Browsing by Publisher "Zerbinis Publications"
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Item Synergistic effect of ponatinib and epigallocatechin-3-gallate induces apoptosis in chronic myeloid leukemia cells through altering expressions of cell cycle regulatory genes(Zerbinis Publications, 2014) Goker B.; Caliskan C.; Caglar H.O.; Kayabasi C.; Balci T.; Tepedelen B.E.; Aygunes D.; Susluer S.Y.; Mutlu Z.; Gunell N.S.; Korkmaz M.; Saydam G.; Gunduz C.; Avci C.B.Purpose: Ponatinib (P) has been used for the treatment of chronic myeloid leukemia (CML) and it is known that inhibition of BCR-ABL fusion protein by ponatinib induces apoptosis of CML cells. Epigallocatechin-3-gallate (EGCG), which is a polyphenol in green tea, induces apoptosis in different types of cancer cells. The purpose of this study was to determine the cytotoxic and apoptotic effects of ponatinib and EGCG combination in K562 CML cell line. This study also aimed to detect alterations of the expression levels of cell cycle-regulation related genes after ponatinib and EGCG combination in K562 CML cell line. Methods: The cytotoxic effects of the compounds on K562 cells were determined in a time- and dose-dependent manner by using WST-1 analysis. The combination index (CI) isobologram was used to analyze the data. Apoptotic effects of P-EGCG were defined by flow cytometry and gene expressions were detected by RT-qPCR. Results: IC50 values of ponatinib and EGCG were 87.13 nM and 50μM, respectively. CI value of the P-EGCG was 0.658 and the combination showed synergistic effect (ED90 value: 28.39 nM ponatinib, 117.12 μg/ml EGCG). Ponatinib, EGCG and P-EGCG induced apoptosis compared to control cells. CyclinDl and CDC25A were downregulated by P-EGCG by 2.49 and 2.63-fold, respectively. TGF-β2 was upregulated by 4.57-fold. Conclusion: EGCG possesses cytotoxic and apoptotic properties and may cooperate with the growth inhibiting activity of ponatinib synergistically against CML cells. P-EGCG mediated apoptosis might be associated with upregulation of TGF-β2 gene and downregulation of cyclinDl and CDC25A genes.Item Enhanced cytotoxicity and apoptosis by thymoquinone in combination with zoledronic acid in hormone- and drugresistant prostate cancer cell lines(Zerbinis Publications, 2014) Dirican A.; Erten C.; Atmaca H.; Bozkurt E.; Kucukzeybek Y.; Varol U.; Tarhan M.O.; Karaca B.; Uslu R.Purpose: Thymoquinone (TQ), an active ingredient of black seed oil (Nigella Sativa), has been shown to possess cytotoxic activity against a variety of cancer cell lines. Our purpose was to investigate if the cytotoxic and apoptotic effect of zoledronic acid (ZA) can be enhanced by the addition of the TQ in hormone- and drug-refractory prostate cancer cells PC-3 and DU-145. Methods: XTT cell proliferation assay was used to assess cytotoxicity; DNA fragmentation and caspase 3/7 activity were also measured. Results: The combination of TQ and ZA resulted in a significant synergistic cytotoxic activity and DN A fragmentation when compared to any single agent alone, in a dose- and time-dependent manner. In addition, TQ and ZA combination increased the caspase 3/7 activity in PC-3 cell line, while this activity could not be demonstrated in DU-145 cell line. Conclusion: TQ and ZA had minimal hematological and non-hematological toxicity profile compared to cytotoxic agents. So, this combination may be an alternative approach for patients who are unable to be treated by conventional treatments because of poor performance status.Item JAK/STAT pathway interacts with intercellular cell adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) while prostate cancer stem cells form tumor spheroids(Zerbinis Publications, 2015) Duzagac F.; Inan S.; Simsek F.E.; Acikgoz E.; Guven U.; Khan S.A.; Rouhrazi H.; Oltulu F.; Aktug H.; Erol A.; Oktem G.Purpose: JAK/STAT is an evolutionarily conserved pathway and very important for second messenger system. This pathway is important in malignant transformation and accumulated evidence indicates that this pathway is involved in tumorigenesis and progression of several cancers. It was possible to assume that activation of JAK/STAT pathway is associated with increase in the expressions of ICAM-1 and VCAM-1. In this study we hypothesized that when cells were maintained as spheroids or monolayers, the structure of cancer stem cells (CSCs) could show differentiation when compared with non-CSCs. Methods: DU-145 human prostate cancer cells were cultured using the Ege University molecular embryology laboratory medium supplemented with 10% fetal bovine serum. Clusters of differentiation 133 (CD133)(+high)/CD44(+high) prostate CSCs were isolated from the DU145 cell line by using BD FACSAria. CD133+/CD44+ CSCs were cultured until confluent with 3% noble agar. The expression of these proteins in CSCs and non-CSCs was analyzed by immunohistochemistry. Results: Different expression profiles were observed in the conventional two-dimensional (2D) and three-dimensional (3D) experimental model system when CSCs and non-CSCs were compared. Human prostate CSCs exhibited intense ICAM-1 and VCAM-1 immunoreaction when compared with non-CSCs. These findings were supported by the fact that VCAM-1 on the surface of cancer cells binds to its counterreceptor, the a4fil integrin (also known as very-late antigen, VLA-4), on metastasis-associated macrophages, triggering VCAM-1-mediated activation of the phosphoinositide 3-kinase growth and survival pathway in cancer cells. Conclusions: The results of this study showed that changes in JAK/STAT pathway are related with adhesion molecules and could affect cancer progression.Item The mean platelet volume may predict the development of isolated bone metastases in patients with breast cancer: A retrospective study of the Young Researchers Committee of the Turkish Oncology Group (TOG)(Zerbinis Publications, 2016) Tanriverdi O.; Menekse S.; Teker F.; Oktay E.; Pilanci K.N.; Gunaldi M.; Kocar M.; Kacan T.; Bahceci A.; Avci N.; Akman T.; Cokmert S.; Yesil-Cinkir H.; Yanmaz M.T.Purpose: To determine the predictive value of the mean platelet volume (MPV) and the MPV/platelet count ratio on the development of isolated bone metastasis in patients with breast cancer. Methods: A total of 121 previously untreatedfemale patients with isolated bone metastases from breast cancer (group 1) were included in this retrospective cohort study. The patients enrolled in this study had similar age, biological subtypes, and duration of follow-up after diagnosis. Group 1 was compared with both 71 previously untreated women with breast cancer with no metastases at all (group 2) and 39 healthy women (group 3). Demographic data, laboratory tests and histological features of all of the patients in groups 1 and 2 were recorded and the study variables from each of the three groups were compared. Results: In group 1, the cut-off value (9.2 fL) for the MPV was determined and patients were stratified into 4 subgroups. The MPV was higher in group 1 than in either group 2 or group 3. Group 1 patients had a MPV of 8.8±3.1 fL (mean 5.1, range: 6.1-15.6) and the cut-off value for MPV was 9.2 fl. For patients in group 1, the MPV distribution was stratified into 4 groups as follows: group A included MPV values <6.08 fL, in group B values ranged from 6.09 to 8.46 fL, group C included values from 8.47 to 10.05 fL, and group D included patients with MPV values >10.06fL MPV and the presence of lymphovascular invasion were found to be independent risk factors for the development of isolated bone metastases. Conclusion: We concluded that MPV can be used to predict the development of isolated bone metastases.Item Borderline ovarian tumors: A contemporary review of clinicopathological characteristics, diagnostic methods and therapeutic options(Zerbinis Publications, 2016) Hasdemir P.S.; Guvenal T.Borderline ovarian tumors (BOTs) differ from the epithelial ovarian malignancies with their excellent prognosis, curability with surgery, and being seen in relatively young ages. Thus, fertility sparing and conservative surgical approaches are currently recommended. Preoperative diagnosis of BOTs can be challenging because, clinical and ultrasonographic features might overlap with invasive carcinomas and sometimes with benign adnexal masses. Certain characteristics such as stage at diagnosis, age of the patient and histologic features are important while deciding the extensiveness and the type of surgery. Detailed evaluation of the entire abdominal cavity and sampling all suspected areas are imperative during operation. Frozen section is essential for the intraoperative diagnosis, despite the fact that the diagnostic value of frozen section is not as high as in invasive ovarian carcinomas. Routine appendectomy and/or contralateral ovarian biopsy in cases of isolated tumor with normal appearing appendix and/or contralateral ovary are not recommended. Conservative approach might improve the recurrence rate without worsening the overall survival. The exact role of laparoscopic surgery with its advantages and disadvantages in the treatment of BOTs needs to be confirmed with further studies.Item Programmed cell death ligand-1 expression in gastroenteropancreatic neuroendocrine tumors(Zerbinis Publications, 2019) Oktay E.; Yalcin G.D.; Ekmekci S.; Kahraman D.S.; 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-L1 and mRNA was evaluated with IHC. Results: The expression of PD-L1 was significantly associated with the high-grade classification (p=0.012). PD-L1 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. © 2019 Zerbinis Publications. All rights reserved.Item Is eribulin treatment prognostic factor in patients with metastatic breast cancer treated with this drug? Retrospective analysis of a multicentre study(Zerbinis Publications, 2019) Oruc Z.; Kaplan M.A.; Geredeli C.; Sari N.Y.; Ozaslan E.; Aytekin A.; Elkiran E.T.; Koca S.; Dogan M.; Turan N.; Yuce O.; Sevinc A.; Ercelep O.; Isikdogan A.Purpose: This study aimed to analyze prognostic factors for survival and the reliability and the effectiveness of eribulin therapy in metastatic breast cancer (MBC) patients. Methods: A total of 80 patients treated with eribulin in 12 medical oncology centers in Turkey between 2013-2017 were retrospectively evaluated. Sixteen potential prognostic variables were assessed for analysis. Results: The patients had received a median of 5 prior chemotherapy regimens and a median of 3 eribulin cycles for MBC. Median progression-free survival (PFS) was 5.5 months (95% Cl: 4.1-7.8) and median overall survival (OS) was 11 months (95 % Cl: 6-15). Multivariate analysis showed that eribulin treatment line was shown to have independent prognostic significance for PFS. PFS difference was demostrated in patients who received 3 chemotherapy lines for advanced disease compared to those who had more than 3 chemotherapy lines [median PFS; 3 lines: 8.6 months (6.2-11) and >3 lines: 4.6 months (3.7-4.6) p=0.00]. The clinical benefit rate (CBR) was 52.5 and 35% in patients treated with three lines and with >3 previous chemotherapeutic regimens. Most common toxicities were neutropenia (62.5%), fatigue (52.5%), alopecia (50%) and nausea (37.5%). Conclusions: Eribulin treatment line was identified as in-depedent prognostic factor for PFS in MBC patients. © 2019 Zerbinis Publications. All rights reserved.Item A retrospective analysis on first-line bevacizumab, cetuximab, and panitumumab-containing regimens in patients with ras-wild metastatic colorectal cancer: A collaborative study by Turkish oncology group (tog)(Zerbinis Publications, 2019) Degirmencioglu S.; Tanriverdi O.; Menekse S.; Dogan M.; Hacioglu B.; Oktay E.; Erdem D.; Arpaci E.; Uluc B.O.; Turhal S.; Yilmaz M.; Pilanci K.N.; Sakin A.; Araz M.; Cokmert S.; Ozdemir O.; Sen E.; Nayir E.Purpose: To compare the efficacy and adverse effect profiles of the first-line treatment of patients with KRAS wild type metastatic colorectal cancer (CRC) in Turkey who were treated based on regimens including bevacizumab, cetuximab and panitumumab. Methods: This retrospective multicenter observational study involved a total of 238 patients who received chemotherapy in combination with either bevacizumab or cetuximab or panitumumab as first-line therapy for KRAS wild-type metastatic colorectal cancer. Patients with full medical records having pathological diagnosis of CRC adenocarcinoma were included in the study. The demographic, laboratory, histopathological and clinical characteristics of the patients were determined, and three groups were compared based on the study variables. Results: The mean age of the entire sample (n=238) was 58±11 years, 64% of which were male. The most frequent tumor localization was the rectum (37%) and G2 was the most common tumor grade (59.7%). About 63% of the patients had metastatic disease at diagnosis, with the most common site of metastasis being lung (14.7%) and liver (52.5%). Overall survival (OS) was 63.9%, while 1-, 3- And 5-year survival rates were 91.7, 56.6 and 36.9%, respectively. The expected mean survival was 49.1 months (95% CI, 42.9-55.3). The 1-, 3- And 5-year progression-free survival (PFS) rates following first-line treatment were 65.3, 26.1 and 5.6%, respectively, while disease free survival (DFS) in patients without metastasis at diagnosis was 68.5%. An analysis carried out disregarding which treatment the patients received (FOLFOX or FOLFIRI) revealed that a panitumumab-containing combination resulted in poorer prognosis compared to bevacizumab or cetuximab-containing combination (p<0.001). With regard to the adverse effect profile, the most common adverse effects were neuropathy and neutropenia in patients receiving FOLFOX-bevacizumab; neutropenia and perforation in patients receiving FOLFIRI-bevacizumab; rash and pustular infection in patients receiving FOLFIRI-cetuximab; and diarrhea in patients who received FOLFIRI-panitumumab combination. Conclusion: is the first multicenter study performed in Turkey evaluating the response to treatment and adverse effects in patients with KRAS wild-type metastatic colorectal cancer. © 2019 Zerbinis Publications. All Rights Reserved.Item Is eribulin treatment prognostic factor in patients with metastatic breast cancer treated with this drug? Retrospective analysis of a multicentre study(Zerbinis Publications, 2020) Oruc Z.; Kaplan M.A.; Geredeli C.; Sari N.Y.; Ozaslan E.; Aytekin A.; Elkiran E.T.; Koca S.; Dogan M.; Turan N.; Yuce O.; Sevinc A.; Ercelep O.; Isikdogan A.Purpose: This study aimed to analyze prognostic factors for survival and the reliability and the effectiveness of eribulin therapy in metastatic breast cancer (MBC) patients. Methods: A total of 80 patients treated with eribulin in 12 medical oncology centers in Turkey between 2013-2017 were retrospectively evaluated. Sixteen potential prognostic variables were assessed for analysis. Results: The patients had received a median of 5 prior chemotherapy regimens and a median of 3 eribulin cycles for MBC. Median progression-free survival (PFS) was 5.5 months (95% Cl: 4.1-7.8) and median overall survival (OS) was 11 months (95 % Cl: 6-15). Multivariate analysis showed that eribulin treatment line was shown to have independent prognostic significance for PFS. PFS difference was demostrated in patients who received 3 chemotherapy lines for advanced disease compared to those who had more than 3 chemotherapy lines [median PFS; 3 lines: 8.6 months (6.2-11) and >3 lines: 4.6 months (3.7-4.6) p=0.00]. The clinical benefit rate (CBR) was 52.5 and 35% in patients treated with three lines and with >3 previous chemotherapeutic regimens. Most common toxicities were neutropenia (62.5%), fatigue (52.5%), alopecia (50%) and nausea (37.5%). Conclusions: Eribulin treatment line was identified as indepedent prognostic factor for PFS in MBC patients. © 2020 Zerbinis Publications. All rights reserved.Item Pralatrexate experience in peripheral T-cell lymphoma: A multicenter retrospective study from Turkey(Zerbinis Publications, 2021) Dal M.S.; Merdin A.; Erkurt M.A.; Ekinci Ö.; Albayrak M.; Hacıoglu S.K.; Kaya A.; Dogu M.H.; Hindilerden F.; Sarici A.; Merter M.; Aras M.R.; Caglıyan G.A.; Cakar M.K.; Aydogdu I.; Kuku I.; Korkmaz S.; Ulas T.; Eser B.; Altuntas F.Purpose: Pralatrexate is a new generation antifolate treatment agent used for the treatment of relapsed or refractory peripheral T-cell lymphomas. This study aims to determine the general characteristics of the patients receiving pralatrexate therapy in Turkey, contributing to the literature on the effectiveness of pralatrexate therapy in peripheral T-cell lymphomas by determining the response levels of such patients to the therapy. The study also attempts to clinically examine the major side effects observed in patients during treatment with pralatrexate. Methods: The study included patients with peripheral T-cell lymphoma followed up in the hematology units of several hospitals in Turkey. Overall, 20 patients aged 18 and over were included in the study. Results: The median age at the time of diagnosis was 58.5 years. PTCL-NOS (Peripheral T-cell lymphoma, not otherwise specified) subtype was in 40% of patients, making the PTCL-NOS the most common subtype in the study. In general, most patients were diagnosed with disease at an advanced stage. Pralatrexate therapy was given to the patients at a median treatment line of 3.5. Pralatrexate dose reduction was required in only 3 patients (15%). Response to pralatrexate therapy with partial remission (PR) and above was observed in 11 (55%) of the patients. Conclusion: Pralatrexate seemed to be a promising novel treatment in relapsed refractory PTCL patients. However, patients receiving pralatrexate should be followed up carefully for skin reactions, mucosal side effects, thrombocytopenia and neutropenia. © 2021 Zerbinis Publications. All rights reserved.Item Pancreatic cancer patients who cannot undergo curative surgery live as much as patients over 70 years old(Zerbinis Publications, 2021) Serkan Y.; Pinar E.A.; Cengiz Y.; Ahmet O.; Ferhat E.; Gulcan B.Purpose: Patients over the age of 65 constitute approximately 54% of newly diagnosed cancers and approximately 70% of cancer-related deaths. These patients aged ≥65 years, who form the majority of clinical practice, are represented less in clinical studies than in real life. We designed this retrospective study to examine the treatment and response of patients to pancreatic cancer in patients over 70 years of age. Methods: Our study is a retrospective study that included patients from 5 centers in Turkey. Inclusion criteria were being over the age of 18 years, diagnosed with pancreatic cancer, and with ECOG performance score between 0-2. These patients were divided into two groups according to their age. The classification was made as patients over 70 years of age in the first group (geriatric group) and patients under 70 years of age (<70 age group) in the second group. Results: Overall survival of the <70 age group was statistically significantly longer (median 10 months vs 9.1 months p=0.027). When the patients who underwent only curative surgery were examined, the survival was statistically significant in favor of the <70 age group (median 20.96 months vs 14.5 months p=0.011). No statistically significant difference was found between the two groups in terms of the overall survival of patients with metastatic diagnosis (median 8.1 months vs 8.4 months p=0.182). Conclusion: The survival of patients with pancreatic cancer aged 70 and over was shorter than other age groups. While this difference was significant in patients who could undergo surgery at an early stage, it was not found in the metastatic patient group. Prospective larger-scale studies are needed to evaluate the treatment of geriatric patients better. © This work by JBUON is licensed under a Creative Commons Attribution 4.0 International License.