A new analogue of 10-deazaaminopterin with markedly enhanced curative effects against human tumor xenografts in mice

Sirotnak, Francis M.; DeGraw, Joseph I.; Colwell, W. T.; Piper, James R.

doi:10.1007/s002800050823

Cited by 75 publications

(61 citation statements)

References 6 publications

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“…This agent has been extensively studied in preclinical and clinical settings, alone and in combination, 20 and has been shown to have superior activity compared with methotrexate against human non-Hodgkin lymphoma in both in vitro and in vivo models. 21,22 The pharmacokinetics and toxicology of pralatrexate, as well as its efficacy and safety in peripheral T-cell lymphoma (PTCL), are previously well described. [23][24][25][26][27][28][29][30][31] Pralatrexate received accelerated approval from the US Food and Drug Administration for patients with relapsed or refractory PTCL at a dose of 30 mg/m 2 weekly by IV push for 6 of 7 (6/7) weeks, based on the results of the PROPEL study.…”

Section: Introductionmentioning

confidence: 99%

Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma

Horwitz

Kim

Foss

et al. 2012

Blood

121

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Section: Introductionmentioning

confidence: 99%

Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma

Horwitz

Kim

Foss

et al. 2012

Blood

121

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“…The authors of an early study showed pralatrexate to be more effectively internalized in malignant cells than methotrexate as the result of the presence of the reduced folate carrier, which is expressed only in malignant and fetal tissue. 76 Once internalized, it is polyglutamylated, resulting in intracellular accumulation. It is less effective as an inhibitor of dihydrofolate reductase than methotrexate, but because of its greater intracellular accumulation, it has more antitumor activity and, theoretically, less toxicity in normal tissue.…”

Section: Pralatrexatementioning

confidence: 99%

Novel therapeutic agents for B-cell lymphoma: developing rational combinations

Reeder

Ansell

2011

Blood

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Several novel targeted therapies have recently emerged as active in the treatment of non-Hodgkin lymphoma, including small molecules that inhibit critical signaling pathways, promote apoptotic mechanisms, or modulate the tumor microenvironment. Other new agents target novel cell surface receptors or promote DNA damage. Although most of these drugs have single-agent activity, none have sufficient activity to be used alone. This article reviews the utility and potential role of these new agents in the treatment of non-Hodgkin lymphoma with a specific focus on data that highlight how these agents may be incorporated into current standard treatment approaches.

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“…28 Methotrexate (MTX) was given at the maximally tolerated dose of 40 mg/kg intraperitoneally twice weekly for 4 doses based on previous data. 29,30 Combination regimens of antibodies and chemotherapy used the same dosing regimens and intervals. Mice were routinely assessed for weight loss, anorexia, and other clinical signs.…”

Section: Lymphoma Xenograft Experimentsmentioning

confidence: 99%

Targeting autocrine and paracrine VEGF receptor pathways inhibits human lymphoma xenografts in vivo

Wang

Teruya‐Feldstein

et al. 2004

Blood

121

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The role of angiogenesis in lymphoproliferative diseases is not well established. We demonstrate here that human lymphoma cells secrete vascular endothelial growth factor (VEGF) and express VEGF receptor 1 (VEGFR-1) and VEGFR-2. Proliferation of non-Hodgkin lymphoma (NHL) cells under serum-free conditions was enhanced by the addition of VEGF and was blocked by VEGFR-1-and VEGFR-2-specific antibodies. To differentiate between VEGF-mediated autocrine and paracrine effects on lymphoma growth, NOD/ SCID mice engrafted with human diffuse large B-cell lymphoma (DLBCL) were treated with species-specific antibodies against human VEGFR-1 (6.12), human VEGFR-2 (IMC-1C11), murine VEGFR-1 (MF-1), or murine VEGFR-2 (DC101). Treatment with 6.12 or DC101 (targeting tumor VEGFR-1 and host VEGFR-2) reduced established DLBCL xenograft growth, whereas treatment with IMC-1C11 or MF-1 (targeting tumor VEGFR-1 and host VEGFR-1) had no effect. Decreased tumor volumes after 6.12 and DC101 treatment correlated with increased tumor apoptosis and reduced vascularization, respectively, supporting the presence of autocrine VEGFR-1-and paracrine VEGFR-2-mediated pathways in lymphomagenesis. Inhibition of paracrine VEGF interactions (DC101) in these models was equivalent to their inhibition with rituximab. Combining DC101 with therapeutic agents (rituximab, 6.12, methotrexate) consistently improved tumor responses over those of single-agent therapy. These data support the further clinical development of VEGFR-targeted approaches for the therapy of aggressive DLBCL. (Blood.

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A new analogue of 10-deazaaminopterin with markedly enhanced curative effects against human tumor xenografts in mice

Abstract: These studies showed significantly enhanced antitumor properties of PDX compared with MTX and EDX. Based upon these results, clinical trials of PDX in patients with metastatic breast and NSC lung cancer appear to be warranted.

Cited by 75 publications

References 6 publications

Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma

Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma

Novel therapeutic agents for B-cell lymphoma: developing rational combinations

Targeting autocrine and paracrine VEGF receptor pathways inhibits human lymphoma xenografts in vivo

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