Expression and localization of thymidine phosphorylase/platelet‐derived endothelial cell growth factor in skin and cutaneous tumors

Asgari, Maryam M.; Haggerty, John G.; McNiff, Jennifer M.; Milstone, Leonard M.; Schwartz, Pauline M.

doi:10.1111/j.1600-0560.1999.tb01846.x

Cited by 34 publications

(23 citation statements)

References 34 publications

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“…Skin biopsies of severe rashes from patients treated with gefitinib showed culture-negative purulent folliculitis (17). An interaction between 5-FU and gefitinib at the cellular level in hair follicles is also possible given the high expression of thymidine phosphorylase, an enzyme involved in the metabolism of 5-FU, in the infundibulum of hair follicles (18). Interestingly, the incidence and increased severity of rash has been correlated with increased survival response in solid tumor patients treated with erlotinib (19), gefitinib (20), and cetuximab (21).…”

Section: Discussionmentioning

confidence: 99%

Phase I Trial of Irinotecan, Infusional 5-Fluorouracil, and Leucovorin (FOLFIRI) with Erlotinib (OSI-774)

Messersmith

Laheru

Senzer

et al. 2004

Clinical Cancer Research

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Results: The study was halted after six patients at the lowest dose level due to unexpectedly severe toxicities, including disfiguring grade 2 rash (three patients), grade 3 diarrhea (three patients), and grade > 3 neutropenia (three patients). All patients required some dose interruption or reduction of either erlotinib or FOLFIRI, and only one patient completed two 6-week cycles of therapy. Five patients had stable disease after one cycle, and one patient had a partial response. No plasma pharmacokinetic interaction was observed that could explain the observed increased toxicity.Conclusions: FOLFIRI combined with erlotinib causes excessive toxicity at reduced doses. These findings contrast with available data regarding the optimal safety profile of trials combining small molecule epidermal growth factor receptor inhibitors with other conventional chemotherapy and highlight the need to perform safety-oriented studies of such combinations.

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Section: Discussionmentioning

confidence: 99%

Phase I Trial of Irinotecan, Infusional 5-Fluorouracil, and Leucovorin (FOLFIRI) with Erlotinib (OSI-774)

Messersmith

Laheru

Senzer

et al. 2004

Clinical Cancer Research

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“…[57][58][59][60][61] Subsequently, it was discovered that this molecule is identical to thymidine phosphorylase (TP), an enzyme involved with intracellular thymidine metabolism and homeostasis. PD-ECGF/TP is also gliostatin (GS), a protein purified from human neurofibroma having neurotrophic actions and effects on glial differentiation.…”

Section: Intracinesmentioning

confidence: 99%

Intracellular Renin and the Nature of Intracrine Enzymes

Ré

2003

Hypertension

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Abstract-Recently, the binding of renin and prorenin to cellular receptors with the subsequent generation of second messengers and the production of physiological effects has been demonstrated. In addition, the internalization of prorenin by target cells has been associated with increased cellular synthesis of angiotensin and cardiac pathology. Also, a renin transcript lacking the sequences encoding a secretory signal has been reported, and this transcript appears to produce a renin that acts in the cell that synthesized it. Some years ago, we coined the term intracrine for a peptide hormone or factor that acts in the intracellular space either after internalization or retention in its cell of synthesis. Thus defined, a wide variety of peptides display intracrine functionality, including hormones, growth factors, transcription factors, and enzymes. For example, considerable evidence indicates that angiotensin II is an intracrine. Also, general principles of intracrine functionality have been developed. Thus, recent evidence demonstrates that the prorenin/renin molecule is an intracrine enzyme. Here, the actions of intracrine enzymes (angiogenin, phosphoglucose isomerase, phospholipase A2, granzyme A and B, thioredoxin, platelet-derived endothelial growth factor, and serine protease inhibitors) are reviewed. Key Words: renin Ⅲ platelet-derived growth factor Ⅲ enzymes Ⅲ angiotensin II Ⅲ phospholipases R enin gene expression leads to the synthesis of prorenin in the juxtaglomerular cells of the kidney, activation and secretion of renin by these cells, the generation of angiotensin I by renin enzymatic activity, and the subsequent generation of angiotensin II either in the plasma or tissues. However, renin, angiotensin I, and angiotensin II can also be taken up by tissues with subsequent enzymatic conversions occurring locally. Moreover, there is considerable evidence, both in animal models and in humans, in favor of the local synthesis of each of the components of the renin-angiotensin system (RAS) in various tissues leading to locally determined angiotensin generation. 1 In addition to evidence indicating local synthesis and uptake in tissues of RAS components, there is growing evidence to indicate the uptake and synthesis of components of the RAS by individual cells, thereby suggesting a new arena for the action of this physiological system. 2 Important among these new observations are studies demonstrating that (1) prorenin and renin can bind to specific cellular receptors with the generation of physiological effects, (2) prorenin, and to a lesser extent, renin, can be internalized by cells whereupon angiotensin II is produced, and (3) there exists a renin transcript in some cells that encodes a renin that is expected to be synthesized as an active, as opposed to a prorenin, and that is expected to remain in the cell because it lacks the sequence encoding the secretory signal piece (renin exon 1A). 2-13 These observations not only reveal prorenin and renin to be hormones in their own right, they suggest that pro...

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“…Ein erhöhter Spiegel der DehydropyrimidinDehydrogenase scheint mit einer erhöh-ten Inzidenz des HFS zu korrelieren. Angesichts der beobachteten Nekrose wurde postuliert, dass Keratinozyten eine ungewöhnlich hohe Aktivität der Thymidinphosphorylase enthalten [2], die zu einer selektiven Akkumulation von Capecitabin-Metaboliten führt und somit das Risiko für die Entstehung eines HFS erhöht. Eine Studie mit Messung der Plasmaspiegel und Konzentrationen von Capecitabin in der Blasenflüssigkeit steht allerdings noch aus.…”

Section: Diskussionunclassified