Mansour, L. A., M. E. Raziky, A. A. Mohamed, E. H. Mahmoud, S. Hamdy, and E. H. El Sayed, "Circulating Hypermethylated RASSF1A as a Molecular Biomarker for Diagnosis of Hepatocellular Carcinoma", Asian Pacific journal of cancer prevention : APJCP, vol. 18, issue 6, pp. 1637-1643, 2017 06 25. Abstract

Background: Detection of circulating DNA can be applied for the diagnosis of many malignant neoplasms, including the hepatocellular carcinoma (HCC). The molecular pathogenesis of HCC is complex, involving different genetic and epigenetic alterations, chromosomal aberrations, gene mutations and altered molecular pathways. RASSF1A is a well-established tumor suppressor gene which suffers frequent inactivation due to promoter hypermethylation of CPG islands in multiple tumors including HCC, resulting in the reduction or loss of gene expression. Objective: To examine the role of circulating RASSF1A as a non-invasive diagnostic marker for HCC. Participant and Methods: A total of 45 HCC patients with a background of HCV infection, 40 cases of HCV infection without tumours and 40 apparently healthy controls were subjected to full history taking, clinical examination, routine laboratory investigations, assessment of serum AFP and detection of circulating hypermethylated RASSF1A gene by methylation-sensitive restriction enzyme digestion and real-time PCR. Results: The level of hypermethylated RASSF1A was significantly elevated in the HCC group as compared to the HCV and control groups (p=0.001 for both). Copy number in serum was associated with increased tumor size (p value <0.001). On the other hand, no significant correlation was observed between RASSF1A and AFP (p=0.5). Using ROC curve analysis, the best cut-off for circulating serum RASSF1A to differentiate the HCC group was 8 copies/μl. Conclusion: The presence of hypermethylated RASSF1A in serum may be a useful and informative biomarker for HCC diagnosis and might be introduced as a screening method for populations at risk of HCC development.

EH, M., F. A, A. OK, and A. AM, "Plasma Circulating Cell-free Nuclear and Mitochondrial DNA as Potential Biomarkers in the Peripheral Blood of Breast Cancer Patients.", Asian Pac J Cancer Prev., vol. 16, issue 18, pp. 8299-305, 2015. Abstract

Abstract
BACKGROUND:

In Egypt, breast cancer is estimated to be the most common cancer among females. It is also a leading cause of cancer-related mortality. Use of circulating cell-free DNA (ccf-DNA) as non-invasive biomarkers is a promising tool for diagnosis and follow-up of breast cancer (BC) patients.
OBJECTIVE:

To assess the role of circulating cell free DNA (nuclear and mitochondrial) in diagnosing BC.
MATERIALS AND METHODS:

Multiplex real time PCR was used to detect the level of ccf nuclear and mitochondrial DNA in the peripheral blood of 50 breast cancer patients together with 30 patients with benign lesions and 20 healthy controls. Laboratory investigations, histopathological staging and receptor studies were carried out for the cancer group. Receiver operating characteristic curves were used to evaluate the performance of ccf-nDNA and mtDNA.
RESULTS:

The levels of both nDNA and mtDNA in the cancer group were significantly higher in comparison to the benign and the healthy control group. There was a statistically significant association between nDNA and mtDNA levels and well established prognostic parameters; namely, histological grade, tumour stage, lymph node status andhormonal receptor status.
CONCLUSIONS:

Our data suggests that nuclear and mitochondrial ccf-DNA may be used as non-invasive biomarkers in BC.

Mossad, N. A., E. H. Mahmoud, E. A. Osman, S. H. Mahmoud, and H. I. Shousha, "Evaluation of squamous cell carcinoma antigen-immunoglobulin M complex (SCCA-IGM) and alpha-L-fucosidase (AFU) as novel diagnostic biomarkers for hepatocellular carcinoma.", Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, vol. 35, issue 11, pp. 11559-64, 2014 Nov. Abstract

Hepatocellular carcinoma (HCC) surveillance lacks a reliable biomarker. Alpha-fetoprotein (AFP) is the most widely used. However, not all HCCs secrete AFP. AFP may be elevated with cirrhosis in the absence of HCC. Serum alpha-L-fucosidase (AFU) and squamous cell carcinoma antigen-immunoglobulin M complex (SCCA-IgM) were found to be useful markers in diagnosing HCC. SCCA-IgM and AFU were assessed by ELISA technique; AFP was measured by enzyme chemiluminescence in serum of 40 patients with HCC, 30 patients with liver cirrhosis, and 20 healthy control participants to compare their accuracy in early diagnosis of HCC. Serum SCCA-IgM and AFU levels were significantly elevated in HCC group compared to cirrhotic group (P value<0.001 and <0.001, respectively). Receiver operating characteristic curve showed the optimal cutoff value for SCCA-IgM was 233 AU/ml with sensitivity 87.5% and specificity 66% and for AFU was 25 U/L with sensitivity 87.5% and specificity 98%. AFP cutoff value was 48 ng/mL with sensitivity of 70% and specificity of 53.3%. The simultaneous determination of AFP and SCCA-IgM activity increased the sensitivity to 92.5% and specificity to 62.1%. There were positive significant correlations between SCCA-IgM and each of AFU (r=0.296, P=0.005) and AFP (r=0.284, P=0.007) and no correlation between AFP and AFU. All markers did not correlate with the tumor size or affected by the Child score. The significant difference between SCCA-IgM and AFU levels among HCC and cirrhotic patients suggests their use as potential diagnostic tools and allows identifying a new group of HCC patients even in the absence of elevated AFP.

Abbas, D., E. Hamdy, and M. M. Helal, "Promoter region polymorphism (−174 G/C) of interleukin-6 gene and SLE; are they associated?", The Egyptian Rheumatologist, vol. 33, no. 2, pp. 69 - 75, 2011. AbstractWebsite

Introduction \{SLE\} is a systemic autoimmune disease with polyclonal B cell hyperactivity, spontaneous lymphocyte proliferation, and the production of pathogenic antibodies to self-antigens. Interleukin-6 is a pleiotropic cytokine with diverse functions including B-cell growth and differentiation. IL-6 levels have been shown to be affected by single nucleotide change from G to C at position −174 in the promoter region of the IL-6 gene. Aim of the work To find out whether single nucleotide polymorphisms in the promoter region of the IL-6 gene (−174 G/C) constitute a genetic susceptibility for \{SLE\} and its association with various disease clinical and immunological features. Patients and methods Forty-two female \{SLE\} patients and 40 healthy controls were genotyped for IL-6 gene promoter region (−174 G/C) polymorphism using PCR. \{SLE\} patients satisfied the 1982 revised criteria of the American Rheumatism Association for the classification of SLE, with a mean age of 32.4 ± 5.5 years and mean disease duration of 5.7 ± 1.5 years. The healthy controls were matched for age and sex, with a mean age of 31.7 ± 4.9 years. All subjects were recruited from the Rheumatology and Rehabilitation and Internal Medicine Departments, Kasr El Aini Hospitals. \{SLE\} clinical and laboratory features were recorded including constitutional, hematological, joint, renal, and neuropsychiatric manifestations, oral ulcers, serositis, malar rash, and photosensitivity and CBC, liver, kidney functions and serum \{C3\} and \{C4\} levels. Positivity for ANAs, Anti-dsDNA and Anti-Sm antibodies were determined. Results Genotypic and allelic distributions showed no significant differences between \{SLE\} patients and controls. The frequency of G allele was higher than C allele in both patients (83.3% vs. 16.7%) and controls (85% vs. 15%). \{SLE\} patients with \{GG\} genotype showed significantly higher frequencies and increased risk of; constitutional manifestations at disease onset (P = 0.02), \{OR\} (95% CI) = 6.55 (1.22–35.12), photosensitivity (P = 0.03), \{OR\} (95% CI) = 4.67 (1.11–19.54), hematological disorders (P = 0.02), \{OR\} (95% CI) = 5.5 (1.29–23.39) and positivity of \{ANAs\} and Anti-dsDNA [P = 0.046, 0.03: \{OR\} (95% CI) = 7 (1.1–45.44), 6.43 (1.23–33.65), respectively]. Furthermore, those patients had significantly lower mean \{WBCs\} counts when compared to \{SLE\} patients with (GC and CC) genotypes (4.54 ± 1.31 vs. 5.98 ± 1.04/dl, P = 0.002). Twenty-five patients had lupus nephritis (LN) proved by renal biopsy but none of them had \{CC\} genotype. \{LN\} patients with \{GG\} genotype had nearly similar mean 24-h proteinuria to those with \{GC\} genotype (2.93 ± 1.07 vs. 2.68 ± 1.06 g/24 h and P = 0.39). No significant difference was found in IL-6 genotype and allele distributions when patients with diffuse proliferative glomerulonephritis (class IV), which has the worst prognostic outcome, were compared to patients with non-class İV\} glomerulonephritis (classes İI\} and III) [P = 0.12, 0.15, respectively]. Conclusion IL-6 promoter region (−174 G/C) polymorphism does not confer susceptibility to \{SLE\} but it is related to the presence of distinct clinical and immunological features. Furthermore, the increased frequency of the high-response G allele suggests that a genetically determined high IL-6 response may have a pathogenic role.

Rasheed, H., D. Mahgoub, R. Hegazy, M. El-Komy, R. Abdel Hay, M. A. Hamid, and E. Hamdy, "Serum ferritin and vitamin d in female hair loss: do they play a role?", Skin pharmacology and physiology, vol. 26, issue 2, pp. 101-7, 2013. Abstract

AIM: Evaluation of serum ferritin and vitamin D levels in females with chronic telogen effluvium (TE) or female pattern hair loss (FPHL), in order to validate their role in these common hair loss diseases.

METHODS: Eighty females (18 to 45 years old) with hair loss, in the form of TE or FPHL, and 40 age-matched females with no hair loss were included in the study. Diagnosis was based upon clinical examination as well as trichogram and dermoscopy. Serum ferritin and vitamin D2 levels were determined for each participant.

RESULTS: Serum ferritin levels in the TE (14.7 ± 22.1 μg/l) and FPHL (23.9 ± 38.5 μg/l) candidates were significantly lower than in controls (43.5 ± 20.4 μg/l). Serum vitamin D2 levels in females with TE (28.8 ± 10.5 nmol/l) and FPHL (29.1 ± 8.5 nmol/l) were significantly lower than in controls (118.2 ± 68.1 nmol/l; p < 0.001). These levels decreased with increased disease severity. Serum ferritin cut-off values for TE and FPHL were 27.5 and 29.4 μg/l, respectively, and those for vitamin D were 40.9 and 67.9 nmol/l.

CONCLUSION: Low serum ferritin and vitamin D2 are associated with hair loss in females with TE and FPHL. Screening to establish these levels in cases of hair loss and supplementing with them when they are deficient may be beneficial in the treatment of disease.

Saleh, A., A. Matsumori, H. Negm, H. Fouad, A. Onsy, M. Shalaby, and E. Hamdy, "Assessment of cardiac involvement of hepatitis C virus; tissue Doppler imaging and NTproBNP study.", Journal of the Saudi Heart Association, vol. 23, issue 4, pp. 217-23, 2011 Oct. Abstract

INTRODUCTION: Hepatitis C disease burden is substantially increasing in Egyptian community, it is estimated that prevalence of Hepatitis C virus (HCV) in Egyptian community reach 22% of total population. Recently there is a global alert of HCV cardiovascular complications.

OBJECTIVE: To evaluate LV diastolic functions of HCV patients using tissue Doppler Imaging and NTPBNP.

METHODS: 30 HCV patients of 30 years, sex & BMI matched controls were evaluated by PCR, ECG, Echocardiography "conventional Doppler, pulsed wave tissue Doppler (PW-TD), strain rate imaging" & NTPBNP to assess LV diastolic functions. Mean age was 32.8 years ± 5.1 in HCV group, 29.8 years ± 6.6 in control group. Cardiovascular anomalies and predisposing factors were excluded.

RESULTS: HCV group has shown significant increase in QTc interval, significant statistical increase in A wave, deceleration time; (p < 0.05), highly significant decrease in tissue Doppler E a (p < 0.001), highly significant decrease in A a (p < 0.001), highly significant increased E/E a ratio (p value < 0.001), significant decrease in E a/A a ratio and significant increase in SRa (p < 0.05). NTPBNP levels showed highly significant increase with mean value 222 pg/ml ± 283 in HCV group and 32.7 pg/ml ± 21.2 in control group (p value < 0.001). The best cut-off value of NTPBNP to detect diastolic dysfunction in HCV group was 213 pg/ml. No statistical differences in SRe/SRa and E/SRe ratios were observed, however they had significant correlation with NTPBNP level and tissue Doppler parameters. The best cut-off value of E/SRe ratio to detect diastolic dysfunction in HCV group was 0.91, with 75% sensitivity and 100% specificity.

CONCLUSION AND RECOMMENDATION: This data show the first direct evidence that HCV infection causes diastolic dysfunction without any other predisposing factors, probably due to chronic inflammatory reaction with mild fibrosis in the heart. Previous studies did not follow strict inclusion and exclusion criteria that confirm the independent role of HCV to cause diastolic dysfunction. Tissue Doppler was more sensitive to diagnose diastolic dysfunction than conventional Doppler.

Abbas, D., Y. Ezzat, E. Hamdy, and M. Gamil, "Angiotensin-converting enzyme (ACE) serum levels and gene polymorphism in Egyptian patients with systemic lupus erythematosus.", Lupus, vol. 21, issue 1, pp. 103-10, 2012 Jan. Abstract

OBJECTIVES: To investigate the association of angiotensin-converting enzyme (ACE) gene polymorphism and serum ACE level among Egyptian SLE patients and its relation to disease activity parameters.

SUBJECTS AND METHODS: We enrolled 50 Egyptian female systemic lupus erythematosus (SLE) patients and 29 healthy controls. Measurement of serum ACE level was done using ELISA, and the ACE genotype was determined by polymerase chain reaction using genomic DNA from peripheral blood.

RESULTS: A significant difference was found in ACE genotypes between SLE patients and controls (χ(2 )= 7.84, p = 0.02). The frequency of ACE DD versus (DI and II) genotypes was significantly higher in SLE patients compared with controls (χ(2 )= 5.57, p = 0.018 and OR for risk of SLE was 3.1 with 95% confidence interval: 1.198.06). Mean serum ACE level was significantly higher in the SLE group compared with controls (p = 0.006). Subjects with DD genotype had a significantly higher mean level than those with DI (p = 0.015) and II genotypes (p = 0.02). Lupus nephritis patients had a significantly higher frequency of DD versus DI and II genotypes compared with lupus patients without nephritis (Fisher's exact test, p = 0.025) and controls (χ (2) =8.74, p = 0.003). SLE patients with vasculopathy had a significantly higher frequency of DD versus DI/II genotypes compared with SLE patients without vasculopathy (Fisher's exact test, p = 0.04) and controls (χ(2 )= 9.84 and p = 0.002). Mean serum ACE level was significantly higher in the lupus nephritis and SLE patients with vasculopathy compared with controls (p = 0.008, p = 0.001, respectively). Significant positive correlations were found between serum ACE level and serum creatinine and 24 h proteinuria (p = 0.03, 0.009, respectively). SLE patients with DD genotype had a statistically significant higher mean SLEDAI score than those with (DI/II) genotypes (p = 0.02). Significant positive correlation was found between serum ACE levels and SLEDAI scores (p = 0.04).

CONCLUSION: ACE genotype and subsequently serum ACE level could be associated with the disease activity of Egyptian SLE patients; in addition, ACE deletion polymorphism might be used as one of the predictive factors for the activity of SLE. Further studies on a larger number of patients should be done to determine the exact prevalence of ACE gene polymorphism among Egyptian SLE patients.