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Mahmoud Delphan, Hamid Agha Alinejad , Maryam Delfan, Sedigheh Dehghan,
Volume 10, Issue 2 (Iranian Quarterly Journal of Breast Diseases 2017)
Abstract

Introduction: Apoptosis and tumor growth are inhibited by intratumoral miR-21 via upregulation of bcl-2. Hence, the aim of the present study was determine the effects of continuous endurance training (ET) and high intensity interval training (HIIT) on intratumoral miR-21 and bcl-2 of breast cancer bearing female mice.
Methods: Eighteen  female BALB/c mice after inducing breast cancer through MC4-L2 cell lines injection  were randomly divided into three groups (n=6) including control, continuous endurance training (ET) and high intensity interval training (HIIT). Then, both experimental groups including ET (75 min/day, constant running speed corresponding to 60–65%) and HIIT (six intervals for 3 min and 20 seconds, 85-90% V̇O2 peak, 90 second of active rest at 30-35% V̇O2 peak separating intervals) performed exercise protocols at 15% inclination, five days a week for ten weeks.  Tumor volume was measured and recorded by caliper every week. miR-21 and bcl-2 gene expression were determined by qReal-time PCR. Statistic data values also were measured by One-way ANOVA.
Results: The results of the present study showed that miR-21 gene expression was significantly reduced in both experimental groups compared to control group (p≤0.001). While, bcl-2 gene expression had no significant change in comparison with control group (p≥0.05). There was also observed a significant reduction in tumor volume of two experimental groups in comparison with control group. It should be noted that tumor volume reduction in HIIT was larger than ET.
Conclusion: HIIT is possibly more effective than ET in attenuating cancer cells progression via its intratumoral effects. 
 
Ehsan Hossenzadeh Nazloo, Maghsoud Peeri, Maryam Delfan,
Volume 13, Issue 1 (Iranian Journal of Breast Disease 2020)
Abstract

Introduction:Regular exercise training inhibits tumor growth and prevents cardiomyopathy in breast cancer patients by activating signaling pathways leading to changes in gene expression. The purpose of the present study was to investigate the effects of 10 weeks of continuous aerobic training on tumor volume and expression of IGF-1, Akt, mTORC1 genes in the myocardium of mice with breast cancer.
Methods:Twelve female BALB/c mice were divided into 2 groups of 6: Continuous Aerobic Exercise and Control. The tumor was induced by the injection of MC4-L2 cells. The aerobic exercise included 75 minutes of steady running at 60% to 65% of VO2 peak, 5 days a week for 10 weeks. Tumor volume was measured by a caliper weekly. Twenty-four hours after the last training session, the mice were killed and their left ventricles were harvested. IGF-1 protein levels were measured with western blotting analysis, and real-time PCR was used to determine the expression of Akt and mTORC1 genes. The comparison of the groups was made using t tests at a significance level of 5%.
Results:IGF-1 did not show significant changes in the Aerobic Exercise group compared with the Control group (P = 0.08). The expression of Akt was significantly higher in the Aerobic Exercise group than in the controls (P = 0.016). The Aerobic Exercise group had also a significantly higher mTORC1 gene expression compared with the Control group (P = 0.022). Tumor volume also showed a significant decrease in the Aerobic Exercise group compared with the Control group (P = 0.03).
Conclusion: It can be concluded that 10 weeks of aerobic exercise training may reduce tumor volume and, possibly, improve heart function in breast cancer patients by increasing the expression of genes.

Maryam Delfan, Zahra Rasekh Nejad , Mahmoud Delphan,
Volume 13, Issue 3 (Iranian Journal of Breast Disease 2020)
Abstract

Introduction: The Il4/Stat-6 signaling axis is one of the most important pathways involved in the growth and development of breast cancer. Hence, the aim of the present study was to investigate the synergistic effect of endurance training along with curcumin on the intratumoral expression of Il4 and Stat-6 in female BALB/c mice with breast cancer.
Methods: Forty BALB/c mice (4-5 weeks old) were randomly divided into four groups including exercise, curcumin, exercise-curcumin, and control. The 4T1 breast Tumors were transplanted subcutaneously in the right flank of all mice. Then, endurance training (5 days per week) was performed, and curcumin (6 times per week) was given by gavage for five weeks. The intratumoral expression of Il4 and Stat-6 were measured using the qRT-PCR method. One-way analysis of variance followed by LSD post hoc test, was used for the statistical analysis. P< 0.05 was considered statistically significant.
Results: A significant decline in tumor growth was observed in all intervention groups compared with the control group (P<0.05). Endurance training with curcumin resulted in a significant reduction in the intratumoral expression of Il4 and Stat-6 in comparison with the control group (P=0.001 for both genes). Significant reductions in the expression of Il4 (P=0.019) and Stat-6 (P=0.001) were also observed in the endurance exercise group. Curcumin only reduced Stat-6 gene expression compared with the control group (P=0. 001).
Conclusion: Five weeks of endurance training with curcumin seems to be more effective in treatment of cancer compared with either of these non-pharmacological strategies alone.

Naeimeh Yazdanshenas, Maghsoud Peeri, Maryam Delfan,
Volume 13, Issue 3 (Iranian Journal of Breast Disease 2020)
Abstract

Introduction: Limiting cancer-induced cardiac atrophy is a highly important for improving the survival rates and quality of life in cancer patients. The purpose of this study was to evaluate the effect of 10 weeks of high-intensity interval training (HIIT) on cardiac muscle weight, NF-kB protein expression, and expression of Atrogin-1 and MuRF-1 genes in the heart muscle of breast cancer–bearing female mice.
Methods: In this experimental study, 12 BALB/c mice with induced breast cancer were divided into control and HIIT groups. The HIIT protocol consisted of six intervals of running at 85%-90% V̇O2 peak, interspersed with 90 seconds of active rest, and five minutes of warm-up and cool-down. The left ventricular tissue was extracted 24 h following the last training session. Western blotting was used to measure protein levels of NF-kB, and quantitative real-time polymerase chain reaction was used to measure Atrogin-1 and MuRF-1 expression in the heart tissue. Data were analyzed using an independent t test at a 0.05 significance level.
Results: The mean cardiac muscle weight in the HIIT group was greater than in the control group (P < 0.001). A significant reduction in NF-kB protein levels (P = 0.004) and expression of Atrogin-1 (P < 0.001) and MuRF-1 (P < 0.001) were observed in the HIIT group when compared with control group.
Conclusion: Ten weeks of HIIT may inhibit NF-kB/Atrogin-1/MuRF-1 axis, leading to decreased atrophy and increased heart weight in mice with breast cancer.


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