Development and Validation of a Sensitive UHPLC-MS/MS–Based Method for the Analysis of Folylpolyglutamate Synthetase Enzymatic Activity in Peripheral Blood Mononuclear Cells: Application in Rheumatoid Arthritis and Leukemia Patients

Conclusions: Collectively, given its sensitivity with low cell numbers and avoidance of radioactive substrates, UHPLC-MS/MS–based analysis of FPGS activity may be eligible for routine therapeutic drug monitoring of MTX in RA and leukemia for therapy (non)response evaluations.
Source: Therapeutic Drug Monitoring - Category: Drugs & Pharmacology Tags: Original Article Source Type: research

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Publication date: Available online 19 October 2019Source: Autoimmunity ReviewsAuthor(s): Andrea Rubbert-Roth, Melinda Zsuzsanna Szabó, Melinda Kedves, György Nagy, Fabiola Atzeni, Piercarlo Sarzi-PuttiniAbstractThe five TNF inhibitors currently approved for the treatment of RA are characterised by differences in their molecular structures, half-lives, administration routes, dosing intervals, immunogenicity, and use in women who wish to become pregnant. TNF inhibitors still represent the first biologic after conventional synthetic DMARD (csDMARD) in the majority of patients according to registry data. This was p...
Source: Autoimmunity Reviews - Category: Allergy & Immunology Source Type: research
Publication date: Available online 19 October 2019Source: Autoimmunity ReviewsAuthor(s): Christopher J. Edwards, Galeazzi Mauro Galeazzi, Salvatore Bellinvia, Ariana Ringer, Theodoros Dimitroulas, George D. KitasAbstractBiological therapies have represented a cornerstone in the treatment of immune-mediated inflammatory diseases. Their advent combined with implementation of a treat-to-target approach has meant that remission or low disease activity are now realistic targets for treatment achieved by a significant number of patients. However, biologicals are not risk free and their elevated costs continue to present an impor...
Source: Autoimmunity Reviews - Category: Allergy & Immunology Source Type: research
We examined the MTXPG3 levels from 123 samples in 76 patients with ALL on maintenance oral methotrexate and mercaptopurine that were collected for clinical care. Male individuals had significantly higher MTXPG3 levels than female individuals which was unrelated to absolute neutrophil count, age, serum creatinine, and average doses of methotrexate or mercaptopurine. The MTXPG3 5th, 10th, 90th, and 95th percentile values are 0, 8.4, 53, and 64, respectively with a median of 24.7 nmol/L. The low 5th percentile MTXPG3 reflects 6 samples from 3 patients, age 16 to 21 years that were considered poorly adherent before coll...
Source: Journal of Pediatric Hematology Oncology - Category: Hematology Tags: Original Articles Source Type: research
Conclusions This review describes how leukocyte-heparanase can be a double-edged sword in tumor progression; it can enhance tumor immune surveillance and tumor cell clearance, but also promote tumor survival and growth. We also discuss the potential of using heparanase in leukocyte therapies against tumors, and the effects of heparanase inhibitors on tumor progression and immunity. We are just beginning to understand the influence of heparanase on a pro/anti-tumor immune response, and there are still many questions to answer. How do the pro/anti-tumorigenic effects of heparanase differ across different cancer types? Does...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Publication date: July 2018Source: Personalized Medicine Universe, Volume 7Author(s): Manahel Mahmood AlSabbaghAbstractBeing an anti-metabolite and anti-inflammatory agent, Methotrexate, a folate analogue, is indicated for a wide spectrum of diseases including moderate to severe chronic inflammatory disorders like psoriasis and rheumatoid arthritis and malignant diseases such as childhood acute lymphoblastic leukaemia and choriocarcinoma. The outcome of Methotrexate treatment varies. Though up to 50% of patients with inflammatory disorders show a favourable response; one third discontinues Methotrexate due to adverse drug ...
Source: Personalized Medicine Universe - Category: Drugs & Pharmacology Source Type: research
Rationale: Chimeric antigen receptor (CAR)-T cell therapy is a novel type of therapy that is being used in an increasing number of patients with acute lymphoblastic leukemia (ALL). Cytokine release syndrome (CRS) is the most common complication following CAR-T treatment, but the current understanding of the clinical manifestations and pathogenesis of CRS is still limited. Patient concerns: A 34-year-old male patient was diagnosed with ALL in June 2015. Complete remission (CR) was achieved after induction chemotherapy. The patient received 8 cycles of consolidation chemotherapy to maintain CR. In May 2017, the patient ...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
ma Á Abstract Methotrexate (MTX) is an antifolate drug used for several diseases. Depending on the disease, MTX can be administered at low-dose (LDMTX) in some autoimmune diseases, like rheumatoid arthritis, or at high-dose (HDMTX) in some cancers, such as acute lymphoblastic leukaemia. After absorption, MTX is metabolized in the liver to 7-hydroxymethotrexate (7-OH-MTX) and in the intestine to 2,4-diamino-N10-methylpteroic acid (DAMPA). Moreover, inside red blood cells (RBCs), MTX is converted to active metabolites, MTX polyglutamates (MTXPGs), contributing to its pharmacodynamics. Due to its narrow therap...
Source: Biomedical Chromatography : BMC - Category: Biomedical Science Authors: Tags: Biomed Chromatogr Source Type: research
Publication date: Available online 13 October 2017 Source:Pharmacological Research Author(s): Claire Speirs, Jamie J.L. Williams, Kirsten Riches, Ian P. Salt, Timothy M. Palmer Exaggerated Janus kinase-signal transducer and activator of transcription (JAK-STAT) signalling is key to the pathogenesis of pro-inflammatory disorders, such as rheumatoid arthritis and cardiovascular diseases. Mutational activation of JAKs is also responsible for several haematological malignancies, including myeloproliferative neoplasms and acute lymphoblastic leukaemia. Accumulating evidence links adenosine 5′-monophosphate (AMP)-activate...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
ConclusionsThe genetic alteration of A20 in the SS case was different from the T‐ALL samples and similar to the cases with refractory autoimmune disease and related to tumorigenesis. The findings lead to discuss whether such SNPs of A20 may link the refractory autoimmune inflammation and the tumorigenesis.
Source: Asia-Pacific Journal of Clinical Oncology - Category: Cancer & Oncology Authors: Tags: Original article Source Type: research
Conclusion Recent evidence shows changes in frequency and function of Th22 and its cytokine IL-22 in patients with MS, which suggests a potential relationship between Th22 cells, IL-22 levels, and the development and disease course of MS and its response to treatment. How Th22 cells and IL-22 levels affect the disease course of MS requires further elucidation. Additional studies on the immunopathogenesis of MS, specifically the roles Th22 cells and IL-22 cytokines may play in disease progression, are warranted and may lead to the development of new therapeutic strategies for treating neuro-inflammatory diseases, such as MS...
Source: Innovations in Clinical Neuroscience - Category: Neuroscience Authors: Tags: Current Issue Demyelinating Disease Genetics Multiple Sclerosis Neurology Review interleukin-22 T helper 22 Source Type: research
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