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.

Expression of indoleamine 2,3-dioxygenase in acute myeloid leukemia and the effect of its inhibition on cultured leukemia blast cells.

Indoleamine 2,3-dioxygenase (IDO), a catabolizing enzyme of tryptophan, is a novel immunosuppressive agent blocking T-cell activation in neoplastic cells, including acute myeloid leukemia (AML) cells. IDO inhibitors as 1-methyl tryptophan (1MT) can abrogate IDO enzymatic activity and may result in an effective immune response. Mononuclear cells (MNCs) were separated from peripheral blood of 25 AML patients and 25 normal adults. IDO expression was detected by RT-PCR and its enzymatic activity by a colorimetric method. MNCs were cultured and the effects of Adriamycin, 1MT and a mixture of both on blast and lymphocyte cell counts after 24 and 72 h were detected. IDO mRNA and activity were detected in 52% of patients and absent in normal subjects. There was a significant correlation between IDO mRNA expression and its enzymatic activity in AML. IDO activity was correlated positively with patient's ages and negatively with hemoglobin levels. There was a significant inhibition of blast cells proliferation with Adriamycin and more inhibition when combined with 1MT. The inhibition was more after 72 h more than 24 h of culture. However, using 1MT alone showed no significant inhibitory effect on blast cells, with a significant increase in lymphocyte counts. Our study confirms the role of indoleamine 2,3-dioxygenase in tumor-induced immune tolerance and points to the possible benefit of 1-methyl tryptophan as immunotherapeutic enhancing the anticancer effects of traditional chemotherapeutics.

Effect of passive smoking on blood lymphocyte apoptosis in children.

BACKGROUND: Passive smoking is a well-known risk factor for both recurrent respiratory infections and disturbed lipid profile. Whether passive smoking problems are related to altered lymphocyte survival and its relation to altered lipid profile are the points of concern in this work. MATERIALS AND METHODS: Urinary cotinine and creatinine levels as well as lipid profile and flow cytometric assessment of apoptosis of peripheral blood lymphocytes (PBL) were assessed in 26 children with history of indoor exposure to cigarette smokers in comparison with 14 matched children with no such history. RESULTS: Lipid profile showed significantly higher mean levels of triglycerides, cholesterol and low-density lipoprotein (LDL) and significantly lower mean levels of high-density lipoprotein (HDL) in passive smoking children compared to nonpassive-smoking ones. Furthermore, cotinine parameters were positively correlated with triglycerides and LDL and negatively correlated with HDL. Early apoptosis of PBL was significantly higher in exposed vs nonexposed ones. CONCLUSIONS: Passive smoking in children could be a risk factor for enhanced lymphocytic apoptosis. It is possible that altered lipid profile may play a role in the increased risk. The impact of this lymphocytic derangement on increased frequency of infections is noticeable.

Selenium and glutathione peroxidase status in adult Egyptian patients with acute myeloid leukemia.

This study was undertaken to evaluate selenium (Se) and glutathione peroxidase (GPX) status in patients with newly diagnosed acute myeloid leukemia (AML) before and after induction therapy. Twenty-five patients with newly diagnosed AML and 15 healthy age- and sex-matched control subjects were included in this study. Serum Se level by the graphite furnace atomic absorption spectrometric technique and GPX activity by an adaptation of Beutler method was performed for the patients before and after receiving the induction therapy. Serum Se level was significantly lower in patients with AML versus control subjects (63.1 ± 8.8 versus 77 ± 8.8 µg/L before therapy with a P value <0.01 and 69 ± 6.8 versus 77 ± 8.8 µg/L after therapy with a P value <0.01).GPX activity was significantly lower in patients with AML versus control subjects (1.6 ± 0.4 versus 3.4 ± 0.7 µ/g protein pretreatment with a P value <0.01 and 1.9 ± 0.6 versus 3.4 ± 0.7 µ/g protein post induction treatment with P value <0.01).Se level and GPX activity significantly increased in AML patients after treatment. Patients who accomplished complete remission after induction harbored significantly higher Se levels than resistant patients before and after treatment. There was no significant correlation between serum Se level and GPX activity. Decreased Se level and reduced GPX activity in AML patients support the association of carcinogenesis and subnormal Se states.