Araştırma Çıktıları
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Item Efficacy and safety profile of COVID-19 vaccine in cancer patients: a prospective, multicenter cohort study(FUTURE MEDICINE LTD, 2022-01-01) Yasin, Ayse Irem; Aydin, Sabin Goktas; Sumbul, Bilge; Koral, Lokman; Simsek, Melih; Geredeli, Caglayan; Ozturk, Akin; Perkin, Perihan; Demirtas, Derya; Erdemoglu, Engin; Hacibekiroglu, Ilhan; Cakir, Emre; Tanrikulu, Eda; Coban, Ezgi; Ozcelik, Melike; Celik, Sinemis; Teker, Fatih; Aksoy, Asude; Firat, Sedat T.; Tekin, Omer; Kalkan, Ziya; Turken, Orhan; Oven, Bala B.; Dane, Faysal; Bilici, Ahmet; Isikdogan, Abdurrahman; Seker, Mesut; Turk, Haci M.; Gumus, MahmutAim: To compare the seropositivity rate of cancer patients with non-cancer controls after inactive SARS-CoV-2 vaccination (CoronaVac) and evaluate the factors affecting seropositivity. Method: Spike IgG antibodies against SARS-CoV-2 were measured in blood samples of 776 cancer patients and 715 non-cancer volunteers. An IgG level >= 50 AU/ml is accepted as seropositive. Results: The seropositivity rate was 85.2\% in the patient group and 97.5\% in the control group. The seropositivity rate and antibody levels were significantly lower in the patient group (p < 0.001). Age and chemotherapy were associated with lower seropositivity in cancer patients (p < 0.001). Conclusion: This study highlighted the efficacy and safety of the inactivated vaccine in cancer patients. Clinical Trials Registration: ClinicalTrials.gov) Plain language summary Cancer patients are at high risk for infection with SARS-CoV-2 and of developing the associated disease, COVID-19, which therefore puts them in the priority group for vaccination. This study evaluated the efficacy and safety of CoronaVac, an inactivated virus vaccine, in cancer patients. The immune response rate, defined as seropositivity, was 85.2\% in the cancer patient group and 97.5\% in the control group. The levels of antibodies, which are blood markers of immune response to the vaccine, were also significantly lower in the patient group, especially in those older than 60 years and receiving chemotherapy. These results highlight the importance of determining the effective vaccine type and dose in cancer patients to protect them from COVID-19 without disrupting their cancer treatment.Item New horizons from novel therapies in malignant pleural mesothelioma(VIA MEDICA, 2020-01-01) Sayan, Mutlay; Mamidanna, Swati; Eren, Mehmet Fuat; Daliparty, Vasudev; Mustafayev, Teuta Zoto; Nelson, Carl; Ohri, Nisha; Jabbour, Salma K.; Mert, Aslihan Guven; Atalar, BanuMalignant pleural mesothelioma (MPM) is a relatively rare, but highly lethal cancer of the pleural mesothelial cells. Its pathogenesis is integrally linked to asbestos exposure. In spite of recent developments providing a more detailed understanding of the pathogenesis, the outcomes continue to be poor. To date, trimodality therapy involving surgery coupled with chemotherapy and/or radiotherapy remains the standard of therapy. The development of resistance of the tumor cells to radiation and several chemotherapeutic agents poses even greater challenges in the management of this cancer. Ionizing radiation damages cancer cell DNA and aids in therapeutic response, but it also activates cell survival signaling pathways that helps the tumor cells to overcome radiation-induced cytotoxicity. A careful evaluation of the biology involved in mesothelioma with an emphasis on the workings of pro-survival signaling pathways might offer some guidance for treatment options. This review focuses on the existing treatment options for MPM, novel treatment approaches based on recent studies combining the use of inhibitors which target different pro-survival pathways, and radiotherapy to optimize treatment.Item Emerging treatment strategies for metastatic triple-negative breast cancer(SAGE PUBLICATIONS LTD, 2022-01-01) Huppert, Laura A.; Gumusay, Ozge; Rugo, Hope S.Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer that is often associated with an aggressive phenotype and a poor prognosis. Cytotoxic chemotherapy remains the mainstay of treatment for most patients with metastatic TNBC (mTNBC), but duration of response is often short and median overall survival is only 12-18 months. Therefore, it is critical to identify novel treatment strategies to improve outcomes for these patients. In this review article, we discuss recent advances in treatment strategies for patients with mTNBC including the use of immune checkpoint inhibitors, targeted therapies, and antibody-drug conjugates. For each topic, we summarize important preclinical and clinical data, discuss implications for clinical practice, and highlight future research directions.Item Regulatory T Cells in Pancreatic Cancer: Of Mice and Men(MDPI, 2022-01-01) Reyes, Carmen Mota; Demir, Elke; Cifcibasi, Kaan; Istvanffy, Rouzanna; Friess, Helmut; Demir, Ihsan EkinSimple Summary Regulatory T cells (Treg) are a major immunosuppressive cell subset in the pancreatic tumor microenvironment. Tregs influence tumor growth by acting either directly on cancer cells or via the inhibition of effector immune cells. Treg cells form a partially redundant network with other immunosuppressive cells such as myeloid-derived suppressor cells (MDSC) that confer robustness to tumor immunosuppression and resistance to immunotherapy. The results obtained in preclinical studies, whereupon Treg depletion, MDSCs concomitantly decreased in early tumors whereas an inverse association was seen in advanced PCa, urge a comprehensive analysis of the immunosuppressive profile of PCa throughout tumorigenesis. One relevant context to analyse these compensatory mechanisms may be patients with locally advanced PCa undergoing neoadjuvant therapy (neoTx). In order to understand these dynamics and to uncover stage-specific actional strategies involving Tregs, pre-clinical models that allow the administration of neoTx to different stages of PCa may be a very useful platform. Regulatory T cells (Treg) are one of the major immunosuppressive cell subsets in the pancreatic tumor microenvironment. Tregs influence tumor growth by acting either directly on cancer cells or via the inhibition of effector immune cells. Treg cells mechanisms form a partially redundant network with other immunosuppressive cells such as myeloid-derived suppressor cells (MDSC) that confer robustness to tumor immunosuppression and resistance to immunotherapy. The results obtained in preclinical studies where after Treg depletion, MDSCs concomitantly decreased in early tumors whereas an inverse association was seen in advanced PCa, urge a comprehensive analysis of the immunosuppressive profile of PCa throughout tumorigenesis. One relevant context to analyse these complex compensatory mechanisms may be the tumors of patients who underwent neoTx. Here, we observed a parallel decrease in the numbers of both intratumoral Tregs and MDSC after neoTx even in locally advanced PCa. NeoTx also led to decreased amounts of alpha SMA(+) myofibroblastic cancer-associated fibroblasts (myCAF) and increased proportions of CD8(+) cytotoxic T lymphocytes in the tumor. In order to understand these dynamics and to uncover stage-specific actional strategies involving Tregs, pre-clinical models that allow the administration of neoTx to different stages of PCa may be a very useful platform.Item The importance of histological patterns on PD-L1 staining heterogeneity: Should we use pattern-based approach for selecting tumor samples for PD-L1 testing in lung(TUBITAK SCIENTIFIC \& TECHNICAL RESEARCH COUNCIL TURKEY, 2021-01-01) Bulutay, Pinar; Firat, Pinar; Zeren, Handan; Erus, Suat; Tanju, Serhan; Dilege, SukruBackground/aim: Programmed death ligand-1 (PD-L1) is a predictive marker for immunotherapeutic agents. However, heterogeneous staining of PD-L1 can cause false-negative results. The aim of this study is to evaluate the importance of histological patterns on PD-L1 staining heterogeneity in lung adenocarcinomas (LAC). Materials and methods: PD-L1 immunohistochemistry (IHC) stain was performed to two different tissue cores of 128 LAC cases, and cut-off values are given for grouping the cases according to the percentage of staining (1\%-10\%, 11\%-49\%, 50\%-100\%). Staining rates between cores were compared and analyzed by their histological patterns. Also, the relation of the PD-L1 expression with the clinicopathological characteristics of the cases was analyzed. Results: Overall, PD-L1 expression was observed in 53 of 128 cases (41.4\%, 1\% cut-off), 23.5\% of them were positive at 10\% cut-off and 14.1\% at 50\% cut-off. PD-L1 expression was significantly related to the high grade micropapillary and solid patterns of adenocarcinomas (p:0.01). Staining cut-offs were mostly similar between cores (43/50, 86\%) (k:0.843). However, 14\% of them were positive only in one core (7 of 50). This false negativity was mostly related to the histological patterns. Conclusion: Our data reveal the heterogeneous staining of PD-L1 expression, also micropapillary and solid patterns show higher rates of PDL expression. Therewithal, these findings also highlight the importance of taking into consideration of histological patterns, when choosing a paraffin block for the PDL1.Item Metastasis Targeted Therapies in Renal Cell Cancer(GALENOS YAYINCILIK, 2018-01-01) Narter, K. Fehmi; Ozveren, BoraMetastatic renal cell cancer is a malignant disease and its treatment has been not been described clearly yet. These patients are generally symptomatic and resistant to current treatment modalities. Radiotherapy, chemotherapy, and hormonal therapy are not curative in many of these patients. A multimodal approach consisting of cytoreductive nephrectomy, systemic therapy (immunotherapy or targeted molecules), and metastasectomy has been shown to be hopeful in prolonging the survival and improving the quality of life in some of these patients. Patients with oligometastatic disease and good performance status have better results following this multimodal approach. Cytoreductive nephrectomy and adjuvant/neoadjuvant systemic therapies (immunotherapy, targeted therapy) have been investigated for treatment options of metastatic renal cancer patients. After better understanding of the genetic basis and the molecular biology of the renal cell carcinoma, targeted molecular therapies and immunotherapies have emerged as more efficient alternative therapy options with moderate adverse effects. Metastasectomy in some of these patients improves survival and quality of life, especially in those with lung and bone metastases. In this review we will summarize treatment options for metastatic renal cancer patients.