Cyclopentenyl cytosine has biological and anti-tumour activity, but does not enhance the efficacy of gemcitabine and radiation in two animal tumour models
| Autor: | Angelique D. Barten-Van Rijbroek, Henk B. Kal, René Leen, Chris van Bree, André B.P. van Kuilenburg, Hans M. Rodermond |
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| Přispěvatelé: | Cancer Center Amsterdam, Radiotherapy, Amsterdam Gastroenterology Endocrinology Metabolism, Laboratory Genetic Metabolic Diseases |
| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
medicine.medical_specialty Lung Neoplasms medicine.drug_class Cytidine Triphosphate Population Mice Nude Cytidine Biology Deoxycytidine Antimetabolite Cyclopentenyl Cytosine Mice chemistry.chemical_compound Therapeutic index Cell Line Tumor Rats Inbred BN Internal medicine Pancreatic cancer Antineoplastic Combined Chemotherapy Protocols medicine Animals Humans Lung cancer education education.field_of_study Drug Synergism Middle Aged medicine.disease Combined Modality Therapy Gemcitabine Rats Pancreatic Neoplasms Disease Models Animal Endocrinology Oncology chemistry Cancer research Female medicine.drug |
| Zdroj: | International journal of oncology, 34(3), 813-819. Spandidos Publications |
| ISSN: | 1019-6439 |
| DOI: | 10.3892/ijo_00000207 |
| Popis: | Cyclopentenyl cytosine (CPEC), targetting the de novo biosynthesis of cytidine triphosphate (CTP), increases the cytotoxicity of gemcitabine (2' ,2'-difluoro-2'-deoxycytidine, dFdC) alone and in combination with irradiation in several human tumour cells in vitro. We investigated whether CPEC enhances the therapeutic ratio of gemcitabine and irradiation in human pancreatic BxPC-3 xenografts and in rat syngeneic L44 lung tumours. These models were selected because gemcitabine and radiation are used to treat both pancreatic and lung cancer patients and both models differ in growth capacity and in gemcitabine-induced radiosensitisation. A profound dose-dependent CTP-depletion was observed after a single injection of CPEC in both tumour tissue and in normal jejunum. In both models, CPEC alone induced a slight but significant tumour growth delay. The combination of CPEC with gemcitabine, at time intervals that showed CTP-depletion after CPEC, enhanced neither tumour growth delay nor toxicity as compared to gemcitabine alone. In addition, no beneficial effect of CPEC was observed in combination with gemcitabine and radiation. These results suggest that CPEC and gemcitabine alone as well as in combination with radiation target a similar cell population in both tumour models. In conclusion, future clinical development of CPEC as a modulator of gemcitabine combined with radiation is unlikely. |
| Databáze: | OpenAIRE |
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