Inhibitory effects of fumagillin and its analogue TNP-470 on the function, morphology and angiogenesis of an oestrogen-induced prolactinoma in Fischer 344 rats

Stępień, H; Grochal, M; Zieliński, Krzysztof; Mucha, S; Kunert‐Radek, Jolanta; Kulig, Andrzej; Stawowy, Andrzej; Pisarek, Hanna

doi:10.1677/joe.0.1500099

Cited by 36 publications

(21 citation statements)

References 24 publications

(27 reference statements)

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“…Thus, it is interesting to note that anti-angiogenic inhibitors such as fumagillin and its analogue TNP-470 have antitumor and antiprolactin activity in the experimentally estrogen-induced pituitary adenoma in F 344 rats. The inhibition of angiogenesis was suggested to be the major cause [14]. The above findings together with the fact that some patients respond to bromocriptine treatment while others do not are in line with the hypothesis that prolactinoma is a heterogeneous disorder [6,15] with complicated and multifactorial etiology and pathogenesis.…”

supporting

confidence: 71%

“…Many researchers consider F 344 rats to be the most sensitive strain to develop estrogeninduced prolactinoma [14,25,26] and SD rats to be relatively insensitive. This has been studied in detail by Weiner et al [27] who implanted subcutaneously 1-cm-long silastic 17-ß-estradiol (E 2 ) tubing into ovariectomized F 344 rats and SD rats.…”

Section: Animal Models For the Investigation Of Pituitary Prolactin-smentioning

confidence: 99%

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Pituitary Prolactin-Secreting Tumor Formation: Recent Developments

et al. 2000

Biol Signals Recept

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Prolactinoma is the most common type of primary pituitary tumors. It occurs more frequently in women than in men. Dopaminergic agonists are effective in the shrinkage of prolactin-secreting pituitary tumor and are preferred in some patients. However, pituitary radiotherapy may enable the long-term removal of prolactin-secreting tumor cells. Recent evidence suggests that prolactinoma is a heterogeneous disorder with complicated and multifactorial etiology and pathogenesis. Apparently, a thorough understanding of prolactinoma tumorigenesis would be important. To facilitate investigations on tumorigenesis of prolactinoma, animal models for prolactinomas have been developed. These models have expedited our progress in the recent years. Many researchers consider the F₃₄₄ rat to be the most sensitive strain of rats to estrogen (E₂)-induced prolactinoma formation. Nonetheless, E₂ treatment for 60 days also induces the formation of pituitary prolactin-secreting adenoma in male Sprague-Dawley (SD) rats. Evidently, the SD rat is also a good animal for prolactinoma investigations. Following E₂ implantation, prolactinomas developed in the eutopic adenohypophysis in situ and/or ectopic pituitary grafted under the renal capsule in SD rats. These observations favor the hypothesis that prolactinoma growth is the result of pathological changes in the adenohypophysis and/or hypothalamus. In the latter case, abnormal release of hypothalamic dopamine, GABA, or brain-gut peptides (such as cholecystokinin, vasoactive intestinal polypeptide, galanin, angiotensin, opioid peptide, gastrin, gastrin-releasing peptide, pancreatic polypeptide, and adrenocorticotropic hormone) results in some of the pathological changes that may lead to hyperprolactinemia and/or prolactinoma development. Dysregulation of prolactin synthesis and secretion may be the result of prolactin gene modulation. In E₂-induced rat prolactinomas, prolactin mRNA contents and the expression of some proto-oncogenes, e.g. c-myc and c-ras, TGFα and TGFβ1 mRNA were significantly changed. The above findings are consistent with results in human prolactinoma development. In addition, in rats abnormal expression of the prolactin gene was correlated with hypomethylated status of CpG sites in exons 1, 2 and 4 of the prolactin gene, as well as the increase in hypersensitive sites to DNase 1 in the encoding region of the prolactin gene. In E₂-treated rats, a point mutation with a base substitution from cytidine (C) to adenine (A) was found at the –36-bp site of the proximal promoter of the prolactin gene in eutopic pituitary prolactinomas, but no change was observed in the same sequence of the prolactin gene in ectopic prolactinoma. The association of a base substitution with the hyperexpression of the prolactin gene in eutopic prolactinomas suggests that different mechanisms may mediate the formation of eutopic and ectopic prolactin-secreting tumors. Melatonin decreases the expression of the prolactin gene in vitro sug...

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supporting

confidence: 71%

Section: Animal Models For the Investigation Of Pituitary Prolactin-smentioning

confidence: 99%

Pituitary Prolactin-Secreting Tumor Formation: Recent Developments

et al. 2000

Biol Signals Recept

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“…It has also been shown that angiogenesis is essential for the growth of oestrogen-induced prolactin-secreting anterior pituitary tumours (Elias & Weiner 1984). It was recently demonstrated that fumagillin and its analogue TNP-470, which are known to selectively inhibit endothelial cell proliferation, inhibited prolactin production and prolactotrophic cell density and proliferation and suppressed neovascularisation in Fischer 374 rats bearing prolactinomas induced by oestrogen treatment (Takachi et al 1994, Stepien et al 1996. These results provide strong evidence for the anti-prolactinoma effects of inhibitors of angiogenesis in this pituitary prolactinoma model.…”

Section: Growth Factors and Their Receptors Involved In Modulating Anmentioning

confidence: 78%

Gene therapy strategies for the treatment of pituitary tumours

Castro

1999

Journal of Molecular Endocrinology

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“…It has also been found that the vascular density was higher in gonadotropinomas that in the non-tumoral anterior pituitary gland (42). The inhibitors of angiogenesis are effective in the suppression of growth of the experimental pituitary tumour (43,44), and the levels of angiogenic cytokines VEGF and bFGF are elevated in the peripheral blood of patients with pituitary adenomas (45). However, Gorczyca & Hardy (46) in angiographic studies detected the presence of additional arteries (which were not part of the portal system) in 66% of their patients with microadenomas of this organ, while Farnoud et al (47) observed changes characteristic for increased vasculogenesis in the basal membrane surrounding cells of pituitary tumours in humans.…”

Section: Angiogenesis and Neoplasms Of Endocrine Glandsmentioning

confidence: 99%

Angiogenesis of endocrine gland tumours--new molecular targets in diagnostics and therapy

Stępień

Kołomecki²,

Pasieka³

et al. 2002

European Journal of Endocrinology

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Angiogenesis is one of the key stages in the development of neoplastic tumours, in which a small group of mutated cells transforms into a large malignant tumour metastasising to the neighbouring tissues and organs. The studies on the significance of neoangiogenesis in the progression of endocrine gland neoplasms have recently become one of the most rapidly evolving branches of molecular endocrinology. The induction of angiogenesis has been demonstrated to result from the imbalance between positive and negative factors which control this process. Our paper presents the results of current studies on the role of factors such as molecular markers of angiogenesis (e.g. vascular endothelial growth factor and basic fibroblast growth factor), metalloproteinases (which regulate the decomposition of the extracellular matrix) and their inhibitors, and adhesive molecules (e.g. soluble vascular cellular adhesion molecule-1 and soluble intracellular adhesion molecule-1) in the pathogenesis and diagnostics of endocrine gland tumours in humans. Also, we discuss new therapeutic strategies for inhibiting the growth of neoplasms by blocking the formation of blood vessels using angiogenesis antagonists, which inhibit various stages of angiogenesis. More and more data are being accumulated suggesting that these preparations could, in the near future, be used in the pharmacotherapy of some endocrine gland neoplasms.

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Inhibitory effects of fumagillin and its analogue TNP-470 on the function, morphology and angiogenesis of an oestrogen-induced prolactinoma in Fischer 344 rats

Cited by 36 publications

References 24 publications

Pituitary Prolactin-Secreting Tumor Formation: Recent Developments

Pituitary Prolactin-Secreting Tumor Formation: Recent Developments

Gene therapy strategies for the treatment of pituitary tumours

Angiogenesis of endocrine gland tumours--new molecular targets in diagnostics and therapy

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