Cancer Chemotherapy with Purine and Pyrimidine Analogues

Heidelberger, Charles

doi:10.1146/annurev.pa.07.040167.000533

Cited by 59 publications

(23 citation statements)

References 87 publications

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“…As with the 'rational drug design' introduced within the pharmaceutical community decades ago (48), predictive mathematical models, in-vitro assays and in-vivo testing need to be integrated in one sole framework for the selection of optimal particulate systems leading to what can be baptized as the rational design of particulate systems.…”

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confidence: 99%

Intravascular Delivery of Particulate Systems: Does Geometry Really Matter?

et al. 2008

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Abstract. In cancer therapy and imaging, the systemic passive delivery of particulate systems has relied on the enhanced permeability and retention (EPR) effect: sufficiently small particles can cross the endothelial fenestrations and accumulate in the tumor parenchyma. The vast majority of man-made particulates exhibit a spherical shape as a result of surface energy minimization during their synthesis. The advent of phage display libraries, which are revealing the extraordinary molecular diversity of endothelial cells, and the development of processes for fabricating particles with shapes other than spherical are opening the path to new design solutions for systemically administered targeted particulates. In this paper, the role of particle geometry (i.e., size and shape) is discussed at the tissue and cellular scales. Emphasis is placed on how the synergistic effect of particle geometry and molecular targeting can enhance the specificity of delivery. The intravascular delivery process has been broken into three events: margination, firm adhesion and control of internalization. Predictions from mathematical models and observations from in-vitro experiments were used to show the relevance of particle geometry in systemic delivery. Rational design of particulate systems should consider, beside the physico-chemical properties of the surface coatings, geometrical features as size and shape. The integration of mathematical modeling with in-vitro and in-vivo testing provides the tools for establishing a rational design of nanoparticles.

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confidence: 99%

Intravascular Delivery of Particulate Systems: Does Geometry Really Matter?

et al. 2008

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“…Maiztegui et al (14) reported that patients with gram-negative bacteremias were infected by or- (15). The differential biochemical resistance mechanisms of microorganisms, particularly the gram-negative organisms, have been documented (3,6,11,16). Various microbial systems have been used to study the effects of these drugs.…”

Section: Methodsmentioning

confidence: 99%

“…The variations in resistance of microorganisms, particularly gram-negative bacilli, to some of these drugs has been documented for several organisms (7,11,16). A microorganism not inhibited by these compounds would have a definite advantage in establishing an infection in the cancer patient.…”

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Effect of Chemotherapeutic Agents upon Microorganisms Isolated from Cancer Patients

Goldschmidt

Bodey

1972

Antimicrob Agents Chemother

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Attempting to explain the predominance of Pseudomonas in leukemic patients, five of the most common gram-negative organisms isolated from sites of infection in cancer patients were exposed to several of the chemotherapeutic agents used in the treatment of this disease (methotrexate, cytosine arabinoside, cyclophosphamide, and 6-mercaptopurine). At concentrations of 125 μg/ml or higher, methotrexate inhibited all organisms except Pseudomonas . Cytosine arabinoside inhibited Escherichia and Klebsiella but appeared to stimulate the growth of Pseudomonas slightly at the higher concentrations. Thus, significant differences existed in individual susceptibilities to these agents. Clinical isolates were more resistant than the corresponding laboratory strains not previously exposed to these compounds. The resistance of Escherichia coli to cyclophosphamide was decreased 26% when it was grown in mixed culture with Pseudomonas . Only Pseudomonas was resistant to all of these compounds whether in pure or mixed culture. These observations may help to explain, in part, the predominant role that Pseudomonas plays as an infectious agent in leukemic patients.

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“…A notable exception is 5fluorouracil, probably the most intensively investigated pyrimidine antimetabolite; it is readily converted to the riboside in both bacterial and mammalian systems, followed by phosphorylation and incorporation into RNA in the case of mammalian cells. But, while active against DNA viruses in cell cultures, its in vivo efficacy is limited [28,29] . In a recent exemplary study [30] on the synthesis of Rous sarcoma virus on monolayer cultures of chick embryo fibroblasts, it was shown that S-fluorouridine inhibits cellular RNA synthesis by more than 80%, largely by irreversible blockage of formation of rRNA.…”

Section: Purine and Pyrimidine Derivativesmentioning

confidence: 99%

Progress with antiviral agents

Shugar

1974

FEBS Letters

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Cancer Chemotherapy with Purine and Pyrimidine Analogues

Cited by 59 publications

References 87 publications

Intravascular Delivery of Particulate Systems: Does Geometry Really Matter?

Intravascular Delivery of Particulate Systems: Does Geometry Really Matter?

Effect of Chemotherapeutic Agents upon Microorganisms Isolated from Cancer Patients

Progress with antiviral agents

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