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The Journal of Pediatrics Jun 1968
Topics: Abnormalities, Drug-Induced; Abortion, Criminal; Adult; Aminopterin; Child, Preschool; Female; Humans; Infant, Newborn; Methotrexate; Pregnancy; Skull
PubMed: 5652604
DOI: 10.1016/s0022-3476(68)80430-5 -
Skinmed 2012T-cell lymphoma accounts for 10% to 15% of all cases of non-Hodgkin lymphoma in the United States (approximately 5000 to 6000 cases a year). Peripheral T-cell lymphoma...
T-cell lymphoma accounts for 10% to 15% of all cases of non-Hodgkin lymphoma in the United States (approximately 5000 to 6000 cases a year). Peripheral T-cell lymphoma (PTCL) comprises a subgroup of rare and aggressive non-Hodgkin lymphomas that develop from T cells in different stages of maturity outside of the thymus. Cutaneous T-cell lymphoma is a subgroup that falls within the T-cell lymphoma population but is classified differently than other PTCLs. Most cases of CTCL are considered indolent and can often be treated with less aggressive therapies. Eight percent to 55% of CTCL cases undergo transformation, and once this transformation occurs, the disease acts similarly to other PTCLs and its classification changes to that of a PTCL. Transformed CTCL requires aggressive systemic therapy. Pralatrexate is the first Food and Drug Administration-approved drug for relapsed and refractory PTCL and has also gained compendia approval for treatment of CTCL. Pralatrexate is an antifolate chemotherapeutic inhibitor of dihydrofolatereductase. It has a high affinity for the one carbon-reduced folate carrier, which leads to better cellular internalization of the drug and has a greater antitumor effect than methotrexate. Several clinical trials have been conducted to evaluate the use of this drug in PTCL and other malignancies such as non-small cell lung cancer. This review offers focused information for dermatologists about pralatrexate and its use as a novel treatment for relapsed or refractory PTCL.
Topics: Aminopterin; Folic Acid Antagonists; Humans; Lymphoma, T-Cell; Lymphoma, T-Cell, Cutaneous; Lymphoma, T-Cell, Peripheral
PubMed: 23008944
DOI: No ID Found -
Biochemical Pharmacology Jan 1975
Topics: Aminopterin; Animals; Antineoplastic Agents; Aspartic Acid; Intestinal Absorption; Intestine, Small; Kinetics; Lethal Dose 50; Male; Methotrexate; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Structure-Activity Relationship
PubMed: 1168470
DOI: 10.1016/0006-2952(75)90332-9 -
Cancer Treatment Reports Feb 1978
Review
Topics: Aminopterin; Animals; Folic Acid; History, 20th Century; Humans; Leucovorin; Leukemia, Experimental; Methotrexate; Mice; Neoplasms; Time Factors
PubMed: 346222
DOI: No ID Found -
Proceedings of the Society For... Feb 1958
Topics: Aminopterin; Folic Acid Antagonists; Methotrexate; Oxidoreductases
PubMed: 13518295
DOI: 10.3181/00379727-97-23764 -
Bioorganic & Medicinal Chemistry Jan 2020Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes severe joints damage and other extra-articular alterations. Despite the efficacy of low-dose...
Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes severe joints damage and other extra-articular alterations. Despite the efficacy of low-dose methotrexate (LD-MTX) in RA treatment, adverse effects are the predominant reasons for discontinuation of therapy. As a therapeutic targeting strategy, the presence of increased concentrations of reactive oxygen species (ROS) in the inflammatory environment can serve as the stimulus for prodrug activation in site-selective drug delivery systems. Our group has previously reported novel ROS sensitive prodrugs (1-3) of MTX and aminopterin (AMT) for site-selective delivery to inflammatory tissue associated with RA, with the aim of reducing side effects in RA therapy. Herein, we investigate the effect and toxicity of the same prodrugs in a rat CIA (collagen-induced arthritis) model of RA. We find that prodrug 1, an arylboronic acid ROS-sensitive MTX-prodrug, displays similar in vivo efficacy as MTX at an equimolar dose, while avoiding adverse effects known to restrict MTX treatment. To further characterize prodrug 1 and its ROS mediated activation, we synthesized compound 4, a negative control lacking the boronic acid moiety. We then investigated the effect of molecules on cell proliferation and cytotoxicity in the presence of the ROS scavenger pyruvate, as well as their stability in buffer and cell media, demonstrating a direct correlation between ROS concentration and the prodrug activity. Moreover, the in vitro ADME properties were investigated, including permeability, rat plasma and microsomal stability.
Topics: Aminopterin; Animals; Antirheumatic Agents; Apoptosis; Arthritis, Experimental; Arthritis, Rheumatoid; Cell Proliferation; Cell Survival; Disease Models, Animal; Dose-Response Relationship, Drug; Hydrogen Peroxide; Injections, Intraperitoneal; Methotrexate; Molecular Structure; Prodrugs; Rats; Reactive Oxygen Species; Structure-Activity Relationship
PubMed: 31843461
DOI: 10.1016/j.bmc.2019.115247 -
British Journal of Haematology May 2009Due to the development of neurological toxicity and resistance to methotrexate (MTX), other antifolates have been evaluated for its potential replacement in the...
Due to the development of neurological toxicity and resistance to methotrexate (MTX), other antifolates have been evaluated for its potential replacement in the treatment of childhood acute lymphoblastic leukaemia (ALL). Aminopterin (AMT) has been suggested to provide clinical advantages over MTX and other antifolates. AMT activity, compared with MTX, was evaluated in ALL and lymphoma preclinical models. The minimum survival fraction at the range of concentrations tested was lower with AMT than with MTX in 3 out of 15 cell lines. Both AMT and MTX significantly extended the event-free survival of mice bearing 3 out of 4 xenografts with equivalent activity.
Topics: Aminopterin; Animals; Cell Line, Tumor; Dose-Response Relationship, Drug; Female; Folic Acid Antagonists; Humans; Inhibitory Concentration 50; Lymphoma; Methotrexate; Mice; Mice, SCID; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Regression Analysis; Xenograft Model Antitumor Assays
PubMed: 19298590
DOI: 10.1111/j.1365-2141.2009.07631.x -
Blood Jan 2018
Topics: Aminopterin; Depsipeptides; Humans; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral
PubMed: 29371206
DOI: 10.1182/blood-2017-11-817734 -
The Lancet. Oncology Oct 2007
Topics: Adolescent; Adult; Aminopterin; Child; Child, Preschool; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 17974054
DOI: 10.1016/s1470-2045(07)70306-6 -
Cancer Treatment and Research 1996In summary, the problem of MTX resistance has been approached in a mechanistic fashion, based on the wealth of information generated over the years. To date, these... (Review)
Review
In summary, the problem of MTX resistance has been approached in a mechanistic fashion, based on the wealth of information generated over the years. To date, these strategies have produced several new classes of anticancer drugs, with a variety of anticipated and unanticipated mechanisms of action. Several of these have shown promising preclinical activity, and these are moving into more stringent testing in the clinic.
Topics: Aminopterin; Animals; Antimetabolites, Antineoplastic; Drug Resistance; Folic Acid Antagonists; Humans; Methotrexate; Thymidylate Synthase
PubMed: 8886454
DOI: 10.1007/978-1-4613-1267-3_8