitative malnutrition. A high BMI was associated with elevated triglycerides, typically considered indicators of obesity. This association may suggest compromised iron homeostasis.
Background
Despite the introduction of several methods and new therapeutics to classify and
treat... more Background Despite the introduction of several methods and new therapeutics to classify and treat breast cancer, it remains the most common cancer among women and contributes to higher mortality rates worldwide. Purpose This study aimed to analyze the expression levels of the androgen receptor (AR), P53 protein, and P53 mutations among molecular subtypes of breast cancers and their correlation with patients’ outcome. Patients and methods Immunostaining for estrogen receptor (ER), progesterone receptor (PR), Ki-67, and human epidermal growth factor receptor 2 (HER2) to stratify breast cancers into basal-like, HER2 type, luminal A or B types. AR, P53 expressions, and P53 mutations was compared among groups. Results Overall, 37.5% of basal-like and 7.1% of HER2 types of invasive breast carcinomas were AR positive. P53 was expressed in 62.5 and 50% of basal-like and HER2 types, respectively. The P53 mutation varied significantly among the molecular subtypes (P<0.0001) and was found in 43.8 and 42.9% of basal-like and HER2 types, respectively. Extensive nodal status, higher stage, and P53 mutation independently predicted the overall survival. AR-negative and P53 mutationpositive tumors had intermediate or poor Nottingham Prognostic Index and were more often nodal positive, higher grade, and higher stage than AR-positive and P53 mutation-negative tumors, respectively, and P53-expressing tumors. Conclusion Our findings highlight the importance of AR, P53, and P53 mutations as differentiating cofactors and suggest that the targeting of these marker pathways could lead to novel therapies for those patients with limited therapeutic options. AR could be a potential therapeutic target for the management of breast cancer.
The Scientific Journal of King Faisal University, Basic and Applied Sciences, 2022
Sarcomas are a heterogeneous group of malignant tumors that arise from mesenchymal cells and can ... more Sarcomas are a heterogeneous group of malignant tumors that arise from mesenchymal cells and can arise anywhere in the body, whether it is soft tissue or bone. Epidermal growth factor receptor (EGFR) expression in pediatric sarcomas is explored in the current study. A key feature of EGFRs is their general involvement in signal transduction and oncogenesis, making them one of the most studied receptor protein-tyrosine kinase families. The study included 104 archived formalinfixed paraffin-embedded blocks assessed using immunohistochemical stains for EGFR expression in rhabdomyosarcoma, osteosarcoma, and Ewing's sarcoma. EGFR gene copy number was analyzed by dual silver in situ hybridization (DISH). EGFR was positively expressed in 56.7% of pediatric sarcoma. Immunostaining for EGFR was significantly associated with deep large tumors, stage, and histologic grade. Significantly, lower chances of overall survival were observed with elevated levels of EGFR five years post-diagnosis. EGFR staining identified independent risk factors for poor patient outcomes. The results of in situ hybridization did not indicate EGFR gene amplification in any of the cases assessed. EGFR overexpression was an independent predictor of pediatric sarcoma outcome, which is highly associated with histologic grade and stage. Results indicate EGFR inhibitors should be potentiated and directed against pediatric sarcoma.
The Scientific Journal of King Faisal University, Basic and Applied Sciences, 2022
The heterogeneity of ovarian cancer (Ov Ca) is attributed to multiple genetic and epigenetic chan... more The heterogeneity of ovarian cancer (Ov Ca) is attributed to multiple genetic and epigenetic changes, rendering it difficult to detect the most relevant molecular alterations. Identifying copy number variations (CNVs) will be helpful in screening patients with a familial history and will ultimately facilitate early diagnosis. This work aims to determine germline CNVs that may be associated with risks for different subtypes of ovarian cancer. Using Affymetrix genome-wide human SNP 6.0 arrays, 138 germline DNA samples of non-familial ovarian cancer were analysed using Golden Helix (SVS7) software. CNVs overlapping the EYA2 (20q13.12) and WNK1 (12p13.33) genes are the top hits with a significant p-value (<0.05). Deletion is more frequent in normal and low-grade carcinomas. Commonly, ovarian cancer is copy neutral (CN2) or has copy number gains (CN3). Amplification at these locations is associated with high-grade cases, which have worse overall survival rates. A CN3 in the WNK1 gene is associated with a higher expression of mRNA. It could be concluded that ovarian cancer is associated with CN3s where the segments of DNA overlap WNK1 and EYA2. The oncogenic effect of WNK1 and EYA2 on ovaries may serve as prognostic markers for ovarian cancer.
Journal of Umm Al-Qura University for Medical Sciences, 2023
BACKGROUND: Medical students are at a high risk of exposure to Blood-borne Pathogens (BBP) throug... more BACKGROUND: Medical students are at a high risk of exposure to Blood-borne Pathogens (BBP) through their earlier clinical exposure. Aim: Herein, we aim to evaluate their knowledge about BBP and demonstrate their attitudes toward reporting the exposure incident. METHODS: A cross-sectional study was conducted using a structured questionnaire amongst medical students-Umm Al-Qura University. RESULTS: With a moderate response rate (66.5%, n = 905), about 90% (n = 817) of participants had previous knowledge about BBP, 53.5% (n = 484) of the students had a high knowledge level about the mode of transmission of BBP, 78.7% (n = 713) demonstrated low attitudes toward the BBP. About 18% (n= 164) of the respondents were exposed at least once to BBP. The main hazards for student exposure to BBP were younger age, females, lacking prior education about BBP at or after the third year, human immunodeficiency virus as a BBP of major concern, and ignorance of reporting procedures. CONCLUSION: Inadequate knowledge about BBP and some gaps in reporting were observed. Actual effective education for prevention and management is essential to minimize occupational exposure. In addition, it is compulsory to ensure students' knowledge and understanding before allowing them to start clinical training.
Background: PTEN is one of the frequently mutated genes in different sarcoma subtypes. This study... more Background: PTEN is one of the frequently mutated genes in different sarcoma subtypes. This study aims to investigate the potential role and alterations of the PTEN gene in various pediatric sarcoma cases. Methods:169 Saudi pediatric sarcomas patients had full clinical and follow-up data. Next generation sequencing (NGS)-based genomic profiling analysis was done for pediatric sarcomas cases, including rhabdomyosarcoma (RMS), osteosarcoma (OS), and Ewing's sarcoma (ES). Detection of PTEN gene mutation and its asocaiation with loss of PTEN protein expression was investigated. Results: PTEN protein expression was lost in 54 (31.9%) of studied cases. For different sarcoma subgroups, Role of NGS based genomic profiling analysis in identifying targetable genetic alterations in pediatric western Saudi Arabia sarcomas patients: Advanced insights into PTEN
Background. In children, osteosarcoma (OS), Ewing's sarcoma (ES), and rhabdomyosarcoma (RMS) are ... more Background. In children, osteosarcoma (OS), Ewing's sarcoma (ES), and rhabdomyosarcoma (RMS) are the most common sarcomas. A link between the anti-programmed death ligand-1 PD-L1 and the tumor suppressor phosphatase and tensin homologue (PTEN) expression has been described in many tumors. The aim of this work is to determine clinicopathological relationships and the possible prognostic significance of PD-L1 and PTEN expression in rhabdomyosarcoma (RMS), Ewing's sarcoma (ES), and osteosarcoma (OS). Materials and Methods. Expression of PD-L1 and PTEN were examined by immunohistochemistry in 45 archival RMS, ES, and OS cases. Results. The positive expression of PD-L1 was found in 16.7% and 31.6% of ES and OS, respectively. The negative PD-L1 was related to a substantially longer survival in ES cases (p = 0.045), but positive PD-L1 expression was significantly associated with the increased tumor stage and vascular invasion in the OS cases (p = 0.005 and p = 0.002), respectively. On the other hand, PTEN loss was strongly associated with deep tumor, high tumor grade, and recurrence in RMS (p = 0.002, p = 0.045, and p = 0.026, respectively). However, PTEN loss was significantly absent in ES as tumor grade increased (p = 0.031). It is noteworthy that tumor recurrence, the loss of PTEN, and positive PD-L1 were all considered predictive factors in OS patients (p = 0.045, p = 0.032, and p = 0.02, respectively). Conclusions. In children, OS and ES have positive PD-L1 expression, which has an independent unfavorable prognostic effect and raises the possibility of using PD-L1 as a therapeutic target. OS, ES, and RMS prognosis are all predicted by PTEN loss.
This retrospective study comprehensively analyses the epidemiological trends of Central Nervous S... more This retrospective study comprehensively analyses the epidemiological trends of Central Nervous System (CNS) cancers in Saudi Arabia over three decades, from 1990 to 2019. Utilizing data from the Institute for Health Metrics and Evaluation (IHME) and the Saudi Cancer Registry, the study examines incidence, prevalence, and mortality rates, offering a detailed depiction of CNS cancer trends in the region. The findings reveal a significant increase in the incidence of CNS cancers, with rates increasing from 1.1 to 3.63 per 100,000 population. Despite this rise, the incidence in Saudi Arabia remains lower than in more developed regions, suggesting regional variations in risk factors and healthcare practices. The study observes a marked decline in mortality rates, from 25% in 1990 to below 10% in 2019, indicative of the effect of advancements in early detection, molecular diagnostics, and therapeutic interventions. Gender disparities were apparent, with males exhibiting higher incidence and mortality rates, aligning with global epidemiological patterns. The study also highlights demographic variability in CNS cancer incidence, with a prominent increase in adult populations, particularly those aged 55 and above. These findings underscore the need for targeted public health strategies and healthcare policies to address the rising incidence and improve patient outcomes. The study advocates for future research focusing on the etiology of CNS cancers, particularly in genetic and environmental factors, and calls for international collaboration in research to understand global variations in CNS cancer trends.
Cathepsin B is a lysosomal cysteinc proteinase that may participate in cancer progression. associ... more Cathepsin B is a lysosomal cysteinc proteinase that may participate in cancer progression. associated with degradation of laminin. It is increased in colorectal carcinoma (CA). Laminin is a major component of basement membrane involved in cell-matrix interactions and tumor progression. The aim of this study was to correlate cathepsin B and tumor-associated laminin in colorectal adenomas (ADs) with increasing grades of dysplasia and in invasive carcinomas (CAs). Forty-five ADs (8 tubular, 16 tubulovillus and 21 villous), 13 adenomas with high-grade dysplasia/carcinoma in situ (AHDs), and 17 invasive CAs were immunostained with polyclonal antibodies to cathepsin B and laminin. Statistical analysis was performed using exact linear by linear association test and Spearman rank correlation coefficient. Cathepsin B-positive tumor cells were seen in 30 (67%) ADs, 13 (100%) AHDs, and 17 (100%) CAs. The grade of cathepsin B staining was significantly increased in AHDs and CAs, compared with ADs (P < .0001). Laminin was continuous in all of the ADs and fragmented in the AHDs and CAs (P < .0001). The degree of cathepsin B staining in tumor cells also correlated with breakdown of laminin. Increased cathepsin B expression and decrease in tumor-associated laminin might suggest a mechanism for progression of ADs to CAs.
Arab Journal of Biochemistry & Molecular Biology, 2006
Recent studies indicate a major role for PTEN and (transforming growth factor Beta1) TGF-ß1 in pr... more Recent studies indicate a major role for PTEN and (transforming growth factor Beta1) TGF-ß1 in prostate cancer. The combined expression of PTEN and TGF-ß1 was found to strongly increase the development of prostatic carcinomas in an animal model, and a prognostic value in human tumors was postulated. The purpose of our study was to analyses the pattern of expression of PTEN and TGF-ß1 in a series of prostate cancer patients using immunohistochemical technology. The expression of PTEN and TGF-ß1 was examined in transrectal ultrasound-guided prostatic biopsies from 41 patients with primary prostatic carcinomas. The results were related to clinicopathological variables and tumor cell proliferation (Ki-67). PTEN was negative in 11 of 41 tumors (26%), and overexpression of TGF-ß1 was 64%. Inverse patterns of protein expression of TGF-ß1 and PTEN were observed in 22 of 41 (53.7%). Low expression of PTEN was significantly associated with elevated proliferation by Ki-67 and correlated significantly with increasing Gleason score. Our findings strongly support the importance of PTEN and TGF-ß1 for the progression of human prostate cancer and loss of PTEN expression may be an important negative prognostic indicator.
Inositol hexaphosphate (InsP6 or IP6) is a naturally occurring polyphosphorylated carbohydrate th... more Inositol hexaphosphate (InsP6 or IP6) is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plant and mammalian cells. It was recently recognized to possess multiple biological functions. IP6 exerts its effects on the body by controlling cell division. It reduces the rate of cellular proliferation, both in vivo and in vitro, and has exhibited an ability to reduce DNA synthesis and also causes differentiation of various cell lines, including HT-29 human colon carcinoma cell. We hypothesize that the tumor suppressor genes such as p53 and WAF1 may be involved in mediating the anti-neoplastic action of lP6. p53 acts as a molecular policeman preventing propagation of genetically damaged cells; it causes the cells to arrest in the Gl phase of cell cycle, and regulates the level of p21 waf1 which acts as a growth inhibitor. We therefore investigated the effects of ip6 on the expression of p53 and WAF1/p21 in PC-3 human prostate carcinoma by immunocytochemistry. Our immunocytochemical studies with anti p53 antibodies (wild type-PAb246 and Pab1620) and anti p21 waf1 (EA10) antibodies demonstrated an increased level of p53 and p21 waf1 after 3 and 6 days of treatment with 3.3 and 5 mM IP6. This increase was dose-dependent; however, a definite time-dependent increase was not observed. These data demonstrate that IP6 up-regulates the expression of the tumor suppressor gene p53 and p21 waf1 gene and their modulation may be one of the mechanisms of the anti-neoplastic action of IP6 since loss of p53 function enhances cancer cells resistance to chemotherapeutic agents, the stimulating function of IP6 on p53 makes it an attractive adjuvant chemotherapeutic agent as well.
Colorectal neoplasia provides an attractive model of tumour biology with normal mucosa-adenoma-ca... more Colorectal neoplasia provides an attractive model of tumour biology with normal mucosa-adenoma-carcinoma sequence. In precancerous and cancerous lesions of the gastrointestinal tract, patterns of differentiation may be characterized by the domination of a particular lineage, for example mucous/goblet cell versus absorptive/columnar cell. It is now possible to employ monoclonal antibodies to apomucins encoded by the MUC gene family and thereby achieves lineage-based classifications for colorectal neoplasm. MUC2 plays an important role in tumour biology. MUC2 apomucin was localized predominantly in the rough endoplasmic reticulum in normal colorectal mucosa, colorectal adenoma, and colorectal adenocarcinoma. The T-antigen (Thomsen-Friedenreich antigen) also known as D-galactose-B[1-3]-N-acetyl-D-galactosamine (Gal-GaINAc) can be identified by a very simple galactose oxidase-Schiff's (GOS) reaction either on tissues or on rectal mucus samples from patients with colorectal neoplasms. T-antigen is expressed in the neoplastic mucosa as well as the remote non-neoplastic.mucosa. It is, however, not expressed in colonic mucosa of normal subjects. We studied the expression of T-antigen by GOS reaction and immunocytochemistry (Anti-Tag Ab) comparing it with immunoreactivity of the MUC2 Mucin in 10 normal, 45 precancerous [5 Crohn's disease, 15 ulcerative colitis (5 without dysplasia and 10 with dysplasia), 25 tubular adenomas, and 25 adenocarcinoma cases. Normal mucosa remote from tubular adenoma and adenocarcinoma was also studied. GOS reaction was negative in all of the 10 normal specimens. Of the 5 Crohn's disease specimens, 2 were positive and 3 negative. In the 5 ulcerative colitis cases without dysplasia, positive reaction was seen in 2 cases and negative in 3. Of the 10 cases of ulcerative colitis with dysplasia, 5 showed positivity in dysplastic areas, and 3 of these were also positive in remote non dysplastic mucosa. Twenty of 25 tubular adenomas yielded a positive reaction in the adenoma, 14 of them showing positivity also in remote mucosa; 3 cases showed a positive reaction only in remote mucosa. Of the 25 adenocarcinomas, 21 showed a positive reaction in the adenocarcinoma as well as the remote mucosa. GOS reaction was intense in well differentiated adenocarcinoma and weak in poorly differentiated adenocarcinoma. Intense reaction was also seen in the intracellular mucus of some aberrant crypts and morphologically normal crypts remote from adenocarcinoma and tubular adenoma. GOS reaction showed an overall sensitivity of 75.7% and specificity of 100% for cancer and precancerous lesions. MUC2 reactivity was slightly more sensitive (84.3%) but less specific (80%) and Tag Ab reactivity even less sensitive (50%) but as specific (100%) for neoplastic and dysplastic mucosa. We conclude that the detection of the carbohydrate moiety T-antigen with the technique used GOS reaction is extremely simple and has a high degree of sensitivity and specificity. It can be used for detection of this tumour marker in remote non-neoplastic mucosa of patients with neoplasia or at risk of developing neoplasia. It, therefore, could be used as a cost effective screening test in rectal biopsy specimens of such patients.
esophageal carcinoma and analyzing their interrelationship with clinicopathological variables. ME... more esophageal carcinoma and analyzing their interrelationship with clinicopathological variables. METHODS: Expression of epidermal growth factor receptor (EGFR) and E-cadherin was determined by immunohistochemical technique in 54 patients with esophageal carcinoma. RESULTS: Expression of EGFR was detected in 36 out of 54 (66.7%) of patients and correlated significantly with histologic grade (P = 0.001). Reduced homogenous expression of E-cadherin was observed in 34 out of 54 (63%) of patients. Significant inverse correlation existed between E-cadherin expression and histologic grade (P = 0.01). The correlation between E-cadherin and EGFR was statistically significant (P = 0.03). CONCLUSION: Combined technique of detecting expression of EGFR and E-cadherin may be useful as an indicator for grading the biological behavior and characteristics of esophageal carcinoma.
Many chromosomes undergo lesions in breast cancer including deletions, insertions, translocations... more Many chromosomes undergo lesions in breast cancer including deletions, insertions, translocations and point changes. Deletions may be extensive or relatively limited and provide a strategy for the identification of cryptic tumour suppressor genes (TSG) based on allelic imbalance at microsatellites. Detection of identical allelic loss on chromosome 11q13 in carcinoma in situ and invasive breast cancer may be helpful in detecting whether or not 11q13 occupy a tumour suppressor gene. Fluorescent in situ hybridization is a sensitive, and rapid method for diagnostic and prognostic evaluation of tumours. It provides an ideal method for analysis of chromosomal amplification and a check on loss of heterozygosity (LOH). The microsatellite loci were analysed by PCR using DNA from microdissected tissue of 22 archival breast cancer cases. From each of the 22 breast cancer cases chosen, a number of foci were microdissected originating from histologically distinctive pieces of tumour (DCIS, IDC, LCIS, ILC) and used for the isolation of DNA. PCR of each DNA preparation for INT-2 and PYGM locus was carried out with one primer of each set tagged with a fluorescent label for subsequent analysis. The PCR products were checked for LOH or microsatellite instability. Since amplification at 11q has been reported, Fluorescent in situ Hybridisation (FISH) using a probe specific to the INT-2 locus assessed its frequency. Two spots of loss of heterozygosity (LOH) were detected at INT-2 and PYGM in 12/22 (57%) and 5/22 (23%) respectively and another two spots of MSI were found at INT-2 and PYGM in 7/22 (32%) and 2/22 (9%) respectively. While by doing fluorescent in situ hybridisation (FISH) to detect amplification at INT-2 locus, only 9% of the cases contain amplification. With respect to pathology, out of 22 cases studied 7 (32 %) were found to contain DCIS while 21 of the 22 contained IDC (95 %). On a global scale, all samples of DCIS showed LOH in at least one locus while LOH was only found in 16/21 (76 %) cases with IDC. These results suggest that LOH on chromosome11q13 play an important rule in breast cancer development and suggest that alterations of candidate genes located in these chromosomal regions may play a role early in breast carcinogenesis.
Mutations of the p53 tumour suppressor gene appear to be one of the most common abnormalities in ... more Mutations of the p53 tumour suppressor gene appear to be one of the most common abnormalities in human cancer including lung cancer. P53 protein has an important role in gene transcription, DNA repair and induction of apoptosis. The p53 gene is frequently mutated in non-small-cell lung cancer (NSCLC); during malignant progression with the majority mutations found in exons 5-8. Missense mutation of the p53 gene usually but not always prolongs the half-life of the protein from minutes to hours and results in nuclear accumulation of the p53 protein, which can be detected by IHC. Immunohistochemistry was used initially to select p53-positive cases and these were then screened for mutations in exons 5-8 by polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE). The identities of the mutations in cases selected by DGGE were then determined by direct sequencing of the PCR products. As a result of IHC, 23/47 (49%) cases were deemed to over express p53 and were analysed by DGGE. Mutations were indicated by DGGE and confirmed by sequencing in 9/23 (39%) of the IHC positive cases. The nature of p53 mutations may provide aetiological information so the aim of this study was to scan the central region of p53 gene for mutation in randomly selected non-small cell lung carcinomas to possibly indicate aetiology of the disease and to determine the frequency of p53 mutation in NSCLC.
Background: Molecular mechanisms that regulate development of hepatocellular carcinoma (HCC) are ... more Background: Molecular mechanisms that regulate development of hepatocellular carcinoma (HCC) are still unclear. Several risk factors may predispose to HCC like viral etiology HBV or HCV, genetic makeup, and environmental exposure. Genetic factors include activation of oncogenes and inactivation of tumor suppressor genes. P27 kip1 , p53 and Ki-67 are important biomarkers involved in hepatic carcinogenesis. Aim of Work: To investigate the relation between p27 kip1 expression in HCC and both clinical and radiological parameters. Also to study the relation between p27 kip1 expression and both Ki-67 and p53 expression. Subjects and Methods: We examined 32 cases of HCC; their mean age was 58.2±6.2 years, including 26 males and 6 females. All of them were subjected to clinical examination, laboratory investigations including, liver function tests, viral markers, AFP assay, imaging studies including abdominal ultrasound and helical multiphasic abdominal CT scans. CT guided biopsy was obtained from all patients. Ten cases had analysis of surrounding non-cancerous tissue. Histopathological examination was done to assess tumor grading. Immunohistochemical evaluation was done to evaluate expression of p27 kip1 , Ki-67 and p53. Results: The p27 kip1 protein positive expression rate in HCC was 56.25% compared to 100% in surrounding non-cancerous tissue. P27 kip1 expression was not related to age, sex, Child grade, and tumor multiplicity or tumor size. However, negative expression rate was significantly higher in cases with ill-defined margins, tumor thrombus, and upper abdominal lymphadenopathy (P< 0.03, 0.02, 0.05 respectively). P27 kip1 expression rate in poorly differentiated group (Grade III-IV) was significantly lower than in well differentiated group (Grade I-II) [P<0.007]. No relation was found between p27 kip1 expression and liver functions, level of AFP, presence of HBsAg or HCV Ab. There was marked reduction of p27 kip1 expression and high expression of Ki-67 in HCC but no correlation was found between p27 kip1 expression and P53 positive expression. Diffuse cytoplasmic immunostaining for p27 kip1 was found in 12 (37.5%) of cases.
For endometrial carcinoma patients, there is a need for improved identification of high-risk grou... more For endometrial carcinoma patients, there is a need for improved identification of high-risk groups that may benefit from postoperative adjuvant therapy. Aberrant expression of several cell-cycle regulators has been reported in endometrial carcinoma, correlations among some of these factors and their prognostic significance have been systematically examined. Immunohistochemical expression of cyclin D1 and tumor-suppressor gene p21 WAF1 in 32 endometrial carcinoma (EC), including 12 low-grade (grade I) and 20 high-grade (grade II or III) tumors was evaluated. Results were compared with the expression of steroid receptor status, progesterone receptor (PR). Positive staining for cyclin D1 and p21 WAF1 was more frequent in higher grade tumors and their expression were significantly frequent in advanced-stage tumors. Ninety percent (18 of 20) of the high grade EC expressed cyclin D1 at a high level, whereas only 42% (5 of 12) of the low grade EC did so (Chi2 = 8.7; P < 0.01). Sixty-five percent (13 of 20) of the high grade EC expressed p21 WAF1 at high levels, but only 17% (2 of 12) of low grade EC did so (Chi2 = 7.0; P < 0.01). Coordinate high level expression of p21 WAF1 and cyclin D1 occurred in 65% (13 of 20) of high grade EC but in only 17% (2 of 12) of the low grade EC (Chi2 = 7.0; P < 0.01). These findings suggest that cyclin D1 and p21 WAF1 are involved in activated cell growth of endometrial carcinoma, and that positive staining for them could be a useful marker for unfavorable patient prognosis.
Introduction and aim of the work: Abdominal ultrasound (US) is often used as the first imaging mo... more Introduction and aim of the work: Abdominal ultrasound (US) is often used as the first imaging modality in a large variety of abdominal complaints and clinically unsuspected gastric carcinomas may be firstly imaged by it. Aim: to determine the value of transabdominal sonography (TAS) in the prediction of gastric cancer. Patients and methods: Two thousands patients with epigastric pain were included in the study, we select twenty two of them had thickening of the gastric wall on (TAS). They were selected from the outpatient clinics of Tropical and Internal Medicine Depatments of El-Minia University Hospital during the period from March 2006 to February 2008. The included patients underwent the following: history, clinical examination, transabdominal ultrasonography, upper gastrointestinal endoscopy and multiple biopsies were taken from the site of lesion for histopathological examination. The TAS results of the stomach evaluation were compared with the pathological findings. Results: The selected patients (22) were classified into 2 groups based on histopathological findings, benign disease group(4 cases) and gastric cancer group(18 cases): The benign group including 2 patients with benign gastric ulcer and 2 patients with gastritis & the malignant group including 12 patients with adenocarcinoma, 5 patients with non-Hodgkin lymphoma and one patient with anaplastic carcinoma. There is statistically significant difference between the benign group and the malignant group as regard the wall thickness, loss of wall layering, wall hypoechogenicity and luminal narrowing while there is no significant difference as regard the presence or absence of gastric mass. Gastric wall thickness on transabdominal ultrasonography of >10 mm is the best cut off point for prediction of gastric malignant tumours with a sensitivity 94.4%, specificity 100%, positive predictive value 100% and negative predictive value 80%. Loss of wall layering has the same sensitivity, specificity and predictive values as gastric wall thickness. Loss of wall layering is the most independent factor for prediction of gastric cancer. Conclusion: Transabdominal sonography findings of a gastric wall thickness >10 mm with loss of layering of the gastric wall were found to be a predictors for gastric cancer and therefore, careful evaluation of the gastric wall should be made during TAS examination.
Conjunctival squamous cell carcinoma (CSCC) is an invasive ocular surface neoplasia ranging from ... more Conjunctival squamous cell carcinoma (CSCC) is an invasive ocular surface neoplasia ranging from dysplasia to carcinoma in situ to invasive squamous cell carcinoma, which is identifi ed as premalignant and malignant epithelial lesions. Often, it is seen in males in tropical countries lying close to the equator where there is excessive exposure to sunlight. Clinical diagnosis requires close examination with a degree of high suspicion. Appropriate and defi nitive diagnosis of conjunctival squamous neoplasia by ocular pathologists and the need for future detailed clinicopathologic studies is recommended. Appropriate and defi nitive diagnosis requires histopathology. We describe a case of CSCC underlying dysplasia with intraepithelial squamous cell neoplasia, where the case was confi rmed by histopathological examination. Th e treatment modality involving surgery and medication and follow-up is described. Th ere was no evidence of recurrence, complication, or metastasis.
Objectives: To develop an alternative medicine, propolis, in emulgel formulation for burn and wou... more Objectives: To develop an alternative medicine, propolis, in emulgel formulation for burn and wound treatment. Methods: The effect of two independent variables: emulsifying agent concentration and oil concentration on the cumulative amount of propolis release (dependent variable) from liquid paraffin and isopropyl palmitate emulgels was investigated. Eight formulations were prepared and evaluated for physical appearance, pH, propolis content, viscosity, and in vitro propolis release. The release results were fitted into different kinetic equations and analyzed using contour plot, interaction surface plot and one-way ANOVA. The selected emulgel formulation was investigated for its wound and burn healing activity in rats. Results: All the prepared emulgels showed acceptable physical properties concerning color, homogeneity, consistency, and pH value. The concentration of emulsifying agent had more pronounced effect on propolis release than oil concentration. Formulations F1-F6 showed "anomalous" drug release, while Formulations F7 and F8 showed zero-order kinetic. Conclusion: The formulation F7 with 5% isopropyl palmitate, 5% emulsifier mixture, 1% hydroxyl propyl methyl cellulose, 1% oleic acid, and 10% propylene glycol is a promising formula for better management of wound and burn.
Introduction
The obesity epidemic has been linked to a wide range of health and nutritional probl... more Introduction The obesity epidemic has been linked to a wide range of health and nutritional problems, including anemia, which is often caused by impaired iron metabolism. The World Health Organization considers anemia and obesity to be global health issues among adolescent girls and women experiencing menstruation. This study aims to examine the association between iron deficiency anemia and obesity/overweight among female medical students. Methodology This cross-sectional descriptive study conducted as an online self-administered questionnaire. Furthermore, blood samples were collected from 206 students to evaluate the complete blood count, iron and lipid profile. Results The convenience sampling technique was used and a total of 206 students were enrolled in the study. The average body mass index (BMI) was 22.51 ± 3.25, with 83.5% (n = 172) falling within the normal weight range, 12.6% (n = 26) as overweight, and 3.9% (n = 8) as obese. Anemia was present in 16.0% (n = 33) of the participants overall. Higher prevalence of anemia was observed among overweight participants with 10 out of 26 (38.5%) subjects compared to obese with two out of eight (25.0%) and normal weight 21 out of 172 (12.2%); this difference was highly significant (P = 0.005). Individuals with anemia exhibited a significant association with those experiencing a diet full of unhealthy fats and carbohydrates (P = 0.05) and a diet containing all essential nutrients (P = 0.01). There is no statistically significant correlation between anemia prevalence and participants' response to the presence of signs of anemia, physical activity or other dietary habits. Obese participants had a significantly higher mean value of triglycerides (129.5 ± 20.5) compared to normal weight and overweight participants (74.5 ± 12.02 and 51.2 ± 15.04), respectively (P = 0.001). Conclusion A dependable assembly exists between obesity and overweight in cases of iron deficient anemia. The prevalence of iron deficiency anemia was substantially higher among overweight/obese females, highlighting that overweight/obesity signifies both quantitative and qualitative malnutrition. A high BMI was associated with elevated triglycerides, typically considered indicators of obesity. This association may suggest compromised iron homeostasis.
Background
Despite the introduction of several methods and new therapeutics to classify and
treat... more Background Despite the introduction of several methods and new therapeutics to classify and treat breast cancer, it remains the most common cancer among women and contributes to higher mortality rates worldwide. Purpose This study aimed to analyze the expression levels of the androgen receptor (AR), P53 protein, and P53 mutations among molecular subtypes of breast cancers and their correlation with patients’ outcome. Patients and methods Immunostaining for estrogen receptor (ER), progesterone receptor (PR), Ki-67, and human epidermal growth factor receptor 2 (HER2) to stratify breast cancers into basal-like, HER2 type, luminal A or B types. AR, P53 expressions, and P53 mutations was compared among groups. Results Overall, 37.5% of basal-like and 7.1% of HER2 types of invasive breast carcinomas were AR positive. P53 was expressed in 62.5 and 50% of basal-like and HER2 types, respectively. The P53 mutation varied significantly among the molecular subtypes (P<0.0001) and was found in 43.8 and 42.9% of basal-like and HER2 types, respectively. Extensive nodal status, higher stage, and P53 mutation independently predicted the overall survival. AR-negative and P53 mutationpositive tumors had intermediate or poor Nottingham Prognostic Index and were more often nodal positive, higher grade, and higher stage than AR-positive and P53 mutation-negative tumors, respectively, and P53-expressing tumors. Conclusion Our findings highlight the importance of AR, P53, and P53 mutations as differentiating cofactors and suggest that the targeting of these marker pathways could lead to novel therapies for those patients with limited therapeutic options. AR could be a potential therapeutic target for the management of breast cancer.
The Scientific Journal of King Faisal University, Basic and Applied Sciences, 2022
Sarcomas are a heterogeneous group of malignant tumors that arise from mesenchymal cells and can ... more Sarcomas are a heterogeneous group of malignant tumors that arise from mesenchymal cells and can arise anywhere in the body, whether it is soft tissue or bone. Epidermal growth factor receptor (EGFR) expression in pediatric sarcomas is explored in the current study. A key feature of EGFRs is their general involvement in signal transduction and oncogenesis, making them one of the most studied receptor protein-tyrosine kinase families. The study included 104 archived formalinfixed paraffin-embedded blocks assessed using immunohistochemical stains for EGFR expression in rhabdomyosarcoma, osteosarcoma, and Ewing's sarcoma. EGFR gene copy number was analyzed by dual silver in situ hybridization (DISH). EGFR was positively expressed in 56.7% of pediatric sarcoma. Immunostaining for EGFR was significantly associated with deep large tumors, stage, and histologic grade. Significantly, lower chances of overall survival were observed with elevated levels of EGFR five years post-diagnosis. EGFR staining identified independent risk factors for poor patient outcomes. The results of in situ hybridization did not indicate EGFR gene amplification in any of the cases assessed. EGFR overexpression was an independent predictor of pediatric sarcoma outcome, which is highly associated with histologic grade and stage. Results indicate EGFR inhibitors should be potentiated and directed against pediatric sarcoma.
The Scientific Journal of King Faisal University, Basic and Applied Sciences, 2022
The heterogeneity of ovarian cancer (Ov Ca) is attributed to multiple genetic and epigenetic chan... more The heterogeneity of ovarian cancer (Ov Ca) is attributed to multiple genetic and epigenetic changes, rendering it difficult to detect the most relevant molecular alterations. Identifying copy number variations (CNVs) will be helpful in screening patients with a familial history and will ultimately facilitate early diagnosis. This work aims to determine germline CNVs that may be associated with risks for different subtypes of ovarian cancer. Using Affymetrix genome-wide human SNP 6.0 arrays, 138 germline DNA samples of non-familial ovarian cancer were analysed using Golden Helix (SVS7) software. CNVs overlapping the EYA2 (20q13.12) and WNK1 (12p13.33) genes are the top hits with a significant p-value (<0.05). Deletion is more frequent in normal and low-grade carcinomas. Commonly, ovarian cancer is copy neutral (CN2) or has copy number gains (CN3). Amplification at these locations is associated with high-grade cases, which have worse overall survival rates. A CN3 in the WNK1 gene is associated with a higher expression of mRNA. It could be concluded that ovarian cancer is associated with CN3s where the segments of DNA overlap WNK1 and EYA2. The oncogenic effect of WNK1 and EYA2 on ovaries may serve as prognostic markers for ovarian cancer.
Journal of Umm Al-Qura University for Medical Sciences, 2023
BACKGROUND: Medical students are at a high risk of exposure to Blood-borne Pathogens (BBP) throug... more BACKGROUND: Medical students are at a high risk of exposure to Blood-borne Pathogens (BBP) through their earlier clinical exposure. Aim: Herein, we aim to evaluate their knowledge about BBP and demonstrate their attitudes toward reporting the exposure incident. METHODS: A cross-sectional study was conducted using a structured questionnaire amongst medical students-Umm Al-Qura University. RESULTS: With a moderate response rate (66.5%, n = 905), about 90% (n = 817) of participants had previous knowledge about BBP, 53.5% (n = 484) of the students had a high knowledge level about the mode of transmission of BBP, 78.7% (n = 713) demonstrated low attitudes toward the BBP. About 18% (n= 164) of the respondents were exposed at least once to BBP. The main hazards for student exposure to BBP were younger age, females, lacking prior education about BBP at or after the third year, human immunodeficiency virus as a BBP of major concern, and ignorance of reporting procedures. CONCLUSION: Inadequate knowledge about BBP and some gaps in reporting were observed. Actual effective education for prevention and management is essential to minimize occupational exposure. In addition, it is compulsory to ensure students' knowledge and understanding before allowing them to start clinical training.
Background: PTEN is one of the frequently mutated genes in different sarcoma subtypes. This study... more Background: PTEN is one of the frequently mutated genes in different sarcoma subtypes. This study aims to investigate the potential role and alterations of the PTEN gene in various pediatric sarcoma cases. Methods:169 Saudi pediatric sarcomas patients had full clinical and follow-up data. Next generation sequencing (NGS)-based genomic profiling analysis was done for pediatric sarcomas cases, including rhabdomyosarcoma (RMS), osteosarcoma (OS), and Ewing's sarcoma (ES). Detection of PTEN gene mutation and its asocaiation with loss of PTEN protein expression was investigated. Results: PTEN protein expression was lost in 54 (31.9%) of studied cases. For different sarcoma subgroups, Role of NGS based genomic profiling analysis in identifying targetable genetic alterations in pediatric western Saudi Arabia sarcomas patients: Advanced insights into PTEN
Background. In children, osteosarcoma (OS), Ewing's sarcoma (ES), and rhabdomyosarcoma (RMS) are ... more Background. In children, osteosarcoma (OS), Ewing's sarcoma (ES), and rhabdomyosarcoma (RMS) are the most common sarcomas. A link between the anti-programmed death ligand-1 PD-L1 and the tumor suppressor phosphatase and tensin homologue (PTEN) expression has been described in many tumors. The aim of this work is to determine clinicopathological relationships and the possible prognostic significance of PD-L1 and PTEN expression in rhabdomyosarcoma (RMS), Ewing's sarcoma (ES), and osteosarcoma (OS). Materials and Methods. Expression of PD-L1 and PTEN were examined by immunohistochemistry in 45 archival RMS, ES, and OS cases. Results. The positive expression of PD-L1 was found in 16.7% and 31.6% of ES and OS, respectively. The negative PD-L1 was related to a substantially longer survival in ES cases (p = 0.045), but positive PD-L1 expression was significantly associated with the increased tumor stage and vascular invasion in the OS cases (p = 0.005 and p = 0.002), respectively. On the other hand, PTEN loss was strongly associated with deep tumor, high tumor grade, and recurrence in RMS (p = 0.002, p = 0.045, and p = 0.026, respectively). However, PTEN loss was significantly absent in ES as tumor grade increased (p = 0.031). It is noteworthy that tumor recurrence, the loss of PTEN, and positive PD-L1 were all considered predictive factors in OS patients (p = 0.045, p = 0.032, and p = 0.02, respectively). Conclusions. In children, OS and ES have positive PD-L1 expression, which has an independent unfavorable prognostic effect and raises the possibility of using PD-L1 as a therapeutic target. OS, ES, and RMS prognosis are all predicted by PTEN loss.
This retrospective study comprehensively analyses the epidemiological trends of Central Nervous S... more This retrospective study comprehensively analyses the epidemiological trends of Central Nervous System (CNS) cancers in Saudi Arabia over three decades, from 1990 to 2019. Utilizing data from the Institute for Health Metrics and Evaluation (IHME) and the Saudi Cancer Registry, the study examines incidence, prevalence, and mortality rates, offering a detailed depiction of CNS cancer trends in the region. The findings reveal a significant increase in the incidence of CNS cancers, with rates increasing from 1.1 to 3.63 per 100,000 population. Despite this rise, the incidence in Saudi Arabia remains lower than in more developed regions, suggesting regional variations in risk factors and healthcare practices. The study observes a marked decline in mortality rates, from 25% in 1990 to below 10% in 2019, indicative of the effect of advancements in early detection, molecular diagnostics, and therapeutic interventions. Gender disparities were apparent, with males exhibiting higher incidence and mortality rates, aligning with global epidemiological patterns. The study also highlights demographic variability in CNS cancer incidence, with a prominent increase in adult populations, particularly those aged 55 and above. These findings underscore the need for targeted public health strategies and healthcare policies to address the rising incidence and improve patient outcomes. The study advocates for future research focusing on the etiology of CNS cancers, particularly in genetic and environmental factors, and calls for international collaboration in research to understand global variations in CNS cancer trends.
Cathepsin B is a lysosomal cysteinc proteinase that may participate in cancer progression. associ... more Cathepsin B is a lysosomal cysteinc proteinase that may participate in cancer progression. associated with degradation of laminin. It is increased in colorectal carcinoma (CA). Laminin is a major component of basement membrane involved in cell-matrix interactions and tumor progression. The aim of this study was to correlate cathepsin B and tumor-associated laminin in colorectal adenomas (ADs) with increasing grades of dysplasia and in invasive carcinomas (CAs). Forty-five ADs (8 tubular, 16 tubulovillus and 21 villous), 13 adenomas with high-grade dysplasia/carcinoma in situ (AHDs), and 17 invasive CAs were immunostained with polyclonal antibodies to cathepsin B and laminin. Statistical analysis was performed using exact linear by linear association test and Spearman rank correlation coefficient. Cathepsin B-positive tumor cells were seen in 30 (67%) ADs, 13 (100%) AHDs, and 17 (100%) CAs. The grade of cathepsin B staining was significantly increased in AHDs and CAs, compared with ADs (P < .0001). Laminin was continuous in all of the ADs and fragmented in the AHDs and CAs (P < .0001). The degree of cathepsin B staining in tumor cells also correlated with breakdown of laminin. Increased cathepsin B expression and decrease in tumor-associated laminin might suggest a mechanism for progression of ADs to CAs.
Arab Journal of Biochemistry & Molecular Biology, 2006
Recent studies indicate a major role for PTEN and (transforming growth factor Beta1) TGF-ß1 in pr... more Recent studies indicate a major role for PTEN and (transforming growth factor Beta1) TGF-ß1 in prostate cancer. The combined expression of PTEN and TGF-ß1 was found to strongly increase the development of prostatic carcinomas in an animal model, and a prognostic value in human tumors was postulated. The purpose of our study was to analyses the pattern of expression of PTEN and TGF-ß1 in a series of prostate cancer patients using immunohistochemical technology. The expression of PTEN and TGF-ß1 was examined in transrectal ultrasound-guided prostatic biopsies from 41 patients with primary prostatic carcinomas. The results were related to clinicopathological variables and tumor cell proliferation (Ki-67). PTEN was negative in 11 of 41 tumors (26%), and overexpression of TGF-ß1 was 64%. Inverse patterns of protein expression of TGF-ß1 and PTEN were observed in 22 of 41 (53.7%). Low expression of PTEN was significantly associated with elevated proliferation by Ki-67 and correlated significantly with increasing Gleason score. Our findings strongly support the importance of PTEN and TGF-ß1 for the progression of human prostate cancer and loss of PTEN expression may be an important negative prognostic indicator.
Inositol hexaphosphate (InsP6 or IP6) is a naturally occurring polyphosphorylated carbohydrate th... more Inositol hexaphosphate (InsP6 or IP6) is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plant and mammalian cells. It was recently recognized to possess multiple biological functions. IP6 exerts its effects on the body by controlling cell division. It reduces the rate of cellular proliferation, both in vivo and in vitro, and has exhibited an ability to reduce DNA synthesis and also causes differentiation of various cell lines, including HT-29 human colon carcinoma cell. We hypothesize that the tumor suppressor genes such as p53 and WAF1 may be involved in mediating the anti-neoplastic action of lP6. p53 acts as a molecular policeman preventing propagation of genetically damaged cells; it causes the cells to arrest in the Gl phase of cell cycle, and regulates the level of p21 waf1 which acts as a growth inhibitor. We therefore investigated the effects of ip6 on the expression of p53 and WAF1/p21 in PC-3 human prostate carcinoma by immunocytochemistry. Our immunocytochemical studies with anti p53 antibodies (wild type-PAb246 and Pab1620) and anti p21 waf1 (EA10) antibodies demonstrated an increased level of p53 and p21 waf1 after 3 and 6 days of treatment with 3.3 and 5 mM IP6. This increase was dose-dependent; however, a definite time-dependent increase was not observed. These data demonstrate that IP6 up-regulates the expression of the tumor suppressor gene p53 and p21 waf1 gene and their modulation may be one of the mechanisms of the anti-neoplastic action of IP6 since loss of p53 function enhances cancer cells resistance to chemotherapeutic agents, the stimulating function of IP6 on p53 makes it an attractive adjuvant chemotherapeutic agent as well.
Colorectal neoplasia provides an attractive model of tumour biology with normal mucosa-adenoma-ca... more Colorectal neoplasia provides an attractive model of tumour biology with normal mucosa-adenoma-carcinoma sequence. In precancerous and cancerous lesions of the gastrointestinal tract, patterns of differentiation may be characterized by the domination of a particular lineage, for example mucous/goblet cell versus absorptive/columnar cell. It is now possible to employ monoclonal antibodies to apomucins encoded by the MUC gene family and thereby achieves lineage-based classifications for colorectal neoplasm. MUC2 plays an important role in tumour biology. MUC2 apomucin was localized predominantly in the rough endoplasmic reticulum in normal colorectal mucosa, colorectal adenoma, and colorectal adenocarcinoma. The T-antigen (Thomsen-Friedenreich antigen) also known as D-galactose-B[1-3]-N-acetyl-D-galactosamine (Gal-GaINAc) can be identified by a very simple galactose oxidase-Schiff's (GOS) reaction either on tissues or on rectal mucus samples from patients with colorectal neoplasms. T-antigen is expressed in the neoplastic mucosa as well as the remote non-neoplastic.mucosa. It is, however, not expressed in colonic mucosa of normal subjects. We studied the expression of T-antigen by GOS reaction and immunocytochemistry (Anti-Tag Ab) comparing it with immunoreactivity of the MUC2 Mucin in 10 normal, 45 precancerous [5 Crohn's disease, 15 ulcerative colitis (5 without dysplasia and 10 with dysplasia), 25 tubular adenomas, and 25 adenocarcinoma cases. Normal mucosa remote from tubular adenoma and adenocarcinoma was also studied. GOS reaction was negative in all of the 10 normal specimens. Of the 5 Crohn's disease specimens, 2 were positive and 3 negative. In the 5 ulcerative colitis cases without dysplasia, positive reaction was seen in 2 cases and negative in 3. Of the 10 cases of ulcerative colitis with dysplasia, 5 showed positivity in dysplastic areas, and 3 of these were also positive in remote non dysplastic mucosa. Twenty of 25 tubular adenomas yielded a positive reaction in the adenoma, 14 of them showing positivity also in remote mucosa; 3 cases showed a positive reaction only in remote mucosa. Of the 25 adenocarcinomas, 21 showed a positive reaction in the adenocarcinoma as well as the remote mucosa. GOS reaction was intense in well differentiated adenocarcinoma and weak in poorly differentiated adenocarcinoma. Intense reaction was also seen in the intracellular mucus of some aberrant crypts and morphologically normal crypts remote from adenocarcinoma and tubular adenoma. GOS reaction showed an overall sensitivity of 75.7% and specificity of 100% for cancer and precancerous lesions. MUC2 reactivity was slightly more sensitive (84.3%) but less specific (80%) and Tag Ab reactivity even less sensitive (50%) but as specific (100%) for neoplastic and dysplastic mucosa. We conclude that the detection of the carbohydrate moiety T-antigen with the technique used GOS reaction is extremely simple and has a high degree of sensitivity and specificity. It can be used for detection of this tumour marker in remote non-neoplastic mucosa of patients with neoplasia or at risk of developing neoplasia. It, therefore, could be used as a cost effective screening test in rectal biopsy specimens of such patients.
esophageal carcinoma and analyzing their interrelationship with clinicopathological variables. ME... more esophageal carcinoma and analyzing their interrelationship with clinicopathological variables. METHODS: Expression of epidermal growth factor receptor (EGFR) and E-cadherin was determined by immunohistochemical technique in 54 patients with esophageal carcinoma. RESULTS: Expression of EGFR was detected in 36 out of 54 (66.7%) of patients and correlated significantly with histologic grade (P = 0.001). Reduced homogenous expression of E-cadherin was observed in 34 out of 54 (63%) of patients. Significant inverse correlation existed between E-cadherin expression and histologic grade (P = 0.01). The correlation between E-cadherin and EGFR was statistically significant (P = 0.03). CONCLUSION: Combined technique of detecting expression of EGFR and E-cadherin may be useful as an indicator for grading the biological behavior and characteristics of esophageal carcinoma.
Many chromosomes undergo lesions in breast cancer including deletions, insertions, translocations... more Many chromosomes undergo lesions in breast cancer including deletions, insertions, translocations and point changes. Deletions may be extensive or relatively limited and provide a strategy for the identification of cryptic tumour suppressor genes (TSG) based on allelic imbalance at microsatellites. Detection of identical allelic loss on chromosome 11q13 in carcinoma in situ and invasive breast cancer may be helpful in detecting whether or not 11q13 occupy a tumour suppressor gene. Fluorescent in situ hybridization is a sensitive, and rapid method for diagnostic and prognostic evaluation of tumours. It provides an ideal method for analysis of chromosomal amplification and a check on loss of heterozygosity (LOH). The microsatellite loci were analysed by PCR using DNA from microdissected tissue of 22 archival breast cancer cases. From each of the 22 breast cancer cases chosen, a number of foci were microdissected originating from histologically distinctive pieces of tumour (DCIS, IDC, LCIS, ILC) and used for the isolation of DNA. PCR of each DNA preparation for INT-2 and PYGM locus was carried out with one primer of each set tagged with a fluorescent label for subsequent analysis. The PCR products were checked for LOH or microsatellite instability. Since amplification at 11q has been reported, Fluorescent in situ Hybridisation (FISH) using a probe specific to the INT-2 locus assessed its frequency. Two spots of loss of heterozygosity (LOH) were detected at INT-2 and PYGM in 12/22 (57%) and 5/22 (23%) respectively and another two spots of MSI were found at INT-2 and PYGM in 7/22 (32%) and 2/22 (9%) respectively. While by doing fluorescent in situ hybridisation (FISH) to detect amplification at INT-2 locus, only 9% of the cases contain amplification. With respect to pathology, out of 22 cases studied 7 (32 %) were found to contain DCIS while 21 of the 22 contained IDC (95 %). On a global scale, all samples of DCIS showed LOH in at least one locus while LOH was only found in 16/21 (76 %) cases with IDC. These results suggest that LOH on chromosome11q13 play an important rule in breast cancer development and suggest that alterations of candidate genes located in these chromosomal regions may play a role early in breast carcinogenesis.
Mutations of the p53 tumour suppressor gene appear to be one of the most common abnormalities in ... more Mutations of the p53 tumour suppressor gene appear to be one of the most common abnormalities in human cancer including lung cancer. P53 protein has an important role in gene transcription, DNA repair and induction of apoptosis. The p53 gene is frequently mutated in non-small-cell lung cancer (NSCLC); during malignant progression with the majority mutations found in exons 5-8. Missense mutation of the p53 gene usually but not always prolongs the half-life of the protein from minutes to hours and results in nuclear accumulation of the p53 protein, which can be detected by IHC. Immunohistochemistry was used initially to select p53-positive cases and these were then screened for mutations in exons 5-8 by polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE). The identities of the mutations in cases selected by DGGE were then determined by direct sequencing of the PCR products. As a result of IHC, 23/47 (49%) cases were deemed to over express p53 and were analysed by DGGE. Mutations were indicated by DGGE and confirmed by sequencing in 9/23 (39%) of the IHC positive cases. The nature of p53 mutations may provide aetiological information so the aim of this study was to scan the central region of p53 gene for mutation in randomly selected non-small cell lung carcinomas to possibly indicate aetiology of the disease and to determine the frequency of p53 mutation in NSCLC.
Background: Molecular mechanisms that regulate development of hepatocellular carcinoma (HCC) are ... more Background: Molecular mechanisms that regulate development of hepatocellular carcinoma (HCC) are still unclear. Several risk factors may predispose to HCC like viral etiology HBV or HCV, genetic makeup, and environmental exposure. Genetic factors include activation of oncogenes and inactivation of tumor suppressor genes. P27 kip1 , p53 and Ki-67 are important biomarkers involved in hepatic carcinogenesis. Aim of Work: To investigate the relation between p27 kip1 expression in HCC and both clinical and radiological parameters. Also to study the relation between p27 kip1 expression and both Ki-67 and p53 expression. Subjects and Methods: We examined 32 cases of HCC; their mean age was 58.2±6.2 years, including 26 males and 6 females. All of them were subjected to clinical examination, laboratory investigations including, liver function tests, viral markers, AFP assay, imaging studies including abdominal ultrasound and helical multiphasic abdominal CT scans. CT guided biopsy was obtained from all patients. Ten cases had analysis of surrounding non-cancerous tissue. Histopathological examination was done to assess tumor grading. Immunohistochemical evaluation was done to evaluate expression of p27 kip1 , Ki-67 and p53. Results: The p27 kip1 protein positive expression rate in HCC was 56.25% compared to 100% in surrounding non-cancerous tissue. P27 kip1 expression was not related to age, sex, Child grade, and tumor multiplicity or tumor size. However, negative expression rate was significantly higher in cases with ill-defined margins, tumor thrombus, and upper abdominal lymphadenopathy (P< 0.03, 0.02, 0.05 respectively). P27 kip1 expression rate in poorly differentiated group (Grade III-IV) was significantly lower than in well differentiated group (Grade I-II) [P<0.007]. No relation was found between p27 kip1 expression and liver functions, level of AFP, presence of HBsAg or HCV Ab. There was marked reduction of p27 kip1 expression and high expression of Ki-67 in HCC but no correlation was found between p27 kip1 expression and P53 positive expression. Diffuse cytoplasmic immunostaining for p27 kip1 was found in 12 (37.5%) of cases.
For endometrial carcinoma patients, there is a need for improved identification of high-risk grou... more For endometrial carcinoma patients, there is a need for improved identification of high-risk groups that may benefit from postoperative adjuvant therapy. Aberrant expression of several cell-cycle regulators has been reported in endometrial carcinoma, correlations among some of these factors and their prognostic significance have been systematically examined. Immunohistochemical expression of cyclin D1 and tumor-suppressor gene p21 WAF1 in 32 endometrial carcinoma (EC), including 12 low-grade (grade I) and 20 high-grade (grade II or III) tumors was evaluated. Results were compared with the expression of steroid receptor status, progesterone receptor (PR). Positive staining for cyclin D1 and p21 WAF1 was more frequent in higher grade tumors and their expression were significantly frequent in advanced-stage tumors. Ninety percent (18 of 20) of the high grade EC expressed cyclin D1 at a high level, whereas only 42% (5 of 12) of the low grade EC did so (Chi2 = 8.7; P < 0.01). Sixty-five percent (13 of 20) of the high grade EC expressed p21 WAF1 at high levels, but only 17% (2 of 12) of low grade EC did so (Chi2 = 7.0; P < 0.01). Coordinate high level expression of p21 WAF1 and cyclin D1 occurred in 65% (13 of 20) of high grade EC but in only 17% (2 of 12) of the low grade EC (Chi2 = 7.0; P < 0.01). These findings suggest that cyclin D1 and p21 WAF1 are involved in activated cell growth of endometrial carcinoma, and that positive staining for them could be a useful marker for unfavorable patient prognosis.
Introduction and aim of the work: Abdominal ultrasound (US) is often used as the first imaging mo... more Introduction and aim of the work: Abdominal ultrasound (US) is often used as the first imaging modality in a large variety of abdominal complaints and clinically unsuspected gastric carcinomas may be firstly imaged by it. Aim: to determine the value of transabdominal sonography (TAS) in the prediction of gastric cancer. Patients and methods: Two thousands patients with epigastric pain were included in the study, we select twenty two of them had thickening of the gastric wall on (TAS). They were selected from the outpatient clinics of Tropical and Internal Medicine Depatments of El-Minia University Hospital during the period from March 2006 to February 2008. The included patients underwent the following: history, clinical examination, transabdominal ultrasonography, upper gastrointestinal endoscopy and multiple biopsies were taken from the site of lesion for histopathological examination. The TAS results of the stomach evaluation were compared with the pathological findings. Results: The selected patients (22) were classified into 2 groups based on histopathological findings, benign disease group(4 cases) and gastric cancer group(18 cases): The benign group including 2 patients with benign gastric ulcer and 2 patients with gastritis & the malignant group including 12 patients with adenocarcinoma, 5 patients with non-Hodgkin lymphoma and one patient with anaplastic carcinoma. There is statistically significant difference between the benign group and the malignant group as regard the wall thickness, loss of wall layering, wall hypoechogenicity and luminal narrowing while there is no significant difference as regard the presence or absence of gastric mass. Gastric wall thickness on transabdominal ultrasonography of >10 mm is the best cut off point for prediction of gastric malignant tumours with a sensitivity 94.4%, specificity 100%, positive predictive value 100% and negative predictive value 80%. Loss of wall layering has the same sensitivity, specificity and predictive values as gastric wall thickness. Loss of wall layering is the most independent factor for prediction of gastric cancer. Conclusion: Transabdominal sonography findings of a gastric wall thickness >10 mm with loss of layering of the gastric wall were found to be a predictors for gastric cancer and therefore, careful evaluation of the gastric wall should be made during TAS examination.
Conjunctival squamous cell carcinoma (CSCC) is an invasive ocular surface neoplasia ranging from ... more Conjunctival squamous cell carcinoma (CSCC) is an invasive ocular surface neoplasia ranging from dysplasia to carcinoma in situ to invasive squamous cell carcinoma, which is identifi ed as premalignant and malignant epithelial lesions. Often, it is seen in males in tropical countries lying close to the equator where there is excessive exposure to sunlight. Clinical diagnosis requires close examination with a degree of high suspicion. Appropriate and defi nitive diagnosis of conjunctival squamous neoplasia by ocular pathologists and the need for future detailed clinicopathologic studies is recommended. Appropriate and defi nitive diagnosis requires histopathology. We describe a case of CSCC underlying dysplasia with intraepithelial squamous cell neoplasia, where the case was confi rmed by histopathological examination. Th e treatment modality involving surgery and medication and follow-up is described. Th ere was no evidence of recurrence, complication, or metastasis.
Objectives: To develop an alternative medicine, propolis, in emulgel formulation for burn and wou... more Objectives: To develop an alternative medicine, propolis, in emulgel formulation for burn and wound treatment. Methods: The effect of two independent variables: emulsifying agent concentration and oil concentration on the cumulative amount of propolis release (dependent variable) from liquid paraffin and isopropyl palmitate emulgels was investigated. Eight formulations were prepared and evaluated for physical appearance, pH, propolis content, viscosity, and in vitro propolis release. The release results were fitted into different kinetic equations and analyzed using contour plot, interaction surface plot and one-way ANOVA. The selected emulgel formulation was investigated for its wound and burn healing activity in rats. Results: All the prepared emulgels showed acceptable physical properties concerning color, homogeneity, consistency, and pH value. The concentration of emulsifying agent had more pronounced effect on propolis release than oil concentration. Formulations F1-F6 showed "anomalous" drug release, while Formulations F7 and F8 showed zero-order kinetic. Conclusion: The formulation F7 with 5% isopropyl palmitate, 5% emulsifier mixture, 1% hydroxyl propyl methyl cellulose, 1% oleic acid, and 10% propylene glycol is a promising formula for better management of wound and burn.
Substantial progress has been made over the past three decades in understanding breast cancer (BC... more Substantial progress has been made over the past three decades in understanding breast cancer (BC) molecular biology, genomics, and targeted therapy. The recent comprehensive molecular and pathological diversity observed in BC patients indicates that BC is not a homogeneous disease; It may be appropriately defined as a myriad of diseases. The explosion of molecular information in the past 10 years has led to a better understanding of the biologic diversity of breast cancers (BCs), and clues to the different etiologic pathways to BC development. It will be useful to study the epigenetics of BC cells and define the mechanisms of both genetic and epigenetic driving alterations beside the mutations. Identifying the oncogenes and tumor suppressor genes is the purpose cancer diagnostics and therapeutics. Oncogenes as well as novel ones involved in the significantly altered regions would enable researchers to identify new causes and molecular pathways that may be targeted at BC treatment. Our main goal is to provide comprehensive understanding of underlying molecular mechanisms and hallmarks of BC, focusing on the identification of fingerprints and novel molecular targets that will greatly improve the cancer predictive, prognostic, and diagnostic biomarkers and, in addition, the possible targets for novel therapies.
13th International Conference on Surgical Pathology & Practice, 2017
Background: Telomerase enzyme is a ribonucleo-protein complex with reverse transcriptase activity... more Background: Telomerase enzyme is a ribonucleo-protein complex with reverse transcriptase activity. The catalytic subunit (Telomerase reverse transcriptase) TERT correlates with poor clinical outcome in various tumors. Tumors expressing this enzyme may be more aggressive and telomerase activity may be a useful prognostic marker. For soft tissue tumor little is known about telomerase activity and most of reports focus on telomerase activity in liposracomas. Aim: This study was conducted to investigate the relationship between expression of the catalytic subunit of telomerase (h-TERT), cell proliferation and hypoxia in a range of soft tissue neoplasms. Material & methods: A tissue microarray was constructed from 101 cases and whole sections were cut from 21 cases of soft tissue neoplasm. Immunocytochemistry for h-TERT, HIF-1 α, p53, p21, Rb, CD31, Ki67 and MDM2 was done. Western blotting for hTERT protein of 12 sarcomas was performed to validate h-TERT expression. Results: h-TERT was expressed in 16% of benign and 65% of malignant neoplasms (p<0.005) with higher expression in leiomyosarcomas, synovial sarcomas, undifferentiated sarcomas and myxofibrosarcomas and lower expression in liposarcomas. h-TERT expression was significantly associated with grade (p=0.000), stage (p=0.000) and size of the tumor (p=0.02). Higher expression of HIF-1 a and Ki67, and loss of Rb expression were associated with high grade sarcomas (p<0.004). Expression of p53 and MDM2, p21 and tumor vascularity were not associated with grade. High expression of HIF-1 α and Rb were significantly associated with the stage (p=0.002, 0.03). Conclusion: hTERT is expressed in a wide range of high grade sarcomas. The positive correlations between proliferation, hypoxia and vascularity support the view that mesenchymal cells are adapted to proliferate in a hypoxic environment. Increased expression of hTERT may be part of this adaptive response.
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Papers by Hanan Abd Elmoneim
The obesity epidemic has been linked to a wide range of health and nutritional problems, including anemia,
which is often caused by impaired iron metabolism. The World Health Organization considers anemia and
obesity to be global health issues among adolescent girls and women experiencing menstruation. This study
aims to examine the association between iron deficiency anemia and obesity/overweight among female
medical students.
Methodology
This cross-sectional descriptive study conducted as an online self-administered questionnaire. Furthermore,
blood samples were collected from 206 students to evaluate the complete blood count, iron and lipid profile.
Results
The convenience sampling technique was used and a total of 206 students were enrolled in the study. The
average body mass index (BMI) was 22.51 ± 3.25, with 83.5% (n = 172) falling within the normal weight
range, 12.6% (n = 26) as overweight, and 3.9% (n = 8) as obese. Anemia was present in 16.0% (n = 33) of the
participants overall. Higher prevalence of anemia was observed among overweight participants with 10 out
of 26 (38.5%) subjects compared to obese with two out of eight (25.0%) and normal weight 21 out of 172
(12.2%); this difference was highly significant (P = 0.005). Individuals with anemia exhibited a significant
association with those experiencing a diet full of unhealthy fats and carbohydrates (P = 0.05) and a diet
containing all essential nutrients (P = 0.01). There is no statistically significant correlation between anemia
prevalence and participants' response to the presence of signs of anemia, physical activity or other dietary
habits. Obese participants had a significantly higher mean value of triglycerides (129.5 ± 20.5) compared to
normal weight and overweight participants (74.5 ± 12.02 and 51.2 ± 15.04), respectively (P = 0.001).
Conclusion
A dependable assembly exists between obesity and overweight in cases of iron deficient anemia. The
prevalence of iron deficiency anemia was substantially higher among overweight/obese females,
highlighting that overweight/obesity signifies both quantitative and qualitative malnutrition. A high BMI
was associated with elevated triglycerides, typically considered indicators of obesity. This association may
suggest compromised iron homeostasis.
Despite the introduction of several methods and new therapeutics to classify and
treat breast cancer, it remains the most common cancer among women and
contributes to higher mortality rates worldwide.
Purpose
This study aimed to analyze the expression levels of the androgen receptor (AR),
P53 protein, and P53 mutations among molecular subtypes of breast cancers and
their correlation with patients’ outcome.
Patients and methods
Immunostaining for estrogen receptor (ER), progesterone receptor (PR), Ki-67, and
human epidermal growth factor receptor 2 (HER2) to stratify breast cancers into
basal-like, HER2 type, luminal A or B types. AR, P53 expressions, and P53
mutations was compared among groups.
Results
Overall, 37.5% of basal-like and 7.1% of HER2 types of invasive breast carcinomas
were AR positive. P53 was expressed in 62.5 and 50% of basal-like and HER2
types, respectively. The P53 mutation varied significantly among the molecular
subtypes (P<0.0001) and was found in 43.8 and 42.9% of basal-like and HER2
types, respectively. Extensive nodal status, higher stage, and P53 mutation
independently predicted the overall survival. AR-negative and P53 mutationpositive
tumors had intermediate or poor Nottingham Prognostic Index and were
more often nodal positive, higher grade, and higher stage than AR-positive and P53
mutation-negative tumors, respectively, and P53-expressing tumors.
Conclusion
Our findings highlight the importance of AR, P53, and P53 mutations as
differentiating cofactors and suggest that the targeting of these marker
pathways could lead to novel therapies for those patients with limited
therapeutic options. AR could be a potential therapeutic target for the
management of breast cancer.
The obesity epidemic has been linked to a wide range of health and nutritional problems, including anemia,
which is often caused by impaired iron metabolism. The World Health Organization considers anemia and
obesity to be global health issues among adolescent girls and women experiencing menstruation. This study
aims to examine the association between iron deficiency anemia and obesity/overweight among female
medical students.
Methodology
This cross-sectional descriptive study conducted as an online self-administered questionnaire. Furthermore,
blood samples were collected from 206 students to evaluate the complete blood count, iron and lipid profile.
Results
The convenience sampling technique was used and a total of 206 students were enrolled in the study. The
average body mass index (BMI) was 22.51 ± 3.25, with 83.5% (n = 172) falling within the normal weight
range, 12.6% (n = 26) as overweight, and 3.9% (n = 8) as obese. Anemia was present in 16.0% (n = 33) of the
participants overall. Higher prevalence of anemia was observed among overweight participants with 10 out
of 26 (38.5%) subjects compared to obese with two out of eight (25.0%) and normal weight 21 out of 172
(12.2%); this difference was highly significant (P = 0.005). Individuals with anemia exhibited a significant
association with those experiencing a diet full of unhealthy fats and carbohydrates (P = 0.05) and a diet
containing all essential nutrients (P = 0.01). There is no statistically significant correlation between anemia
prevalence and participants' response to the presence of signs of anemia, physical activity or other dietary
habits. Obese participants had a significantly higher mean value of triglycerides (129.5 ± 20.5) compared to
normal weight and overweight participants (74.5 ± 12.02 and 51.2 ± 15.04), respectively (P = 0.001).
Conclusion
A dependable assembly exists between obesity and overweight in cases of iron deficient anemia. The
prevalence of iron deficiency anemia was substantially higher among overweight/obese females,
highlighting that overweight/obesity signifies both quantitative and qualitative malnutrition. A high BMI
was associated with elevated triglycerides, typically considered indicators of obesity. This association may
suggest compromised iron homeostasis.
Despite the introduction of several methods and new therapeutics to classify and
treat breast cancer, it remains the most common cancer among women and
contributes to higher mortality rates worldwide.
Purpose
This study aimed to analyze the expression levels of the androgen receptor (AR),
P53 protein, and P53 mutations among molecular subtypes of breast cancers and
their correlation with patients’ outcome.
Patients and methods
Immunostaining for estrogen receptor (ER), progesterone receptor (PR), Ki-67, and
human epidermal growth factor receptor 2 (HER2) to stratify breast cancers into
basal-like, HER2 type, luminal A or B types. AR, P53 expressions, and P53
mutations was compared among groups.
Results
Overall, 37.5% of basal-like and 7.1% of HER2 types of invasive breast carcinomas
were AR positive. P53 was expressed in 62.5 and 50% of basal-like and HER2
types, respectively. The P53 mutation varied significantly among the molecular
subtypes (P<0.0001) and was found in 43.8 and 42.9% of basal-like and HER2
types, respectively. Extensive nodal status, higher stage, and P53 mutation
independently predicted the overall survival. AR-negative and P53 mutationpositive
tumors had intermediate or poor Nottingham Prognostic Index and were
more often nodal positive, higher grade, and higher stage than AR-positive and P53
mutation-negative tumors, respectively, and P53-expressing tumors.
Conclusion
Our findings highlight the importance of AR, P53, and P53 mutations as
differentiating cofactors and suggest that the targeting of these marker
pathways could lead to novel therapies for those patients with limited
therapeutic options. AR could be a potential therapeutic target for the
management of breast cancer.