methotrexate

P=N/A, N=130, Recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University | Trial completion date: Apr 2030 --> Dec 2029 | Trial primary completion date: Apr 2030 --> Dec 2029

We analyze how crosstalk between GSK-3β and mTOR complexes (mTORC1/mTORC2) creates a resistant phenotype that limits the efficacy of conventional cytotoxic agents such as methotrexate, actinomycin D, and etoposide. Importantly, we highlight emerging therapeutic strategies to target this axis, including GSK-3β activators (lithium, 9-ING-41), mTOR inhibitors (rapamycin analogs, dual PI3K/mTOR inhibitors), and combination regimens that synergistically restore chemosensitivity. Preclinical data from trophoblastic and related malignancies demonstrate that dual targeting of GSK-3β and mTOR can reverse resistance phenotypes and enhance treatment responses. This comprehensive review provides a translational framework for developing molecularly targeted therapies in chemoresistant gestational choriocarcinoma, with potential implications for personalized treatment algorithms and clinical trial design in this rare but highly treatable malignancy.

Kidney samples were collected 24 h after administration under ketamine-xylazine anaesthesia. Western blot results demonstrated increased expression of E-selectin, caspase-3, and β1-integrin, with strongest increases detected in the MTX group. These findings indicate that 5-FU, CIS and MTX induce oxidative stress, DNA damage and alterations in apoptosis- and adhesion-related pathways in renal tissue, suggesting drug-specific mechanisms underlying chemotherapy-associated nephrotoxicity.

Although considerable research has been conducted and numerous results have been obtained, the available evidence remains predominantly of moderate quality. Consequently, current guidelines from CPIC and the DPWG do not recommend routine MTX dose adjustments based solely on single gene variants. It is, therefore, imperative to develop and validate multifactorial risk prediction tools that integrate a range of other clinical factors. Accordingly, the establishment of a comprehensive pharmacogenetics-guided dosing guideline for MTX remains an elusive goal.

Additionally, three cancer cell subpopulations with distinct chemosensitivity profiles were identified; Subpopulation 2, characterized by high expression of CCNA2, UBE2C, and CENPF, demonstrated significantly reduced sensitivity to methotrexate, doxorubicin, cisplatin, ifosfamide, and etoposide. This study provides a preliminary characterization of the metabolic landscape of OS and its associated immune microenvironment. Targeting SLC7A7-deficient monocytes may represent promising strategies for enhancing the efficacy of immunotherapy in OS.

P1, N=20, Active, not recruiting, OHSU Knight Cancer Institute | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2026 --> Dec 2027 | Recruiting --> Active, not recruiting

P1, N=0, Withdrawn, Children's Oncology Group | N=29 --> 0 | Not yet recruiting --> Withdrawn

P1, N=24, Recruiting, St. Jude Children's Research Hospital | Trial primary completion date: Jul 2026 --> Oct 2026

We report the case of a 4-year-old girl initially diagnosed with oligoarticular JIA and treated with methotrexate followed by a tumor necrosis factor inhibitor, without significant clinical improvement and despite persistently normal inflammatory markers...This case highlights common diagnostic pitfalls in pediatric rheumatology and underscores the importance of considering genetic causes of chronic arthropathy when clinical and laboratory features are atypical for inflammatory disease. Early molecular diagnosis prevents unnecessary immunosuppressive therapy and enables appropriate multidisciplinary management.

Compared with the model group, both the EMO and methotrexate (MTX) treatment groups demonstrated attenuated synovial hyperplasia and cartilage destruction, along with significantly downregulated expression levels of key NF-κB pathway proteins, HIF-1α, and VEGF in joint tissues (p < 0.001)...This study demonstrates that EMO alleviates pathological damage in RA by inhibiting the activation of the NF-κB signaling pathway, which subsequently downregulates pathological angiogenesis and inflammatory responses mediated by the HIF-1α/VEGF axis. These findings provide a robust experimental basis for the potential application of EMO as a therapeutic agent for RA.

Herein, we propose a carrier-free, tumor microenvironment (TME)-responsive nanoplatform (FAM NPs-FA) constructed via coordination-driven self-assembly of Survivin antisense oligodeoxynucleotide (ASO), methotrexate (MTX), and Fe3+ ions...Meanwhile, the released Survivin ASO specifically silences Survivin mRNA, suppressing anti-apoptotic protein expression, and accelerating tumor cell apoptosis. Moreover, combined with the chemotherapeutic effects of MTX, this nanoplatform demonstrates exceptional synergistic therapeutic efficacy against tumors while minimizing adverse impacts on healthy tissues, thus opening a versatile and effective carrier-free platform for TME-responsive synergistic cancer therapy integrating gene regulation, reactive oxygen species generation, and chemotherapy.

This study evaluates the efficacy of liraglutide (LIRA), a glucagon-like peptide-1 receptor agonist, in RA management, particularly in conjunction with methotrexate (MTX), a standard RA therapy on complete Freund's adjuvant (CFA)-induced arthritis. Liraglutide presents opportunities for repurposing metabolic agents in the treatment of autoimmune illnesses. Liraglutide modulates metabolic dysfunction, normalizes autophagy markers, inflammatory pathways, and lower apoptotic signals in complete Freund's adjuvant-induced arthritis in rats.