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Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Finally, for women with hormone-receptor-positive (i.e., ER+ve and/or PR+ve) breast cancer, endocrine therapies can be provided, which is the main topic of this chapter. It is also worth noting that extended endocrine therapy with antiestrogen agents such as tamoxifen and letrozole for up to five years or longer can be offered to suitable patients with ER+ve breast cancers to lower the long-term risk of the disease re-occurring. In this case the drugs are acting as chemopreventive agents, and this approach is discussed further in Chapter 12.
Obstetrical Pathophysiology of Cocaine
Published in Richard J. Konkol, George D. Olsen, Prenatal Cocaine Exposure, 2020
J. Christopher Glantz, James R. Woods
Progesterone receptors have been localized to aortic media smooth muscle in the baboon, and to a lesser extent in myocardial and interstitial cells.128 Administration of estrogen increases the progesterone receptor content in these tissues.129 In humans, progesterone receptors have been identified in aortic smooth muscle and myocardium, but not in vessels of the uterus, breast, kidney, or gastrointestinal tract.130 To determine whether the rise in progesterone might explain cocaine’s increased toxicity during pregnancy, Plessinger and Woods catheterized oophorectomized nonpregnant sheep and administered intramuscular progesterone at a dose of 10 mg/kg/day for 3 days.131 During these 3 days, adrenergic receptor sensitivity was monitored using daily challenges with intravenous norepinephrine. Additionally, daily bolus infusions of 1 mg/kg and 2 mg/kg cocaine were administered. Progesterone treatment did not modify alpha adrenergic receptor sensitivity as measured by cardiovascular response to norepinephrine. In contrast, the hypertensive and chronotropic responses to cocaine increased twofold and threefold, respectively, when compared to responses observed before the initial dose of progesterone had been administered (Figure 3.14). Increased cardiovascular toxicity associated with pregnancy appears to be due to an effect of progesterone on the action of cocaine, but does not involve a change in alpha adrenergic receptor sensitivity.
Preclinical and clinical development of new progesterone receptor antagonists with high receptor specificity for breast cancer treatment
Published in A. R. Genazzani, Hormone Replacement Therapy and Cancer, 2020
J. Hoffmann, H. Hess-Stumpp, R. B. Lichtner, U. Fuhrmann, G. Siemeister, M. R. Schneider
The physiological effects of progesterone are mediated by two nuclear receptor proteins (members of the nuclear receptor superfamily of transcription factors), termed A and B, which arise from a single gene and act as ligand-activated transcription factors to regulate the expression of target genes. The structure and functional properties of the progesterone receptor isoforms, and how functional differences between these proteins are likely to impact on the overall physiological role of the receptor in reproductive systems, are discussed in detail by Conneely and colleagues1.
Potential of paracetamol for reproductive disruption: molecular interaction, dynamics, and MM-PBSA based in-silico assessment
Published in Toxicology Mechanisms and Methods, 2023
Sayed Aliul Hasan Abdi, Abuzer Ali, Shabihul Fatma Sayed, Amena Ali, Shaivad Shabee Hulhasan Abadi, Abu Tahir, Mohd Amir Afjal, Hina Rashid, Omar M. Aly, Sumathi Nagarajan
Apart from estrogen and androgen receptors, progesterone receptors also play an important role in the homeostasis of the reproductive system. In addition, the role of progesterone receptors in maintaining the homeostasis of the reproductive system has been reported by various studies, and an association of progesterone receptors has been found with male infertility (Baulieu 2000; Wetendorf and DeMayo 2012). The molecular interactions of paracetamol with progesterone receptor were associated with residues ARG 766, GLN 725, and MET 756 with hydrogen bond, and residues LEU 763, VAL 760, and MET 759 were stabilized with Pi Alkyl bond (Supplementary Figure 10). The bisphenol and progesterone receptors were associated LEU 718, LEU 887, MET 756, LEU 763, VAL 760, GLN 725, MET 759, LEU 797, PHE 778, MET 801. The GLN 725 and MET 759 were stabilized with hydrogen bonds and LEU 718, LEU 887, MET 756, LEU 763, and VAL 760 were stabilized with Alkyl and Pi Alkyl bonds. Pi–sigma, Pi–Pi T shaped, and Pi sulfur bonds were associated with residues LEU 797, PHE 778, and MET 801, respectively (Supplementary Figure 11). The Ulipristal acetate and progesterone receptor were stabilized with hydrogen bonds with residues TYR 795, LYS 810, TRP 802, and LEU 799 were stabilized with Alkyl and Pi Alkyl bond. The residue SER 796 was stabilized with a carbon hydrogen bond (Supplementary Figure 12). The binding energies of the progesterone receptor with paracetamol, bisphenol, and tamoxifen were −6.57, −5.15, and −6.53 kcal/mol, respectively. The molecular interaction analyses of 1XP9, 1QKM, 5CJ6 and 4OAR are given in Table 2.
Understanding the killer-cell immunoglobulin like receptor polymorphism in retinoblastoma
Published in Ophthalmic Genetics, 2023
Ritu Aggarwal, Madhulika Sharma, Usha Singh, Kay Poulton, Tanvi Bhatia, Navdeep Mangat, Nandita Kakkar, Deepak Bansal
Among the inhibitory KIRs, we observed KIR2DL5 to be a predisposing gene for retinoblastoma. The role of KIR2DL5 in predisposition to several cancers, including multiple myeloma, Kaposi’s sarcoma, breast cancer, and HNSCC, has been well documented (9,16–18). Their role in the causation of progesterone receptor-positive breast cancer was described by Larki et al (15). The other inhibitory gene which exhibited a significant role was KIR2DL2. Similar to our observation, Larki et al. reported increased susceptibility to estrogen receptor- positive breast cancer (15). Increased susceptibility to breast cancer has been reported in the Brazilian population as well (19). Further, the phase-I clinical trial of IPH2101, a humanized IgG4 monoclonal antibody against common KIRs, in combination with immunomodulating agent lenalidomide, showed promising novel, steroid sapring, dual immune therapy for multiple myeloma (20).
Cytoprotective effect and clinical outcome of perioperative progesterone in brain tumors, a randomized microscopically evidence study
Published in Egyptian Journal of Anaesthesia, 2022
Omyma Shehata Mohamed, Mohab Mohamad Darwish, Marian fathy Gayyed, George abdelshaheed Hanna, Walid Zeidan Nanous, Mina Maher Raouf
The current study recognized upregulation of nuclear receptors for progesterone with enhanced intensity and proportion of staining uptake in participants treated by progesterone (PR group) presented by high significant difference in the score (p-0.0001) and better postoperative course (earlier weaning and shorter ICU stay). Progesterone has multiple widely distributed receptors in the brain and through activation of tow common pathways (genomic and non-genomic) may exert its neuroprotective actions [19]. In the genomic pathway, progesterone binds to its intracellular receptor (PR) and activate a transcription factor which in turn regulate the gene expression. Meanwhile, through the non-genomic route progesterone exerts an activating effect on G protein (mPRs) [20]. The antitumor effect of progesterone has been proven to be produced by restoring the proliferative balance, the ability for apoptosis, and increasing the drugs chemosensitivity [4].