Fabrication of bimetallic Ag@ZnO nanocomposite and its anti-cancer activity on cervical cancer via impeding PI3K/AKT/mTOR pathway.

INTRODUCTION: Bimetallic nanoparticles, specifically Zinc oxide (ZnO) and Silver (Ag), continue to much outperform other nanoparticles investigated for a variety of biological uses in the field of cancer therapy. This study introduces biosynthesis of bimetallic silver/zinc oxide nanocomposites (Ag@ZnO NCs) using the Crocus sativus extract and evaluates their anti-cancer properties against cervical cancer. METHODS: The process of generating bimetallic nanoparticles (NPs), namely Ag@ZnO NCs, through the utilization of Crocus sativus extract proved to be uncomplicated and eco-friendly. Various methods, such as UV-vis, DLS, FTIR, EDX, and SEM analyses, were utilized to characterize the generated Ag@ZnO NCs. The MTT assay was employed to assess the cytotoxic properties of biosynthesized bimetallic Ag@ZnO NCs against the HeLa cervical cancer cell line. Moreover, the impact of Ag@ZnO NCs on HeLa cells was assessed by examining cell survival, ROS production, MMP levels, and induced apoptosis. Through western blot analysis, the expression levels of the PI3K, AKT, mTOR, Cyclin D, and CDK proteins seemed to be ascertained. Using flow cytometry, the cancer cells' progression through necrosis and apoptosis, in addition to the cell cycle analysis, were investigated. RESULTS: Bimetallic Ag@ZnO NCs that were biosynthesized showed a high degree of stability, as demonstrated by the physicochemical assessments. The median size of the particles in these NCs was approximately 80-90 nm, and their zeta potential was -14.70 mV. AgNPs and ZnO were found, according to EDX data. Further, Ag@ZnO NCs hold promise as a potential treatment for cervical cancer. After 24 hours of treatment, a dosage of 5 µg/mL or higher resulted in a maximum inhibitory effect of 58 ± 2.9. The concurrent application of Ag/ZnO NPs to HeLa cells resulted in elevated apoptotic signals and a significant generation of reactive oxygen species (ROS). As a result, the bimettalic Ag@ZnO NCs treatment has been recognized as a chemotherapeutic intervention by inhibiting the production of PI3K, AKT, and mTOR-mediated regulation of propagation and cell cycle-regulating proteins. CONCLUSIONS: The research yielded important insights into the cytotoxic etiology of biosynthesized bimetallic Ag@ZnO NCs against HeLa cells. The biosynthesized bimetallic Ag@ZnO NCs have a significant antitumor potential, which appears to be associated with the development of oxidative stress, which inhibits the development of the cell cycle and the proliferation of cells. Therefore, in the future, biosynthesized bimetallic Ag@ZnO NCs may be used as a powerful anticancer drug to treat cervical cancer.

Clinical Outcomes and Prognostic Analysis of 101 Patients of Central Neurocytoma: A 10-Year Treatment Experience at a Single Institution.

Objective: Central neurocytoma (CN) is a rare type of tumor that currently lacks an optimal treatment protocol. This study aimed to explore the clinical outcomes of CN in a cohort of 101 patients and identify prognostic factors associated with multiple treatment modalities. Methods: This monocentric study retrospectively analyzed the clinical data of 101 CN patients who underwent surgical resection. The patients were followed up, and their overall survival (OS) and progression-free survival (PFS) were calculated. Results: For the entire cohort, the 5- and 10-year OS rates were 88.7% and 82.8%, respectively, and the 5- and 10-year PFS rates were 86.5% and 64.9%, respectively. Of the 82 (81.19%) patients with CN who underwent gross total resection (GTR), 28 (28/82, 34.1%) also received radiotherapy (RT). Of the 19 (18.81%) patients with CN who underwent subtotal resection (STR), 11 (11/19, 57.9%) also received RT or stereotactic radiosurgery (SRS). Compared to STR, GTR significantly improved the 5-year OS (92.4% vs. 72.4%, P=0.011) and PFS (92.4% vs. 60.4%, P=0.009) rates. Radiotherapy did not affect OS in the GTR group (p=0.602), but it had a statistically significant effect on OS in the STR group (P<0.001). However, the OS (P=0.842) and PFS (P=0.915) in the STR plus radiotherapy group were comparable to those in the GTR alone group. Compared to STR alone, STR plus radiotherapy improved the 5-year PFS rate from 25% to 75% in patients with atypical CN (P=0.004). Cox regression models and a competing risk model showed that the removal degree and radiotherapy were independent prognostic factors for survival. With improvements in modern radiotherapy techniques, severe radiotherapy toxicity was not observed. Conclusion: Our findings support the use of GTR whenever possible. Radiotherapy can improve the prognosis of patients who undergo STR, especially in atypical CNs having a higher tendency to relapse. Close imaging follow-up is necessary. Our findings will help clinicians to select optimal, individualized treatment strategies to improve OS and PFS for patients with CN.

Long-Term Survival Outcomes and Treatment Experience of 64 Patients With Esthesioneuroblastoma.

Background: Esthesioneuroblastoma (ENB) is a rare sinonasal malignancy, lacking a unified staging system and treatment. Management at a single center was retrospectively evaluated to inform future treatment options and prognostic factors. Methods: Clinical data of 64 consecutive ENB patients, including prognostic factors and treatment methods, were reviewed retrospectively. Data were collected to calculate overall survival (OS) and progression free survival (PFS). Results: The majority of tumors 84.4% were within Kadish C stage, 79.7% were within T3 or T4, and 64.0% were within Hyams grade III or IV. A total of 50 (78.1%) patients received surgery and combined radiotherapy with or without chemotherapy, 10 (15.6%) received surgery with or without chemotherapy alone, and 4 (6.3%) received radiotherapy with or without chemotherapy alone. The majority of patients (79.7%) underwent endoscopic resection (endoscopic and endoscopically assisted). Surgery combined with radiotherapy with or without chemotherapy resulted in significantly better OS (84.4 vs. 50.6%, 84.4 vs. 37.5%) compared to surgery alone and radiotherapy alone (P = 0.0064). Endoscopic surgery group (endoscopic and endoscopically assisted) resulted in significantly better 5-year PFS (61.7 vs. 22.2%) compared to the open surgery group (P < 0.001). Although endoscopic surgery group was not a statistically significant predictor of 5-year OS (P = 0.54), the 5-year OS was 79.3% for the endoscopic surgery group and 76.2% for the open surgery group. A Cox regression analysis identified intracranial extension and surgery combined with radiotherapy as independent factors affecting 5-year OS while cervical lymph node metastasis and Hyams grade IV as independent factors affecting 5-year PFS. Conclusion: Our findings suggest that surgery combined with radiotherapy is the best treatment approach for ENB. For advanced tumors, endoscopic surgery is an effective treatment, and its survival rate is equal to or better than open surgery.

Comparison of Dosimetric Gains Provided by Intensity-Modulated Radiotherapy, Volume-Modulated Arc Therapy, and Helical Tomotherapy for High-Grade Glioma.

PURPOSE: Because of the poor prognosis for high-grade glioma (HGG) patients, it is important to increase the dose of the tumor to improve the efficacy while minimizing the dose of organs at risk (OARs). Thus, we evaluated the potential dosimetric gains of helical tomotherapy (HT) versus intensity-modulated radiotherapy (IMRT) or volume-modulated arc therapy (VMAT) for high-grade glioma (HGG). METHODS: A total of 42 HGG patients were retrospectively selected who had undergone helical tomotherapy; then, IMRT and VMAT plans were generated and optimized for comparison after contouring crucial neuronal structures for neurogenesis and neurocognitive function. IMRT and VMAT were optimized with the Eclipse treatment planning system (TPS) (Version 11.0.31) and HT using TomoTherapy Hi-Art Software (Version 2.0.7) (Accuray, Madison, WI, USA). All three techniques were optimized for simultaneously delivering 60 Gy to planning target volume (PTV) 1 and 50-54 Gy to PTV2. We also analyzed the homogeneity index (HI) and conformity index (CI) of PTVs and organ at risk (OAR) sparing. RESULTS: There was no significant difference in the PTV coverage among IMRT, VMAT, or HT. As for the HI, HT plans (PTV1 HI: 0.09 ± 0.03, PTV2 HI: 0.17 ± 0.05) had the best homogeneity when compared to IMRT plans (PTV1 HI: 0.10 ± 0.04, PTV2 HI: 0.18 ± 0.04) and VMAT plans (PTV1 HI: 0.11 ± 0.03, PTV2 HI: 0.20 ± 0.03). The CI value of HT (PTV1 CI: 0.98 ± 0.03, PTV2: 0.98 ± 0.05) was closest to the optimal value. Except for the IMRT and VMAT groups, there were statistically significant differences between the other two groups of the CI values in both PTV1 and PTV2. The other comparison values were statistically significant except for the optic nerve, and VMAT had the best sparing of the optic chiasm. The mean and max doses of OARs declined significantly in HT. CONCLUSIONS: For high-grade glioma patients, HT had superior outcomes in terms of PTV coverage and OAR sparing as compared with IMRT/VMAT.