methotrexate

This study highlights the importance of OTULIN in OS chemoresistance and provides a promising approach for targeting the OTULIN-GPX4 axis to improve the prognosis of OS patients. Our findings offer new insights into the molecular mechanisms underlying OS chemoresistance and suggest potential therapeutic targets for future clinical interventions.

The infant recovered after the high-dose methotrexate chemotherapy. These results demonstrate that leukapheresis is a feasible treatment option for acute hyperleukocytic leukemia in infants with ALL.

Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (EBV-LPD) occur in immunocompromised patients, such as those receiving methotrexate or other immunosuppressive drugs or after allogenic transplantation. EBV-LPD is also reported to be a rare side effect in patients receiving long-term dasatinib or imatinib...The subsequently removed splenic mass was largely composed of non-neoplastic cytotoxic T cells resulting from a reaction to EBV-infected B cells. EBV-LPD should be included in the differential diagnosis of patients who develop lymphadenopathy during dasatinib treatment, regardless of its duration.

Considering the high risks associated with a spinal cord biopsy, the rarity of the disease and the lack of specificity of its clinicoradiological presentation, the diagnosis of spinal cord lymphoma is often delayed. Searching for other lymphomatous locations or assaying CSF IL-10 may be helpful in this disease, which can cause irreversible handicap.

While PBL is typically highly aggressive and requires prompt treatment, MTX-LPD cases can sometimes resolve without further treatment, depending on the clinical course. However, in cases where the disease shows progression or when spontaneous regression does not occur, additional therapeutic interventions may be necessary to manage the disease effectively.

P1, N=42, Recruiting, St. Jude Children's Research Hospital | Trial completion date: Jul 2025 --> Jun 2027

Representative drugs selected for further investigation included docetaxel, methotrexate, panobinostat, idarubicin, camptothecin, and pevonedistat. In conclusion, we identified several highly effective agents with potent anti-tumor activity in chondrosarcoma cells, independent of IDH mutation status. These agents represent promising candidates for chondrosarcoma therapy and warrant further preclinical investigation and potential inclusion in clinical trials.

Patients with MIBC treated with AMVAC followed by a risk-adapted approach to local consolidation achieved a 2-year MFS rate of 73%. The primary end point was not met, but 17% of all enrolled patients and 48% of the AS group avoided cystectomy without metastatic disease.

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.

This study aimed to understand the evolution of cognitive changes following methotrexate (MTX) or 5- fluorouracil (5-FU) chemotherapy, assessing three time-points: acute (96-hour), sub-acute (31-days) and chronic (93-days). These results provide valuable insight into the complexity of a mediator of neuroinflammation in CICI. While neuroinflammation may be a promising therapeutic target, further markers should be assessed to elucidate the full neuroimmune response, and thus which aspects to target and when, to ensure optimal outcomes for cancer patients treated with chemotherapy.

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

Methotrexate and Inj. Carboplatin from June to August 2004 followed by optimum cytoreduction in September 2004...Tab Etoposide was given from December 2004 to October 2006...Now she is living with better quality of life with adjunct Ayurvedic treatment, including Oral Ayurvedic Medicines possessing Rasayana (immunomodulatory) and hepato-protective activity and 12 sets of Panchakarma Chikitsa. In this case of Stage IIIA Ovarian carcinoma and second primary Breast carcinoma with BRCA 1 genetic mutation (HBOC syndrome), a long-term 13 years of disease-free survival, and 20 years of overall survival is achieved with the integration of Ayurvedic treatment and conventional cancer treatment.

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.

More recently, ferroptosis-a novel, non-apoptotic form of cell death-was identified in NRAS-mutant HT-1080 fibrosarcoma cells exposed to erastin and other NRLs...Overall, the published data support the idea that multi-layered endogenous antioxidant defense mechanisms in the liver limit the occurrence of pathophysiologically relevant LPO under normal conditions. Only when these defense mechanisms are severely compromised does ferroptosis become a significant mode of drug-induced cell death.

Chrysin prevented cyclophosphamide, doxorubicin, cisplatin, methotrexate, paracetamol, alcohol, carbon tetrachloride, tert-butyl hydroperoxide (tBHP) and thioacetamide. Chrysin's most common hepatoprotective biochemical and molecular mechanisms involve the ability to control enzyme synthesis, scavenge free radicals, boost the antioxidant response, induce apoptosis, and modify the synthesis of proinflammatory and profibrotic cytokines.Chrysin is a valuable nutraceutical with broad therapeutic feasibility, but to confirm its representative hepatoprotective potential, clinical studies are advised. It would also be interesting to use cutting-edge drug delivery techniques or include bio-enhancers.

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.

Hormonal or endocrine therapy includes selective estrogen receptor modulators (SERMs) such as raloxifene, tamoxifen and toremifene, selective estrogen-receptor degraders (SERDs) including elacestrant and fulvestrant, and aromatase inhibitors such as anastrozole, letrozole, and exemestane...These agents include taxanes (docetaxel, nab-paclitaxel, and paclitaxel), anthracyclines (doxorubicin, epirubicin), anti-metabolites (capecitabine, gemcitabine, fluorouracil, methotrexate), alkylating agents (carboplatin, cisplatin, and cyclophosphamide), and drugs that target microtubules (eribulin, ixabepilone, ado-trastuzumab emtansine). Patients with ER-positive tumors are treated with 5-10 years of endocrine therapy and chemotherapy. For patients with metastatic breast cancer, standard first-line and follow-up therapy options include targeted approaches such as CDK4/6 inhibitors, PI3K inhibitors, PARP inhibitors, and anti-PDL1 immunotherapy, depending on the tumor type and molecular profile.

P3, N=488, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Mar 2025

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.

P2, N=53, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Oct 2025

Combination treatment of regorafenib and oral methotrexate in patients with KRAS-mutant NSCLC was limited due to toxicity, and the study did not meet its primary end point. Computational modeling may aid in repurposing therapeutic options though caution must be exercised with tolerability.

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.

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.

P3, N=182, Recruiting, Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Not yet recruiting --> Recruiting

This splice-site PDGFRB variant favors the development of myofibroma featuring an acquired oncogenic variant in the same gene and resistance to targeted therapy.

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.

Venetoclax was given for 21 days with each cycle of mini-hyper-CVD (cyclophosphamide, vincristine, dexamethasone alternating with methotrexate and cytarabine). In summary, for patients with newly diagnosed ALL, venetoclax plus mini-HCVD is well-tolerated with promising efficacy. NCT03319901.

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.

Dexamethasone (DXM) was used in average-risk 2 (AR2) T-ALL and B-ALL during induction, 10 and 6 mg/m2/day, respectively. Leucovorin rescue was delayed to 42 h instead of 36 h after initiation of high-dose methotrexate, and a postconsolidation MRD time point was added to stratify patients...The HR was 2.15 (99% CI: 0.67-6.85) for very low-risk but 0.34 (99% CI: 0.13-0.89) for AR2. The particularly favorable results observed in the T-ALLs and AR2 subgroups suggest the benefit of using DXM in specific patient groups and highlight the importance of risk stratification.

Adalimumab trough levels above 4.0 mg/L were associated with remission/low disease activity throughout the first year of adalimumab therapy and can be considered a lower target level for therapeutic drug monitoring of adalimumab therapy.

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.

EBV-associated T-cell lymphoma with haemophagocytic lymphohistiocytosis can affect not only children but also adolescents and young adults, highlighting the need for awareness of the high fatality risk.Early recognition of EBV-associated haemophagocytic lymphohistiocytosis (EBV-HLH) is crucial; when a patient presents with fever, pancytopaenia and hepatosplenomegaly.Future prospective studies are warranted to determine the treatment strategy and the optimal patient population that requires early bone marrow transplantation when initial treatment is inadequate.

He was administered alemtuzumab twice (at the time of initial treatment and relapse) and cyclophosphamide, vincristine, and hydrocortisone chemotherapy. Furthermore, novel therapeutic drugs (venetoclax and tofacitinib) were administered based on previous case reports...Consideration should be given to suspending treatment, adjusting the administration interval, or administering G-CSF if necessary. The treatment interval can be appropriately adjusted, making it a valuable treatment option for refractory T-PLL.

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.

P3, N=5949, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Oct 2025

P3, N=847, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Sep 2025