A chemotherapy-associated senescence bystander effect in breast cancer cells.

A bystander effect typically refers to the death, altered growth or damage of cells that have not directly received chemotherapy or irradiation. Cancer cells derived from solid tumors readily undergo senescence in response to chemotherapeutic agents, prompting us to test for the existence of a senescence bystander effect. MCF-7 breast cancer cells were acutely exposed to Adriamycin to trigger senescence.

Determination of ERCC2 Lys751Gln and GSTP1 Ile105Val gene polymorphisms in colorectal cancer patients: relationships with treatment outcome.

Introduction: Glutathione S-transferase P1 (GSTP1) and excision-repair cross-complementing repair deficiency group 2 protein (ERCC2 or XPD) may modulate the activity of platinum derivatives. The SNPs, Ile105Val for GSTP1 and Lys751Gln for ERCC2, may affect the efficiency of oxaliplatin in patients treated with an oxaliplatin-based regimen for metastatic colorectal carcinoma.

Patients & Methods: A total of 107 patients treated with first-line chemotherapy, 59 with an oxaliplatin-based regimen and 48 with an irinotecan-based regimen, were included retrospectively.

Functional study of the 830C>G polymorphism of the human carboxylesterase 2 gene.

Purpose: Carboxylesterase 2 (CES2) is involved in the activation of the anticancer drug irinotecan to its active metabolite SN-38. We previously identified a single nucleotide polymorphism (SNP), with an allele frequency around 10%, as possibly involved in enzyme expression (Clin Pharmacol Ther 76:528-535, 2004), which could explain the large individual variation in SN-38 disposition.

Methods: The 830C>G SNP, located in the 5' untranslated region of the gene, was analysed in various DNA samples extracted from: (1) the National Cancer Institute NCI-60 panel of human tumour cell lines; (2) a collection of 104 samples of normal tissue from colorectal cancer patients; (3) blood samples from a population of 95 normal subjects; (4) a collection of 285 human livers.

Relationships between genetic polymorphisms and anticancer drug cytotoxicity vis-à-vis the NCI-60 panel.

Introduction: The National Cancer Institute (NCI)-60 panel consists of 60 human tumor cell lines initially established for screening thousands of molecules for antiproliferative activity. It has been powerful for deciphering the relationships between anticancer drug cytotoxicity and cell molecular characteristics. We tested its potential interest for establishing relationships between the polymorphism of genes involved in drug metabolism and transport or in DNA repair, and drug cytotoxicity extracted from NCI databases.

Pharmacogenetics of human carboxylesterase 2, an enzyme involved in the activation of irinotecan into SN-38.

Purpose: Irinotecan, a drug widely used in the treatment of advanced colorectal cancers, is a prodrug requiring activation to 7-ethyl-10-hydroxycamptothecin (SN-38) by carboxylesterase 2 (hCE2). The existence of functional polymorphisms in the gene encoding this enzyme could explain the individual variability in drug efficacy and toxicity. We have explored this possibility in looking for single nucleotide polymorphisms and their functional consequence.