Manal Basyouni Ahmed

HER1 R497K and HER2 I655V polymorphisms are linked to development of breast cancer.

BACKGROUND: Polymorphism of the genes of Human Epidermal growth factor receptor1 (HER1) and receptor2 (HER2) have been reported to be linked to pathogenesis of several malignant tumors but still there is contradiction regarding their association with breast cancer. OBJECTIVE: In this case control study we aimed to analyze the frequency of HER1 R497K (rs 11543848) and HER2 I655V (rs 1136201) Polymorphisms in breast cancer. SUBJECT AND METHOD: The frequency of HER1 Arg(R) 497Lys (K) and HER2 Ile (I) 655Val (V) polymorphisms were tested in 64 breast cancer patients and 86 normal control by polymerase chain reaction followed by restriction fragment polymorphism detection. Immunohistochemical analysis was done for HER2 protein on the available 18 malignant tissue samples. RESULTS: HER1 497K and HER2 655V variant had significantly increased breast cancer risk (OR=2.6, 95% CI 1.6–4.2, OR=2.2, 95% CI 1.2–4.1, p< 0.05) respectively. Moreover, combined HER1 K497 and HER2 V655 variant was detected in 26.6% malignant in comparison to 8.14% of control group (OR=4.1, 95% CI 1.58–10.57), but, no significant association was noticed between both Polymorphisms and clinicopathological features of the disease. As regard HER2 immunohistochemical expression no significant correlation was revealed with HER2 655V polymorphism. CONCLUSIONS: Our findings suggest that HER1 497K and HER2 655V polymorphisms are potential risk factor for development of breast cancer.

Prognostic significance of survivin and tumor necrosis factor-alpha in adult acute lymphoblastic leukemia

OBJECTIVES Acute lymphoblastic leukemia (ALL) is an aggressive cancer especially in adults as only 20-40% are cured with current treatment regimens. DESIGN AND METHODS We measured survivin and tumor necrosis factor-alpha (TNF-α) in serum of 30 ALL patients before and after induction therapy and compared to 30 age and sex matched normal adults. RESULTS Survivin at cutoff value 15.18 pg/mL was detected in all ALL patients before therapy but in only 83.33% after therapy and not detected in the control group; P<0.001. However TNF-α at cutoff value 60.05 pg/mL was detected in 90% ALL patients before therapy and 86.6% after therapy that was significantly higher than the control group (20%); P<0.001. Survivin showed a significant positive correlation with TNF-α (P<0.05), bone marrow blast cells (P<0.01), peripheral blast cells (P<0.05) and Philadelphia chromosome (P<0.01). CONCLUSIONS Survivin may have an important role in the development of acute leukemia and it could serve as a significant prognostic marker.

Relation of Osteoprotegerin, Visfatin and Ghrelin to Metabolic Syndrome in Type 2 Diabetic Patients.

BACKGROUND It is now realized that insulin resistance plays a principal role in initiating the pathologic manifestations of the metabolic syndrome (MetS). OBJECTIVES The aim of this study was to assess the possible role of osteoprotegerin, visfatin and ghrelin in the pathogenesis of MetS among type 2 diabetes mellitus (T2DM). DESIGN AND METHODS Serum blood samples were obtained from 116 subjects (39 T2DM; 48 T2DM with MetS; 29 healthy controls). Glycemic status and lipid profile were assessed by enzymatic method. Osteoprotegerin, visfatin, ghrelin and insulin were measured by ELISA method. RESULTS Osteoprotegerin and visfatin were significantly higher, while ghrelin was significantly lower in diabetic patients compared to healthy control group (p<0.05). Moreover, Osteoprotegerin and visfatin showed significant higher levels in T2DM patients with MetS than those without MetS (p<0.05). The best cut-off values for the investigated markers were determined by ROC curve. Osteoprotegerin (1.06 ng/mL), visfatin (32.27 ng/mL) and ghrelin (33.65 pg/mL) presented sensitivity of 76%, 92% and 39.1%; respectively and specificity of 41%, 69.2% and 62.9%; respectively, in predicting MetS among T2DM. Among the investigated parameters, Visfatin was the one which predicts MetS among diabetic patients [AUC=0.88, p<0.05]. CONCLUSION Osteoprotegerin, visfatin and ghrelin might be implicated in the pathogenesis of diabetes. Moreover, osteoprotegerin and visfatin may have additional potential role in the development of the metabolic syndrome. Visfatin was superior among studied parameters in predicting MetS among T2DM.

Evaluation of nestin in lung adenocarcinoma: relation to VEGF and Bcl-2

Abstract Context: Nestin is a marker of multipotent precursor cells that is up regulated in cancer. Objective: To explore its diagnostic role and its relationship to vascular endothelial growth factor (VEGF) and Bcl-2 in lung adenocarcinoma. Materials and methods: Evaluation of nestin expression in lung biopsies by real-time PCR and serum VEGF and Bcl-2 by ELISA in 27 adenocarcinoma patients and 15 control subjects. Results: Nestin was significantly higher in lung adenocarcinoma patients especially with advanced grade and stage and it was significantly correlated to VEGF and Bcl-2. Conclusion: Nestin can be considered as a potential diagnostic marker in lung adenocarcinoma.

Calcineurin Level and Activity in Breast Cancer: Relation to Apoptosis

Background: Calcineurin (CN) is a Ca2+/calmodulin- dependent phosphatase and has been implicated in both transcription-dependent and transcription-independent apoptosis. Objectives: We aim to interpret the correlation between calcineurin and apoptosis in relation to pathogenesis of breast cancer. Methods: Both calcineurin level and activity as well as caspas-3 activity were evaluated in tissue homogenate of 50 breast cancer patients, 20 patients with fibroadenoma and 15 healthy women. Results: Calcineurin activity was significantly increased in malignant breast tissues compared with fibroadenoma and normal breast tissue (p=0.00) without significant changes in its level (p>0.05). While caspase-3 showed a significant higher activity in malignant group compared to other groups (p