Objectives: Leptin receptor (LEPR) is a member of the class I cytokine receptor super-family that... more Objectives: Leptin receptor (LEPR) is a member of the class I cytokine receptor super-family that is known implicated in the initiation and progression of breast cancer. We have investigated the effect of Q223R polymorphism on the breast cancer susceptibly in a sample of Iranian subjects. Materials and methods: We utilized a polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method to investigate the association of LEPR Q223R polymorphism with breast cancer risk in a case control study consisting of 100 breast cancer cases and 100 controls without breast cancer. Serum levels of leptin and soluble leptin receptor (sOB-R) were measured by ELISA method. Results: The genotype (QQ, QR, and RR) distributions were 25, 56, and 19 % in breast cancer cases and 54, 40, and 6% in controls, respectively. The frequency of 223 RR genotype was significantly elevated in breast cancer cases as compared to controls (χ(2)= 20.072, P<0.001). Similar significance differences were also found in allele frequencies for Q and R between two groups (χ(2)= 19.027, P< 0.001). Additionally, there were significant association between Q223R genotypes and breast cancer risk; homozygotes for RR genotype (OR= 6.840; 95% confidence interval [CI] = 2.434-19.218), heterozygotes for QR (OR=3.024; 95% CI = 1.620-5.644, P = 0.001), and QR+RR genotype (OR= 3.522; 95% CI = 1.934-6.414, P < 0.001), respectively. Conclusion: Our results showed that the LEPR Q223R polymorphism is associated with increased breast cancer risk as well as tumor grade in a sample of Iranian subjects.
Scandinavian Journal of Clinical & Laboratory Investigation, 2009
Adiponectin is an adipose tissue-secreted hormone with important metabolic effects. There have be... more Adiponectin is an adipose tissue-secreted hormone with important metabolic effects. There have been inconsistent reports about SNPs of the adiponectin gene and risk of type 2 diabetes (T2DM). The aim of this study was to investigate any association between SNPs (+45 T/G and +276 G/T) of the adiponectin gene with serum adiponectin levels, metabolic factors and risk of T2DM in obese individuals. Genotyping for two common SNPs of adiponectin gene was performed in 50 unrelated obese type 2 diabetic patients and 52 obese non-diabetic control subjects by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Lipid profile was measured by enzymatic methods. Serum adiponectin, insulin, leptin and glucose levels were measured by immunoassay, and glucose oxidase methods, respectively. It was observed that obesity and T2DM are associated with low serum adiponectin levels. The G allele and TG/GG genotype of SNP 45 occurred more frequently than the T allele and TT genotype in T2DM patients compare to the controls (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). Subjects with the G/G + TG genotype of SNP 45 were at increased risk for T2DM [Odds Ratio (OR) 2.574; 95% Confidence Interval (CI) 1.051-6.302; p=0.036] compared with those T/T genotype. There was no statistically significant difference in allele and genotype frequencies of SNP 276 comparing control group with T2DM group. Thus, our results demonstrated that, adiponectin SNP 45T/G, rather than SNP 276G/T, is more associated with risk of T2DM in obese individuals.
Background: breast cancer is one of the leading causes of cancer mortality worldwide. 5-fluoroura... more Background: breast cancer is one of the leading causes of cancer mortality worldwide. 5-fluorouracil (5-FU) is one of the chemotherapy drugs to treat breast cancer, but it is associated with several side effects. Combination therapy is a way to increase the effectiveness of chemo drugs and decrease their usage dose. Quercetin (Quer) is one of the natural polyphenols with anti-cancer properties. This study investigated the apoptotic effect of 5-FU in combination with Quer compared with 5-FU alone on MCF7 breast cancer cells.Method and Results: Different single and combined concentrations of 5-FU and Quer were applied to MCF 7 cells for 48 hours. Cell viability, apoptosis, gene expression of Bax and Bcl2, and colony number were assessed using MTT assay, flow cytometry, quantitative real-time PCR, and Colony formation assay, respectively. The combination of 5-FU and Quer compared to 5-FU alone improved apoptosis by increasing and decreasing the gene expression of Bax and Bcl2, respecti...
Objective(s): Combination chemotherapy is a beneficial intervention for breast cancer, versus sin... more Objective(s): Combination chemotherapy is a beneficial intervention for breast cancer, versus single therapy. We investigated the effect of Metformin (Met) on Lapatinib (Lap)-induced apoptosis in SK-BR3 cells. Materials and Methods: Toxic effect of Met and Lap on SK-BR3 cells was measured using MTT assay. Flow cytometry was used to measure the co-treatment effect of Met on lapatinib-induced apoptosis. The relative expression of Bax, Bcl2, and P21 was measured using a real-time PCR. The activity of caspase 3 and 9 was measured using an ELISA kit. The protein level of AMPK and Akt was determined using Western blot analysis. Results: Metformin and lapatinib alone and combined form showed significant time- and dose-dependent toxic effects on SK-BR3 cell viability. The greatest synergistic inhibitory effect on the cell viability [combination index (CI) = 0.51] was remarkable at Met 100 mM combined with Lap 100 nM. The combination has a stronger apoptotic death (46%) versus lapatinib alon...
Background: Angiogenesis provides the oxygen and nutrients needed for metastasis and tumor growth... more Background: Angiogenesis provides the oxygen and nutrients needed for metastasis and tumor growth, so by inhibiting angiogenesis, metastasis to other parts of the body can be prevented at the first steps of cancer. 5-Fluorouracil (5-FU) as a common chemotherapy drug and Quercetin as a natural compound both have anti-angiogenic properties. Objectives: In the current study improvement of the anti-angiogenic property of 5-FU by combination with quercetin was investigated. Methods: After treating the cells with alone or a combination of drugs the angiogenesis, vascular endothelial growth factor receptors (VEGFRs) gene expression, migration, and viability of the cells were evaluated using chicken chorioallantoic membrane (CAM) assay, real-time RT-PCR, wound healing and MTT assay, respectively. Results: Treatment with alone 5-FU and Que led to a significant reduction in angiogenesis, VEGFR2 and VEGFR1gene expression, migration, and Cell viability. The reductions were significant in the co...
Objectives: Leptin receptor (LEPR) is a member of the class I cytokine receptor super-family that... more Objectives: Leptin receptor (LEPR) is a member of the class I cytokine receptor super-family that is known implicated in the initiation and progression of breast cancer. We have investigated the effect of Q223R polymorphism on the breast cancer susceptibly in a sample of Iranian subjects. Materials and methods: We utilized a polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method to investigate the association of LEPR Q223R polymorphism with breast cancer risk in a case control study consisting of 100 breast cancer cases and 100 controls without breast cancer. Serum levels of leptin and soluble leptin receptor (sOB-R) were measured by ELISA method. Results: The genotype (QQ, QR, and RR) distributions were 25, 56, and 19 % in breast cancer cases and 54, 40, and 6% in controls, respectively. The frequency of 223 RR genotype was significantly elevated in breast cancer cases as compared to controls (χ(2)= 20.072, P<0.001). Similar significance differences were also found in allele frequencies for Q and R between two groups (χ(2)= 19.027, P< 0.001). Additionally, there were significant association between Q223R genotypes and breast cancer risk; homozygotes for RR genotype (OR= 6.840; 95% confidence interval [CI] = 2.434-19.218), heterozygotes for QR (OR=3.024; 95% CI = 1.620-5.644, P = 0.001), and QR+RR genotype (OR= 3.522; 95% CI = 1.934-6.414, P < 0.001), respectively. Conclusion: Our results showed that the LEPR Q223R polymorphism is associated with increased breast cancer risk as well as tumor grade in a sample of Iranian subjects.
Scandinavian Journal of Clinical & Laboratory Investigation, 2009
Adiponectin is an adipose tissue-secreted hormone with important metabolic effects. There have be... more Adiponectin is an adipose tissue-secreted hormone with important metabolic effects. There have been inconsistent reports about SNPs of the adiponectin gene and risk of type 2 diabetes (T2DM). The aim of this study was to investigate any association between SNPs (+45 T/G and +276 G/T) of the adiponectin gene with serum adiponectin levels, metabolic factors and risk of T2DM in obese individuals. Genotyping for two common SNPs of adiponectin gene was performed in 50 unrelated obese type 2 diabetic patients and 52 obese non-diabetic control subjects by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Lipid profile was measured by enzymatic methods. Serum adiponectin, insulin, leptin and glucose levels were measured by immunoassay, and glucose oxidase methods, respectively. It was observed that obesity and T2DM are associated with low serum adiponectin levels. The G allele and TG/GG genotype of SNP 45 occurred more frequently than the T allele and TT genotype in T2DM patients compare to the controls (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). Subjects with the G/G + TG genotype of SNP 45 were at increased risk for T2DM [Odds Ratio (OR) 2.574; 95% Confidence Interval (CI) 1.051-6.302; p=0.036] compared with those T/T genotype. There was no statistically significant difference in allele and genotype frequencies of SNP 276 comparing control group with T2DM group. Thus, our results demonstrated that, adiponectin SNP 45T/G, rather than SNP 276G/T, is more associated with risk of T2DM in obese individuals.
Background: breast cancer is one of the leading causes of cancer mortality worldwide. 5-fluoroura... more Background: breast cancer is one of the leading causes of cancer mortality worldwide. 5-fluorouracil (5-FU) is one of the chemotherapy drugs to treat breast cancer, but it is associated with several side effects. Combination therapy is a way to increase the effectiveness of chemo drugs and decrease their usage dose. Quercetin (Quer) is one of the natural polyphenols with anti-cancer properties. This study investigated the apoptotic effect of 5-FU in combination with Quer compared with 5-FU alone on MCF7 breast cancer cells.Method and Results: Different single and combined concentrations of 5-FU and Quer were applied to MCF 7 cells for 48 hours. Cell viability, apoptosis, gene expression of Bax and Bcl2, and colony number were assessed using MTT assay, flow cytometry, quantitative real-time PCR, and Colony formation assay, respectively. The combination of 5-FU and Quer compared to 5-FU alone improved apoptosis by increasing and decreasing the gene expression of Bax and Bcl2, respecti...
Objective(s): Combination chemotherapy is a beneficial intervention for breast cancer, versus sin... more Objective(s): Combination chemotherapy is a beneficial intervention for breast cancer, versus single therapy. We investigated the effect of Metformin (Met) on Lapatinib (Lap)-induced apoptosis in SK-BR3 cells. Materials and Methods: Toxic effect of Met and Lap on SK-BR3 cells was measured using MTT assay. Flow cytometry was used to measure the co-treatment effect of Met on lapatinib-induced apoptosis. The relative expression of Bax, Bcl2, and P21 was measured using a real-time PCR. The activity of caspase 3 and 9 was measured using an ELISA kit. The protein level of AMPK and Akt was determined using Western blot analysis. Results: Metformin and lapatinib alone and combined form showed significant time- and dose-dependent toxic effects on SK-BR3 cell viability. The greatest synergistic inhibitory effect on the cell viability [combination index (CI) = 0.51] was remarkable at Met 100 mM combined with Lap 100 nM. The combination has a stronger apoptotic death (46%) versus lapatinib alon...
Background: Angiogenesis provides the oxygen and nutrients needed for metastasis and tumor growth... more Background: Angiogenesis provides the oxygen and nutrients needed for metastasis and tumor growth, so by inhibiting angiogenesis, metastasis to other parts of the body can be prevented at the first steps of cancer. 5-Fluorouracil (5-FU) as a common chemotherapy drug and Quercetin as a natural compound both have anti-angiogenic properties. Objectives: In the current study improvement of the anti-angiogenic property of 5-FU by combination with quercetin was investigated. Methods: After treating the cells with alone or a combination of drugs the angiogenesis, vascular endothelial growth factor receptors (VEGFRs) gene expression, migration, and viability of the cells were evaluated using chicken chorioallantoic membrane (CAM) assay, real-time RT-PCR, wound healing and MTT assay, respectively. Results: Treatment with alone 5-FU and Que led to a significant reduction in angiogenesis, VEGFR2 and VEGFR1gene expression, migration, and Cell viability. The reductions were significant in the co...
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