Balkan Medical Journal

18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography as a Valuable Diagnostic Tool in Patients with Ovarian Cancer and Its Correlation with Tumor Marker Cancer Antigen-125

Inhibition of PI3K and Hedgehog Signaling Pathway Inhibits Hypoxia-Induced Vasculogenic Mimicry Formation in Ovarian Cancer Stem Cells

Inhibition of the Hedgehog and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathways has been shown to suppress tumor proliferation and stem cell activity. However, the precise role of these pathways in vasculogenic mimicry (VM) of ovarian cancer stem cells (OCSCs) remains unclear. To investigate the roles of the PI3K/AKT and Hedgehog signaling pathways in VM formation and the underlying mechanisms in OCSCs. OCSCs were induced through serum-free culture of SK-OV-3. Hypoxia-inducible factor-1α (HIF-1α) knockdown was achieved by transfection with sh-HIF-1α. Cells were treated with the PI3K agonist 740 Y-P, the PI3K inhibitor LY294002, the Hedgehog agonist purmorphamine, and the Hedgehog inhibitor cyclopamine under hypoxic conditions. Expression of HIF-1α, epithelial-to-endothelial transition (EET) markers, and components of the PI3K and Hedgehog pathways was analyzed using immunofluorescence and Western blotting. VM capacity was assessed using a Matrigel three-dimensional (3D) culture assay. Cell proliferation and invasion were evaluated by MTS, EdU, and Transwell assays. VM formation was further examined in an OCSC xenograft model. OCSCs accounted for more than 85% of seventh-generation SK-OV-3 cells cultured under serum-free conditions. Hypoxia markedly increased HIF-1α expression, which activated the PI3K and Hedgehog signaling pathways. HIF-1α knockdown suppressed activation of these pathways. Treatment with LY294002 and cyclopamine, as well as HIF-1α knockdown, inhibited hypoxia-induced upregulation of N-cadherin and VE-cadherin, as well as the formation of branching points and 3D channels. Moreover, both LY294002 and cyclopamine significantly reduced cell proliferation, invasion, and VM formation in vitro and in xenografted OCSCs. HIF-1α knockdown inhibits activation of the PI3K and Hedgehog signaling pathways, thereby reducing EET and VM formation in hypoxia-induced OCSCs.

ELK4 Promotes Cell Cycle Progression and Stem Cell-like Characteristics in HPV-associated Cervical Cancer by Regulating the FBXO22/PTEN Axis

Cervical cancer (CC) is a prevalent gynecological carcinoma, and patients infected with human papillomavirus (HPV) have a higher morbidity rate. To explore the effects of ETS-like transcription factor 4 (ELK4) in patients with HPV In vitro cell lines and human-sample study. The ELK4 levels in human tissue (65 HPV ELK4 was highly expressed in the HPV ELK4 facilitated cell cycle progression and stem cell-like characteristics by regulating the FBXO22/PTEN axis. Thus, ELK4 could be a potential therapeutic target to arrest the progress of HPV-associated CC.

Efficacy and Safety of Bevacizumab-Combined Chemotherapy for Advanced and Recurrent Endometrial Cancer: A Systematic Review and Meta-analysis

Bevacizumab-combined chemotherapy is a new regimen for advanced/recurrent endometrial cancer. To evaluate the efficacy and safety of bevacizumab-combined chemotherapy in advanced/recurrent endometrial cancer. Systematic review and meta-analysis. Eligible studies were retrieved from Embase, PubMed, and Cochrane Library. The data of primary outcomes including progression-free survival and overall survival and secondary outcomes including overall survival, response rate, and adverse events (grade ≥2) were extracted, pooled, and used for the meta-analysis to compare the efficacy and safety of bevacizumab-combined chemotherapy with other treatments in patients with advanced/recurrent endometrial cancer. Notably, 2 randomized-controlled and 5 single-arm trials of bevacizumab-combined chemotherapy or bevacizumab single-agent therapy for endometrial cancer were included. Meta-analysis indicated that bevacizumab-combined chemotherapy significantly increased the progression-free survival rate (hazard ratio=0.82, 95% confidence interval=0.70, 0.97) and overall survival rate (hazard ratio=0.83, 95% confidence interval=0.70, 0.98) compared with chemotherapy alone. The rates of overall, complete, and partial response to bevacizumab-combined chemotherapy were 76%, 22%, and 21%, respectively. The 6 and 12-month disease-free progression rates after bevacizumab-combined chemotherapy were 79% and 62%, respectively. Anemia (23%), leukopenia (46%), neutropenia (51%), hypertension (16%), and fatigue (24%) were the general adverse events after bevacizumab-combined chemotherapy. Bevacizumab-combined chemotherapy may have a higher efficacy in improving the overall and progression-free survival in patients with advanced/recurrent endometrial cancers compared with chemotherapy alone.

FLOT2 Promotes the Proliferation and Epithelial-mesenchymal Transition of Cervical Cancer by Activating the MEK/ERK1/2 Pathway

As prevalent cancer in women, approximately 569,847 cases of cervical cancer occur every year. This study aimed to explore the role of FLOT2 and its related mechanism in the development of cervical cancer. Cell culture study and animal experimentation. Quantitative reverse-transcription polymerase chain reaction PCR and Western blot analysis were performed to evaluate the expression of FLOT2. Flow cytometry was applied for the evaluation of cell apoptosis. Cell Counting Kit-8 and colony formation were utilized for proliferation measurement. Cervical cancer mice model was employed to measure the role of FLOT2 in vivo. FLOT2 mRNA and protein levels were dramatically elevated ( FLOT2 aggravates the proliferation and epithelialmesenchymal transition of cervical cancer by activating the MEK/ ERK1/2 and AKT pathways.