Sequence-dependent administration of 5-fluorouracil maintains methotrexate antineoplastic activity in human estrogen-negative breast cancer and protects against methotrexate cytotoxicity in human bone marrow.

Background: Breast cancer is a leading cause of morbidity and mortality in women in developed countries and in increasingly developing countries. In general, estrogen receptor (ER)-positive breast cancers have a better prognosis and are often more responsive to anti-estrogen therapy. Unfortunately, ER-negative breast cancers are more aggressive and unresponsive to anti-estrogens.

Biomarkers in toxicology and risk assessment: informing critical dose-response relationships.

Tremendous advances have been made in the study of biomarkers related to carcinogenesis during the past 20 years. This perspective will briefly review improvements in methodology and instrumentation that have increased our abilities to measure the formation, repair, and consequences of DNA adducts. These biomarkers of exposure, along with surrogates such as protein adducts, have greatly improved our understanding of species differences in metabolism and effects of chemical stability and DNA repair on tissue differences in molecular dose.

Raloxifene and selective cell cycle specific agents: a case for the inclusion of raloxifene in current breast cancer treatment therapies.

Background: Breast cancer patients are at increased risk of osteoporosis. Contributing factors include age and/or chemotherapy. The selective estrogen modulator, raloxifene (RAL), effective in the prevention of breast cancer and approved for the treatment and prevention of osteoporosis, may prove beneficial in current breast cancer treatment modules.

Sequence-dependent administration of raloxifene and 5-fluorouracil/pemetrexed protects against pemetrexed cytotoxicity in human bone marrow.

Background: Pemetrexed (Alimta) is a new-generation multitargeted antifolate that inhibits several key enzymes in the de novo pathways of pyrimidine and purine biosynthesis, including thymidylate synthase (TS), dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFT). Alimta has demonstrated antitumor activity in a broad array of human malignancies, e.g.