Advances in Anti-Cancer Drug Development: Metformin as Anti-Angiogenic Supplemental Treatment for Glioblastoma.

According to the WHO 2016 classification, glioblastoma is the most prevalent primary tumor in the adult central nervous system (CNS) and is categorized as grade IV. With an average lifespan of about 15 months from diagnosis, glioblastoma has a poor prognosis and presents a significant treatment challenge. Aberrant angiogenesis, which promotes tumor neovascularization and is a prospective target for molecular target treatment, is one of its unique and aggressive characteristics. Recently, the existence of glioma stem cells (GSCs) within the tumor, which are tolerant to chemotherapy and radiation, has been linked to the highly aggressive form of glioblastoma. Anti-angiogenic medications have not significantly improved overall survival (OS), despite various preclinical investigations and clinical trials demonstrating encouraging results. This suggests the need to discover new treatment options. Glioblastoma is one of the numerous cancers for which metformin, an anti-hyperglycemic medication belonging to the Biguanides family, is used as first-line therapy for type 2 diabetes mellitus (T2DM), and it has shown both in vitro and in vivo anti-tumoral activity. Based on these findings, the medication has been repurposed, which has shown the inhibition of many oncopromoter mechanisms and, as a result, identified the molecular pathways involved. Metformin inhibits cancer cell growth by blocking the LKB1/AMPK/mTOR/S6K1 pathway, leading to selective cell death in GSCs and inhibiting the proliferation of CD133+ cells. It has minimal impact on differentiated glioblastoma cells and normal human stem cells. The systematic retrieval of information was performed on PubMed. A total of 106 articles were found in a search on metformin for glioblastoma. Out of these six articles were Meta-analyses, Randomized Controlled Trials, clinical trials, and Systematic Reviews. The rest were Literature review articles. These articles were from the years 2011 to 2024. Appropriate studies were isolated, and important information from each of them was understood and entered into a database from which the information was used in this article. The clinical trials on metformin use in the treatment of glioblastoma were searched on clinicaltrials.gov. In this article, we examine and evaluate metformin's possible anti-tumoral effects on glioblastoma, determining whether or not it may appropriately function as an anti-angiogenic substance and be safely added to the treatment and management of glioblastoma patients.

Nurturing families: A feasibility randomised controlled trial of a whole-family intervention with vulnerable families in Jordan.

Armed conflict and forced displacement can significantly strain nurturing family environments, which are essential for child well-being. Yet, limited evidence exists on the effectiveness of family-systemic interventions in these contexts. We conducted a two-arm, single-masked, feasibility Randomised Controlled Trial (fRCT) of a whole-family intervention with Syrian, Iraqi and Jordanian families in Jordan. We aimed to determine the feasibility of intervention and study procedures to inform a fully-powered RCT. Eligible families were randomised to receive the Nurturing Families intervention or enhanced usual care (1:1). Masked assessors measured outcomes at baseline and endline; primary outcome measures were caregiver psychological distress, family functioning, and parenting practices. Families and implementing staff participated in qualitative interviews at endline. Of the 62 families screened, 60 (98%) were eligible, 97% completed the baseline and 90% completed the endline. Qualitative feedback indicated specific improvements in adolescent well-being, caregiver distress and parenting, and family relationships. Data highlighted high participant engagement and adequate facilitator fidelity and competence. Outcome measures had good psychometric properties (most α > 0.80) and sensitivity to change, with significant changes seen on most measures in the intervention but not control group. Findings indicate the acceptability and feasibility of intervention and study procedures. Subsequent full-scale evaluation is needed to determine effectiveness.