The role of estrogens and estrogen receptors in normal prostate growth and disease
Tóm tắt
Từ khóa
Tài liệu tham khảo
Matzkin, 1992, Immunohistochemical evidence of the existence and localization of aromatase in human prostatic tissues, Prostate, 21, 309, 10.1002/pros.2990210407
Risbridger, 2003, Estrogens and prostate cancer, Endocr Relat Cancer, 10, 187, 10.1677/erc.0.0100187
Zondek, 1986, Hormone levels in the fetal and neonatal prostate, Acta Endocr, 112, 447, 10.1530/acta.0.1120447
Wernet, 1990, Morphological and immunohistochemical investigations of the utriculus prostaticus from the fetal period up to adulthood, Prostate, 17, 19, 10.1002/pros.2990170104
Rajfer, 1978, Sex steroid imprinting of the immature prostate, Invest Urol, 16, 186
Henderson, 1988, The early in utero oestrogen and testosterone environment of blacks and whites: potential effects on male offspring, Br J Cancer, 57, 216, 10.1038/bjc.1988.46
Platz, 2004, The epidemiology of sex steroid hormones and their signaling and metabolic pathways in the etiology of prostate cancer, J Steroid Biochem Mol Biol, 92, 237, 10.1016/j.jsbmb.2004.10.002
Ekbom, 2000, Duration of gestation and prostate cancer risk in offspring, Cancer Epidemiol Biomarkers Prev, 9, 221
Ekbom, 1996, Perinatal characteristics in relation to incidence of and mortality from prostate cancer, Br Med J, 313, 337, 10.1136/bmj.313.7053.337
Driscoll, 1980, Effects of prenatal maternal estrogen on the male urogenital system, Obstet Gynecol, 56, 537
Yonemura, 1995, Temporal and spatial factors in diethylstilbestrol-induced squamous metaplasia in the developing human prostate. II. Persistent changes after removal of diethylstilbestrol, Acta Anatom, 153, 1, 10.1159/000147709
Giusti, 1995, Diethylstilbestrol revisited: a review of the long-term health effects, Ann Int Med, 122, 778, 10.7326/0003-4819-122-10-199505150-00008
Arai, 1983, Long-term effects of perinatal exposure to sex steroids and diethylstilbestrol on the reproductive system of male mammals, vol. 84, 235
Prins, 1997, Developmental estrogenization of the prostate gland, 247
Prins, 2006, The role of estrogens in normal and abnormal development of the prostate gland, Ann N Y Acad Sci, 1089, 1, 10.1196/annals.1386.009
McLachlan, 2001, Environmental signaling: what embryos and evolution teach us about endocrine disrupting chemicals, Endocr Rev, 22, 319, 10.1210/er.22.3.319
Ho, 2006, Developmental exposure estradiol and bisphenol A (BPA) increases susceptibility to prostate carcinogenesis and epigenetically regulates phosphodisesterase type 4 variant (PDE4D4) in the rat prostate, Cancer Res, 66, 5624, 10.1158/0008-5472.CAN-06-0516
Kaufman, 2005, The decline of androgen levels in elderly men and its clinical and therapeutic implications, Endocrin Rev, 26, 833, 10.1210/er.2004-0013
Ho, 2004, Estrogens and antiestrogens: key mediators of prostate carcinogenesis and new therapeutic candidates, J Cell Biochem, 91, 491, 10.1002/jcb.10759
King, 2006, Effect of increasing ratio of estrogen:androgen on proliferation of normal and human prostate stromal and epithelial cells and the malignant cell line LNCaP, Prostate, 66, 105, 10.1002/pros.20327
Thomas, 1994, Effects of estrogen on the prostate, J Androl, 15, 97, 10.1002/j.1939-4640.1994.tb00409.x
Castagnetta, 1995, Human prostate cancer: a direct role for oestrogens, 269
Price, 1936, Normal development of the prostate and seminal vesicles of the rat with a study of experimental postnatal modifications, Am J Anat, 60, 79, 10.1002/aja.1000600105
Leav, 1988, Biochemical alterations in sex hormone-induced hyperplasia and dysplasia of the dorsolateral prostates of Noble rats, J Natl Cancer Inst, 80, 1045, 10.1093/jnci/80.13.1045
Coffey, 1990, Clinical and experimental studies of benign prostatic hyperplasia, Urol Clin North Am, 17, 461, 10.1016/S0094-0143(21)00960-5
DeKlerk, 1979, Comparison of spontaneous and experimentally induced canine prostatic hyperplasia, J Clin Invest, 64, 842, 10.1172/JCI109532
Krieg, 1981, Stroma of human benign prostatic hyperplasia: preferential tissue for androgen metabolism and oestrogen binding, Acta Endocr, 96, 422, 10.1530/acta.0.0960422
Lee, 1981, Effect of estradiol on the rat prostate in the presence and absence of testosterone and pituitary, J Androl, 2, 293, 10.1002/j.1939-4640.1981.tb00633.x
Gilleran, 2003, The role of prolactin in the prostatic inflammatory response to neonatal estrogen, Endocrinology, 144, 2046, 10.1210/en.2002-0038
Lane, 1997, Suppression of testosterone and estradiol-17beta-induced dysplasia in the dorsolateral prostate of Noble rats by bromocriptine, Carcinogenesis, 18, 1505, 10.1093/carcin/18.8.1505
Huggins, 1941, Studies on prostatic cancer. I. The effect of castration, of estrogen, and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate, Cancer Res, 1, 293
Prins, 1992, Neonatal estrogen exposure induces lobe-specific alterations in adult rat prostate androgen receptor expression, Endocrinology, 130, 3703, 10.1210/en.130.6.3703
Nevalainen, 1993, Hormone regulation of human prostate in organ culture, Cancer Res, 53, 5199
Jarred, 2000, Evidence that estrogens directly alter androgen-regulated prostate development, Endocrinology, 141, 3471, 10.1210/en.141.9.3471
Committee NRN, 1999, A unified nomenclature system for the nuclear receptor superfamily, Cell, 97, 161, 10.1016/S0092-8674(00)80726-6
Walter, 1985, Cloning of the human estrogen receptor cDNA, Proc Natl Acad Sci USA, 82, 7889, 10.1073/pnas.82.23.7889
Laudet, 2002
White, 1987, Structural organization and expression of the mouse estrogen receptor, Mol Endocrinol, 1, 735, 10.1210/mend-1-10-735
Miksicek, 1994, Steroid receptor variants and their potential role in cancer, Sem Cancer Biol, 5, 369
Kuiper, 1996, Cloning of a novel estrogen receptor expressed in rat prostate and ovary, Proc Natl Acac Sci USA, 93, 5925, 10.1073/pnas.93.12.5925
Mosselman, 1996, ER B: identification and characterization of a novel human estrogen receptor, FEBS, 392, 49, 10.1016/0014-5793(96)00782-X
Leung, 2006, Estrogen receptor (ER)-beta isoforms: a key to understanding ER-beta signaling, Proc Natl Acad Sci USA, 103, 13162, 10.1073/pnas.0605676103
Mangelsdorf, 1995, The nuclear receptor superfamily: the second decade, Cell, 83, 835, 10.1016/0092-8674(95)90199-X
Aranda, 2001, Nuclear hormone receptors and gene expression, Physiol Rev, 81, 1269, 10.1152/physrev.2001.81.3.1269
Ueda, 2002, Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways, J Biol Chem, 277, 7076, 10.1074/jbc.M108255200
Katzenellenbogen, 2000, Estrogen receptors: selective ligands, partners, and distinctive pharmacology, Recent Prog Horm Res, 55, 163
Delaunay, 2000, Functional differences between the amino-terminal domains of estrogen receptors alpha and beta, Mol Pharmacol, 58, 584, 10.1124/mol.58.3.584
Watanabe, 1997, Agonist effect of tamoxifen is dependent on cell type, ERE-promoter context, and estrogen receptor subtype: functional difference between estrogen receptors α and β, Biochem Biophys Res Commun, 236, 140, 10.1006/bbrc.1997.6915
Cowley, 1999, A comparison of transcriptional activation by ER alpha and ER beta, J Steroid Biochem Mol Biol, 69, 165, 10.1016/S0960-0760(99)00055-2
Kuiper, 1997, The novel estrogen receptor-b subtype: potential role in the cell- and promoter-specific actions of estrogens and anti-estrogens, FEBS Lett, 410, 87, 10.1016/S0014-5793(97)00413-4
Kim, 2003, Domains of estrogen receptor alpha (ERalpha) required for ERalpha/Sp1-mediated activation of GC-rich promoters by estrogens and antiestrogens in breast cancer cells, Mol Endocrinol, 17, 804, 10.1210/me.2002-0406
Shiau, 2002, Structural characterization of a subtype-selective ligand reveals a novel mode of estrogen receptor antagonism, Nat Struct Biol, 9
Stoica, 1999, Regulation of estrogen receptor-alpha gene expression by 1,25-dihydroxyvitamin D in MCF-7 cells, J Cell Biochem, 75, 640, 10.1002/(SICI)1097-4644(19991215)75:4<640::AID-JCB10>3.0.CO;2-8
Kuiper, 1997, Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors α and B, Endocrinology, 138, 863, 10.1210/en.138.3.863
Kuiper, 1998, Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor β, Endocrinology, 139, 4252, 10.1210/en.139.10.4252
Harris, 2002, The ligand binding profiles of estrogen receptors alpha and beta are species dependent, Steroids, 67, 379, 10.1016/S0039-128X(01)00194-5
Harris, 2002, Characterization of the biological roles of the estrogen receptors, ERalpha and ERbeta, in estrogen target tissues in vivo through the use of an ERalpha-selective ligand, Endocrinology, 143, 4172, 10.1210/en.2002-220403
Montano, 1995, The carboxy-terminal F domain of the human estrogen receptor: role in the transcriptional activity of the receptor and the effectiveness of antiestrogens as estrogen antagonists, Mol Endocrinol, 9, 814, 10.1210/me.9.7.814
Koide, 2007, Identification of Regions within the F domain of the human estrogen receptor {alpha} that are important for modulating transactivation and protein–protein interactions, Mol Endocrinol, 21, 829, 10.1210/me.2006-0203
Gougeleta, 2007, Oestrogen receptors pathways to oestrogen responsive elements: The transactivation function-1 acts as the keystone of oestrogen receptor (ER)alpha-mediated transcriptional repression of ERalpha, J Steroid Biochem Mol Biol, 104, 110, 10.1016/j.jsbmb.2007.03.002
Ignar-Trowbridge, 1992, Coupling of dual signaling pathways: epidermal growth factor action involves the estrogen receptor, Proc Natl Acad Sci USA, 89, 4658, 10.1073/pnas.89.10.4658
Coleman, 2001, Intracellular signaling pathways: nongenomic actions of estrogens and ligand-independent activation of estrogen receptors, Front Biosci, 6, D1379, 10.2741/Coleman
Klotz, 2002, Requirement of estrogen receptor-alpha in insulin-like growth factor-1 (IGF-1)-induced uterine responses and in vivo evidence for IGF-1/estrogen receptor cross-talk, J Biol Chem, 277, 8531, 10.1074/jbc.M109592200
Klotz, 2000, Activation of a uterine insulin-like growth factor I signaling pathway by clinical and environmental estrogens: requirement of estrogen receptor-alpha, Endocrinology, 141, 3430, 10.1210/en.141.9.3430
Safe, 2004, Nuclear receptor-mediated transactivation through interaction with Sp proteins, Prog Nucleic Acid Res Mol Biol, 77, 1, 10.1016/S0079-6603(04)77001-4
Kushner, 2000, Estrogen receptor pathways to AP-1, J Steroid Biochem Mol Biol, 74, 311, 10.1016/S0960-0760(00)00108-4
Schulze, 1990, Histological localization of estrogen receptors in normal and diseased human prostates by immunocytochemistry, Prostate, 16, 331, 10.1002/pros.2990160408
Schulze, 1987, Immunocytochemical localization of estrogen receptors in the normal male and female canine urinary tract and prostate, Endocrinology, 121, 1773, 10.1210/endo-121-5-1773
Brenner, 1990, Estrogen and progestin receptors in the reproductive tract of male and female primates, Biol Reprod, 42, 11, 10.1095/biolreprod42.1.11
Prins, 1997, Neonatal estrogen exposure up-regulates estrogen receptor expression in the developing and adult rat prostate lobes, Endocrinology, 138, 1801, 10.1210/en.138.5.1801
Tsurusaki, 2003, Zone-dependent expression of estrogen receptors alpha and beta in human benign prostatic hyperplasia, J Clin Endocr Metab, 88, 1333, 10.1210/jc.2002-021015
Tilley, 1989, Effect of pubertal development on estrogen receptor levels and stromal morphology in the guinea pig prostate, Prostate, 15, 195, 10.1002/pros.2990150213
Adams, 2002, Expression of estrogen receptor beta in the fetal, neonatal, and prepubertal human prostate, Prostate, 52, 69, 10.1002/pros.10103
Kruithof-Dekker, 1996, Elevated estrogen receptor expression in human prostatic stromal cells by androgen ablation therapy, J Urol, 156, 1194, 10.1016/S0022-5347(01)65749-5
Tilley, 1987, Effects of ageing and hormonal manipulations on the level of oestrogen receptors in the guinea-pig prostate, J Endocr, 112, 139, 10.1677/joe.0.1120139
Shapiro, 2005, Immunolocalization of estrogen receptor alpha and beta in human fetal prostate, J Urol, 174, 2051, 10.1097/01.ju.0000176472.90432.5b
Kozak, 1982, Nuclei of stroma: site of highest estrogen concentration in human benign prostatic hyperplasia, Prostate, 3, 433, 10.1002/pros.2990030503
Risbridger, 2001, Evidence that epithelial and mesenchymal estrogen receptor-α mediates effects of estrogen on prostatic epithelium, Develop Biol, 229, 432, 10.1006/dbio.2000.9994
Prins, 2001, Estrogen imprinting of the developing prostate gland in mediated through stromal estrogen receptor α: studies with αERKO and βERKO mice, Cancer Res, 61, 6089
Eddy, 1996, Targeted disruption of the estrogen receptor gene in male mice causes alteration of spermatogenesis and infertility, Endocrinology, 137, 4796, 10.1210/en.137.11.4796
Donaldson, 1996, Morphometric study of the gubernaculum in male estrogen receptor mutant mice, J Androl, 17, 91, 10.1002/j.1939-4640.1996.tb01756.x
Li, 2000, Frequent methylation of estrogen receptor in prostate cancer: correlation with tumor progression, Cancer Res, 60, 702
Lau, 2000, Expression of estrogen receptor (ER)-α and ER-β in normal and malignant prostatic epithelial cells: regulation by methylation and involvement in growth regulation, Cancer Res, 60, 3175
Bonkhoff, 1999, Estrogen receptor in prostate cancer and premalignant lesions, Am J Pathol, 155, 641, 10.1016/S0002-9440(10)65160-7
Leav, 2001, Comparative studies of the estrogen receptors beta and alpha and the androgen receptor in normal human prostate gland, dysplasia, and in primary and metastatic carcinoma, Am J Pathol, 1, 79, 10.1016/S0002-9440(10)61676-8
Hernandez, 2006, Association between estrogen receptor alpha gene polymorphism and risk of prostate cancer in black men, J Urol, 175, 523, 10.1016/S0022-5347(05)00240-5
Tanaka, 2003, Polymorphisms of estrogen receptor alpha in prostate cancer, Mol Carcinogen, 37, 202, 10.1002/mc.10138
Enmark, 1997, Human estrogen receptor β—gene structure, chromosomal localization, and expression pattern, JCEM, 82, 42584265
Prins, 1998, Estrogen receptor-β messenger ribonucleic acid ontogeny in the prostate of normal and neonatally estrogenized rats, Endocrinology, 139, 874, 10.1210/en.139.3.874
Makela, 2000, Differential expression of estrogen receptors alpha and beta in adult rat accessory sex glands and lower urinary tract, Mol Cell Endocrinol, 164, 109, 10.1016/S0303-7207(00)00233-1
Chang, 1999, Estrogen receptor-β: implications for the prostate gland, Prostate, 40, 115, 10.1002/(SICI)1097-0045(19990701)40:2<115::AID-PROS7>3.0.CO;2-3
Asano, 2003, Regulation of estrogen receptor alpha and beta expression by testosterone in the rat prostate gland, Endocr J, 50, 281, 10.1507/endocrj.50.281
Fixemer, 2003, Differential expression of estrogen receptor beta in human prostate tissue, premalignant changes and in primary, metastatic and recurrent prostatic adenocarcinoma, Prostate, 54, 79, 10.1002/pros.10171
Fujimura, 2001, Differential expression of estrogen receptor beta (ERbeta) and its C-terminal truncated splice variant ERbetacx as prognostic predictors in human prostatic cancer, Biochem Biophys Res Commun, 289, 692, 10.1006/bbrc.2001.6038
Hanstein, 1999, Functional analysis of a novel estrogen receptor beta isoform, Mol Endocrinol, 13, 129, 10.1210/me.13.1.129
Maruyama, 1998, A novel isoform of rat estrogen receptor beta with 18 amino acid insertion in the ligand binding domain as a putative dominant negative regular of estrogen action, Biochem Biophys Res Commun, 246, 142, 10.1006/bbrc.1998.8590
Petersen, 1998, Identification of estrogen receptor beta 2: a functional variant of estrogen receptor beta expressed in normal rat tissues, Endocrinology, 139, 1082, 10.1210/en.139.3.1082
Imamov, 2004, Estrogen receptor beta regulates epithelial cellular differentiation in the mouse ventral prostate, Proc Natl Acad Sci USA, 101, 9375, 10.1073/pnas.0403041101
Weihua, 2001, A role for estrogen receptor beta in the regulation of growth of the ventral prostate, Proc Natl Acad Sci USA, 98, 6330, 10.1073/pnas.111150898
Weihua, 2002, Estrogen receptor beta in the prostate, Mol Cell Biol, 193, 1
Couse, 2000, Receptor null mice reveal contrasting roles for estrogen receptor alpha and beta in reproductive tissues, J Steroid Biochem Mol Biol, 74, 287, 10.1016/S0960-0760(00)00105-9
Dupont, 2000, Effect of single and compound knockouts of estrogen receptors alpha (ERalpha) and beta (ERbeta) on mouse reproductive phenotypes, Development, 127, 4277, 10.1242/dev.127.19.4277
McPherson, 2007, Essential role for estrogen receptor beta in stromal-epithelial regulation of prostatic hyperplasia, Endocrinology, 148, 566, 10.1210/en.2006-0906
McMurray, 2001, Estrogen, prolactin, and autoimmunity: actions and interactions, Int Immunopharm, 1, 995, 10.1016/S1567-5769(01)00045-5
Yellayi, 2000, Normal development of thymus in male and female mice requires estrogen/estrogen receptor-alpha signaling pathway, Endocrine, 12, 207, 10.1385/ENDO:12:3:207
Harris, 2003, Evaluation of an estrogen receptor-beta agonist in animal models of human disease, Endocrinology, 144, 4241, 10.1210/en.2003-0550
DeMarzo, 1999, Proliferative inflammatory atrophy of the prostate implications for prostatic carcinogenesis, Am J Pathol, 155, 1985, 10.1016/S0002-9440(10)65517-4
Montano, 1998, Transcriptional regulation of the human quinone reductase gene by antiestrogen-liganded estrogen receptor-α and estrogen receptor-β, Fertil Steril, 273, 25443
Nelson, 2002, The diet, prostate inflammation, and the development of prostate cancer, Cancer Metast Rev, 21, 3, 10.1023/A:1020110718701
Pasquali, 2001, Loss of estrogen receptor beta expression in malignant human prostate cells in primary cultures and in prostate cancer tissues, J Clin Endocr Metab, 86, 2051, 10.1210/jc.86.5.2051
Horvath, 2001, Frequent loss of estrogen receptor-beta expression in prostate cancer, Cancer Res, 61, 5331
Zhu, 2004, Dynamic regulation of estrogen receptor-beta expression by DNA methylation during prostate cancer development and metastasis, Am J Pathol, 164, 1883, 10.1016/S0002-9440(10)63760-1
Zhang, 2007, AP-2 regulates the transcription of estrogen receptor (ER)-beta by acting through a methylation hotspot of the 0N promoter in prostate cancer cells, Oncogene, 26, 7246, 10.1038/sj.onc.1210537
Cheng, 2004, Expression of estrogen receptor beta in prostate carcinoma cells inhibits invasion and proliferation and triggers apoptosis, FEBS Lett, 566, 169, 10.1016/j.febslet.2004.04.025
Lai, 2004, Metastases of prostate cancer express estrogen receptor-beta, Urology, 64, 814, 10.1016/j.urology.2004.05.036
Wilson, 1980, The pathogenesis of benign prostatic hyperplasia, Am J Med, 68, 745, 10.1016/0002-9343(80)90267-3
Guerini, 2005, The androgen derivative 5alpha-androstane-3beta,17beta-diol inhibits prostate cancer cell migration through activation of the estrogen receptor beta subtype, Cancer Res, 65, 5445, 10.1158/0008-5472.CAN-04-1941
Garcia, 2006, 2-Methoxyestradiol inhibits prostate tumor development in transgenic adenocarcinoma of mouse prostate: role of tumor necrosis factor-alpha-stimulated gene 6, Clin Cancer Res, 12, 980, 10.1158/1078-0432.CCR-05-2068
Schulz, 1988, Evaluation of the cytotoxic activity of diethylstilbestrol and its mono- and diphosphate towards prostatic carcinoma cells, Cancer Res, 48, 2867
Kim, 2002, Raloxifene, a mixed estrogen agonist/antagonist, induces apoptosis in androgen-independent human prostate cancer cell lines, Cancer Res, 62, 5365
Neubauer, 2003, The selective estrogen receptor modulator trioxifene (LY133314) inhibits metastasis and extends survival in the PAIII rat prostatic carcinoma model, Cancer Res, 63, 6056
Corey, 2002, Inhibition of androgen-independent growth of prostate cancer xenografts by 17beta-estradiol, Clin Cancer Res, 8, 1003
Raghow, 2002, Toremifene prevents prostate cancer in the transgenic adenocarcinoma of mouse prostate model, Cancer Res, 62, 1370
Bergan, 1999, A Phase II study of high-dose tamoxifen in patients with hormone-refractory prostate cancer, Clin Cancer Res, 5, 2366
Stein, 2001, Phase II trial of toremifene in androgen-independent prostate cancer: a Penn cancer clinical trials group trial, Am J Clin Oncol, 24, 283, 10.1097/00000421-200106000-00015
Steiner, 2003, Phase IIA clinical trials to test the efficacy and safety of Toremifene in men with high-grade prostatic intraepithelial neoplasia, Clin Prostate Cancer, 2, 32, 10.3816/CGC.2003.n.009
Ellem, 2006, Aromatase and prostate cancer, Minerva Endocrinol, 31, 1
Narashimamurthy, 2004, Aromatase inhibitors: a new paradigm in breast cancer treatment, Curr Med Chem Anticancer Agents, 4, 523, 10.2174/1568011043352669
Ellem, 2004, Local aromatase expression in human prostate is altered in malignancy, J Clin Endocrinol Metab, 89, 2431, 10.1210/jc.2003-030933
Smith, 2002, Selective aromatase inhibition for patients with androgen-independent prostate carcinoma, Cancer, 95, 1864, 10.1002/cncr.10844
Santen, 2001, Use of the aromatase inhibitor anastrozole in the treatment of patients with advanced prostate carcinoma, Cancer, 92, 2095, 10.1002/1097-0142(20011015)92:8<2095::AID-CNCR1550>3.0.CO;2-Y
Wang, 2002, Dietary genistein suppresses chemically induced prostate cancer in Lobund-Wistar rats, Cancer Lett, 186
Mentor-Marcel, 2005, Dietary genistein improves survival and reduces expression of osteopontin in the prostate of transgenic mice with prostatic adenocarcinoma (TRAMP), J Nutr, 135, 989, 10.1093/jn/135.5.989
Jones, 2005, Resveratrol-induced gene expression profiles in human prostate cancer cells, Cancer Epidemiol Biomarkers Prev, 14, 596, 10.1158/1055-9965.EPI-04-0398
Lee, 2003, Soy and isoflavone consumption in relation to prostate cancer risk in China, Cancer Epidemiol Biomarkers Prev, 12, 665
Ozasa, 2004, Serum phytoestrogens and prostate cancer risk in a nested case–control study among Japanese men, Cancer Sci, 95, 65, 10.1111/j.1349-7006.2004.tb03172.x
Manson, 2005, Innovative agents in cancer prevention, Rec Results Cancer Res, 166, 257, 10.1007/3-540-26980-0_17