Plant Extracted Natural Compounds Impact on Stage IV Breast Cancer Survival Time and Remission.

OBJECTIVES: To utilize multiple naturally-occurring bioalkaloids, bioactive "compounds of interest" from multiple sources, to influence prostate, breast, and uterine cancer pathways in cancer patients and cancer patients in remission. Other cancer types may be applicable. To utilize specific naturally-occurring bioalkaloids and bioactive "compounds of interest" to suppress cancer proliferation-stimulation/growth activities induced by normal cancer metabolism including environmental estrogen impact, estrogen-mimicking compounds, estrogen-influencing and testosterone-type compounds. To utilize DNA interaction with proliferating cancer cells via intercalation, which has a binding impact activity that then impairs DNA polymerase furthering DNA strand breakage and complete apoptosis. In addition, these bioactive compounds through intercalation, prevent cancer-cell DNA strand breakage from re-connection and repair, (limitlessness) while depleting nuclear topoisomerase, the enzyme also targeted by a number of conventional chemotherapy routes. Finally; a number of the bioalkaloids binds to cancer telomeres capping them at specific number or reducing them to "one and done." Natural GRAS compounds, in previous studies that background this research, reduced secondary bonding of TMPRSS2-ERG fusing affecting testosterone \& estrogen hormone influence in cell proliferation. Variant mRNAs of, for example, the TMPRSS2-ERG fusing pathway were affected whereas normalized mRNAs in all other cells were not, a mechanism and chemistry not readily understood. To utilize natural extracted plant compounds as a means to influence DIABLO (direct inhibitor of apoptosis binding protein with low isoelectric point) by downregulating over 350 genes which influence extracellular matrix (ECM) receptor interaction, and complement coagulation cascades were upregulated. To utilize applications of, or ingestion of, specifically grown plant species/subspecies, extract the "compounds of action" or "compounds of activity" but maintaining an "entourage-affect by protecting "multi-compound complex arrangement chemistry" to maintain normal metabolic functionality of the compounds of interest.. BACKGROUND DATA: Pharmaceutica has, since the turn of the 1800s to the 1900s, tried to find, extract and/or synthesize plant \& biological compounds that have the highest activity in a given medical treatment regime. In many cases the object was to get to the heart of the active compound, discarding non-active compounds,and, in other cases for various reasons including stockholder satisfaction, to be able to patent the synthesis chemistry and prevent duplication by competitors. The one point of this important to this work is that the natural multi-compounds were the "compounds of action" for centuries and in most cases, in the natural form they were utilized in pre-20th century medicine, while the action of control was usually much slower, the side affects were non-existent. Recent research (sic) now places a more important role of the "multi-compound" and the "entourage-effect' they have as cancer cells are quick to evolve, like viruses, and where the pharmaceutica "single compound of action" approach works well when ALL the cancer cells are eliminated, does not work well when surviving cells evolve to create resistance...a common outcome to most advanced stage cancers. The "entourage-effect" using the "multi-compound" natural extracted compounds appears to negate the evolution/resistance response of cancerous cells by having multiple "chemistries of action" involved the cancer-control process which then hides/disguises the metabolic pathway of control from the surviving cancer cells. OUTLINE: Patients are randomized to 1 of 2 arms. Arm I: Patients receive oral natural supplements comprising indole-3-carbinol, perillyl alcohol, glucuronic acid, and flavonoids daily for 12 months. Patients also consume whole foods comprising indole-3-carbinol and a diet that eliminates exogenous growth hormones. Arm II: Patients do not receive natural supplements or consume whole foods or a special diet. Levels of compounds of interest are measured by inductively-coupled plasma mass spectrometry, high performance liquid chromatography, gas chromatography, and matrix-assisted laser desorption/ionization time of flight mass spectrometry. After completion of study therapy, patients are followed periodically for 6 months and monitored for a second 6 months period. 1. Krimsky S (December 2001). "An epistemological inquiry into the endocrine disruptor thesis". Ann. N. Y. Acad. Sci. 948 (1): 130-42. doi:10.1111/j.1749-6632.2001.tb03994.x. PMID 11795392. 2. Marinucci L, Bodo M, Balloni S, Locci P, Baroni T. "Sub-Toxic Nicotine Concentrations Affect Extracellular Matrix and Growth Factor Signaling Gene Expressions in Human Osteoblasts." J Cell Physiol. 2014 Apr 29. doi: 10.1002/jcp.24661. PMID: 24777817 3. Camargo IC, Leite GA, Pinto T, Ribeiro-Paes JT. "Histopathologycal findings in the ovaries and uterus of albino female rats promoted by co-administration of synthetic steroids and nicotine." Exp Toxicol Pathol. 2014 Jul;66(4):195-202. doi: 10.1016/j.etp.2014.01.005. Epub 2014 Feb 18. PMID: 24556002 4. Raval AP. "Nicotine addiction causes unique detrimental effects on women's brains." J Addict Dis. 2011 Apr;30(2):149-58. doi: 10.1080/10550887.2011.554782. Review. PMID: 21491296 5. Holloway AC, Salomon A, Soares MJ, Garnier V, Raha S, Sergent F, Nicholson CJ, Feige JJ, Benharouga M, Alfaidy N. "Characterization of the adverse effects of nicotine on placental development: in vivo and in vitro studies." Am J Physiol Endocrinol Metab. 2014 Feb 15;306(4):E443-56. doi: 10.1152/ajpendo.00478.2013. Epub 2013 Dec 24. PMID: 24368670 6. Bavarva JH, Tae H, Settlage RE, Garner HR. "Characterizing the Genetic Basis for Nicotine Induced Cancer Development: A Transcriptome Sequencing Study." PLoS One. 2013 Jun 18;8(6):e67252. Print 2013. PMID: 23825647 7. Hayes, Tyrone B.; Anderson, Lloyd L.; Beasley, Val R.; de Solla, Shane R.; Iguchi, Taisen; et al. (2011). "Demasculinization and feminization of male gonads by atrazine: Consistent effects across vertebrate classes". The Journal of Steroid Biochemistry and Molecular Biology 127 (1-2): 64-73. doi:10.1016/j.jsbmb.2011.03.015. PMID 21419222 8. Atrazine: Chemical Summary. Toxicity and Exposure Assessment for Children's Health (Report). U.S. Environmental Protection Agency. 4/24/2007 9. Mizota, K.; Ueda, H. (2006). "Endocrine Disrupting Chemical Atrazine Causes Degranulation through Gq/11 Protein-Coupled Neurosteroid Receptor in Mast Cells". Toxicological Sciences 90 (2): 362-8. doi:10.1093/toxsci/kfj087. PMID 16381660 10. Thomas, Christoforos; Strom A.; Lindberg K.; Gustafsson J. (22 June 2010). "Estrogen receptor beta decreases survival of p53-defective cancer cells after DNA damage by impairing G2/M checkpoint signaling". Breast Cancer Research and Treatment 127 (2): 417-427. doi:10.1007/s10549-010-1011-z. PMID 20623183