Browsing by Author "Bulut, G"

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    Trastuzumab in combination with AT-101 induces cytotoxicity and apoptosis in Her2 positive breast cancer cells
    Bulut, G; Atmaca, H; Karaca, B
    Aim: AT-101 is a polyphenolic compound with potent anti-apoptotic effects in various cancers. In this study, the possible synergistic cytotoxic and apoptotic effect of trastuzumab/AT-101 combination was investigated in HER2-positive breast cancer cell lines. Materials & methods: SKBR-3, MDA-MB-453 and MCF-10A cell lines were treated with a trastuzumab/AT-101 combination. Synergistic cytotoxicity and apoptosis effects were shown and then PI3K and Akt protein levels were studied. Result: The trastuzumab/AT-101 combination induced synergistic cytotoxicity and apoptosis in both breast cancer cells but not in MCF-10A cells. Combination treatment induced cytotoxicity via inhibiting PI3K/AKT but not the MAPK/ERK pathway. Conclusion: The trastuzumab/AT-101 combination may be a good candidate for patients with trastuzumab-resistant Her2-positive breast cancer and inhibition of the PI3K/AKT pathway may be one of the underlying mechanisms.
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    Inflammatory Prognostic Index in Metastatic Renal Carcinoma Treated with Nivolumab
    Ekinci, F; Erdogan, AP; Yildirim, S; Bulut, G; Yilmaz, C; Barutca, S
    Objective: To evaluate the utility of inflammatory prognostic index (IPI), albumin, c-reactive protein (CRP), and lactate dehydrogenase (LDH) as predictive biomarkers of oncologic outcome in metastatic renal cell cancer (mRCC) patients treated with nivolumab. Methodology: Seventy-five mRCC patients treated with nivolumab between January 2017 and June 2020 were enrolled. Several factors were retrospectively investigated, including IPI, CRP, LDH, and albumin level, for their association with progression-free survival (PFS) and overall survival (OS). The IPI was calculated as CRP x NLR/albumin. Univariate and multivariate analyses were performed to assess the prognostic value of relevant factors.Results: When analysed according to the calculated IPI score, it is seen that the group with <2.153 has an OS duration of 96.3 months, while the group with >= 2.153 has a shorter time of 42.9 months (p=0.02). In the analysis performed according to albumin level, it was reported that those with low levels (22.8 months) had worse median OS than those with high levels (92.8 months) (p=0.004). According to the cox regression analysis results, it was determined that those with a high IPI score significantly increased the risk of death compared to those with a low score (HR:2.4, p=0.023). However, this significance could not be confirmed in the multivariate analysis. It was analysed that those with low albumin levels significantly increased the risk of death compared to both Conclusion: Those with high IPI scores and low albumin levels were associated with worse median OS. However, only the multivariate analysis analysed albumin level as an independent prognostic variable. Prospective and more extensive research is needed to consolidate the potential prognostic power of these markers.
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    Metastatic Pancreatic Cancer Second-Line Treatment Options: Is the Difference Only in Cost?
    Yildirim, S; Erdogan, AP; Karateke, M; Yilmaz, C; Özveren, A; Bulut, G; Ekinci, F; Almuradova, E
    Introduction Although pancreatic cancer ranks seventh in cancer-related deaths, it is an extremely fatal disease, and more than 330,000 people die from this disease worldwide. Although there are many first-line treatment studies in the literature, there are almost no prospective studies regarding second-line therapy. Therefore, there is no standard approach in the second-line treatment of pancreatic cancer. We decided to conduct this study to investigate second-line treatments with problems such as cost, treatment efficacy, and toxicity. Methods Patients older than 18 years old who applied to Ege University Hospital medical oncology department with a diagnosis of metastatic pancreatic cancer, who received first-line chemotherapy due to their illness, and who had progressed afterwards were included in the study. The files of the patients who applied between 2013 and 2017 were examined. Results Our study's primary endpoint was progression-free survival, and it was found that the median progression-free survival was 3.2 months in the Xelox patients, 3.7 months in the gemcitabine-nab paclitaxel patients, and 3.5 months in the other regimens. When the secondary endpoint was evaluated, overall survival, the median overall survival was 5.9 months in the Xelox patients, 5.3 months in the gemcitabine-nab paclitaxel patients, and 4.8 months in the other regimens. Conclusion As a result, second-line treatments were compared, and no statistically significant difference was found between them. For this reason, the side effects of previously used drugs and the side effects of new drugs to be used, as well as their costs, should be evaluated when choosing a treatment.
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    Octreotide in combination with AT-101 induces cytotoxicity and apoptosis through up-regulation of somatostatin receptors 2 and 5 in DU-145 prostate cancer cells
    Degirmenci, M; Erdogan, AP; Bulut, G; Atmaca, H; Uzunoglu, S; Karaca, B; Karabulut, B; Uslu, R
    Prostate cancer (PCa) is the most common type of cancer among males. Although survival rate of early-stage PCa is high, treatment options are very limited for recurrent disease. In this study, the possible synergistic cytotoxic and apoptotic effect of octreotide in combination with AT-101 was investigated in DU-145 hormone and drug refractory prostate cancer cell line. To enlighten the action mechanisms of the combination treatment, expression levels of somatostatin receptors 2 and 5 (SSTR2 and SSTR5) were also investigated. Cell viability was measured by XTT assay. Apoptosis was assessed through DNA fragmentation analysis and caspase 3/7 assay. mRNA and protein levels of SSTR2 and SSTR5 were evaluated by qRT-PCR and western blot analysis, respectively. Octreotide in combination with AT-101 inhibited cell viability and induced apoptosis synergistically in DU-145 cells as compared to any agent alone. Combination treatment increased both SSTR2 and SSTR5 mRNA and protein levels in DU-145 cells. The data suggest that this combination therapy may be a good candidate for patients with advanced metastatic PCa do not respond to androgen deprivation.
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    Programmed cell death ligand-1 expression in gastroentero-pancreatic neuroendocrine tumors
    Oktay, E; Yalcin, GD; Ekmekci, S; Kahraman, DS; Yalcin, A; Degirmenci, M; Dirican, A; Altin, Z; Ozdemir, O; Surmeli, Z; Diniz, G; Ayhan, S; Bulut, G; Erdogan, A; Uslu, R
    Purpose: Gastroenteropancreatic tumors (GEPNETs) is a heterogeneous disease with variable clinical course. While promising therapeutic options exist for other adult cancers, there are no new molecular-based treatments developed for GEPNETs. One of the main targets of cancer immunotherapy is the Programmed Cell Death Ligand-1 (PD-L1) pathway. Our purpose was to investigate the profile of PD-L1 expression in different organs of GEPNETs and compare the conventional immunohistochemistry (IHC) with the RNA expression analysis via real time polymerase chain reaction (RT-PCR) in order to determine which patients might be appropriate for immune check point-targeted therapy. Methods: A total of 59 surgically or endoscopically resected GEPNET tissues were retrospectively collected. The expression of PD-LI and mRNA was evaluated with IHC. Results: The expression of PD-L1 was significantly associated with the high-grade classification (p=0.012). PD-LI mRNA expression in tumor samples appeared to be higher compared to the corresponding normal tissues. In appendix, stomach and small intestine, the expression of PD-L1 mRNA was higher in the tumor tissues compared to the respective controls. In pancreas and colon, control tissues tend to have a higher PD-L1 mRNA expression compared to tumor tissues. PD-L1 mRNA expression was higher in GEP carcinomas (p=0.0031). Conclusion: RT-PCR was found to be more sensitive in detecting PD-L1 expression than conventional IHC. This study may provide an important starting point and useful background information for future research about immunotherapy for appendix, stomach and small intestine neuroendocrine carcinomas.
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    Contribution of complete response to treatment to survival in patients with unresectable metastatic colorectal cancer: A retrospective analysis
    Bulut, G; Oytun, MG; Almuradova, E; Harman, M; Uslu, R; Karabulut, B
    Background The aim of the study is to reveal the contribution of complete response (CR) to treatment to overall survival (OS) in patients with unresectable metastatic colorectal cancer. In addition, to evaluate progression-free survival (PFS) in patients who attained CR to treatment and to examine the clinicopathologic features of the patient group with CR. Methods This article is a retrospective chart review. Patients diagnosed with metastatic colorectal cancer were divided into two groups. The systemic treatment was compared with the patients who received a full response according to the Response Evaluation Criteria in Solid Tumors (RECIST1.1) and those who did not attain CR (progression partial response and stable response) in terms of both PFS and OS data, and the effect of attaining CR to treatment on prognosis was evaluated. Results A total of 222 patients were included in the study. 202 of 222 patients could be evaluated in terms of complete response. All data from their files were tabulated and analyzed retrospectively. The mean age of diagnosis of the study group was 60.13 12.52 years. The total number of patients who attained CR to treatment was 31 (15.3%); 171 (84.6%) patients did not attain CR. Patients who had a CR had longer median PFS times than patients who did not have a CR (15.2 vs. 7.4 months, P<0.001). Patients who had CR had longer median survival times than patients who did not have a CR (39.2 vs. 16.9 months, P<0.001). In subgroup patients who underwent primary surgery, the number of patients who attained CR was statistically higher compared with the number of patients who did not attain CR (p<0.001). Complete response was less common in the presence of liver metastasis and bone metastasis (p = 0.041 and p = 0.046, respectively), had a negative prognostic effect. In other words, 89.1% of patients with liver metastasis, 100.0% of patients with bone metastasis, and 88.7% of those who died did not have a CR to the treatment. According to multivariate analysis, CR to treatment, primary surgery, first-line chemotherapy (combination compared with fluoropyrimidine), and no bone metastasis were found to be predictors for OS. Conclusion Providing CR with systemic treatment in patients with unresectable metastatic colorectal cancer (mCRC) contributes to prognosis. The primary resection in our secondary acquisitions from the study, the number of metastatic regions and the combination therapy regimens also contributed to the prognosis.