PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14365/2
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Browsing PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection by Subject "1st-Line Treatment"
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Article Citation - WoS: 44Citation - Scopus: 48Changes in Wnt and Tgf-Beta Signaling Mediate the Development of Regorafenib Resistance in Hepatocellular Carcinoma Cell Line Huh7(Frontiers Media Sa, 2021) Karabiçici, Mustafa; Azbazdar, Yagmur; Ozhan, Gunes; Senturk, Serif; Firtina Karagonlar, Zeynep; Erdal, EsraHepatocellular carcinoma (HCC) is an aggressive, chemo resistant neoplasm with poor prognosis and limited treatment options. Exploring activated pathways upon drug treatment can be used to discover more effective anticancer agents to overcome therapy resistance and enhance therapeutic outcomes for patients with advanced HCC. Human tumor-derived cell lines recapitulate HCC diversity and are widely used for studying mechanisms that drive drug resistance in HCC. In this study, we show that regorafenib treatment activates Wnt/beta-catenin signaling only in hepatoblast-like HCC cell lines and induces enrichment of markers associated with hepatic stem/progenitor cells. Moreover, activation of Wnt/beta-catenin signaling via Wnt3a/R-Spo1 treatment protects these cells from regorafenib induced apoptosis. On the other hand, regorafenib resistant cells established by long-term regorafenib treatment demonstrate diminished Wnt/beta-catenin signaling activity while TGF-beta signaling activity of these cells is significantly enhanced. Regorafenib resistant cells (RRCs) also show increased expression of several mesenchymal genes along with an induction of CD24 and CD133 cancer stem cell markers. Moreover, regorafenib resistant cells also exhibit significantly augmented in vitro and in vivo migration capacity which could be reversed by TGF-beta type 1 receptor (TGFb -R1) inhibition. When combined with regorafenib treatment, TGF beta-R1 inhibition also significantly decreased colony formation ability and augmented cell death in resistant spheroids. Importantly, when we knocked down TGF beta-R1 using a lentiviral plasmid, regorafenib resistant cells entered senescence indicating that this pathway is important for their survival. Treatment of RRCs with TGF beta-R1 inhibitor and regorafenib significantly abolished pSTAT3, pSMAD2 and pERK (44/42) expression suggesting the involvement of both canonical and non-canonical pathways. In conclusion, our data suggest that HCC tumors with aberrant activation in the Wnt/beta-catenin pathway, might have higher intrinsic regorafenib resistance and the inhibition of this pathway along with regorafenib administration might increase regorafenib-induced cell death in combinational therapies. However, to resolve acquired regorafenib resistance developed in HCC patients, the combined use of TGF-beta pathway inhibitors and Regorafenib constitute a promising approach that can increase regorafenib sensitization and prevent tumor recurrence.Article Citation - WoS: 6Citation - Scopus: 6External Validation of a Novel Risk Model in Patients With Favorable Risk Renal Cell Carcinoma Defined by International Metastatic Renal Cell Carcinoma Database Consortium (imdc): Results From the Turkish Oncology Group Kidney Cancer Consortium (tkcc) Database(Cig Media Group, Lp, 2023) Yekeduz, Emre; Karakaya, Serdar; Erturk, Ismail; Tural, Deniz; Ucar, Gokhan; Oztas, Nihan Senturk; Arikan, Rukiye; Arslan, ÇağatayIn this report, we validated a novel prognostic model structured by the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) for patients with metastatic renal cell carcinoma. The former favor-able risk group was divided into 2 new categories: very favorable and favorable. Patients with very favorable risk had better survival than those with the novel favorable risk. Further studies are needed to evaluate whether less intensive therapies could be as effective as current combinations of therapies in the very favorable risk group. Background: A novel prognostic model was recommended for patients with metastatic RCC (mRCC) by the Interna-tional mRCC Database Consortium (IMDC). In this study, we aimed to externally validate a novel risk model for the IMDC-favorable risk group in patients with mRCC. Methods: The Turkish Oncology Group Kidney Cancer Consortium (TKCC) is a multicenter registry that includes 13 cancer centers in Turkey. As described by Schmidt et al., 3 parameters (ie, time from diagnosis to systemic therapy < 3 vs. >3 years, Kar nofsky Perfor mance Status [KPS] 80 vs. > 80, and the presence of brain, liver, or bone metastasis) were used to divide the IMDC favorable risk group into 2 new categories: very favorable and favorable risk groups. The primary endpoint was overall survival (OS). Time to treatment failure (TTF) and objective response rate (ORR) in the very favorable and favorable risk groups were the secondary endpoints. Results: A total of 545 patients with mRCC from all IMDC risk groups and 112 patients from the favorable risk group were included in this study. According to the novel classification model, 44 (39.3%) and 68 (60.7%) patients with former favorable risk were categorized into very favorable and favorable risk groups, respectively. The median OS (55.8 months vs. 34.2 months, P = .025) and TTF (25.5 months vs. 15.5 months, P = .010) were longer in the very favorable risk group than in the favorable risk group. The concordance index of the new IMDC model in all patients was 0.65 for OS. Despite the higher ORR in the very favorable risk group than in the favorable risk group, the difference between the groups was not statistically significant (52.4% vs. 44.7, P = .573). Conclusions: This was the first study to externally validate the novel IMDC risk model presented in the American Society of Clinical Oncology Genitourinary Cancers Symposium 2021.Article Citation - WoS: 3Citation - Scopus: 3Perceptions and Expectations: a Study on Prognostic Perception and Quality of Life in Patients With Metastatic Renal and Bladder Cancer(LIPPINCOTT WILLIAMS & WILKINS, 2024) Bölek, Hatice; Arslan, Çagatay; Başaran, Mert; Cicin, Irfan; Ozguroglu, Mustafa; Tural, Deniz; Ürün, YükselPURPOSEDurable complete response rates for metastatic renal cell carcinoma (mRCC) and metastatic bladder cancer (mBC) are low despite new therapy. Palliative care focuses on life extension and quality of life (QoL), not cure. This study aims to investigate patients' perceptions of treatment outcomes in mRCC and mBC and to assess the influence of QoL and optimism levels on these perceptions.METHODSFrom March 15, 2023, to January 15, 2024, a multicenter, cross-sectional online survey was carried out, targeting patients diagnosed with mRCC and mBC. The survey comprised structured questions aimed at evaluating perceptions concerning disease cure, symptom improvement, daily activity performance, and life extension due to treatment. Additionally, to evaluate optimism and QoL, the European Organization for Research and Treatment of Cancer 30.3 QoL questionnaire and life orientation test were implemented. Study on patients' perceptions of treatment outcomes in metastatic kidney and bladder cancer shows high optimism, inaccurate cure beliefs.RESULTSIn total, 169 patients participated in the survey; the majority of the patients stated their general health status as good (72.2%) and excellent (13.6%). Patients who rated their overall health status as good-excellent had a higher median general QoL and optimism score compared with those who rated it as fair-poor. In all, 85.2% of patients considered the possibility of a cure very likely or likely. Most participants believed treatment could provide symptom relief (30.2% very likely, 49.1% likely), enhanced ability to perform daily activities (28.4% very likely, 55.6% likely), and life extension (32.5% very likely, 53.3% likely). Patients responding very likely and likely to these questions regarding treatment outcomes had higher QoL and optimism scores than those responding a little likely and not possible.CONCLUSIONThe majority of patients with mRCC and mBC held inaccurate beliefs about treatment outcomes. Better QoL and optimism were associated with increased inaccuracy.
