Methotrexate for advanced cancer of the breast

Vogler, William R.; Furtado, V.P.; Huguley, Charles M.

doi:10.1002/1097-0142(196801)21:1<26::aid-cncr2820210106>3.0.co;2-y

Cited by 22 publications

(1 citation statement)

References 9 publications

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“…In contrast to the novel tubulin inhibitor PT, the folic acid analogue MTX is well established in cancer therapy. It has been used since the 1950s to treat solid tumors, like breast cancer, − as well as leukemia. − MTX binds folic acid’s target enzyme dihydrofolate reductase and leads to the inhibition of the de novo synthesis of the nucleoside thymidine. Hence, in its polyglutamylated form, MTX prevents DNA biosynthesis. ,, In a previous study, we could demonstrate an enhanced combined cytotoxicity of poly(I:C) nanoplexes by synthetic polyglutamylated MTX ligands .…”

Section: Introductionmentioning

confidence: 99%

Combination Chemotherapy of L1210 Tumors in Mice with Pretubulysin and Methotrexate Lipo-Oligomer Nanoparticles

et al. 2019

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In the current study, nanoparticles containing the antimetabolite drug methotrexate (MTX) and the novel tubulin-binding drug pretubulysin (PT) were developed for combination chemotherapy. Polyelectrolyte complexes were formed based on ∼20 nm cationic nanomicelles of lipo-oligomer 454 with the anionic MTX at the molar ratio of 3:1, resulting in spherical nanoparticles with sizes of 150 nm (454 MTX). Particle formation in the presence of PT, which also interacts with 454, resulted in coloaded micelle complexes (454 PT+MTX) of 170 nm as demonstrated by transmission electron microscopy and dynamic light scattering measurements. Both drugs were incorporated to a high extent (∼85% for MTX, ∼70% for PT). Nanoparticles were stable in up to 20% serum and physiological NaCl solution. Cellular internalization of 454 PT+MTX into L1210 leukemia and KB cervix carcinoma cells was determined by confocal light scattering microscopy. The antitumor activity of the drug combination PT+MTX in both cell lines was strongly increased by drug formulation with 454 with IC50 values of PT+MTX decreasing 11-fold from 0.22 nM to 19 pM on L1210 cells and 6-fold from 2.8 to 0.48 nM on KB cervix carcinoma cells. Systemic treatment of NMRI nu/nu mice bearing subcutaneous L1210 tumors with 454 PT+MTX nanoparticles resulted in a more effective delay of tumor growth in comparison to the free drug combination of PT+MTX without 454. Importantly, nanoparticle formulation of PT+MTX with 454 increased the survival of mice by more than 100% compared to that of the buffer treated group and more than 40% compared to that of the free drug group.

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Section: Introductionmentioning

confidence: 99%

Combination Chemotherapy of L1210 Tumors in Mice with Pretubulysin and Methotrexate Lipo-Oligomer Nanoparticles

et al. 2019

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Disseminated Breast Carcinoma

Spigel¹

1973

Arch Intern Med

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Twenty-three patients with disseminated carcinoma of the breast were treated with a combination chemotherapy protocol employing cyclophosphamide, vincristine sulfate, methotrexate, fluorouracil, and prednisone. Ten of these patients had at least a partial response (greater than 50% reduction in tumor mass), a rate not dissimilar to the employment of single agents. However, of particular significance is the fact that four of the responses were complete remissions. This is a unique occurrence, since in a review of 1,590 patients treated with single agents only a single complete response is cited. Response did not seem to be related to prior therapy and did appear to correlate with increased survival. Toxic reaction was generally mild and readily reversible. Virtually all patients were treated and managed on an outpatient basis.Carci noma of the breast, by vir¬ tue of incidence and mortality, is the single most significant neoplastic disease occurring in women in the United States. The magnitude of this entity, which by itself accounts for 25% of all carcinomas in women and produces roughly 67,000 new cases per year, is most cogently underscored by

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Toxic and therapeutic effects of methotrexate-folinic acid (leucovorin) in advanced cancer and leukemiaWriting committee for the southeastern cancer study group

Vogler

Jacobs

1971

Cancer

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Methotrexate for advanced cancer of the breast

Cited by 22 publications

References 9 publications

Combination Chemotherapy of L1210 Tumors in Mice with Pretubulysin and Methotrexate Lipo-Oligomer Nanoparticles

Combination Chemotherapy of L1210 Tumors in Mice with Pretubulysin and Methotrexate Lipo-Oligomer Nanoparticles

Disseminated Breast Carcinoma

Toxic and therapeutic effects of methotrexate-folinic acid (leucovorin) in advanced cancer and leukemiaWriting committee for the southeastern cancer study group

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