Purinogenic lymphocytotoxicity: Clues to a wider chemotherapeutic potential for the adenosine deaminase inhibitors

Kefford, Richard; Fox, Richard M.

doi:10.1007/bf00446213

Cited by 13 publications

(1 citation statement)

References 37 publications

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“…Of the three haloadenine nucleosides, the 2-chloro-derivative appears most active. Because of the unusual sensitivity of lymphoid cells to purine antimetabolites and inhibitors of purine degradation (6), evaluation of the therapeutic potential of 2-chlorodeoxyadenosine (2-CDA) has focused on lymphoproliferative disorders (7). The purpose of this paper is to report an assessment of the cytotoxicity of 2-CDA to cells from human solid tumors, using an in vitro human tumor colony-forming assay.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity of 2-Chlorodeoxyadenosine in a Human Tumor Colony-Forming Assay

Hutton¹,

Hoff²

1986

Cancer Drug Delivery

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We have utilized a human tumor colony forming assay to test the antitumor activity of 2-chlorodeoxyadenosine and to compare its activity with that of 9-beta-D-arabinofuranosyl-2-fluoroadenine, a related analog now in phase I/II clinical trials. The overall in vitro response rate (defined as less than 50% survival of tumor colony forming units) for 2-chlorodeoxyadenosine was: 8% and 23% at 1.0 and 10.0 micrograms/ml as a 1 hour pulse exposure, respectively; 11% and 31% at 1.0 and 10.0 micrograms/ml, as a continuous exposure, respectively. 2-Chlorodeoxyadenosine and 9-beta-D-arabinofuranosyl-2-fluoroadenine did not have identical spectra of antitumor activities in vitro, suggesting that both may be worthy of further clinical trial.

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Section: Introductionmentioning

confidence: 99%

Cytotoxicity of 2-Chlorodeoxyadenosine in a Human Tumor Colony-Forming Assay

Hutton¹,

Hoff²

1986

Cancer Drug Delivery

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Treatment of multiple myeloma with deoxycoformycin

Belch

1985

Cancer Chemother. Pharmacol.

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A comparison of adenosine deaminase activity in intact human plasma cells and lymphocytes in vitro showed that plasma cells had at least as much activity of this enzyme as did T or non-T lymphocytes. This observation led us to examine the effectiveness of deoxycoformycin in the treatment of multiple myeloma. Thirteen patients with advanced refractory myeloma were treated with deoxycoformycin at 5 mg/m2 daily for 3 days every 2 weeks until response or progression. Of the seven evaluable patients who received more than one cycle of therapy, two had a greater than 50% reduction in the level of myeloma protein and two had a demonstrable reduction in soft tissue disease. Toxicity consisted of marked nausea, anorexia lasting several days, and mild transient confusion in some patients. Plasma levels of deoxyadenosine and adenosine peaked on day 4 or 5 with average values of 1.9 and 0.6 microM, respectively. Red cell levels of dATP reached approximately 40% of ATP levels. The viability of plasma cells was shown to be greatly reduced in in vitro incubations with deoxycoformycin and low levels of deoxyadenosine (ID50 of 6 microM).

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Purinergic signalling and immune cells

Burnstock

Boeynaems

2014

Purinergic Signalling

260

222

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This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5′-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells.

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Purinogenic lymphocytotoxicity: Clues to a wider chemotherapeutic potential for the adenosine deaminase inhibitors

Cited by 13 publications

References 37 publications

Cytotoxicity of 2-Chlorodeoxyadenosine in a Human Tumor Colony-Forming Assay

Cytotoxicity of 2-Chlorodeoxyadenosine in a Human Tumor Colony-Forming Assay

Treatment of multiple myeloma with deoxycoformycin

Purinergic signalling and immune cells

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