Gonadotropin-Releasing Hormone Agonist Suppression of Ovarian Tumorigenesis in Mice of the Wx/wv Genotype1

Blaakær, Jan; Baeksted, Margit; Micic, S.; Albrectsen, Pernille; Rygaard, Jørgen; Bock, Johannes E.

doi:10.1095/biolreprod53.4.775

Cited by 42 publications

(21 citation statements)

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“…8,12,14,16,17,21 The use of goserelin and bicalutamide was found to be well-tolerated, with the majority of toxicities reported as grade 1 or grade 2. Only 1 patient was discontinued from the study because of toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…16 In animal studies in F1-Wx/Wv mice, which normally uniformly develop bilateral complex tubular adenomas correlated with a 4-fold increase in follicle-stimulating hormone (FSH) and luteinizing hormone (LH), treatment with goserelin versus placebo resulted in the significant suppression of gonadotropins (P 5 .0005) and no tumor development (P 5 .00005). 17 Finally, recent data have shown the importance of the suppression of vascular endothelial growth factor (VEGF) in regulating ovarian cancer growth. 18,19 Moreover, it has been suggested that loss of ovarian function promotes tumorigenesis by resulting in increased gonadotropins, which promote vascularization via increased levels of VEGF.…”

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confidence: 99%

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A phase II evaluation of goserelin and bicalutamide in patients with ovarian cancer in second or higher complete clinical disease remission

Levine

Park

Juretzka

et al. 2007

Cancer

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The mechanism of the gas‐phase elimination kinetics of 2‐ethoxypyridine has been studied through the electronic structure calculations using density functional methods: B3LYP/6‐31G(d,p), B3LYP/6‐31++G(d,p), B3PW91/6‐31G(d,p), B3PW91/6‐31++G(d,p), MPW1PW91/6‐31G(d,p), MPW1PW91/6‐31++G(d,p), PBEPBE/6‐31G(d,p), PBEPBE/6‐31++G(d,p), PBE1PBE1/6‐31G(d,p), and PBE1PBE1/6‐31++G(d,p). The elimination reaction of 2‐ethoxypyridine occurs through a six‐centered transition state geometry involving the pyridine nitrogen, the substituted carbon of the aromatic ring, the ethoxy oxygen, two carbons of the ethoxy group, and a hydrogen atom, which migrates from the ethoxy group to the nitrogen to give 2‐pyridone and ethylene. The reaction mechanism appears to occur with the participation of π‐electrons, similar to alkyl vinyl ether elimination reaction, with simultaneous ethylene formation and hydrogen migration to the pyridine nitrogen producing 2‐pyridone. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2011

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

A phase II evaluation of goserelin and bicalutamide in patients with ovarian cancer in second or higher complete clinical disease remission

Levine

Park

Juretzka

et al. 2007

Cancer

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“…This situation pertains especially to the early post-menopausal years when both gonadotrophin levels and the age-specific incidence of epithelial ovarian cancer are high. In animal models elevated gonadotrophin levels have been associated with tumour development (Biskind & Biskind, 1944) and gonadotrophin suppression by a GnRHagonist in mice that are genetically manipulated to develop ovarian tumours inhibited tumourgenesis (Blaakaer et al, 1995). Human ovarian cancer cell lines were stimulated by gonadotrophins in vitro (Simon et al, 1983).…”

Section: Through the Fallopian Tubesmentioning

confidence: 99%

Hormonal aspects of epithelial ovarian cancer: review of epidemiological evidence

Riman

Persson

Nilsson

1998

Clinical Endocrinology

174

120

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“…Sterile, germ-cell-deficient homozygous Wv mice having !1% of normal number of oocytes at birth develop epithelial morphological changes including surface invaginations, inclusion cysts, and tumors associated with elevated gonadotropin levels similar to aged women (Murphy & Beamer 1973). Interestingly, when the FSH levels in these mice were suppressed by Gonadotropin-releasing hormone agonist (Zoladex, 3.6 mg slow-release goserelin depot injection every 28 days from the age of 7 days up to 245 days), no tumor developed (Blaakaer et al 1995). Furthermore, these mice being sterile never ovulate and thus the concept of incessant ovulation does not explain the origin of ovarian cancer in these mice.…”

Section: Introductionmentioning

confidence: 99%

FSH–FSHR3–stem cells in ovary surface epithelium: basis for adult ovarian biology, failure, aging, and cancer

Bhartiya

Singh

2015

Reproduction

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Despite extensive research, genetic basis of premature ovarian failure (POF) and ovarian cancer still remains elusive. It is indeed paradoxical that scientists searched for mutations in FSH receptor (FSHR) expressed on granulosa cells, whereas more than 90% of cancers arise in ovary surface epithelium (OSE). Two distinct populations of stem cells including very small embryonic-like stem cells (VSELs) and ovarian stem cells (OSCs) exist in OSE, are responsible for neo-oogenesis and primordial follicle assembly in adult life, and are modulated by FSH via its alternatively spliced receptor variant FSHR3 (growth factor type 1 receptor acting via calcium signaling and the ERK/MAPK pathway). Any defect in FSH-FSHR3-stem cell interaction in OSE may affect folliculogenesis and thus result in POF. Ovarian aging is associated with a compromised microenvironment that does not support stem cell differentiation into oocytes and further folliculogenesis. FSH exerts a mitogenic effect on OSE and elevated FSH levels associated with advanced age may provide a continuous trigger for stem cells to proliferate resulting in cancer, thus supporting gonadotropin theory for ovarian cancer. Present review is an attempt to put adult ovarian biology, POF, aging, and cancer in the perspective of FSH-FSHR3-stem cell network that functions in OSE. This hypothesis is further supported by the recent understanding that: i) cancer is a stem cell disease and OSE is the niche for ovarian cancer stem cells; ii) ovarian OCT4-positive stem cells are regulated by FSH; and iii) OCT4 along with LIN28 and BMP4 are highly expressed in ovarian cancers.Reproduction (2015) 149 R35-R48

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Gonadotropin-Releasing Hormone Agonist Suppression of Ovarian Tumorigenesis in Mice of the Wx/wv Genotype1

Cited by 42 publications

References 0 publications

A phase II evaluation of goserelin and bicalutamide in patients with ovarian cancer in second or higher complete clinical disease remission

A phase II evaluation of goserelin and bicalutamide in patients with ovarian cancer in second or higher complete clinical disease remission

Hormonal aspects of epithelial ovarian cancer: review of epidemiological evidence

FSH–FSHR3–stem cells in ovary surface epithelium: basis for adult ovarian biology, failure, aging, and cancer

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