P4, N=6, Completed, Radboud University Medical Center | Phase classification: P2 --> P4

The case provides additional support that IT pemetrexed can offer symptomatic relief and may be considered as a treatment option in advanced LM. Furthermore, the case illustrates that an increased dose of lorlatinib may efficiently control LM in patients with ALK-rearranged NSCLC, following progression on standard lorlatinib dosage.

PTOV1 and Cyfra21-1 are upregulated in LUAC patients who are resistant to neoadjuvant chemotherapy. Both markers not only have predictive value for chemosensitivity in these patients, but are also independent factors affecting neoadjuvant chemosensitivity.

Conversely, the *1b/*1b and *1b/*15 mutations in SLCO1B1 may have a protective effect against DILI. The proposed predictive model facilitates early individual risk assessment, enabling the implementation of proactive prevention strategies.

The diagnosis of PCL was eventually established. After treatment with methotrexate, followed by external beam radiotherapy, the choroidal infiltrate was normalized on B scan.

Immunohistochemistry showed increased immune expression of Nrf2 and HO-1 and decreased expression of TLR-4, TNF-α, Caspase-3, and NF-κB in 5b (5 mg/kg) + MTX group and 5b (10 mg/kg) + MTX group as compared to the MTX group. Hence, the results of this study favor the use of (5b) against MTX-induced nephrotoxicity.

They are safe, tolerable, contribute to prolonged survival, and enhance immune functions in tumor-bearing rats without leaving residues in vital organs. These results provide a promising foundation for future cancer treatment research.

The first-line treatment for LGL leukemia is historically based on immunosuppressive agents (methotrexate, cyclophosphamide, or cyclosporine). However, cytokines blocking molecules or Jak/STAT inhibitors represent a new conceptual therapeutic approach for LGL leukemia. In this review, we present an overview of the spectrum of LGL proliferations, potential links between LGL expansion and autoimmunity, and therapeutic approaches.

The MDLS model offers a robust and precise tool for predicting breast cancer prognosis and tailoring personalized treatment strategies. Its integration of multi-omics and machine learning highlights its potential clinical applications, particularly in improving the effectiveness of immunotherapy and identifying therapeutic targets for high-MDLS patients.

Medical treatment for r-axSpA involves the use of a stepwise strategy, starting with administration of nonsteroidal anti-inflammatory drugs and physiotherapy, and progressing to sulfasalazine or methotrexate and biologics including TNF-α inhibitors or IL-17 inhibitors as needed. Use of Janus kinase inhibitors has been recently reported.

P2, N=64, Recruiting, Northwestern University | Not yet recruiting --> Recruiting | Initiation date: May 2025 --> Nov 2024

ENG rs1800956 and PKD1L2 rs16954698 were found to be potentially influential variants associated with delayed MTX clearance. These findings provide insights into HD-MTX-induced nephrotoxicity and may contribute to reducing adverse reactions through treatment modification.

Notably, the 100 mg/kg dose provided more robust protection than the 50 mg/kg dose, indicating a dose-dependent efficacy. This investigation thus supports the conclusion that morin hydrate, at both dosage levels, effectively mitigates MTX-induced renal damage.

At the molecular level, ETO downregulated the protein expression of toll-like receptor 4 (TLR4), nuclear factor kappa-B (NF-κB), and p38 mitogen-activated protein kinase (p38 MAPK) in inflamed rat lungs. In conclusion, our findings indicate that oral administration of ETO ameliorates MTX-induced lung injury by inhibiting oxidative stress and suppressing the TLR4/NF-κB and TLR4/p38-MAPK inflammatory signaling pathways.

First-line treatment consists of neo-adjuvant chemotherapy with doxorubicin, cisplatin, and methotrexate and surgery. In recent years, RPs have been recognized not only for their traditional role in ribosome assembly but also for their extra-ribosomal functions, many of which are linked to the onset and progression of cancer. In this review we focus on the role and possible interplay of MYC and RPs expression in association with drug resistance and worse prognosis in OS and discuss therapeutic options that target de-regulated MYC, RiBi, or RPs, which are already clinically available or under evaluation in clinical trials.

Furthermore, synergistic effects were observed when combining potential compounds with Alimta. Compound 16e emerged as a leading candidate, demonstrating superior inhibition and selectivity for MTHFD2, favorable pharmacokinetics, and potent antitumor efficacy in MOLM-14 xenograft models.

In HCC cells, knockdown of DHFR or treatment with pralatrexate enhanced the sensitivity of HCC cells to molecularly targeted agents, such as sorafenib, regorafenib, lenvatinib, cabozantinib, or anlotinib...Therefore, pralatrexate upregulates the sensitivity of HCC cells to molecularly targeted drugs. These results expand our understanding of folate metabolism and HCC and can help provide more options for HCC treatment.

Among 69 patients with complete treatment information, 58 received platinum-based chemotherapy, with paclitaxel being the most commonly used combination chemotherapy drug (n = 25), followed by pemetrexed (n = 21). Paclitaxel with immunotherapy may have better benefits as a first-line treatment. Anatomic location and immunotherapy use are prognostic factors.

P2, N=64, Not yet recruiting, Northwestern University | Trial completion date: May 2031 --> May 2030 | Trial primary completion date: May 2030 --> May 2029

It discusses the evidence on pharmacologic treatments, including drugs used for symptomatic relief such as non-steroidal anti-inflammatory drugs, and those used to control the disease process; this last group comprises conventional synthetic disease modifying anti-rheumatic drugs (DMARDs), including methotrexate, leflunomide, and sulfasalazine, and biologic and targeted DMARDs, including anti-tumor necrosis factor (TNFα), anti-interleukin-17 (IL-17), anti-IL-12/23, and anti-IL-23 agents, as well as Janus kinase (JAK) inhibitors and phosphodiesterase 4 (PDE4) antagonists. Although these drugs are usually tailored to the clinical profile of the patient, biomarkers predictive of response to therapy are needed so that a more personalized approach can be followed.

A methotrexate (MTX)-loaded dual phosphate- and pH-responsive nanodrug (pHA@MOF-Au/MTX) is next engineered by integrating Fe-based metal-organic frameworks and gold nanoparticles for improved chemo/chemodynamic therapy of TNBC...Furthermore, sequential EGCG and pHA@MOF-Au/MTX treatment showed remarkable anti-tumor effects in a mouse model of TNBC, with a tumor growth inhibition rate of 79.9%, and a pulmonary metastasis rate of 96.8%. Altogether, the combination strategy developed in this study can improve the efficacy of chemo/chemodynamic therapy in TNBC and represents an innovative application of EGCG.

The docking results revealed strong binding affinities of 7-O-methyl-cyanidin-3-O-(2″-galloyl)-galactoside with Keap1 and amentoflavone with MAPK. These insights pave the way for future experimental validation and therapeutic development of sumac-based phytoconstituents against MTX-induced nephrotoxicity.

NOTCH2 and PTP4A3 alterations are associated with clinical outcomes in pemetrexed-treated PM patients. The inhibition of NOTCH pathway may be exploited to eradicate CSCs and improve patients' survival.

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.