MTX-LPD can occur in the liver. Clinician should suspect hepatic MTX-LPD when a liver mass is detected in patient who had been treating with MTX for RA.

We applied targeted next-generation sequencing for detection of recurrent single nucleotide variants, copy number alterations and zygosity abnormalities in diagnostic specimens from 78 PCNSL patients treated with a standard methotrexate-based regimen, to identify prognostically significant molecular subgroups...These genomic aberrations identify a high-risk molecular subgroup that may inform risk stratification in PCNSL. Further elucidation of the mechanisms of therapeutic resistance associated with the high-risk genetic phenotype is requisite to facilitate precision medicine and progress in therapy.

The patient was treated with a chemotherapy regimen of pemetrexed and carboplatin. Mesothelioma with predominantly intrapulmonary growth is extremely rare and poses a diagnostic pitfall. For this entity, subtle morphological features, selection of immunohistochemical markers, and electron microscopy are of great significance for definite diagnosis.

Here we examine the biochemical and cellular effects of a propargyl linked, non-classical antifolate that shows exceptional potency and resilience in the background of methotrexate resistance, UCP1162...Leucovorin suppressed the cellular effects of UCP1162, consistent with UCP1162 working as an antifolate...Long-term exposure to UCP1162 resulted in static culture expressing stem cell genes (CD34, ABCG2, ABCB1), adaptive genes (TCN2, CDKN1A), and genes that might serve as therapeutic targets (TPBG/5T4, TNFRSF10A, ACE). These findings suggest that UCP1162 is a unique tool for studying cellular responses to long-term antifolate treatment and holds promise as a lead compound capable of overcoming some forms of antifolate resistance.

P1/2, N=34, Completed, The First Hospital of Jilin University | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Mar 2024

The combination of MTX and resveratrol effectively attenuated pro-inflammatory activity in THP-1 cells, as evidenced by the downregulation of mRNA and chemokine expression. These findings suggest that the synergistic effects of MTX and resveratrol hold promise for enhancing cancer therapeutics.

Their conjugation with the drugs Irinotecan, Imatinib, and Methotrexate was also confirmed using UV-Vis, FTIR, and Dynamic light scattering (DLS). The result of the methylthiazol tetrazolium (MTT) assay showed that conjugated AgNPs and AuNPs with Irinotecan had a higher toxic effect on the A549 cancer cell line than AgNPs and AuNPs conjugated with Imatinib. This study provides a promising avenue for further investigation and development of nanoparticle-drug conjugates as a potential cancer immunotherapy strategy.

P=N/A, N=25, Not yet recruiting, Peking University People's Hospital

HD-MTX combined with TMZ as the first-line strategy may improve patient prognosis, and early application of gene sequencing is beneficial for evaluating prognosis.

This study provides a mechanistic rationale to clinical evidence correlating the poor outcome of patients with mesothelioma and with eosinophil-derived CLC-P/Gal10, opening new prospects for intervention in this fatal solid tumour.

P2, N=16, Recruiting, Wake Forest University Health Sciences | Trial completion date: Jan 2025 --> Jan 2027 | Trial primary completion date: Oct 2024 --> Mar 2025

P2, N=50, Active, not recruiting, Yancheng First People's Hospital | Recruiting --> Active, not recruiting | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Jun 2023 --> Dec 2023

A chemotherapy regimen includes a combination of high-dose Methotrexate (MTX), doxorubicin, and cisplatin...CUR and MTX combined determined a β-Catenin decrease and a trend toward reducing NF-kB and matrix metalloproteinases (MMP-2 and MMP-9). Our findings suggest CUR as a support to OS treatment, improving outcomes and reducing the adverse effects of current therapies.

Here, in this study, we investigated the detrimental impact of an 8-week chronic unpredictable stress (CUS) protocol on the progression of arthritis and psoriasis using collagen-induced arthritis (CIA) and imiquimod (IMQ)-induced psoriasis rat models, respectively. Moreover, the therapeutic efficacy of MTX was notably reduced in stressed rats compared to non-stressed, underscoring the detrimental effects of chronic stress on treatment outcomes. Taken together, our results emphasize the importance of considering chronic stress as a critical factor in the management of autoimmune diseases.

Our results indicate that there is a statistically significant correlation between the rs1131596 SLC19A1 polymorphism and the development of MTX-induced hepatotoxicity (p = 0.03), but there is no significant association between any of the studied polymorphisms and mucositis or other side effects, such as nausea, emesis, diarrhea, neutropenia, skin rash and infections. In addition, when genotype TT of rs1131596 and genotype AA of rs56292801 are both present in a patient then there is a higher risk of developing severe hepatotoxicity (p = 0.0104).

Methods SD rats were randomized into normal control, model, methotrexate (MTX) and HQGP groups, with 6 rats in each group...In myocardial tissue, the expression of GAS5 increased significantly, the expression of miR-21 decreased significantly, the release of LDH, the mRNA and protein levels of TLR4, NF-κB p65, caspase-1 and NLRP3 decreased significantly, and the mRNA expression of GSDMD reduced while the protein level significantly reduced. Conclusion HQGP improves myocardial injury in AA rats by inhibiting miR-21/TLR4 signalling through up-regulation of lncRNA GAS5, inhibiting pyroptosis, and reducing pro-inflammatory cytokine expression.

Data on the use of zoledronic acid (ZA) in juvenile CRMO are scarce...The patient's condition stayed stable while taking naproxen (20 mg/kg/day) and methotrexate (10 mg/week) for 1.5 years until he experienced right elbow pain, swelling, no overlying skin erythema, and a restricted range of motion...Non-steroidal anti-inflammatory drugs and methotrexate were initially effective in treating our patient's condition, but a recurrence necessitated treatment modification. To the best of our knowledge, this case is the first documented instance of the use of ZA in CRMO in Iraq and Arab nations.

He received 4 cycles of pemetrexed/cisplatin with proton therapy (PT) delivered halfway through for a bronchial stump positive margin. Immunosuppressive agents given with RT may be considered for patients with autoimmune disease. Avoidance of biopsy, tissue manipulation, debridement, or any form of soft-tissue or hard-tissue violation needs to be discussed across the multidisciplinary spectrum to avoid nonhealing lesions shortly after RT.

Apart from methotrexate (MTX) and biologics such as tumor necrosis factor (TNFi), interleukin-12/23 (IL-12/23i), and IL-17 inhibitors (IL-17i), traditionally used for the treatment of PsA, recently biologics such as IL-23i and targeted synthetic agents like JAK inhibitors (JAKi) have been introduced in the daily clinical practice for the treatment of this disease...While IL-23i has not been shown to increase the risk for common or opportunistic infections, a well-established association of JAKi with herpes zoster warrants the attention of rheumatologists. In this narrative review, we summarize the infectious complications of available treatment options by drug class in patients with PsA.

And the use of methotrexate (MTX) can restore the heterochromatin state altered by LAP2α depletion...These results indicate the important role of LAP2α in regulating ALT activity and offer insights into the interplay between lamina-associated proteins and telomeres in maintaining telomere length. Importantly, our findings may help identify a more appropriate target population for the osteosarcoma therapeutic drug, MTX.

In a randomized trial of children with CD initiating anti-TNF, 40% were HLA DQ-A1*05 positive, which was associated with a trend toward increased risk of both treatment failure and ADA. These risks were mitigated, but not eliminated, by adding oral methotrexate. HLA DQ-A1*05 is an important biomarker for prognosis and risk stratification.

P4, N=182, Recruiting, Medical University of Vienna

Identifying these MicroRNAs can be helpful in predicting the efficacy of the chemotherapy or introducing it as combination therapy. Our research has been shown that hsa-MiR-320a can serve as a biomarker of PMX efficacy and also has the potential to be used in combination therapy.

P2, N=57, Terminated, Spanish Lung Cancer Group | Phase classification: P2a --> P2

She was diagnosed with rheumatoid arthritis with Castleman like histopathology in lymph nodes and was treated with methotrexate and hydroxychloroquine sulfate combined with glucocorticoids. In the first year after sur-gery, the patient' s condition remained stable and there was no growth of lymph nodes in the right axilla. The patient passed away due to severe infection in the second year after the surgery.

Our study illuminates the role of lncRNA-NEAT1 in LUAD, where it mediates resistance to PEM through the activation of autophagy via the miR-379-3p/HIF1A axis. This work paves the way for new therapeutic strategies for managing PEM resistance in LUAD patients.

In particular, the lipid paradox associated with RA highlights the complex relationship between RA treatments (MTX, JAKis, tumor necrosis factor (TNF) inhibitors, and interleukin (IL)-6 receptor inhibitors), inflammation, different lipid profiles, and CV risk. In the absence of contraindications and when MTX is tolerated, this commentary suggests the concomitant use of MTX and JAKis as a preferred option for optimizing CV protection in patients with RA.

MTX treatment induces secretion of IL-1 from activated RA-FLS which by autocrine signaling augments their release of GM-CSF. This unexpected effect of MTX might contribute to the persistence of synovitis.

P2, N=64, Not yet recruiting, Northwestern University

This suggests a correlation between PGRMC1 and pemetrexed-induced iron-dependent cell death. Our study contributes to the development of more effective therapeutic strategies to improve the prognosis of patients with lung adenocarcinoma, particularly those facing drug resistance challenges.

Although patients presenting with typical clinical features are easy to diagnose, atypical skin findings are challenging for the clinician. In the presence of atypical skin and clinical findings in addition to muscle enzyme elevation, JDM should be considered in the differential diagnosis.Abbreviations: AHCE: asymptomatic hyper-CKemia; AST: aspartate aminotransferase; C: complement; CK: creatine kinase; IVIG: intravenous immunoglobulin; IIM: idiopathic inflammatory myopathy; JDM: juvenile dermatomyositis; LDH: lactate dehydrogenase; MAA: myositis-associated antibodies; MDA5: melanoma differentiation-associated gene 5; MRC: Medical Research Council; MRI: magnetic resonance imaging; MSA: myositis-specific antibodies; MTX: methotrexate NXP2: nuclear matrix protein 2; STIR: short tau inversion recovery; US: ultrasound.

At the end of the study, the rats were anesthetized (ketamine and xylazine) and killed using CO2. The treatment groups, particularly thymoquinone, did not experience any appreciable pathological changes. The thymoquinone was found to have the strongest protective effect against the heart damage caused by MTX.

The developed method was useful for therapeutic drug monitoring of MTX and suitable for assessing the risks and benefits of chemotherapy in patients with primary central nervous system lymphoma. Intravenous mannitol did not increase MTX concentration in the CSF of patients.

P2/3, N=204, Completed, Guang'anmen Hospital of China Academy of Chinese Medical Sciences | Unknown status --> Completed

The present study suggested the usefulness of IL-10 in the prognosis of VRL. This study showed a relation between IL-10 in AH and tumoral activity, and for the first time with disease relapse.

P=N/A, N=188, Not yet recruiting, Dongzhimen Hospital, Beijing University of Chinese Medicine; Dongzhimen Hospital, Beijing University of Chinese Medicine

Considering the importance of MTX in cancer treatment, AP appears to have highly promising potential as a cardioprotective and hepatoprotective agent in anti-tumoral therapy. Key words: MDA, GSH, Caspase-3, p53, Oxidative stress, Apoptosis.

Treatment included intravenous leucovorin, blood and platelet transfusions, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Despite initial critical presentation, the patient showed significant improvement, with recovery of blood counts and resolution of symptoms. He was discharged with stable hemoglobin, platelet, and white blood cell counts.

MTX-BL NLCs were inhibited the expression of inflammatory cytokines (tumor necrosis factor-alpha, and interleukin-17) . It can be concluded that newer targeting strategies for NLCs for dual-drug delivery of nano-lipid carriers could be administered topically for the treatment of psoriasis.

In the in vivo study, a C57BL/6J mouse model of lung adenocarcinoma (LUAD) allografts was established, and various interventions were administered for 14 days (Model group: administered normal saline via oral gavage; Pemetrexed (PEM) group: intraperitoneally injected with a solution of pemetrexed, once every 3d; XLPYR group: administered XLPYR via oral gavage; Combination (COMBI) group: received XLPYR via oral gavage simultaneously with intraperitoneal injection of pemetrexed solution)...It suppressed LUAD cell proliferation, migration, and invasion, while reducing VEGF concentration in the cell supernatant. The regulatory mechanism may involve inhibiting PI3K/Akt protein phosphorylation and downregulating angiogenesis-related factors, such as HIF-1α, VEGF, and Ang-2.

In our study, both the MTX + HCQ combination therapy and MTX monotherapy demonstrated improvements in symptoms, conditions and quality of life for patients with RA. Notably, the combination therapy could achieve better outcomes across all indices compared to MTX monotherapy, highlighting its potential as the optimal first-line treatment for RA.

In addition, antifibrotic effects, anti-caspase-3, and PCNA enhancement activity were recorded. PFD exhibited a protective potential and mitigated the MTX-induced testiculopathy via suppression of testicular oxidative stress, inflammation, fibrosis, and apoptosis and retaining the testicular proliferative efficacy as confirmed by histological, immunohistochemical, and biochemical methods.