PubMed İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/11727/4810
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Item Significance of liver metastasis volume in breast cancer patients treated with stereotactic body radiotherapy(2021) Oymak, Ezgi; Guler, Ozan Cem; Onal, Cem; 0000-0002-2742-9021; 34477885; AGG-9214-2022; D-5195-2014Purpose This study analyzed the impact of liver metastasis (LM) volume on treatment outcomes in breast cancer (BC) patients treated with stereotactic body radiotherapy (SBRT). Methods This single-institution retrospective analysis included 40 oligometastatic (<= 5 metastases) BC patients with 58 liver metastases treated with SBRT between April 2013 and March 2021. The prognostic factors for local control (LC), overall survival (OS), and progression-free survival (PFS) rates were assessed. Results Median follow-up time was 28.1 months. Isolated and solitary LM were seen in 26 (65%) and 24 (60%) patients, respectively. Median time to disease recurrence was 10.7 months post liver SBRT. The 2-year OS, PFS, and LC rates were 71.4%, 27.5%, and 86.8%, respectively. In univariate analysis, patients with a gross tumor volume (GTV) of <= 6 cc and a planning target volume (PTV) of <= 38 cc demonstrated a significantly better median OS than those with GTV > 6 cc and PTV > 38 cc. In multivariate analysis, the predictive factors for worse OS were GTV > 6 cc (HR = 3.07 [95% CI, 1.14-8.22; p = 0.03]) and PTV > 38 cc (HR = 5.91 [95% CI, 1.92-18.21; p = 0.002]). No significant factor for PFS was found. Only 2 patients experienced rib fracture at 4 and 6 months post treatment, and 1 patient had a grade II duodenal ulcer. Conclusion Liver SBRT is an effective and safe treatment option for oligometastatic BC patients with excellent LC, promising survival, and limited toxicity. Patients with smaller tumors displayed better OS than their counterparts, validating the effectiveness of a local treatment for this group.Item Kinome-wide RNAi screening for mediators of ABT-199 resistance in breast cancer cells identifies Wee1 as a novel therapeutic target(2021) Aka, Yeliz; Acikbas, Ufuk; Kutuk, Ozgur; 34171479Antiapoptotic and proapoptotic BCL-2 protein family members regulate mitochondrial apoptotic pathway. Small molecule inhibitors of antiapoptotic BCL-2 proteins including BCL-2-specific inhibitor ABT-199 (Venetoclax) are in clinical development. However, the efficiency of ABT-199 as a single agent in solid tumors is limited. We performed a high-throughput RNAi kinome screen targeting 691 kinases to identify potentially targetable kinases to enhance ABT-199 response in breast cancer cells. Our studies identified Wee1 as the primary target kinase to overcome resistance to ABT-199. Depletion of Wee1 by siRNA-mediated knockdown or inhibition of Wee1 by the small molecule Wee1 inhibitor AZD1775 sensitized SKBR3, MDA-MB-468, T47D and CAMA-1 breast cancer cells to ABT-199 along with decreased MCL1. BH3-only proteins PUMA and BIM functionally contribute to apoptosis signaling following co-targeting BCL-2 and Wee1. Suppression of Wee1 function increased mitochondrial cell death priming. Furthermore, we found that Wee1 inhibition altered MCL1 phosphorylation and protein stability, which led to HUWE1-mediated MCL1 degradation. Our findings suggest that Wee1 inhibition can overcome resistance to ABT-199 and provide a rationale for further translational investigation of BCL-2 inhibitor/Wee1 inhibitor combination in breast cancer.Item Associations between the expression of mucins (MUC1, MUC2, MUC5AC and MUC6) and clinicopathologic parameters of human breast carcinomas(2020) Oral, Onur; Unverdi, Hatice; Kumcu, Emrah; Turkbey, Duygu; Dogan, Serdar; Hucumenoglu, Sema; 33154304Aims: The aim of this study is to evaluate the relationships between the expression of mucins in invasive breast carcinomas and clinicopathologic parameters. Materials and Methods: We examined 150 cases of invasive breast carcinoma, using the 2012 World Health Organization (WHO) classification of the tumors of the breast. We studied the expression of MUC1, MUC2, MUC5AC, and MUC6 by immunohistochemistry. We also evaluated normal breast tissue and ductal carcinoma in situ (DCIS) lesions in nearby invasive tumor areas. Results: In invasive breast carcinomas, MUC1, MUC2, MUC5AC, and MUC6 were expressed in 98.6%, 11.3%, 9.9, and 8.5% of cases, respectively. MUC2, MUC5AC, and MUC6 were overexpressed in invasive tumors and DCIS lesions were compared with normal breast tissue. The apical pattern of MUC1 was correlated with low grade and ER expression. MUC2 was correlated with mucinous carcinoma and an inverse association with invasive ductal carcinoma, not otherwise specified (NOS). MUC6 expression was associated with lymphovascular invasion. Conclusions: Most invasive breast tumors express MUC1 and the apical pattern of MUC1 is correlated with low grade and ER expression. MUC6 expression is associated with indicators of poor prognosis. Further comprehensive studies need to evaluate the role of mucins as a potential biomarker and to be used as a specific therapeutic target against breast cancer.Item Radiotherapy After Skin-Sparing Mastectomy and Implant-Based Breast Reconstruction(2019) Sari, Sezin Yuce; Guler, Ozan Cem; Gultekin, Melis; Yildirim, Berna Akkus; Onal, Cem; Ozyigit, Gokhan; Yildiz, Ferah; 0000-0001-6908-3412; 31255547; AAC-5654-2020We aimed to evaluate the cosmetic results of radiotherapy in 170 breast cancer patients after implant-based reconstruction. Cosmetic results were excellent or fair in most patients after radiotherapy. However, bolus use, lymphatic irradiation, and the volume receiving at least 110% of the prescribed dose being >1% significantly deteriorated the outcomes. Introduction: We evaluated the cosmetic results of radiotherapy (RT) after implant-based reconstruction (IBR). Patients and Methods: We retrospectively evaluated 170 patients with 171 breast cancers treated between December 2004 and January 2016 in 2 university hospitals. RT fields were reconstructed breast (RB) only in 24 (14%), and RB and regional lymphatics in 147 (86%) breasts, respectively. All but 1 patient received a total 50 Gy with conventional fractionation. All patients received systemic chemotherapy. One hundred thirty-eight (81%) patients received hormonal therapy; 118 tamoxifen and 20 aromatase inhibitor. Results: Median follow-up time was 46.8 months (range, 1-163 months). The 5-year disease-free and overall survival rate was 83% and 93%, respectively. Cosmetic results were considered excellent in 111 (65%), fair in 46 (27%), and bad in 14 (8%) RB by patients. Thirty-four (20%) RB had restorative surgery; because of surgeons' preference because of implant natural life time span in 5, and contracture, fibrosis, deformation, or dislocation of the implant, or cellulitis in the remaining. Statistically significant adverse factors in univariate analysis for impaired cosmetic outcome were bolus use on the RB, lymphatic irradiation, and volume that received at least 110% of the prescribed dose being >1%. The use of bolus material was the only prognostic factor for deterioration of the cosmetic result in multivariate analysis. Conclusion: RT after IBR yields acceptable cosmetic results. Although only 111 (65%) of RBs were considered to have excellent cosmetic results, only a small percentage of patients needed reoperation because of bad cosmetic outcome. (C) 2019 Elsevier Inc. All rights reserved.