methotrexate

SLC30A9 maintains a low-zinc environment and mitochondrial integrity, thereby inhibiting mtDNA-mediated cGAS-STING pathway activation. Targeting SLC30A9 to disrupt this protective mechanism provides a novel therapeutic strategy for overcoming chemoresistance in osteosarcoma.

The ICAM-1-derived cIBR peptide selectively binds to the I-domain of LFA-1, a receptor highly expressed on leukemia T cells; thus, the MTX-cIBR conjugate can be used to target methotrexate (MTX) to leukemic T cells and reduce its off-target toxicity...Computational analyses further demonstrated that MTX exhibited lower binding free energy (ΔG) and greater binding stability toward DHFR than MTX-cIBR. These findings suggest that MTX-cIBR retains selective cytotoxic activity toward LFA-1-expressing leukemia T cells through altered cellular uptake and exhibits different interaction characteristics with DHFR compared with unconjugated MTX.

P2, N=30, Completed, Australasian Leukaemia and Lymphoma Group | Active, not recruiting --> Completed

Additionally, they bolster the intracellular antioxidant defense system. These findings unveil a sophisticated regulatory network and suggest that with strict control of systemic exposure through optimized topical formulations, these FDA-approved agents could be further investigated as potential localized treatments for pigmentary disorders.

In conclusion, our data indicate that curcumin attenuates MTX-induced neurobehavioral deficits and biochemical alterations. The protective effects of curcumin are likely mediated, at least in part, by restoring redox homeostasis and modulating TNF-α/BDNF signaling, suggesting a potential therapeutic avenue for mitigating chemotherapy-induced neurotoxicity.

The safety profile of upadacitinib remained consistent with previous analyses, with no new safety concerns through 7 years. Upadacitinib and adalimumab (continuous or rescue treatment) maintained disease activity targets throughout the 7-year treatment period. Upadacitinib exhibited an acceptable benefit-risk profile for long-term RA treatment.

All patients received nonsteroidal anti-inflammatory drugs as initial therapy, and one required additional treatment with oral methotrexate and adalimumab. Serum cytokine analysis was performed in three cases, revealing elevated levels of both pro- and anti-inflammatory cytokines, such as interleukin (IL)-6, IL-10, and IL-33 in the pre-treatment state. These cases underscore the clinical heterogeneity of CNO/CRMO.

Stereotactic brain biopsy confirmed PCNSL, and the patient was initiated on high-dose methotrexate-based chemotherapy with adjunctive dexamethasone. This case highlights that PCNSL can occur despite immunologic preservation in HIV and may present acutely with seizures. Early contrast-enhanced MRI, careful timing of corticosteroid use relative to biopsy, and timely referral are essential, particularly in resource-limited settings.

Despite the initiation of corticosteroids and methotrexate, the patient showed clinical deterioration over four weeks...Following neoadjuvant chemotherapy, surgery, and radiation, the patient achieved complete remission of her myositis, with normalisation of creatine phosphokinase (CPK) levels, resolution of rash, and recovery of muscle strength, confirming the paraneoplastic aetiology. This case underscores the imperative to pursue malignancy screening in DM patients unresponsive to immunosuppressive therapy, regardless of age. It highlights the critical role of thorough physical examination and the superiority of breast imaging in young women with dense breasts.

To evaluate the intracranial delivery of BTK inhibitor(BTKi), patient-derived PCNS-LBCL xenografted mice models were treated with highly-selective BTKi orelabrutinib, either monotherapeutically or in combining with methotrexate...The mutations in CSF circulating tumor DNA (ctDNA) rather than plasma-ctDNA were more consistent to those in tumor tissue, indicating that CSF-ctDNA is a useful tool for monitoring PCNS-LBCL. In summary, our data provided the molecular rationale as well as clinical evidences that incorporation of BTKi into frontline induction therapy is a promising strategy for ND PCNS-LBCL.

P4, N=12, Recruiting, BioMarin Pharmaceutical | Not yet recruiting --> Recruiting

Tumor tissue and serial plasma samples were collected from 15 patients with aUC treated with dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC). While the NOIR-SS-based assay proved sensitive and informative, limitations include the cost and time required for sequencing, potential temporal discordance between tissue and plasma sampling, and the absence of correction for clonal hematopoiesis of indeterminate potential. Overall, ctDNA profiling using this targeted panel and NOIR-SS suggested the feasibility of sensitive, non-invasive molecular monitoring in aUC, and may have future clinical applicability if validated prospectively in larger cohorts.