[Correlation between telomerase gene expression and different stages of breast cancer and obesity]

Background: Breast cancer is the most common cancer in women. Obesity is known as a risk factor for breast cancer acting directly on breast cancer by producing adipocytokines. On the other hand, it seems that telomerase activity and especially expression of its catalytic subunit [hTERT] are critical for cancer initiation and development

Objective: To determine the relationship between obesity grades and adipocytokines associated with expression of hTERT gene at different stages of breast cancer

Methods: This was an analytical study carried out on 65 breast cancer patients during 2009-2010. Blood sample and fresh tumour tissue were collected from all patients. Expression of hTERT gene in tumour tissue was evaluated using quantitative real-time PCR and the plasma level of adipocytokines also tested

Findings: Expression of hTERT gene was detected in 53 samples with an expression level which significantly correlated with BMI, stage, and grade of cancer. Also, there was a positive significant correlation between hTERT expression level and leptin level [r=0.484, P=0.008] however, no correlation with other adipocytokines including IL-6 [r=-0.041, P=0.83] and TNF-alpha [r=-0.059, P=0.76] was observed

Conclusion: Considering the data, it could be concluded that obesity, as the source of leptin, may play a direct role in occurrence and development of breast cancer

Inhibitory effect of zinc, copper and selenium on telomerase activity in tumor tissues and t47d breast cancer cell line

The present study was performed to investigate the effects of trace elements particularity Se, Zn and Cu on tumor genesis in breast cancer. The inhibitory effect of Se, Zn and Cu, on telomerase activity was analyzed in human breast tumor tissues and breast cancer [T47D] cells. Tissue specimens from 24 women with benign breast disease and 32 women with breast cancer specimens [ductal carcinoma, lobular carcinoma] were collected during surgery. In addition venous blood samples were obtained for assessing the trace elements. T47D cell line was cultured and treated with trace elements. Telomerase activity then was measured with TRAP assay in cell line and tissue extracts. There was a significant difference between tissue and serum levels of Cu, Se and the ratio of Cu/Zn in patients and controls [P<0.001]. After treating with 100 microm/L Zn So4, 10 um /L Cu So4 for 6 hours, telomerase activity of T47D cells was markedly increased. But after treating with 10, and 30 um /L selenium-L- methionin, telomerase activity was markedly inhibited. Telomerase activity of T47D cells for 24 hours were 0.93, 0.60 and for 48 hours were 0.76, 0.12 respectively [control 49.2%]. There were variations in serum level of Zn and Cu in breast cancer patients. Association between trace elements level and telomerase activity level can be exploited as prognostic and diagnostic marker for breast cancer

Relationship between dhea and dhea-s with anthropometric indices in women with different grades of obesity

Dehydroepiandrosterone [DHEA] and dehydroepiandrosterone sulfate [DHEA-S] are the most abundant steroids in human plasma. The aim of this study was to evaluate the relationship between DHEA and DHEA-S and anthropometric indices in women with different grades of obesity. This cross- sectional study investigated 170 women; 35 normal weight [BMI= 18.9-24.9], 33 overweight, [BMI = 25-29.9] as 36 women [BMI= 30-34.9] as obese grade I, 33 [BMI = 35-39.9] as obese grade II and 33 [BMI>40] as obese grade III. Body mass index was defined as weight in kilograms divided by the square of the height in meters. Serum levels of dehydroepiandrosterone, dehydroepiandrosterone sulfate and glucose were measured by commercially available enzyme immunoassay kits and the glucose oxidase method, respectively. There was a negative and significant correlation between DHEA and age in the normal [r=-0.457, P=0.006] overweight [r=-0.414, P=0.017] obese l [r=-0.402, P=0.015] obese ll [r=-0.391, P=0.024] and obese III [r=-0.354, P=0.043] groups, respectively. Also a negative and significant correlation was found between DHEA-S and age in overweight [r=-0.394, P=0.019], obese grade I [r=-0.455, P=0.005] and obese grade II [r=-0.390, P=0.023] groups respectively. We found a positive and significant correlation between DHEA and frame size in individuals of the Obese I, Obese II and Obese III groups, and also a positive and significant correlation between DHEA-S and frame sizes in individuals of these three groups. Results showed that serum levels of DHEA decrease with increasing grades of obesity, whereas serum levels of DHEA-S increase with increasing obesity

Variation of adiponectin levels in normal and obese subjects: possible correlation with lipid profiles

Data available suggests that Adiponectin, an adipocyte-derived peptide, is associated with adiposity and could effect the regulation of glucose and lipid metabolism in humans. The aim of this study was to evaluate the association between serum adiponectin concentrations and anthropometric indices and lipid profiles among Iranian women with different grades of obesity. In this analytical descriptive study of 157 non-diabetic women [33 normal weight, BMI< 25 kg/m2 and 124 overweight and obese, BMI >/= 25kg/m2], serum adiponectin and leptin levels were measured using an enzyme-linked immunoassay. Fasting glucose and lipid profile levels determined by the glucose oxidize and enzymatic methods, respectively. Mean serum adiponectin concentration significantly decreased with obesity [p<0.05]. Although adiponectin showed a significant negative correlation with BMI [r=-0.321], it was correlated with serum leptin [r=-0.139], glucose [r=0.259], LDL-C [r=-0.125], TGs [r=-0.210] levels, TSF [r=-0.145], WHR [r=-0.159], and positively with serum HDL-C concentration [r=0.218] in all subjects [p<0.05]. Results of multiple regression analyses showed that adiponectin as a dependent variable had a significant correlation with BMI [beta =-0.605, P=0.017], waist circumference [beta =0.624, p=0.029], WHR [beta =-0.251, p=0.048], frame [beta =0.260, p=0.018], TC/HDL-C ratio [beta =-0.1.309, p=0.040] and LDL/HDL ratio [beta =-1.343, p=0.007] and changes in waist size had a significant effect on serum adiponectin levels. Our results suggested that adiponectin had an inverse correlation with adiposity indices and unfavorable lipid profiles, and that variation of waist circumference mostly affected Iranian women

Relationship between insulin like growth factor-1 and leptin in type II diabetic patients

Diabetes is a common endocrine disease in humans. Leptin secretion is influenced by many factors and although the growth hormone/insulin like growth factor [GH/IGF] axis plays an important role in the regulation of body composition, the physiological interaction between Leptin and IGF-1 system remain unknown. The aim of this study was to investigate the correlation between Leptin and IGF-1 in type II diabetics and controls. This case-control study was consisted of 38, type 2 diabetics [20 males and 18 females, mean age 49.33 +/- 11.33, years] and 46 healthy controls [16 males and 30 females, mean age 49.52 +/- 7.99, years]. We measured the concentrations of fasting plasma glucose [FPG], IGF-1, hemoglobin A1C [HbA1c] and insulin like growth factor binding protein-3[IGFBP-3] in both groups. FPG was measured by the enzymatic glucose oxidase method and the Hb Gold analyzer HPLC was used to measure HbA1C. For determination of leptin, IGF-1, IGFBP-3 and insulin concentrations, the enzyme linked immunosorbent assay [ELISA] method was used. P< 0.05 was considered statistically significant. Means of BMI and age did not differ significantly between the two groups. Mean serum levels of IGF-1, leptin, insulin, FPG and HbA1c concentrations in type 2 diabetics were significantly higher than in controls [p<0.05]. In both groups, mean serum levels of leptin in males, were statistically lower than in females. Strong correlations were found between IGF-1 and IGFBP-3, leptin and insulin, IGF-1 and age, and between BMI and FPG in both patients and controls [p<0.05]. A negative correlation was observed between IGF-1 and HbA1c in patients and controls [p< 0.05]. It is concluded that leptin and the IGF-1 system, could influence body composition and fat content, particularly in obese and overweight diabetic patients

[Changes of serum leptin levels in healthy women with different grades of obesity and its correlation with hormonal and anthropometric factors]

Obesity is associated with a number of endocrine and metabolic abnormalities. Leptin is a peptide that is strongly correlated with adiposity and is a potential determinant of obesity and its complications. The aim of this study was to evaluate the relationship between serum leptin levels with anthropometric and hormonal factors in healthy women with different grades of obesity. This cross- sectional study enrolled 38 women with BMI ranging between 18.9-24.9, as the normal weight group, 35 women with BMI 24.9-29.9, as overweight, 37 women with 29.9-34.9, as obese grade I and 34 women with BMI 34.9-39.9, as obese grade II. Body Mass Index was defined as the weight in kilograms divided by the square of the height in meters. Serum levels of dehydroepiandrosterone sulfate, insulin, cortisol and Leptin were measured by commercially available enzyme immunoassay kits. There was a dramatic, continuous increase in serum leptin concentration when the degree of obesity was increased and concordance was seen with serum insulin concentrations. There was a direct and significant correlation between serum leptin concentration and BMI in obese subjects[r= 0.736, P< 0.001]. We found significant correlation between dehydroepiandrosterone sulfate concentrations and cortisol [r= 0.237, P< 0.05]. There was a significant negative correlation between leptin and insulin in grade 2 obese subjects[r= - 0.566, p< 0.05] and a significant positive correlation between cortisol and dehydroepiandrosterone sulfate in grade 2 obese subjects [r=0.610, P<0.001]. Serum leptin levels continuously rose with increasing degrees of obesity and serum leptin concentrations were strongly correlated with BMI. Concentrations of insulin and cortisol increase with increasing serum leptin levels

[Comparison of serum leptin levels of non-diabetic and diabetic obese subjects and its relationship to anthropometric indices]

Leptin, the product of the ob gene, plays a significant role in the pathogenesis of obesity and type 2 diabetes mellitus. The aim of this study was to compare serum leptin level in non-diabetic and type 2 diabetic obese subjects and assess its relationship to anthropometric indices. This cross-sectional study was performed on 35 obese subjects with type 2 diabetes and 35 non-obese, non-diabetics. Fasting lipid profiles were measured using enzymatic methods. The NycoCard HbA1c Kit was used to measure HbA1c. Serum leptin, insulin and glucose levels were measured by an enzyme immunoassay, using a commercially available kit and glucose oxidase methods respectively. The insulin resistance index was calculated by homeostasis model assessment [HOMA-IR]. The mean of insulin resistance index [HOMA-IR], HbA1c, diastolic blood pressure, triglyceride and fasting glucose in diabetics were significantly higher than in non-diabetic subjects [P < 0.05]. Serum leptin levels were significantly lower in diabetics than in non-diabetics [21.51 +/- 2.18 vs. 30.36 +/- 2.46] and were significantly higher in women than in men [31.85 +/- 17.96 vs.12.80 +/- 9.02] in the diabetic and [36.11 +/- 10.99 vs. 23.55 +/- 15.72] in non-diabetic groups. There was a direct and significant correlation between serum leptin levels with hip circumference [r= 0.450, p= 0.04] in diabetics and [r=0.590, p=0.000] in non-diabetics, and between leptin and BMI [r= 0.666, p= 0.000] in diabetic and [r= 0.490, p= 0.003] in non-diabetic groups. Since the mean serum leptin level is lower in obese diabetes, compared to non-diabetics, further studies are required to clarify the mechanisms of lower leptin levels in obese diabetic subjects

[Study of correlation between serum leptin levels and body composition in healthy obese and non-obese women]

Leptin, the product of the ob gene, is a hormone secreted by adipocytes, and results in a decrease in food intake an increase in energy expenditure via hypothalamic interactions. In animal models, obesity can be caused by leptin deficiency or dysfunction of hypothalamic leptin receptor. The aim of this study was to examin the relation between serum leptin levels and body composition. In this study, we measured serum concentration of leptin in 51 normal weight subjects [BMI < 25 kg/m[2]] and 50 obese subjects [BMI >/= 25] by ELISA. BMI was defined as the weight in kilogram divided by the square of height in meters and body composition was determined by bioimpedance analyzer. The mean +/- SE] serum leptin concentrations were 17.5 +/- 0.81 ng per milliliter in obese subjects and 4.9 +/- 0.55 ng per milliliter in the normal weight women [p< 0.0005]. There were a strong positive correlation between serum leptin concentration and body fat mass [r= 0.53] and BMI [r = 0.41] in obese women and lean body mass was inversely related to leptin concentration in normal weight subjects [r = - 0.28]. Significant relation between leptin and WHR neither in obese nor in normal weight group was not observed. We conclude that circulating leptin raised continuously with increasing adiposity and body fat mass is the main predictor of serum leptin concentration

[Study of prostate specific antigen gene expression and telomerase in breast cancer patients]

Breast cancer is the most common disease in women. In the expansion and progression of breast tumors combination of tumor markers including prostate specific antigen and telomerase are engaged. The aim of this study was to evaluate relationship between telomerase activity and prostate specific antigen gene expression in breast cancer patients and controls. This study was a case-control and consisted of 25 women diagnosed with breast benign tumors as control and 35 malignant tumors as cases. Telomerase activity was measured in tumor cytosol of samples by TRAP assay. PSA protein was measured using ultra sensitive immunoflourometric assay and PSA mRNA expression was making cleared using RTPCR techniques in all tumor tissues. Using TRAP assay, presence of the telomerase activity was positive in all of the breast cancer patients. The difference of relative telomerase activity [RTA] values between stages and also all grades were more statistically significant [p<0.05]. The PSA mRNA were detected only in benign tumors and stage I and grade I malignant tumor cytosols. Difference of tumor cytosol PSA levels between the cases and control groups and also between all grades and stages of diseases were significant [p <0.05]. In all, there was an inverse significant correlation between the RTA and PSA protein levels in the case groups [r=-0.42, p<0.05]. Our results showed a reverse relationship between PSA mRNA expression and increasing telomerase gene expression during breast cancer progression and development. In all, measurement of telomerase activity could be favorable biomarker along with PSA in breast cancer diagnosis

Study of correlation between serum zinc levels and telomerase activity in bladder cancer patients

Telomerase is an active gene existing in almost all human cancerous cells. This enzyme is essential for immortality and recycling of these living cells, however it normally has not been expressed in the somatic cells. Role of zinc as a probably interfering microelement in telomerase gene expression and activity in human bladder cancer is the main subject of this study. Thirty three voided urine samples were gathered from patients, which were previously identified as bladder carcinoma cases using cytological methods. They had previously not given any treatment. Telomerase activity was determined using polymerase chain reaction, which refers to the telomeric repeat amplification protocol. In order to distinguish the fine signals, obtained the procedure was linked to an ELISA system [TRAP assay]. The patients' grades and stages were determined independently through cystoscopy. Also, the serum zinc levels of these patients and control groups measured by atomic absorption spectrophotometer [AAS]. As a result; 17 [51%] of the 33-bladder carcinoma tested patients revealed positive results for cytology, whereas using TRAP assay presence of the telomerase was positive in all of the tested bladder carcinoma cases. Only 30% [3 of 10] of the grade I tumors, 83.3% [5 of 6] of the grade II tumors and 50% [9 of 18] of the grade III tumors were diagnosed by cytology. The detection accuracy rates was statistically significant [100% for telomerase vs. 51% for cytology]. The difference of relative telomerase activity [RTA] values between grades I, II and III was not statistically significant. Difference of serum zinc levels between the cases and control groups were significant [p= 0.04]. Zinc levels in the both affected genders had dominant decreases, besides this shift was slightly more significant [p=0.04] in the female patients. In all, there was an inverse significant correlation between the RTA and serum zinc level in the case group [r= -0.060, p= 0.48]. In conclusion our results showed a reverse relationship between zinc deficiency and increasing telomerase activity in our series of bladder cancer

[Correlation between leptin serum levels with lipid profile and anthropometric indices in women with different grades of obesity]

Background and Objective: leptin is a 16 KDa peptide which has a close correlation with adiposity. However, its effect on lipid profile is controversial in human. Therefore, this study was performed to investigate correlation between variations in serum leptin levels with lipid profile and anthropometric indices in women with different grades of obesity

Materials and Methods: the current cross-sectional study was carried out on 149 healthy non diabetic women, including 33 normal weight [BMI<24.9 kg/m2] and 116 women with different grades of obesity [BMI>25 kg/m2] with age range of 15-49 years, respectively. Serum levels of leptin, fasting blood glucose and lipid profile [total cholesterol, triglyceride and HDL-cholesterol] were measured using high sensitive immunoassay, glucose oxidase and enzymatic methods, respectively

Results: mean serum leptin levels were 15.34, 32.78, 42.13, 43.22 and 45.23 ng/ml in normal, overweight, obese grade I, obese grade II, and obese grade III women, respectively. Difference in mean of leptin serum level, lipid profile, and anthropometric indices was statistically significant between different groups [p<0.001]. Leptin Serum levels had significant correlation with BMI [p<0.05, r=0.623]. In addition, it showed a direct significant correlation with levels of fasting blood glucose [r=0.297] and lipid profile [total cholesterol [r=0.347], triglyceride [r=0.428], and LDL-cholesterol [0.367]] [p<0.05]. In contrast, it showed an indirect correlation with HDL-C serum levels [r= -0.320, p<0.05]

Conclusion: results of the current study showed that leptin serum level has a close direct correlation with adiposity indices and lipid profile and its level increases significantly with increasing grades of obesity

[Sperm DNA oxidative damages in infertile men]

Sperm DNA oxidative damage due to free radicals is a major contributing factor in a variety of human diseases, including male infertility. The aim of the present study was to compare the levels of sperm DNA oxidative damage in infertile [according to WHO criteria] and fertile men. Semen samples were obtained after 3 to 7 days of abstinence from 25 infertile and 23 fertile men who referred to infertility Center of Tabriz University of Medical Sciences. After semen analysis, sperm cells were separated from seminal fluid by percoll gradient centrifugation and kept at -20°C for next further analysis. Sperm DNA was extracted and its concentration and purity were determined by UV-spectrophotometer. DNA damage was studied by DNA Chromatography-mass spectrometry [GC/MS]. Analysis of 8 hydroxy Guanine [8-OHG] as a marker of DNA oxidative damage by GC/MS was shown that rate of basal DNA oxidative damage in infertile group was 100-fold greater than fertile group. There was also correlation between semen parameter [morphology, motility and sperm count] and DNA oxidative damage. Result of this study showed that elevation of sperm DNA oxidative damage could be one of possible reasons for male infertility