Zeliha Gunnur Dikmen

Serum N -glycans profiled by UHPLC-HILIC-FLD were combined with machine learning to predict and distinguish NSCLC patients from healthy controls and classify disease stage.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Nonetheless, deeper molecular understanding of NSCLC has resulted in novel therapeutic approaches, including targeted therapy and immunotherapy, which have improved patient prognosis and outcomes in recent years. Immune checkpoint inhibitors (ICIs), with or without chemotherapy, are now considered valuable components of treatment for NSCLC cases that do not have specific actionable genetic mutations. Patients with actionable genetic mutations are candidates for targeted therapies. The primary focus of this review is the rationale for using ICIs in the perioperative setting for patients with resectable NSCLC and in advanced disease settings. Furthermore, we compare the benefits of using ICIs with the challenges associated with their clinical implementation in resectable and advanced NSCLC. Finally, we emphasize the development of novel treatment strategies that potentially provide an optimal treatment choice for patients with advanced NSCLC.

To investigate the relationship between serum human epididymis protein 4 (HE4) levels and metabolic parameters of positron emission tomography (PET) imaging in patients with lung cancer. Sixty non-small cell lung cancer (NSCLC) patients were included in this prospective study. Demographic information, smoking status, comorbid pathologies, preoperative HE4 levels, PET imaging metabolic parameters, disease stage and histopathology were recorded. Significant positive correlations between serum HE4 levels and all the metabolic parameters were observed (p < 0.05). In univariate regression analyses, it was observed that high serum HE4 levels could indicate tumor be squamous cell carcinoma (SCC) (p = 0.029), advanced T stage (p = 0.041), and have high maximum standart uptake value (SUVmax) (p = 0.017). Serum HE4 levels can be used as a biomarker to predict tumor burden and metabolic activity for NSCLC patients. Although sufficient per power analysis, this study may have benefited from further expansion, and by patient heterogeneity in TNM stage and tumor histology, potentially affecting the assessment of parameter relationships.

Telomerase and telomeres are crucial in cancer cell immortalization, making them key targets for anticancer therapies. Currently, 6-thio-dG (THIO) combined with the anti-PD-1 inhibitor Cemiplimab is under phase II clinical investigation (NCT05208944) in NSCLC patients resistant to prior immunotherapies. This study presents the design, synthesis, and evaluation of novel bimodular conjugate molecules combining telomere-targeting nucleoside analogs and phosphatidyl diglyceride groups. Among them, dihexanoyl-phosphatidyl-THIO (diC6-THIO) showed high anticancer activity with sub-µM EC50 values in vitro across various cancer cell lines. In mouse colorectal cancer models, diC6-THIO demonstrated strong anticancer effects alone and in combination with PD1/PD-L1 inhibitors. Administration of this compound resulted in the efficient formation of Telomere dysfunction Induced Foci (TIFs) in vitro, indicating an on-target, telomerase-mediated telomere-modifying mechanism of action for the molecule. Systemic treatment also activated CD4⁺ and CD8⁺ T cells while reducing regulatory T cells, indicating immune system enhancement. Notably, diC6-THIO exhibits an improved solubility profile while maintaining comparable anticancer properties, further supporting its potential as a promising therapeutic candidate. These findings highlight diC6-THIO as a promising telomere-targeting prodrug with dual effects on telomere modification and immune activation.

Telomerase and telomeres are crucial in cancer cell immortalization, making them key targets for anticancer therapies. Currently, 6-thio-dG combined with the anti-PD1 inhibitor Cemiplimab is under Phase 2 clinical investigation (NCT05208944) in NSCLC patients resistant to prior immunotherapies. This study presents the design, synthesis, and evaluation of novel bimodular conjugate molecules combining telomere-targeting nucleoside analogs and phosphatidyl diglyceride groups. Among them, dihexanoyl-phosphatidyl-THIO (diC6-THIO) showed high anticancer activity with sub-µM EC50 values in vitro across various cancer cell lines. In mouse colorectal cancer models, diC6-THIO demonstrated strong anticancer effects alone and in combination with PD1/PD-L1 inhibitors. Administration of this compound resulted in the efficient formation of Telomere dysfunction Induced Foci (TIFs) in vitro, indicating an on-target, telomerase-mediated telomere-modifying mechanism of action for the molecule. Systemic treatment also activated CD4+ and CD8+ T cells while reducing regulatory T cells, indicating immune system enhancement. These findings highlight diC6-THIO as a promising telomere-targeting prodrug with dual effects on telomere modification and immune activation.

Amaç:Osteoartrit, çoğunlukla dizleri etkileyen en yaygın eklem hastalığıdır. Son yıllarda, düşük dereceli kronik inflamasyonla seyreden multifaktöriyel bir hastalığın osteoartrit patogenezinde rol oynadığı düşünülmektedir. Bu çalışmanın amacı diz osteoartriti olan hastalarda hastalığın radyolojik evreleri ve hastanın günlük yaşam aktivite düzeyleri ile serum kıkırdak oligomerik matriks proteini (COMP) ve matriks metaloproteinaz-3 (MMP-3) düzeyleri arasındaki ilişkiyi araştırmaktır. Materyal ve Metod:Seksen beş hasta Kellgren-Lawrence ölçeğine göre üç gruba ayrıldı. 1. grup Evre I, 2. grup Evre II/III ve 3. grup Evre IV hastalar dahil edildi. Hastaların günlük yaşam aktivitelerinde ağrı şiddetini ve fonksiyonel durumlarını değerlendirmek için Görsel Analog Skala (VAS), Western Ontario ve McMaster Üniversiteleri Osteoartrit İndeksi (WOMAC), Lequesne algofunctional diz indeksi ve Diz Yaralanması ve Osteoartrit Sonuç Skoru Kısa Formu (KOOS-PS) kullanıldı. Bulgular:Her üç hasta grubunda da serum COMP ve MMP-3 düzeyleri benzer bulundu. Serum COMP düzeyleri ile VAS, Lequesne skorları arasında zayıf korelasyon saptandı. Serum MMP-3 düzeyleri ile VAS, Lequesne ve KOOS-PS arasında da zayıf bir korelasyon olduğu belirlendi. Sonuç:Diz osteoartrit gruplarının farklı radyolojik evreleri ile günlük yaşam aktivitelerinde ağrı şiddeti ve fonksiyonel durum olan klinik parametreler ile serum COMP ve MMP-3 düzeyleri arasında anlamlı farklılık saptanmadı. Bu konuda daha büyük örneklem gruplarıyla yapılacak çalışmalara gereksinim vardır.