Scopus İndeksli Açık & Kapalı Erişimli Yayınlar

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    Association of Tumor Strain Ratio with Prognostic Factors in Invasive Breast Cancer
    (2022) Karan, Belgin; Purbager, Aysin; https://orcid.org/0000-0002-7034-7806
    We evaluate the correlations between tumor strain ratio value and prognostic factors for breast cancers. Fifty-seven women with invasive breast cancer underwent ultrasound elastography prior to surgery. Elastography strain ratio (SR), defined as the fat-to-lesion ratio, was recorded for each lesion using the software in the ultrasound equipment. We evaluated the associations between tumor SR and pathological prognostic factors such as tumor subtype, tumor size, axillary lymph node metastasis, histological grade, vascular invasion, and hormonal receptor status. We found a significant correlation between tumor SR and progesterone receptor (PR) status (p = 0.02). Tumors with axillary lymph node metastasis had a higher SR value than those without lymph node metastasis; however, this difference was not significant. Strain elastography revealed that grade 3 tumors had softer tissues than grade 1 and 2 tumors, although this was not statistically significant. The tumor SR value was not significantly correlated with tumor subtypes, tumor size, vascular invasion, and estrogen receptor or cell surface human epidermal growth factor 2 status (p > 0.05). The present study demonstrated no significant correlation between SR values and prognostic factors, except for PR status. However, tumors with LN metastasis tended to exhibit greater stiffness, and higher grade tumors exhibited lower stiffness owing to necrosis. Further studies with large study population on tumor-associated stiffness are required.
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    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-5195-2014
    Purpose 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.
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    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; 34171479
    Antiapoptotic 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.