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کاربرد نوع شرط:
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: MBC,Tamoxifen,polymorphisms,CYP2D6,response to treatment
- چکیده:
- چکیده انگلیسی: Background: Metastatic breast cancer (MBC) represents a major health problem in Egypt and worldwide. Prognostic and predictive factors for patients with MBC are highly required for better management and improved survival. The aim of this study was to assess the prognostic and predictive value(s) of CYP2D6 polymorphisms in Tamoxifen responders and non-responders. Methods: A cohort of 157 hormone receptor positive, locally recurrent inoperable and/or metastatic (MBC) Egyptian female patients was assessed for CYP2D6 polymorphisms. Data were correlated to relevant clinic-pathological features of the patients, response to tamoxifen, and survival rates. Results: CYP2D6 polymorphisms were detected in 44/157 cases (28%), 30 of them (68.2%) were refractory and 14 (31.8%) were responders (P=0.027). The CYP2D6 *3,*4 variants were significantly prevalent in the refractory group 26/30 (86.6%), while the *10/*10 and *10/*3 variants were more common in the responders 12/14 (85.71%, P=0.027). CYP2D6 polymorphism associated significantly with Her-2 amplification (P=0.001) as well as reduced overall survival rates in both refractory and responder patients (p < 0.001). Conclusion: CYP2D6 polymorphisms can significantly predict response to Tamoxifen treatment, and also associates with poor overall survival rates in MBC patients
- انتشار مقاله: 17-05-1399
- نویسندگان: Ibrahim Malash,Osman Mansour,Sabry Shaarawy,Mona S Abdellateif,Anan Omar,Rabab Gaafer,Abdel-Rhaman N Zekri,Ola S Ahmed,Abeer Bahnassy
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Breast cancer,Doxorubicin,siRNA,Telomerase
- چکیده:
- چکیده انگلیسی: Background: Telomerase activity is up regulated in most breast cancer subtypes but not in the adjacent normal tissues. Thus, it is a promising target for anticancer therapy. The present work investigated the effects of telomerase inhibition by siRNA on breast cancer cell lines and studied the feasibility of whether the combined effect of doxorubicin with siRNA treatment on breast cancer cells potentiates a rapid cellular response to the cytotoxic effect of chemotherapy. Methods: This study was performed on Luminal A (MCF-7), triple negative (MDA-MB-468), and HER-2/neu (SKBR-3) human breast cancer cell lines, wherein telomerase activity inhibition by hTERT siRNA and doxorubicin was detected by measuring telomerase activity using Telomeric Repeat Amplification Protocol (TRAP assay), assessing cell viability through MTT assay, and evaluating apoptosis through scanning electron microscopy (SEM) and through estimating caspase-3 and -8 activities using enzyme-linked immunosorbent assay (ELISA). Results: In the present study, hTERT siRNA effectively reduced telomerase activity and cell viability to more than 90% and 60%, respectively, in most breast cancer cell lines within 72 hours after transfection. The combination of hTERT siRNA and doxorubicin showed a cumulative effect compared with either treatment alone (P < 0.05). Meanwhile, SEM demonstrated apoptotic morphologic cell changes. Conclusion: Telomerase inhibition is a promising strategy for the effective treatment of breast cancer. When used in combination with doxorubicin, it could potentiate the cytotoxic effect of the drug on breast cancer cells.
- انتشار مقاله: 03-01-1399
- نویسندگان: Salma Aboelela,Abeer Ashmawy,Sabry Shaarawy,Mohammed EL- Hefny,Amina Medhat
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Thyroid cancer,Papillary Thyroid Carcinoma,Vit D,PDGF,IGF-1
- چکیده:
- چکیده انگلیسی: Background: Thyroid cancer (TC) is a common malignant tumor, however the role of total vitamin D: 25(OH)D, Platelet Derived Growth Factor (PDGF) and Insulin Like Growth Factor 1 (IGF-1) in the development of TC is still unclear. Aim: To assess the roles of 25(OH)D, PDGF and IGF-1 in the progression of thyroid diseases. METHODS: The serum levels of 25(OH)D, PDGF and IGF-1 were assessed in 70 patients with papillary thyroid cancer (PTC), 60 patients with benign thyroid nodules (BN) compared to 60 normal controls (NC) using ELISA technique. Results: There was a significant decrease in the serum level of 25(OH)D in TC patients compared to NC (P<0.001) and BN patients (P=0.006). There was a significant increase in the serum levels of PDGF and IGF-1 in TC patients (P<0.001), and BN patients (P<0.001) compared to NC, while there were no significant differences between TC and BN (P=0.087, and 0.258; respectively). PDGF correlated significantly with IGF-1 (r=0.412, P<0.001), TSH (r=0.146, P=0.045), and inversely correlated with 25(OH)D (r= -0.156, P=0.013) and FT4 (r=-0.178, P=0.014). There was a significant inverse correlation between the serum levels of IGF-1 and FT4 (r=-0.172, P=0.017). Sensitivity and specificity for assessment of TC patients were (65.7% and 58.3%, P= 0.001) for 25(OH)D, (65.7% and 58.3%, P=0.021) for IGF-1, and (68.6% and 61.7%, P=0.006) for PDGF. Multivariate analysis demonstrated that serum 25(OH)D (OR=0.578, 95%CI= 0.426-0.783), IGF-1 (OR=1.019, 95%CI= 1.010-1.029) and PDGF (OR=1.007, 95%CI= 1.004-1.009) were considered independent risk factors for thyroid cancer (P<0.001, for all). Conclusion: 25(OH) D, IGF-1 and PDGF are significantly different in TC and BN cases compared to control. They have an important role in the progression of TC. However, these data should be validated on a larger sample size.
- انتشار مقاله: 06-01-1399
- نویسندگان: Mona S Abdellateif,Sabry Shaarawy,Yasmine F Elesawy,Mona Mansour,Effat Tharwat,Noha H Ibrahim,Marwa S Eissa
- مشاهده