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Quantitative Evaluation of Multiple Treatment Regimens for Treatment-Resistant Depression.
Int J Neuropsychopharmacol
January 2025
Center for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, No.1200 Cailun Road, Shanghai 201203, China.
Objective: This study aims to quantitatively evaluate the efficacy and safety of various treatment regimens for treatment-resistant depression (TRD) across oral, intravenous, and intranasal routes to inform clinical guidelines.
Methods: A systematic review identified randomized controlled trials on TRD, with efficacy measured by changes in the Montgomery-Åsberg Depression Rating Scale (MADRS). We developed pharmacodynamic and covariate models for different administration routes, using Monte Carlo simulations to estimate efficacy distribution.
Epigenomics-guided precision oncology: Chromatin variants in prostate tumor evolution.
Int J Cancer
January 2025
Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
Prostate cancer is a common malignancy that in 5%-30% leads to treatment-resistant and highly aggressive disease. Metastasis-potential and treatment-resistance is thought to rely on increased plasticity of the cancer cells-a mechanism whereby cancer cells alter their identity to adapt to changing environments or therapeutic pressures to create cellular heterogeneity. To understand the molecular basis of this plasticity, genomic studies have uncovered genetic variants to capture clonal heterogeneity of primary tumors and metastases.
View Article and Find Full Text PDFA Theoretical Study on the Efficacy and Mechanism of Combined YAP-1 and PARP-1 Inhibitors in the Treatment of Glioblastoma Multiforme Using Peruvian Maca .
Curr Issues Mol Biol
January 2025
Centro de Investigación en Ingeniería Molecular-CIIM, Universidad Católica de Santa María, Urb. San José s/n, Umacollo, Arequipa 04013, Peru.
Glioblastoma multiforme (GBM) is one of the most aggressive and treatment-resistant forms of brain cancer. Current therapeutic strategies, including surgery, chemotherapy, and radiotherapy, often fail due to the tumor's ability to develop resistance. The proteins YAP-1 (Yes-associated protein 1) and PARP-1 (Poly-(ADP-ribose)-polymerase-1) have been implicated in this resistance, playing crucial roles in cell proliferation and DNA repair mechanisms, respectively.
View Article and Find Full Text PDFMuscarinic receptor agonists and positive allosteric modulators in animal models of psychosis: protocol for a systematic review and meta-analysis.
F1000Res
January 2025
German Center for Mental Health (DZPG), partner site München/Augsburg, Munich, Germany.
Background: Muscarinic receptor agonism and positive allosteric modulation is a promising mechanism of action for treating psychosis, not present in most D2R-blocking antipsychotics. Xanomeline, an M1/M4-preferring agonist, has shown efficacy in late-stage clinical trials, with more compounds being investigated. Therefore, we aim to synthesize evidence on the preclinical efficacy of muscarinic receptor agonists and positive allosteric modulators in animal models of psychosis to provide unique insights and evidence-based information to guide drug development.
View Article and Find Full Text PDFThe effects of clinical and pharmacological factors on the ratio of clozapine to norclozapine in psychiatric patients.
Front Pharmacol
January 2025
Department of Psychiatry, Medical University of Warsaw, Warsaw, Poland.
Background: Due to its exceptional effectiveness, clozapine (CLO), whose metabolite is norclozapine (NCLO), is a drug of choice in the management of treatment-resistant schizophrenia. The purpose of this study was to assess the factors modifying the CLO/NCLO ratio (CNR).
Methods: A total of 446 blood samples (233 of which were drawn from females and 213 from males, aged from 18 to 77 years) were analyzed in this study.
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