Cytochrome P450-mediated metabolism of estrogens and its regulation in human
Abstract
Estrogens are eliminated from the body by metabolic conversion to estrogenically inactive metabolites that are excreted in the urine and/or feces. The first step in the metabolism of estrogens is the hydroxylation catalyzed by cytochrome P450 (CYP) enzymes. Since most CYP isoforms are abundantly expressed in liver, the metabolism of estrogens mainly occurs in the liver. A major metabolite of estradiol, 2-hydroxyestradiol, is mainly catalyzed by CYP1A2 and CYP3A4 in liver, and by CYP1A1 in extrahepatic tissues. However, CYP1B1 which is highly expressed in estrogen target tissues including mammary, ovary, and uterus, specifically catalyzes the 4-hydroxylation of estradiol. Since 4-hydroxyestradiol generates free radicals from the reductive-oxidative cycling with the corresponding semiquinone and quinone forms, which cause cellular damage, the specific and local formation of 4-hydroxyestradiol is important for breast and endometrial carcinogenesis. Changes in the expression level of estrogen-metabolizing CYP isoforms not only alter the intensity of the action of estrogen but may also alter the profile of its physiological effect in liver and target tissues. Generally, many CYP isoforms are induced by the substrates themselves, resulting in enhanced metabolism and elimination from the body. Of particular interest is a novel finding that human CYP1B1 is regulated by estradiol via the estrogen receptor. This fact suggests that the regulation of CYP enzymes involved in estrogen metabolism by estrogen itself would be physiologically significant for the homeostasis of estrogens at local organs. In this mini-review, we discuss the CYP-mediated metabolism of estrogens and the regulation of the estrogen-metabolizing CYP enzymes in relation to the risk of cancer.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the liver approximately 80% of 17β-estradiol is hydroxylated to the 2 position and 20% at the 4 position.
“In the liver approximately 80% of 17β-estradiol is hydroxylated to the 2 position and 20% at the 4 position [322].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [322]
Cites
1 retracted
Sasaki, M., Tanaka, Y., Kaneuchi, M., et al. (2003) · PubMed · Cited by 79 · see citing works
RetractedThe Steroid and Thyroid Hormone Receptor Superfamily
Evans, R. M. (1988) · Science · doi:10.1126/science.3283939 · Cited by 7,442 · see citing works
P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature
Nelson, D. R., Koymans, L. M. H., Kamataki, T., Stegeman, J. J., Feyereisen, R., Waxman, D. J., Waterman, M. R., Gotoh, O., Coon, M. J., Estabrook, R. W., et al. (1996) · Pharmacogenetics · doi:10.1097/00008571-199602000-00002 · Cited by 2,946 · see citing works
Poland, A., & Knutson, J. C. (1982) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.22.040182.002505 · Cited by 2,515 · see citing works
Kuehl, P. M., Zhang, J., Lin, Y., Lamba, J. K., Assem, M., Schuetz, J. D., Watkins, P. B., Daly, A. K., Wrighton, S. A., Hall, S. D., et al. (2001) · Nature Genetics · doi:10.1038/86882 · Cited by 2,162 · see citing works
The Aryl Hydrocarbon Receptor Complex
Hankinson, O. (1995) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.35.040195.001515 · Cited by 1,649 · see citing works
Functional domains of the human estrogen receptor
Kumar, V., Green, S., Stack, G., Berry, M., Jin, J.-R., & Chambon, P. (1987) · Cell · doi:10.1016/0092-8674(87)90581-2 · Cited by 1,316 · see citing works
INDUCTION OF CYTOCHROME P4501A1
Whitlock, J. P. (1999) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.39.1.103 · Cited by 1,126 · see citing works
Estrogens, Progestogens, Normal Breast Cell Proliferation, and Breast Cancer Risk
Pike, M. C., SPICER, D. V., Dahmoush, L., & Press, M. F. (1993) · Epidemiologic Reviews · doi:10.1093/oxfordjournals.epirev.a036102 · Cited by 1,009 · see citing works
Functional role of estrogen metabolism in target cells: review and perspectives
Zhu, B. T. (1998) · Carcinogenesis · doi:10.1093/carcin/19.1.1 · Cited by 964 · see citing works
Source of Estrogen Production in Postmenopausal Women1
GRODIN, J. M., SIITERI, P. K., & MACDONALD, P. C. (1973) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-36-2-207 · Cited by 959 · see citing works
AH RECEPTOR SIGNALING PATHWAYS
Schmidt, J. V., & Bradfield, C. A. (1996) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.12.1.55 · Cited by 899 · see citing works
Activation of chemically diverse procarcinogens by human cytochrome P-450 1B1.
Shimada, T., Hayes, C. L., Yamazaki, H., et al. (1996) · PubMed · Cited by 793 · see citing works
Fotsis, T., Zhang, Y., Pepper, M. S., Adlercreutz, H., Montesano, R., Nawroth, P. P., & Schweigerer, L. (1994) · Nature · doi:10.1038/368237a0 · Cited by 736 · see citing works
Safe, S. H. (1986) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.26.040186.002103 · Cited by 710 · see citing works
The Repressed Nuclear Receptor CAR Responds to Phenobarbital in Activating the Human CYP2B6 Gene
Sueyoshi, T., Kawamoto, T., Zelko, I. N., Honkakoski, P., & Negishi, M. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.10.6043 · Cited by 659 · see citing works
17 beta-estradiol hydroxylation catalyzed by human cytochrome P450 1B1.
Hayes, C. L., Spink, D. C., Spink, B. C., Cao, J. Q., Walker, N. J., & Sutter, T. R. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.18.9776 · Cited by 631 · see citing works
Adipose tissue as a source of hormones
Siiteri, P. K. (1987) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/45.1.277 · Cited by 600 · see citing works
Tumor-specific expression of cytochrome P450 CYP1B1.
Murray, G. I., Taylor, M. C., McFadyen, M. C. E., McKay, J., Greenlee, W. F., Burke, M. D., & Melvin, W. T. (1997) · PubMed · Cited by 532 · see citing works
Sex Is A Major Determinant of Cyp3a4 Expression in Human Liver
Wolbold, R., Klein, K., Burk, O., Nussler, A. K., Neuhaus, P., Eichelbaum, M. F., Schwab, M. G., & Zanger, U. M. (2003) · Hepatology · doi:10.1002/hep.1840380424 · Cited by 527 · see citing works
Klauber, N., Parangi, S., Flynn, E. A., Hamel, E., & D’Amato, R. J. (1997) · PubMed · Cited by 524 · see citing works
Characterization of 21 newly established esophageal cancer cell lines
Shimada, Y., Imamura, M., Wagata, T., Yamaguchi, N., & Tobe, T. (1992) · Cancer · doi:10.1002/1097-0142(19920115)69:2 · Cited by 494 · see citing works
Is Estradiol a Genotoxic Mutagenic Carcinogen?1
Liehr, J. G. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.1.0386 · Cited by 486 · see citing works
Lee, A. J., Cai, M. X., Thomas, P. E., Conney, A. H., & Zhu, B. T. (2003) · Endocrinology · doi:10.1210/en.2003-0192 · Cited by 457 · see citing works
Selective Estrogen Receptor Modulators
Frasor, J., Stossi, F., Danes, J. M., Komm, B., Lyttle, C., & Katzenellenbogen, B. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3326 · Cited by 447 · see citing works
MacDonald, P. C., Edman, C. D., Hemsell, D. L., Porter, J. C., & Siiteri, P. K. (1978) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(78)90287-9 · Cited by 440 · see citing works
Hormones and mammary carcinogenesis in mice, rats, and humans: a unifying hypothesis.
Nandi, S., Guzman, R. C., & Yang, J. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.9.3650 · Cited by 424 · see citing works
4-Hydroxylation of estrogens as marker of human mammary tumors.
Liehr, J. G., & Ricci, M. J. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.8.3294 · Cited by 417 · see citing works
Feigelson, H., & Henderson, B. (1996) · Carcinogenesis · doi:10.1093/carcin/17.11.2279 · Cited by 416 · see citing works
Santner, S. J., Feil, P. D., & Santen, R. J. (1984) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-59-1-29 · Cited by 407 · see citing works
P450 enzymes of estrogen metabolism
Martucci, C. P., & Fishman, J. (1993) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(93)90057-k · Cited by 396 · see citing works
Toward the Primary Prevention of Cancer
Henderson, B. E., Ross, R. K., & Pike, M. C. (1991) · Science · doi:10.1126/science.1957166 · Cited by 356 · see citing works
Pascussi, J., Gerbal‐Chaloin, S., Drocourt, L., Maurel, P., & Vilarem, M. (2003) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/s0304-4165(02)00483-x · Cited by 330 · see citing works
Regulation ofCYP3AGene Transcription by the Pregnane X Receptor
Goodwin, B. J., Redinbo, M. R., & Kliewer, S. A. (2002) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.42.111901.111051 · Cited by 328 · see citing works
Hanna, I. H., Dawling, S., Roodi, N., et al. (2000) · PubMed · Cited by 313 · see citing works
Induction of uterine adenocarcinoma in CD-1 mice by catechol estrogens.
Newbold, R. R., & Liehr, J. G. (2000) · PubMed · Cited by 293 · see citing works
Abnormal oxidative metabolism of estradiol in women with breast cancer.
Schneider, J., Kinne, D. W., Fracchia, A. A., Pierce, V. K., Anderson, K. E., Bradlow, H. L., & Fishman, J. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.9.3047 · Cited by 254 · see citing works
Human CYP1B1 Is Regulated by Estradiol via Estrogen Receptor
Tsuchiya, Y., Nakajima, M., Kyo, S., Kanaya, T., Inoue, M., & Yokoi, T. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-0166 · Cited by 249 · see citing works
Self-citationOxidation of 17 alpha-ethynylestradiol by human liver cytochrome P-450.
Guengerich, F. P. (1988) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)13356-7 · Cited by 236 · see citing works
Is Estradiol a Genotoxic Mutagenic Carcinogen?
Liehr, J. G. (2000) · Endocrine Reviews · doi:10.1210/er.21.1.40 · Cited by 235 · see citing works
Bailey, L. R., Roodi, N., Dupont, W. D., & Parl, F. F. (1998) · PubMed · Cited by 220 · see citing works
Kharat, I., & Saatcioglu, F. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.18.10533 · Cited by 216 · see citing works
Liehr, J. G., Ricci, M. J., Jefcoate, C. R., et al. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9220 · Cited by 210 · see citing works
Hakkola, J. (1997) · Carcinogenesis · doi:10.1093/carcin/18.2.391 · Cited by 207 · see citing works
Ambrosone, C. B., Freudenheim, J. L., Graham, S., et al. (1995) · PubMed · Cited by 201 · see citing works
Taioli, E., Trachman, J. D., Chen, X., Toniolo, P. G., & GARTE, S. J. (1995) · PubMed · Cited by 180 · see citing works
Miki, Y., Nakata, T., Suzuki, T., Darnel, A. D., Moriya, T., Kaneko, C., Hidaka, K., Shiotsu, Y., Kusaka, H., & Sasano, H. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-020670 · Cited by 171 · see citing works
Ball, P., & Knüppen, R. (1980) · PubMed · Cited by 158 · see citing works
Goodman, M. T., McDuffie, K., Kolonel, L. N., Terada, K. Y., Donlon, T. A., Wilkens, L. R., Guo, C., & Marchand, L. L. (2001) · PubMed · Cited by 157 · see citing works
Ritter, J. K., Sheen, Y. Y., & Owens, I. S. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39016-7 · Cited by 155 · see citing works
Estrogen Stimulates Transcription of c-junProtooncogene
Weisz, A., Cicatiello, L., Persico, E., et al. (1990) · Molecular Endocrinology · doi:10.1210/mend-4-7-1041 · Cited by 149 · see citing works
Seegers, J. C., Aveling, M.-L., van Aswegen, C. H., et al. (1989) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(89)90455-x · Cited by 145 · see citing works
Spurdle, A. B., Goodwin, B. J., Hodgson, E., et al. (2002) · Pharmacogenetics · doi:10.1097/00008571-200207000-00003 · Cited by 134 · see citing works
Estradiol Metabolism by Complementary Deoxyribonucleic Acid-Expressed Human Cytochrome P450s
Aoyama, T., Korzekwa, K. R., Nagata, K., Gillette, J. R., Gelboin, H. V., & Gonzalez, F. J. (1990) · Endocrinology · doi:10.1210/endo-126-6-3101 · Cited by 130 · see citing works
Role of human hepatic cytochrome P450 1A2 and 3A4 in the metabolic activation of estrone
Shou, M. (1997) · Carcinogenesis · doi:10.1093/carcin/18.1.207 · Cited by 121 · see citing works
Nutter, L. M., Wu, Y. Y., Ngo, E. O., et al. (1994) · Chemical Research in Toxicology · doi:10.1021/tx00037a004 · Cited by 120 · see citing works
Longuemaux, S., Deloménie, C., Gallou, C., et al. (1999) · PubMed · Cited by 118 · see citing works
Wormke, M., Stoner, M. A., Saville, B., & Safe, S. H. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01830-5 · Cited by 118 · see citing works
Molecular epidemiology of breast cancer: genetic variation in steroid hormone metabolism
Kristensen, V. N., & Børresen‐Dale, A. (2000) · Mutation Research/Reviews in Mutation Research · doi:10.1016/s1383-5742(00)00018-1 · Cited by 116 · see citing works
Characterization of DNA damage induced by 3,4-estrone-o-quinone in human cells.
Nutter, L. M., Ngo, E. O., & Abul‐Hajj, Y. J. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)55309-6 · Cited by 100 · see citing works
Blanco, J. G., Edick, M. J., Hancock, M. L., Winick, N. J., Dervieux, T., Amylon, M. D., Bash, R. O., Behm, F. G., Camitta, B. M., Pui, C., et al. (2002) · Pharmacogenetics · doi:10.1097/00008571-200211000-00004 · Cited by 100 · see citing works
Organization and function of a dioxin-responsive enhancer.
Fisher, J. M., Wu, L., Denison, M. S., & Whitlock, J. P. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)38723-x · Cited by 97 · see citing works
Li, J. J., Li, S. A., Oberley, T. D., et al. (1995) · PubMed · Cited by 95 · see citing works
Formation of 2- and 4-Hydroxyestrogens by Brain, Pituitary, and Liver of the Human Fetus*
Ball, P., & Knüppen, R. (1978) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-47-4-732 · Cited by 94 · see citing works
Lee, A. J., Kosh, J. W., Conney, A. H., & Zhu, B. T. (2001) · PubMed · Cited by 92 · see citing works
Adlercreutz, H., Fotsis, T., Höckerstedt, K. A. V., Hämäläinen, E. K., Bannwart, C., Bloigu, S., Valtonen, A., & Ollus, A. (1989) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(89)90138-6 · Cited by 90 · see citing works
The human cytochrome Cyp1A2 gene contains regulatory elements responsive to 3-methylcholanthrene.
Quattrochi, L. C., & Tukey, R. H. (1989) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)09111-4 · Cited by 89 · see citing works
Kocabaş, N. A., Şardaş, S., Cholerton, S., et al. (2002) · Archives of Toxicology · doi:10.1007/s00204-002-0387-x · Cited by 88 · see citing works
Murayama, N., Soyama, A., Saito, Y., Nakajima, Y., Komamura, K., Ueno, K., Kamakura, S., Kitakaze, M., Kimura, H., Goto, Y., et al. (2004) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.055798 · Cited by 86 · see citing works
Critical Enhancer Region to Which AhR/ARNT and Sp1 Bind in the Human CYP1B1 Gene
Tsuchiya, Y. (2003) · The Journal of Biochemistry · doi:10.1093/jb/mvg075 · Cited by 77 · see citing works
Self-citationHernández, J., Watson, R. W. G., Wood, T. C., & Weinshilboum, R. M. (1992) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(25)08603-9 · Cited by 77 · see citing works
Goodman, M. T., McDuffie, K., Hernandez, B. Y., et al. (2001) · Gynecologic Oncology · doi:10.1006/gyno.2001.6154 · Cited by 74 · see citing works
Murata, M., Shiraishi, T., Fukutome, K., et al. (1998) · Japanese Journal of Clinical Oncology · doi:10.1093/jjco/28.11.657 · Cited by 74 · see citing works
Tayeb, M. T., Clark, C., Haites, N. E., Sharp, L., Murray, G. I., & McLeod, H. L. (2003) · British Journal of Cancer · doi:10.1038/sj.bjc.6600825 · Cited by 72 · see citing works
Weisz, J., Bui, Q. D., Roy, D., et al. (1992) · Endocrinology · doi:10.1210/endo.131.2.1386303 · Cited by 66 · see citing works
Identification of a novel splice‐site mutation in the CYP1A2 gene
Allorge, D., Chevalier, D., Lo‐Guidice, J., Cauffiez, C., Suard, F., Baumann, P., Eap, C. B., & Broly, F. (2003) · British Journal of Clinical Pharmacology · doi:10.1046/j.1365-2125.2003.01858.x · Cited by 65 · see citing works
Jacobs, M. N., Dickins, M., & Lewis, D. F. V. (2003) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(03)00021-9 · Cited by 65 · see citing works
CATECHOLOESTROGENS (2-AND 4-HYDROXYOESTROGENS):
Ball, P., & Knüppen, R. (1980) · European Journal of Endocrinology · doi:10.1530/acta.0.0930001-b · Cited by 54 · see citing works
Xenobiotic Responsive Element in the 5′-Upstream Region of the Human P-450c Gene1
Kubota, M., Sogawa, K., Kaizu, Y., et al. (1991) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a123562 · Cited by 53 · see citing works
Chung, I., & Bresnick, E. (1997) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1996.9815 · Cited by 53 · see citing works
White, T. E. K., & Gasiewicz, T. A. (1993) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1993.1718 · Cited by 52 · see citing works
Estrogen Regulation of the Cytochrome P450 3A Subfamily in Humans
Williams, E. T., Leyk, M., Wrighton, S. A., Davies, P. J., Loose, D. S., Shipley, G. L., & Strobel, H. W. (2004) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.104.068908 · Cited by 51 · see citing works
Development of an AntiPeptide Antibody That Binds to the C-Terminal Region of Human CYP1B1
Tang, Y., Chen, G.-F., Thompson, P. A., et al. (1999) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(24)15290-7 · Cited by 49 · see citing works
17-Beta-Hydroxysteroid Dehydrogenase in Human Breast and Endometrial Carcinoma
Sasano, H., Suzuki, T., Takeyama, J., Utsunomiya, H., Ito, K., Ariga, N., & Moriya, T. (2000) · Oncology · doi:10.1159/000055281 · Cited by 46 · see citing works
NADPH-Dependent Metabolism of Estrone by Human Liver Microsomes
Lee, A. J., Mills, L. H., Kosh, J. W., Conney, A. H., & Zhu, B. T. (2002) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.300.3.838 · Cited by 41 · see citing works
Metabolism of exogenous 4- and 2-hydroxyestradiol in the human male
Emons, G., Merriam, G. R., Pfeiffer, D. G., et al. (1987) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(87)90508-5 · Cited by 36 · see citing works
Weisz, J. (1992) · Endocrinology · doi:10.1210/en.131.2.655 · Cited by 33 · see citing works
Takemoto, K., Nakajima, M., Fujiki, Y., Katoh, M., Gonzalez, F. J., & Yokoi, T. (2004) · Archives of Toxicology · doi:10.1007/s00204-004-0550-7 · Cited by 28 · see citing works
Self-citationHudson, C. E. (2001) · Carcinogenesis · doi:10.1093/carcin/22.5.763 · Cited by 20 · see citing works
Antiestrogens: clinical applications of pharmacology
Jordan, V. C. (2000) · Journal of the Society for Gynecologic Investigation · doi:10.1016/s1071-5576(99)00059-3 · Cited by 17 · see citing works
Pickwell, G. V., Shih, H., & Quattrochi, L. C. (2003) · Biochemical Pharmacology · doi:10.1016/s0006-2952(03)00037-6 · Cited by 14 · see citing works
Endometrial Carcinoma in Tamoxifen-Treated Breast Cancer Patient
Esteller, M., García, Á., Martínez-Palones, J. M., et al. (1999) · International Journal of Gynecological Pathology · doi:10.1097/00004347-199910000-00015 · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Schiffer, L., Barnard, L., Baranowski, E. S., Gilligan, L. C., Taylor, A. E., Arlt, W., Shackleton, C. H. L., & Storbeck, K.-H. (2019) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2019.105439 · Cited by 450 · see citing works
“17β-estradiol is hydroxylated to the 2 position and 20% at the 4 position [322].”
Jennen, D. G. J., Magkoufopoulou, C., Ketelslegers, H. B., van Herwijnen, M. H. M., Kleinjans, J. C. S., & van Delft, J. H. M. (2010) · Toxicological Sciences · doi:10.1093/toxsci/kfq026 · Cited by 220 · see citing works
Estrogens in adipose tissue physiology and obesity-related dysfunction
Kuryłowicz, A. (2023) · Biomedicines · doi:10.3390/biomedicines11030690 · Cited by 178 · see citing works
Role of sex steroid receptors in pathobiology of hepatocellular carcinoma
Kalra, M., Mayes, J., Assefa, S., Kaul, A. K., & Kaul, R. (2008) · World Journal of Gastroenterology · doi:10.3748/wjg.14.5945 · Cited by 141 · see citing works
Iqbal, J., Sun, L., Cao, J., Yuen, T., Lu, P., Bab, I., Leu, N. A., Srinivasan, S., Wagage, S., Hunter, C. A., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1220919110 · Cited by 126 · see citing works
The ambiguous aspects of oxygen
Napolitano, G., Fasciolo, G., & Venditti, P. (2022) · Oxygen · doi:10.3390/oxygen2030027 · Cited by 30 · see citing works
- Authors
- Tsuchiya, Y., Nakajima, M., & Yokoi, T.
- Affiliations
- Kanazawa University (JP)
- Corresponding author
- Yokoi, Tsuyoshi
- Venue
- Cancer Letters
- Publisher
- Elsevier BV
- Published
- 2005-09
- Volume
- 227
- Issue
- 2
- Pages
- 115-124
- ISSN
- 0304-3835 (ISSN-L)
- OpenAlex
- W2094879937
- Cited by
- 616
- References
- 92
- Citations by year
- 2026: 22 · 2025: 45 · 2024: 29 · 2023: 30 · 2022: 38 · 2021: 28 · 2020: 27 · 2019: 34 · 2018: 25 · 2017: 31 · 2016: 34 · 2015: 21 · 2014: 41 · 2013: 27 · 2012: 25
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Letters (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
- Keywords
- estrogen metabolism, cytochrome P450, CYP1A2, CYP3A4, CYP1B1, 4-hydroxyestradiol, 2-hydroxyestradiol, enzyme induction, breast cancer, endometrial cancer, free radical generation, semiquinone, estrogen homeostasis
- MeSH terms
- Animals, Cytochrome P-450 Enzyme System, Estrogens, Humans, Neoplasms, Polymorphism, Genetic, Receptors, Estrogen, Gene Expression Regulation, Enzymologic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
