{'fraction_non_alphanumeric': 0.019938650306748466, 'fraction_numerical': 0.0019171779141104294, 'mean_word_length': 5.5225, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 1, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Development and biochemical pharmacology of toremifene, an antiestrogenic antitumor drug

The intention with the present series of experiments was to develop and characterize a new, selective, effective, and safe drug for the treatment of breast cancer. Toremifene was selected after biochemical and pharmacological tests. Early in the development of the drug, a new method was devised with which to measure the number of living tumor cells in cell cultures. The method is based on firefly luciferase enzyme which converts the chemical energy of adenosine triphosphate, basic energy source of all living cells, into light. This light can be measured with a luminometer. The method gives results comparable to those obtainable by other conventionally used in vitro methods. The antitumor action of Toremifene is targeted at estrogen receptors which mediate the growth stimulus of estrogens in hormone-dependent breast cancers. Toremifene binds competitively with estradiol to the estrogen receptors. The Toremifene-receptor complex is bound to nuclear chromatin and subsequently the growth-stimulating activity of the estrogens are inhibited. Toremifene has only weak, species-specific intrinsic estrogenic actions in the uterus, but it does block the estrogen-induced uterotrophic effect. Toremifene inhibits the growth of estrogen receptor positive breast cancer cells in vitro and in vivo at reasonable concentrations (about 1 pM) and doses (about 3 mglkg). At doses about 5-20-fold higher, which are still not toxic to experimental animals, Toremifene has an oncolytic effect on estrogen receptor negative murine uterine sarcoma. Toremifene is not distributed specifically intotumor tissues, which is why its biological activity is targeted at the estrogen receptors of cancer cells. Toremifene is metabolized extensively. N-dernethyltoremifene is the main metabolite in human serum and has hormonal effects similar to those of the parent drug. Didemethyltoremifene also has antiestrogenic effects, but concentrations in biological fluids are too low to be of biological significance. Toremifene is detoxified by deamination and subsequent oxidations; (deaminohydroxy) toremifene and carboxytoremifene have only weak hormonal effects if any. Combinations of toremifene and interferons have an additive and, at best, synergistic antitumor interaction. In conclusion: a new drug for the safe treatment of breast cancer has been developed and characterized. The drug has a specific mechanism of action. Combination with biological response modifiers may further improve the clinical usefulness of Toremifene.