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Ponte Academic Journal
Apr 2015, Volume 71, Issue 4

Conceptual basis for cancer treatment: from single drugs to kits with serial programmed actions of multiple substances-drugs

Author(s): BURLAKA D

J. Ponte - Apr 2015 - Volume 71 - Issue 4



Abstract:
Well-known paradoxical effect that both high-dose estrogens and anti-estrogens cause tumor regressions. In this case important is an understanding of the properties of a tumor. Aims: 1) To study of the influence of the same hormonal environment on tumor growth and character of change of the receptors level in tumors with different hormone sensitivity. Methods: Concentration femtomoles/mg protein (fM/mg) of estrogen receptor (ER) was determined in transplanted mice mammary tumors with intensive reproduction mode (2-6 parturition without lactating) (n=20) and virgin (n=20). The levels of ER were determined by means of the dextran-coated charcoal technique. Mice of line ?3H/Sn (n=69) contained in cages on 5 female +2 male (normal reproduction) in a room with daylight. Virgin female mice (n=47). Results: The data provides both estrogen-positive and ?negative tumors that actually are evoked from the same tissue, so that one can determine at what level(s) the hormone sensitivity or dependency exists. The widely accepted hypothesis that the interaction of estrogen with its cellular receptors determines the hormone dependency of mammary tumors should now be challenged on the basis of the following observations: a) tumors occuring in experimental animals with permanent high estrogen levels are receptor-positive(~20-100fM/mg) and with low estrogen levels (<2fM/mg) are receptor-negative; b) tumors regrowing after complete or partial regression as a result of endocrine ablation or hormone administration are no considered to be autonomous or hormone dependence but environment dependence; c) growth of a tumor at cyclically changing hormonal level leads to heterogeneity of mammary tumors that complicates hormone therapy. Conclusions: 1) Series of parameters of a tumor such as the invasiveness, heterogeneity and others are consequence of adaptic properties of tumoral cells. 2) Ability of tumoral cells to adapt for change of a surrounding microenvironment answers on a question on a paradoxicality of a hormone therapy. 3) High sensitivity of tumors to change of steroids concentration (10-9M) discovers an epigenetic path of redifferentiation a tumor oncogenome i.e. multiple-stage therapy.
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