13 research outputs found
Advanced CRISPR/Cas9 strategies for overcoming hippo pathway-associated drug resistance mechanisms in estrogen receptor-positive breast cancer
No full text2022-ACIL-08-21348-TÜSEB
2022-A2-YL-27690-TÜSEBMeme kanseri, farklı alt tipleri bulunan heterojen bir hastalıktır ve kadınlar arasında en sık görülen kanser türüdür. Tedaviye karşı gelişen direnç, etkin tedavi oluşturulmasında ciddi bir engeldir. Meme kanserlerinin yaklaşık %70'ini oluşturan östrojen reseptör pozitif (ER+) meme kanserli hastalarda, Tamoksifen tedavisi yaygın olarak kullanılır. Ancak, Tamoksifen'in yan etkileri ve gelişen ilaç direnci tedavideki önemli sorunlardır. Östrojen sinyalizasyonundaki düzensizliklerin tedavi başarısızlığına katkıda bulunduğu bilinmektedir. Son yıllarda yapılan çalışmalarda Hippo sinyal yolağındaki değişimlerin ilaç direnci gelişiminde rol oynadığı gösterilmiştir. Hippo yolağı, hücrenin kök hücre özelliklerini, apoptozu ve proliferasyonunu düzenler. WWOX geni, çeşitli kanserlerin ilerlemesinde rol oynayan bir tümör baskılayıcı gendir ve yüksek ekspresyonu etkin Tamoksifen tedavisi ile ilişkilidir. WWOX'un down regülasyonunun Hippo yolağıyla ilişkili Tamoksifen direncine neden olduğu düşünülse de WWOX'un ligandı WBP2’nin Tamoksifen direnciyle ilişkisi tam olarak bilinmemektedir. Bu nedenle mevcut çalışmada, WWOX ve WBP2 genlerinin Hippo sinyal yolağı ile ilişkisi incelendi. CRISPR/Cas9 gen düzenleme yöntemi kullanılarak MCF-7 ve tamoksifen dirençli MCF-7 hücre dizinlerinde bu genlerin Tamoksifen direncindeki potansiyel etkinliği araştırıldı. Ayrıca, WWOX ve WBP2'nin ER+ meme kanseri hastalarında Tamoksifen direnci için terapötik hedef ve prognostik biyobelirteç olma potansiyelleri değerlendirildi. Elde edilen bulguların, ER+ meme kanserinde Hippo yolağı ile ilişkili Tamoksifen direnç gelişim mekanizmasının anlaşılmasına ve etkin tedavi yöntemlerinin geliştirilmesine katkı sağlayacağı öngörüldü.Breast cancer, characterized by its heterogeneity and various subtypes, is the most prevalent cancer among women. The emergence of resistance to therapy poses a significant obstacle to achieving effective treatment outcomes. In approximately 70% of breast cancer cases, which are estrogen receptor-positive (ER+), Tamoxifen therapy is a common treatment modality. However, the adverse effects and development of resistance to Tamoxifen present substantial challenges. Dysregulation in estrogen signaling pathways is known to contribute to therapeutic failure. The Hippo signaling pathway has been implicated in the development of drug resistance, regulating critical cellular processes such as stem cell properties, apoptosis, and proliferation. The WWOX gene, a known tumor suppressor, plays a crucial role in the progression of various cancers, and its high expression has been correlated with effective Tamoxifen therapy. Although the downregulation of WWOX is believed to contribute to Tamoxifen resistance through the Hippo pathway, the involvement of WWOX ligand WBP2 in this resistance mechanism remains unclear. This study aims to elucidate the relationship between WWOX and WBP2 genes and the Hippo signaling pathway. Using the CRISPR/Cas9 gene editing technique, the potential role of these genes in Tamoxifen resistance was investigated in both MCF-7 and Tamoxifen-resistant MCF-7 cell lines. Furthermore, the study assessed the therapeutic target and prognostic biomarker potential of WWOX and WBP2 in ER+ breast cancer patients concerning Tamoxifen resistance. The findings are anticipated to contribute to a deeper understanding of the mechanisms underlying Hippo pathway-related Tamoxifen resistance in ER+ breast cancer and to the development of more effective treatment strategies
Merkez bankası döviz rezervlerine yönelik bir uygulama: klasik ve robust regresyon yöntemlerinin karşılaştırılması
No full textZaman serisi verileri uygulamalı araştırmalarda çok sık bir şekilde kullanılmaktadır. Mevsimsel olmayan serilerde regresyon analizi uygularken kullanılan çeşitli klasik ve robust regresyon modelleri mevcuttur. Tüm kullanılan yöntemlerin ortak amacı öngörüde bulunmak ve karşılaştırma yapmaktır. Çalışmada karşılaştırma kriterleri olarak Hata Ka-reler Ortalaması (Mean Squared Error-MSE), Hata Kareleri Ortalamasının Karekökü (Root Mean Square Error-RMSE), Ortalama Mutlak Yüzde Hata (Mean Absolute Percentage Error-MAPE), Ortalama Mutlak Hata (Mean Absolute Error-MAE) ve Çoklu Açıklayıcılık Katsayısı (Multiple Explanatoriness Coefficient-) kullanılmıştır. Çalış-manın amacı, mevsimsel olmayan serilerde kullanılan çeşitli regresyon modelleri ve robust regresyon yöntemlerinin etkinliklerini Merkez Bankası Brüt Döviz Rezervlerini temel alarak karşılaştırmaktır
Nevşehir ili konut fiyatlarını etkileyen faktörlerin hedonik fiyat modeli ile incelenmesi
No full textÇalışmamızda Nevşehir ilinde satılan dairelerin fiyatını etkileyen faktörler Hedonik Fiyat Modeli ile belirlenecektir. Bu amaç doğrultusunda ortalama bir ailenin ihtiyaçlarına cevap verecek 31 oda sayısına sahip konutlar ile ilgilenilmiştir. Söz konusu veri seti anket yöntemi ve sahibinden.com sitesine ait ilanlardan derlenmiştir. Nevşehir ilinin üç ilçesini kapsayan çalışmada örneklem Tabakalı Örnekleme yöntemi ile oluşturulmuştur ve tabaka olarak ilçeler kullanılmıştır. Elde edilen sonuçlara dayanarak Fiyat Tahmin Robotu adını verdiğimiz ve programı MS Access ile tarafımızdan yazılan bir robot hazırlanmıştır. Bu robot sayesinde çalışmanın bulguları günlük hayata fayda sağlayacak şekilde tüketicinin hizmetine sunulmuştur
Synergistic anti-tumorigenic effects of cabazitaxel and usnic acid combination on metastatic castration-resistant prostate cancer cells
No full textBackground Prostate cancer (PC) affects millions of men, causing high mortality rates. Despite the treatment approaches, the options for metastatic castration-resistant prostate cancer (mCRPC), a lethal form of advanced PC, are still limited. Cabazitaxel (Cbx) is the last taxane-derived chemotherapeutic approved for Docetaxel-resistant mCRPC patients. However, its effects are limited due to the activation of several pathways. Therefore, new approaches are needed to increase the efficacy of Cbx. Usnic acid (UA) is a natural product with well-known anti-tumorigenic and synergistic effects with various chemotherapeutics. Although the cytotoxicity of UA and Cbx has been evaluated on mCRPC cells, the anti-tumorigenic effect of UA combination with any taxane has not been investigated yet. Thus, we aimed to evaluate the possible synergistic effect of Cbx+UA in mCRPC cells. Methods Cell viability and apoptosis were analyzed using WST-1 and Annexin-V. Morphological changes were visualized by fluorescent staining. Finally, cell cycle, mitochondrial health, and ROS levels were determined. Results Based on WST-1 results, 25 mu M UA exhibited significant additive and synergistic effects with the use of Cbx. Annexin V and cell cycle results showed that UA significantly enhanced the Cbx efficacy at increasing doses compared to using only Cbx (**p<0.01). Moreover, combined treatment significantly increased ROS levels and mitochondrial membrane depolarization compared with Cbx alone (**p<0.01). Conclusions Thus, the results suggest that UA increased the anti-tumorigenic effects of Cbx on mCRPC cells by increasing apoptosis, causing an increase in intracellular ROS and disrupting mitochondrial health. Consequently, combining UA and Cbx offers a new combined therapeutic strategy for mCRPC treatment
Samsun ili konut fiyatlarını etkileyen faktörlerin hedonik fiyat modeli ile analizi
No full textThe most important needs of people has been sheltering and feeding since the early ages. Today it has been made to different perspectives based on a budget satisfy the feeling of pleasure from these requirements. Beside the housing needs satisfied, housing property is also important. Certainly people both housing requests and features of the house are heterogeneous. Heterogeneous changes occurring in the price of good model to examine the factors which caused is called the hedonic pricing model. In this study, hedonistic price model explored for the factors that affect the price of housing in the province of Samsun. For this purpose, according to average family needs, 31 houses are examined. The data are taken from the advertising of Sahibinden.com website. Three central districts of Samsun (Canik, İlkadım Atakum) including advertisements in the study are selected by a stratified sampling method and the districts are taken as stratified. To provide benefits for daily life, the results obtained from the study are given with a MS Access programming application
Comparison of forescasting methods for interval-valued time series
No full textThis study examines the interval-valued time series which is an ongoingness issue in time series. The study aims to obtain new time series forecasting methods using different combination of several analysis methods and modeling techniques and to determine the methods and models that provide the optimal accuracy by comparing the forecasting accuracy of the proposed methods. Different approaches and appropriate modeling techniques are used for analyzing interval-valued time series. The data of experimental study is obtained by analyzing the interval-valued time series via forecasting methods. These values represent variables in the variance analysis of our study. The obtained results are analyzed by using statistical analysis. Kruskal-Wallis H test and Mann-Whitney U-test are applied to evaluate the performance. Which one of the methods provided better forecasting results and their pros and cons are examined. Four real time series are used in the implementation and the forecasting performance of the methods are compared and evaluated
Determining the Factors Affecting the Price of Beetle in Turkish Market via Hedonic Price Model
No full textBeetle, as a legendary car, which its production dates back to 1938 and continues until 2003, sold more than 25 million in the world. It is also at premium and has many fans in Turkey too. Beetle, called as "Vosvos" or "turtle" in Turkey, may even be more expensive in the spot market than top model cars
Expression of bcl-2 and laminin in rectosigmoid hirschsprung disease: Correlations with hirschsprung-associated enterocolitis
No full textBackground Hirschsprung disease (HD) involves aganglionosis of the intestinal segment, with unclear etiology and challenging histopathological identification. The etiology of Hirschsprung-associated enterocolitis (HAEC) remains elusive. This study aims to explore the potential roles of Laminin and BCL-2 in the etiology of HD and HAEC by examining their expression levels. Methods Tissues from 20 Rectosigmoid Hirschsprung patients (10 with and 10 without postoperative HAEC) and 10 controls were analyzed retrospectively. Protein expression was analyzed using immunohistochemistry, mRNA levels were measured using Real-Time PCR, and DNA mutations were found using Sanger Sequencing. Results BCL-2 immunohistochemistry indicated decreased expression in HD patients' aganglionic tissues compared to ganglionic tissues (p 0.05). DNA sequencing discovered a novel BCL-2 gene mutation in HD patients. Conclusion BCL-2 and Laminin immunohistochemistry can differentiate ganglionic and aganglionic tissues. Reduced BCL-2 mRNA expression in HD patients indicates a disease that affects the whole gut. More research is needed on the new BCL-2 gene mutations. Impact statement This is the first study to examine the correlation between BCL-2 and Laminin expression changes and enterocolitis developing in HD. It is a previously unreported contribution to the literature that mRNA expression was lower than expected in all intestinal tissues of HD patients, including the intestinal tissues considered to be healthy. Mutagenic changes have been detected in the gene of some HD patients. A definitive novel mutation, which has not been reported in the literature before, was detected in one patient
Expression of bcl-2 and laminin in rectosigmoid hirschsprung disease: Correlations with hirschsprung-associated enterocolitis
No full textBackground Hirschsprung disease (HD) involves aganglionosis of the intestinal segment, with unclear etiology and challenging histopathological identification. The etiology of Hirschsprung-associated enterocolitis (HAEC) remains elusive. This study aims to explore the potential roles of Laminin and BCL-2 in the etiology of HD and HAEC by examining their expression levels. Methods Tissues from 20 Rectosigmoid Hirschsprung patients (10 with and 10 without postoperative HAEC) and 10 controls were analyzed retrospectively. Protein expression was analyzed using immunohistochemistry, mRNA levels were measured using Real-Time PCR, and DNA mutations were found using Sanger Sequencing. Results BCL-2 immunohistochemistry indicated decreased expression in HD patients' aganglionic tissues compared to ganglionic tissues (p 0.05). DNA sequencing discovered a novel BCL-2 gene mutation in HD patients. Conclusion BCL-2 and Laminin immunohistochemistry can differentiate ganglionic and aganglionic tissues. Reduced BCL-2 mRNA expression in HD patients indicates a disease that affects the whole gut. More research is needed on the new BCL-2 gene mutations. Impact statement This is the first study to examine the correlation between BCL-2 and Laminin expression changes and enterocolitis developing in HD. It is a previously unreported contribution to the literature that mRNA expression was lower than expected in all intestinal tissues of HD patients, including the intestinal tissues considered to be healthy. Mutagenic changes have been detected in the gene of some HD patients. A definitive novel mutation, which has not been reported in the literature before, was detected in one patient
