The role of progesterone and the progesterone receptor in cancer: progress in the last 5 years

References

• Proietti C, Salatino M, Rosemblit C, et al. Progestins induce transcriptional activation of signal transducer and activator of transcription 3 (Stat3) via a Jak- and Src-dependent mechanism in breast cancer cells. Mol Cell Biol. 2005;25(12):4826–4840.
   PubMed Web of Science ®Google Scholar
• Tsai SY, Carlstedt-Duke J, Weigel NL, et al. Molecular interactions of steroid hormone receptor with its enhancer element: evidence for receptor dimer formation. Cell. 1988;55(2):361–369.
   PubMed Web of Science ®Google Scholar
• Condon JC, Hardy DB, Kovaric K, et al. Up-regulation of the progesterone receptor (PR)-C isoform in laboring myometrium by activation of nuclear factor-kappaB may contribute to the onset of labor through inhibition of PR function. Mol Endocrinol. 2006;20(4):764–775.
   PubMedGoogle Scholar
• Pichon MF, Pallud C, Brunet M, et al. Relationship of presence of progesterone receptors to prognosis in early breast cancer. Cancer Res. 1980;40(9):3357–3360.
   PubMed Web of Science ®Google Scholar
• Dowsett M, Cuzick J, Wale C, et al. Retrospective analysis of time to recurrence in the ATAC trial according to hormone receptor status: a hypothesis-generating study. J Clin Oncol. 2005;23(30):7512–7517.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Zhao D, Gong C, et al. Prognostic role of hormone receptors in endometrial cancer: a systematic review and meta-analysis. World J Surg Oncol. 2015;13:208–219.
   PubMed Web of Science ®Google Scholar
• Check JH. The role of progesterone and the progesterone receptor in cancer. Exp Rev Endo Metab. 2017;12:187–197.
   PubMed Web of Science ®Google Scholar
• Valadez-Cosmes P, Germán-Castelán L, González-Arenas A, et al. Expression and hormonal regulation of membrane progesterone receptors in human astrocytoma cells. J Steroid Biochem Mol Biol. 2015;154:176–185.
   PubMed Web of Science ®Google Scholar
• Smith JL, Kupchak BR, Garitaonandia I, et al. Heterologous expression of human mPRalpha, mPRbeta and mPRgamma in yeast confirms their ability to function as membrane progesterone receptors. Steroids. 2008;73(11):1160–1173.
   PubMed Web of Science ®Google Scholar
• Valadez-Cosmes P, Vázquez-Martínez ER, Cerbón M, et al. Membrane progesterone receptors in reproduction and cancer. Mol Cell Endocrinol. 2016;434:166–175.
   PubMed Web of Science ®Google Scholar
• Zhu Y, Bond J, Thomas P. Identification, classification, and partial characterization of genes in humans and other vertebrates homologous to a fish membrane progestin receptor. Proc Natl Acad Sci U S A. 2003;100(5):2237–2242.
   PubMed Web of Science ®Google Scholar
• Pang Y, Dong J, Thomas P. Characterization, neurosteroid binding and brain distribution of human membrane progesterone receptors d and {epsilon} (mPRd and mPR{epsilon}) and mPRd involvement in neurosteroid inhibition of apoptosis. Endocrinology. 2013;154(1):283–295.
   PubMed Web of Science ®Google Scholar
• Faivre EJ, Lange CA. Progesterone receptors upregulate Wnt-1 to induce epidermal growth factor receptor transactivation and c-Src-dependent sustained activation of Erk1/2 mitogen-activated protein kinase in breast cancer cells. Mol Cell Biol. 2007;27(2):466–480.
   PubMed Web of Science ®Google Scholar
• Faivre EJ, Daniel AR, Hillard CJ, et al. Progesterone receptor rapid signaling mediates serine 345 phosphorylation and tethering to specificity protein 1 transcription factors. Mol Endocrinol. 2008;22(4):823–837.
   PubMedGoogle Scholar
• Béguelin W, Díaz Flaqué MC, Proietti CJ, et al. Progesterone receptor induces ErbB-2 nuclear translocation to promote breast cancer growth via a novel transcriptional effect: erbB-2 function as a coactivator of Stat3. Mol Cell Biol. 2010;30(23):5456–5472.
   PubMed Web of Science ®Google Scholar
• Daniel AR, Hagan CR, Lange CA. Progesterone receptor action: defining a role in breast cancer. Expert Rev Endocrinol Metab. 2011;63:359–369.
   Google Scholar
• Saitoh M, Ohmichi M, Takahashi K, et al. Medroxyprogesterone acetate induces cell proliferation through up-regulation of cyclin D1 expression via phosphatidylinositol 3-kinase/Akt/nuclear factor-kappaB cascade in human breast cancer cells. Endocrinology. 2005;146(11):4917–4925.
   PubMed Web of Science ®Google Scholar
• Narayanan R, Adigun AA, Edwards DP, et al. Cyclin-dependent kinase activity is required for progesterone receptor function: novel role for cyclin A/Cdk2 as a progesterone receptor coactivator. Mol Cell Biol. 2005;25(1):264–277.
   PubMed Web of Science ®Google Scholar
• Cahill MA, Jazayeri JA, Catalano SM, et al. The emerging role of progesterone receptor membrane component 1 (PGRMC1) in cancer biology. Biochim Biophys Acta. 2016;1866(2):339–349.
   PubMed Web of Science ®Google Scholar
• Mifsud W, Bateman A. Membrane-bound progesterone receptors contain a cytochrome b5-like ligand-binding domain. Genome Biol. 2002;3(12):RESEARCH0068.
   PubMed Web of Science ®Google Scholar
• Ahmed IS, Rohe HJ, Twist KE, et al. Pgrmc1 (progesterone receptor membrane component 1) associates with epidermal growth factor receptor and regulates erlotinib sensitivity. J Biol Chem. 2010;285(32):24775–24782.
   PubMed Web of Science ®Google Scholar
• Szczesna-Skorupa E, Kemper B. Progesterone receptor membrane component 1 inhibits the activity of drug-metabolizing cytochromes P450 and binds to cytochrome P450 reductase. Mol Pharmacol. 2011;79(3):340–350.
   PubMed Web of Science ®Google Scholar
• Kabe Y, Nakane T, Koike I, et al. Haem-dependent dimerization of PGRMC1/Sigma-2 receptor facilitates cancer proliferation and chemoresistance. Nat Commun. 2016;7:11030.
   PubMed Web of Science ®Google Scholar
• Peluso JJ, Pappalardo A, Losel R, et al. Expression and function of PAIRBP1 within gonadotropin-primed immature rat ovaries: PAIRBP1 regulation of granulosa and luteal cell viability. Biol Reprod. 2005;73(2):261–270.
   PubMed Web of Science ®Google Scholar
• Mir SU, Schwarze SR, Jin L, et al. Progesterone receptor membrane component 1/Sigma-2 receptor associates with MAP1LC3B and promotes autophagy. Autophagy. 2013;9(10):1566–1578.
   PubMed Web of Science ®Google Scholar
• Kim JY, Kim SY, Choi HS, et al. Progesterone receptor membrane component 1 suppresses the p53 and Wnt/ß-catenin pathways to promote human pluripotent stem cell self-renewal. Sci Rep. 2018;8(1):3048.
   PubMedGoogle Scholar
• Zhang Y, Ruan X, Willibald M, et al. May progesterone receptor membrane component 1 (PGRMC1) predict the risk of breast cancer? Gynecol Endocrinol. 2016;32(1):58–60.
   PubMed Web of Science ®Google Scholar
• Willibald M, Wurster I, Meisner C, et al. High level of progesterone receptor membrane component 1 (PGRMC 1) in tissue of breast cancer patients is associated with worse response to anthracycline-based neoadjuvant therapy. Horm Metab Res. 2017;49(8):595–603.
   PubMed Web of Science ®Google Scholar
• Hampton KK, Stewart R, Napier D, et al. PGRMC1 elevation in multiple cancers and essential role in stem cell survival. Adv Lung Cancer (Irvine). 2015;4(3):37–51.
   PubMedGoogle Scholar
• Mir SU, Ahmed IS, Arnold S, et al. Elevated progesterone receptor membrane component 1/sigma-2 receptor levels in lung tumors and plasma from lung cancer patients. Int J Cancer. 2012;131(2):E1–9.
   PubMed Web of Science ®Google Scholar
• Ruan X, Zhang Y, Mueck AO, et al. Increased expression of progesterone receptor membrane component 1 is associated with aggressive phenotype and poor prognosis in ER-positive and negative breast cancer. Menopause. 2017;24(2):203–209.
   PubMed Web of Science ®Google Scholar
• Peluso JJ, Liu X, Saunders MM, et al. Regulation of ovarian cancer cell viability and sensitivity to cisplatin by progesterone receptor membrane component-1. J Clin Endocrinol Metab. 2008;93(5):1592–1599.
   PubMed Web of Science ®Google Scholar
• Tsai HW, Ho CL, Cheng SW, et al. Progesterone receptor membrane component 1 as a potential prognostic biomarker for hepatocellular carcinoma. World J Gastroenterol. 2018;24(10):1152–1166.
   PubMed Web of Science ®Google Scholar
• Hirai Y, Utsugi K, Takeshima N, et al. Putative gene loci associated with carcinogenesis and metastasis of endocervical adenocarcinomas of uterus determined by conventional and array-based CGH. Am J Obstet Gynecol. 2004;191(4):1173–1182.
   PubMed Web of Science ®Google Scholar
• Albrecht C, Huck V, Wehling M, et al. In vitro inhibition of SKOV-3 cell migration as a distinctive feature of progesterone receptor membrane component type 2 versus type 1. Steroids. 2012;77(14):1543–1550.
   PubMed Web of Science ®Google Scholar
• Lachmann M, Gelbmann D, Kálmán E, et al. PIBF (progesterone induced blocking factor) is overexpressed in highly proliferating cells and associated with the centrosome. Int J Cancer. 2004;112(1):51–60.
   PubMed Web of Science ®Google Scholar
• Polgar B, Kispal G, Lachmann M, et al. Molecular cloning and immunologic characterization of a novel cDNA coding for progesterone-induced blocking factor. J Immunol. 2003;171(11):5956–5963.
   PubMed Web of Science ®Google Scholar
• Check JH, Cohen R. The role of progesterone and the progesterone receptor in human reproduction and cancer. Exp Rev Endocrinol Metab. 2013;8:469–484.
   PubMedGoogle Scholar
• Rafiee M, Rezaei A, Alpour R, et al. Progesterone induced blocking factor influences the expression of membrane progesterone receptors (mPRs) in peripheral CD4+ T-lymphocytes in normal fertile females. Hormones (Athens). 2021 April;20:507–514.
   Google Scholar
• Polgar B, Barakonyi A, Xynos I, et al. The role of gamma/delta T cell receptor positive cells in pregnancy. Am J Reprod Immunol. 1999;41(4):239–244.
   PubMed Web of Science ®Google Scholar
• Cohen RA, Check JH, Dougherty MP. Evidence that exposure to progesterone alone is a sufficient stimulus to cause a precipitous rise in the immunomodulatory protein the progesterone induced blocking factor (PIBF). J Assist Reprod Genet. 2016;33:221–229.
   PubMed Web of Science ®Google Scholar
• Srivastava MD, Thomas A, Srivastava BI, et al. Expression and modulation of progesterone induced blocking factor (PIBF) and innate immune factors in human leukemia cell lines by progesterone and mifepristone. Leuk Lymphoma. 2007;48:1610–1617.
   PubMed Web of Science ®Google Scholar
• Anderle C, Hammer A, Polgár B, et al. Human trophoblast cells express the immunomodulator progesterone-induced blocking factor. J Reprod Immunol. 2008;79(1):26–36.
   PubMed Web of Science ®Google Scholar
• González-Arenas A, Valadez-Cosmes P, Jiménez-Arellano C, et al. Progesterone-induced blocking factor is hormonally regulated in human astrocytoma cells, and increases their growth through the IL-4R/JAK1/STAT6 pathway. J Steroid Biochem Mol Biol. 2014;144 Pt B:463–470.
   PubMed Web of Science ®Google Scholar
• Gutiérrez-Rodríguez A, Hansberg-Pastor V, Proliferative C-AI. Invasive effects of progesterone-induced blocking factor in human glioblastoma cells. Biomed Res Int. 2017;2017:1295087.
   PubMed Web of Science ®Google Scholar
• Kyurkchiev D, Naydenov E, Tumangelova-Yuzeir K, et al. Cells isolated from human glioblastoma multiforme express progesterone-induced blocking factor (PIBF). Cell Mol Neurobiol. 2014;34(4):479–489.
   PubMed Web of Science ®Google Scholar
• Kozma N, Halasz M, Polgar B, et al. Progesterone-induced blocking factor activates STAT6 via binding to a novel IL-4 receptor. J Immunol. 2006;176(2):819–826.
   PubMed Web of Science ®Google Scholar
• Piña-Medina AG, Hansberg-Pastor V, González-Arenas A, et al. Progesterone promotes cell migration, invasion and cofilin activation in human astrocytoma cells. Steroids. 2016;105:19–25.
   PubMed Web of Science ®Google Scholar
• Germán-Castelán L, Manjarrez-Marmolejo J, González-Arenas A, et al. Progesterone induces the growth and infiltration of human astrocytoma cells implanted in the cerebral cortex of the rat. Biomed Res Int. 2014;2014:393174.
   PubMed Web of Science ®Google Scholar
• Check JH, Check DL. A hypothetical model suggesting some possible ways that the progesterone receptor may be involved in cancer proliferation. Int J Mol Sci. 2021;22:12351.
   PubMed Web of Science ®Google Scholar
• Szekeres-Bartho J, Halasz M, Palkovics T. Progesterone in pregnancy; receptor-ligand interaction and signaling pathways. J Reprod Immunol. 2009;83(1–2):60–64.
   PubMed Web of Science ®Google Scholar
• Pence H, Petty WM, Rocklin RE. Suppression of maternal responsiveness to paternal antigens by maternal plasma. J Immunol. 1975;114:525–528.
   PubMed Web of Science ®Google Scholar
• Szekeres-Bartho J, Kilar F, Falkay G, et al. The mechanism of the inhibitory effect of progesterone on lymphocyte cytotoxicity: i. Progesterone-treated lymphocytes release a substance inhibiting cytotoxicity and prostaglandin synthesis. Am J Reprod Microbiol. 1985;9:15–18.
   PubMed Web of Science ®Google Scholar
• Szekeres-Bartho J, Annan B, Debre P, et al. Immunoregulatory effects of a suppressor factor from healthy pregnant women’s lymphocytes after progesterone induction. Cell Immunol. 1989;122:281–294.
   PubMed Web of Science ®Google Scholar
• Check JH, Szekeres Bartho J, O’Shaughnessy A. Progesterone induced blocking factor seen in pregnancy lymphocytes soon after implantation. Am J Reprod Immunol. 1996;35:277–280.
   PubMed Web of Science ®Google Scholar
• Szekeres-Bartho J, Falkay G, Torok A, et al. The mechanism of the inhibitory effect of progesterone on lymphocyte cytotoxicity: II. Relationship between cytotoxicity and the cyclooxygenase pathway of arachidonic acid metabolism. Am J Reprod Immunol Microbiol. 1985;9:19–22.
   PubMed Web of Science ®Google Scholar
• Szekeres-Bartho J, Barakonyi A, Polgar B, et al. The role of gamma/delta T cells in progesterone-mediated immunomodulation during pregnancy: a review. Am J Reprod Immunol. 1999;42:44–48.
   PubMed Web of Science ®Google Scholar
• Faust Z, Laskarin G, Rukavina D, et al. Progesterone induced blocking factor inhibits degranulation of NK cells. Am J Reprod Immunol. 1999;42:71–75.
   PubMed Web of Science ®Google Scholar
• Check JH, Szekeres-Bartho J, Nazari P, et al. A corpus luteum is not a prerequisite for the expression of progesterone induced blocking factor by T-lymphocytes a week after implantation. J Assist Reprod Genet. 2001;18:603–607.
   PubMed Web of Science ®Google Scholar
• Check JH, Arwitz M, Gross J, et al. Evidence that the expression of progesterone-induced blocking factor by maternal T-lymphocytes is positively correlated with conception. Am J Reprod Immunol. 1997;38(1):6–8.
   PubMed Web of Science ®Google Scholar
• Check JH, Aly J. Improving the chance of successful implantation – part 2 – circumventing immune rejection and the fetal semi-allograft. Clin Exp Obst Gyn. 2018;45:9–13.
   Web of Science ®Google Scholar
• Check DL, Check JH. Novel methods of improving fecundity and various pathological disorders based on a hypothetical model of embryo implantation. Gynecol Reprod Health. 2020;4:1–15.
   Google Scholar
• Hudic I, Fatusic Z, Szekeres-Bartho J, et al. Progesterone-induced blocking factor and cytokine profile in women with threatened pre-term delivery. Am J Reprod Immunol. 2009;61(5):330–337.
   PubMed Web of Science ®Google Scholar
• Salazar Garcia MD, Mobley Y, Henson J, et al. Early pregnancy immune biomarkers in peripheral blood may predict preeclampsia. J Reprod Immunol. 2018;125:25–31.
   PubMed Web of Science ®Google Scholar
• Check JH, Sarumi M, Diantonio A, et al. Serum levels of the progesterone induced blocking factor do not precipitously rise in women with gynecologic cancer in contrast to women exposed to progesterone. Clin Exp Obstet Gynecol. 2015;42:563–567.
   PubMed Web of Science ®Google Scholar
• Check JH, Dougherty P, DiAntonio G, et al. Comparison of levels of the immunomodulatory protein, the progesterone induced blocking factor in people with BRCA2 mutation associated with and not associated with a high rate of cancer. Proc Am Soc Cancer Res. 2015;75(abstract):1282.
   Google Scholar
• Check JH, Rosenberg A, Check DL, et al. Serum levels of the immunomodulatory protein, progesterone induced blocking factor (PIBF) which is found in high levels during pregnancy is not higher in women with progesterone (P) receptor (R) positive vs. negative breast cancer. Clin Exp Obst Gynecol. 2017;44:187–189.
   PubMed Web of Science ®Google Scholar
• Szekeres-Bartho J, Polgar B. PIBF. the double edged sword. Pregnancy and tumor. Am J Reprod Immunol. 2010;64(2):77–86.
   PubMed Web of Science ®Google Scholar
• Check JH, Check D. Therapy aimed to suppress the production of the immunosuppressive protein progesterone induced blocking factor (PIBF) may provide palliation and/or increased longevity for patients with a variety of different advanced cancers – a review. Anticancer Res. 2019;39:3365–3372.
   PubMed Web of Science ®Google Scholar
• Klijn JG, de Jong FH, Bakker GH, et al. Antiprogestins, a new form of endocrine therapy for human breast cancer. Cancer Res. 1989;49(11):2851–2856.
   PubMed Web of Science ®Google Scholar
• Rose FV, Barnea ER. Response of human ovarian carcinoma cell lines to antiprogestin mifepristone. Oncogene. 1996;12(5):999–1003.
   PubMed Web of Science ®Google Scholar
• Schneider CC, Gibb RK, Taylor DD, et al. Inhibition of endometrial cancer cell lines by mifepristone (RU 486). J Soc Gynecol Investig. 1998;5(6):334–338.
   PubMedGoogle Scholar
• Li DQ, Wang ZB, Bai J, et al. Effects of mifepristone on proliferation of human gastric adenocarcinoma cell line SGC-7901 in vitro. World J Gastroenterol. 2004;10(18):2628–2631.
   PubMed Web of Science ®Google Scholar
• Zheng G, Shen Z, Chen H, et al. Metapristone suppresses non-small cell lung cancer proliferation and metastasis via modulating RAS/RAF/MEK/MAPK signaling pathway. Biomed Pharmacother. 2017;90:437–445.
   PubMed Web of Science ®Google Scholar
• Goyeneche AA, Carón RW, Telleria CM. Mifepristone inhibits ovarian cancer cell growth in vitro and in vivo. Clin Cancer Res. 2007;13(11):3370–3379.
   PubMed Web of Science ®Google Scholar
• Freeburg EM, Goyeneche AA, Seidel EE, et al. Resistance to cisplatin does not affect sensitivity of human ovarian cancer cell lines to mifepristone cytotoxicity. Cancer Cell Int. 2009 Feb;17(9):4.
   Google Scholar
• Gamarra-Luques CD, Goyeneche AA, Hapon MB, et al. Mifepristone prevents repopulation of ovarian cancer cells escaping cisplatin-paclitaxel therapy. BMC Cancer. 2012 Jun;22(12):200.
   Google Scholar
• Freeburg EM, Goyeneche AA, Telleria CM. Mifepristone abrogates repopulation of ovarian cancer cells in between courses of cisplatin treatment. Int J Oncol. 2009;34(3):743–755.
   PubMed Web of Science ®Google Scholar
• Tieszen CR, Goyeneche AA, Brandhagen BN, et al. Antiprogestin mifepristone inhibits the growth of cancer cells of reproductive and non-reproductive origin regardless of progesterone receptor expression. BMC Cancer. 2011 May;27(11):207.
   Google Scholar
• Rocereto TF, Saul HM, Aikins JA Jr, et al. Phase II study of mifepristone (RU486) in refractory ovarian cancer. Gynecol Oncol. 2000;77(3):429–432.
   PubMed Web of Science ®Google Scholar
• Rocereto TF, Brady WE, Shahin MS, et al. A phase II evaluation of mifepristone in the treatment of recurrent or persistent epithelial ovarian, fallopian or primary peritoneal cancer: a gynecologic oncology group study. Gynecol Oncol. 2010;116(3):332–334.
   PubMed Web of Science ®Google Scholar
• Ramondetta LM, Johnson AJ, Sun CC, et al. Phase 2 trial of mifepristone (RU-486) in advanced or recurrent endometrioid adenocarcinoma or low-grade endometrial stromal sarcoma. Cancer. 2009;115(9):1867–1874.
   PubMed Web of Science ®Google Scholar
• Philibert D. RU38486: an original multifaceted antihormone in vivo. In: Agarwal M, editor. Adrenal Steroid Antagonism. Berlin: Walter de Gruyer and Co; 1984. p. 77–101.
   Google Scholar
• Perrault D, Eisenhauer EA, Pritchard KI, et al. Phase II study of the progesterone antagonist mifepristone in patients with untreated metastatic breast carcinoma: a national cancer institute of canada clinical trials group study. J Clin Oncol. 1996;14(10):2709–2712.
   PubMed Web of Science ®Google Scholar
• Robertson JF, Willsher PC, Winterbottom L, et al. Onapristone, a progesterone receptor antagonist, as first-line therapy in primary breast cancer. Eur J Cancer. 1999;35(2):214–218.
   PubMed Web of Science ®Google Scholar
• Jonat W, Bachelot T, Ruhstaller T, et al. Randomized phase II study of lonaprisan as second-line therapy for progesterone receptor-positive breast cancer. Ann Oncol. 2013;24(10):2543–2548.
   PubMed Web of Science ®Google Scholar
• Check JH, Sansoucie L, Chern J, et al. Mifepristone treatment improves length and quality of survival of mice with spontaneous leukemia. Anticancer Res. 2009;29(8):2977–2980.
   PubMed Web of Science ®Google Scholar
• Check JH, Sansoucie L, Chern J, et al. Mifepristone treatment improves length and quality of survival of mice with spontaneous lung cancer. Anticancer Res. 2010;30:119–122.
   PubMed Web of Science ®Google Scholar
• Check JH, Dix E, Wilson C, et al. Progesterone receptor antagonist therapy has therapeutic potential even in cancer restricted to males as evidenced from murine testicular and prostate cancer studies. Anticancer Res. 2010;30:4921–4924.
   PubMed Web of Science ®Google Scholar
• Mahajan DK, London SN. Mifepristone (RU486): a review. Fertil Steril. 1997;68(6):967–976.
   PubMed Web of Science ®Google Scholar
• Schreiber C, Creinin M. Mifepristone in abortion care. Semin Reprod Med. 2005;23(1):82–91.
   PubMed Web of Science ®Google Scholar
• Check JH, Dix E, Sansoucie L, et al. Mifepristone may halt progression of extensively metastatic human adenocarcinoma of the colon – case report. Anticancer Res. 2009;29(5):1611–1613.
   PubMed Web of Science ®Google Scholar
• Check JH, Dix E, Cohen R, et al. Efficacy of the progesterone receptor antagonist mifepristone for palliative therapy of patients with a variety of advanced cancer types. Anticancer Res. 2010;30:623–628.
   PubMed Web of Science ®Google Scholar
• Check JH, Check D, Srivastava MD, et al. Treatment with mifepristone allows a patient with end-stage pancreatic cancer in hospice on a morphine drip to restore a decent quality of life. Anticancer Res. 2020;40:6997–7001.
   PubMed Web of Science ®Google Scholar
• Check JH, Wilson C, Cohen R, et al. Evidence that mifepristone, a progesterone receptor antagonist can cross the blood brain barrier and provide palliative benefits for glioblastoma multiforme grade IV. Anticancer Res. 2014;34:2385–2388.
   PubMed Web of Science ®Google Scholar
• Check JH, Check D, Poretta T, et al. Palliative benefits of oral mifepristone for the treatment of metastatic fibroblastic osteosarcoma. Anticancer Res. 2021;41(4):2111–2115.
   PubMed Web of Science ®Google Scholar
• Check JH, Check D, Wilson C, et al. Long-term high-quality survival with single-agent mifepristone treatment despite advanced cancer. Anticancer Res. 2016;36:6511–6513.
   PubMed Web of Science ®Google Scholar
• Check DL, Check JH. Significant palliative benefits of single agent mifepristone for advanced lung cancer that previously failed standard therapy. Med Clin Sci. 2019;1(2):1–5.
   Google Scholar
• Check JH, Check D, Poretta T. Mifepristone extends both length and quality of life in a patient with advanced non-small cell lung cancer that has progressed despite chemotherapy and a check-point inhibitor. Anticancer Res. 2019;39:1923–1926.
   PubMed Web of Science ®Google Scholar
• Check DL, Check JH, Poretta T, et al. Prolonged high-quality life in patients with non-small cell lung cancer treated with mifepristone who advanced despite osimertinib. Cancer Sci Res. 2020;3(2):1–5.
   Google Scholar
• Check DL, Check JH, Poretta T. Conservative laparoscopic surgery plus mifepristone for treating multifocal renal cell carcinoma. Cancer Sci Res. 2020;3(2):1–4.
   Google Scholar
• Ponikwicka-Tyszko D, Chrusciel M, Stelmaszewska J, et al. Molecular mechanisms underlying mifepristone’s agonistic action on ovarian cancer progression. EBioMedicine. 2019;47:170–183.
   PubMed Web of Science ®Google Scholar
• Heikinheimo O, Lähteenmäki PL, Koivunen E, et al. Metabolism and serum binding of RU 486 in women after various single doses. Hum Reprod. 1987;2(5):379–385.
   PubMed Web of Science ®Google Scholar
• Ji Y, Rankin C, Grunberg S, et al. Double-blind phase III randomized trial of the antiprogestin agent mifepristone in the treatment of unresectable meningioma: SWOG S9005. J Clin Oncol. 2015;33(34):4093–4098.
   PubMed Web of Science ®Google Scholar
• Check JH, Nazari P, Goldberg J, et al. A model for potential tumor immunotherapy based on knowledge of immune mechanisms responsible for spontaneous abortion. Med Hypoth. 2001;57:337–343.
   PubMed Web of Science ®Google Scholar
• Check JH, Check D. Mifepristone may be the best single pharmaceutical agent for treatment of a variety of advanced cancers. Cancer Sci Res. 2021;4:1–6.
   Google Scholar
• Check D, Check JH, Wilson C. Alpelisib combined with low dose mifepristone for treating advanced breast cancer may cause hypokalemia even when this complication does not occur from single use of the anticancer agents. Cancer Sci Res. 2020;3:1–4.
   Google Scholar
• Check JH, Check DL, Dougherty MP. Progesterone receptor antagonists – a novel treatment for severe hyponatremia from the endocrine paraneoplastic syndrome. J Endocrinol Res. 2021;3:40–43.
   Google Scholar
• Yoshitani N, Satou K, Saito K, et al. A structure-based strategy for discovery of small ligands binding to functionally unknown proteins: combination of in silico screening and surface plasmon resonance measurements. Proteomics. 2005;5(6):1472–1480.
   PubMed Web of Science ®Google Scholar
• Hand RA, Craven RJ. Hpr6.6 protein mediates cell death from oxidative damage in MCF-7 human breast cancer cells. J Cell Biochem. 2003;90(3):534–547.
   PubMed Web of Science ®Google Scholar
• Craven RJ. Ag-205 for the treatment of breast cancer (2017). Pharmacology and nutritional sciences faculty patents. 52 [cited 2021 Mar 6]. http://uknowledge.uky.edu/pharmacol_patents/52
   Google Scholar
• Tohme S, Simmons RL, Tsung A. Surgery for cancer: a trigger for metastases. Cancer Res. 2017;77(7):1548–1552.
   PubMed Web of Science ®Google Scholar
• Klein-Hitpass L, Cato AC, Henderson D, et al. Two types of antiprogestins identified by their differential action in transcriptionally active extracts from T47D cells. Nucleic Acids Res. 1991;19(6):1227–1234.
   PubMed Web of Science ®Google Scholar
• Beck CA, Zhang Y, Weigel NL, et al. Two types of anti-progestins have distinct effects on site-specific phosphorylation of human progesterone receptor. J Biol Chem. 1996;271(2):1209–1217.
   PubMed Web of Science ®Google Scholar
• Afhüppe W, Sommer A, Müller J, et al. Global gene expression profiling of progesterone receptor modulators in T47D cells provides a new classification system. J Steroid Biochem Mol Biol. 2009;113(1–2):105–115.
   PubMed Web of Science ®Google Scholar
• Lewis JH, Cottu PH, Lehr M, et al. Onapristone extended release: safety evaluation from phase I-II studies with an emphasis on hepatotoxicity. Drug Saf. 2020;43(10):1045–1055.
   PubMed Web of Science ®Google Scholar
• Cottu PH, Bonneterre J, Varga A, et al. I study of onapristone, a type I antiprogestin, in female patients with previously treated recurrent or metastatic progesterone receptor-expressing cancers. PLoS One. 2018;13(10):e0204973.
   PubMed Web of Science ®Google Scholar
• Islam MS, Afrin S, Jones SI, et al. Selective progesterone receptor modulators-mechanisms and therapeutic utility. Endocr Rev. 2020;41(5):bnaa012.
   PubMed Web of Science ®Google Scholar