Euclidean and fractal geometry of microvascular networks in normal and neoplastic pituitary tissue

Ieva, Antonio Di; Grizzi, Fabio; Gaetani, Paolo; Goglia, Umberto; Tschabitscher, Manfred; Mortini, Pietro; Baena, Riccardo Rodriguez y

doi:10.1007/s10143-008-0127-7

Cited by 29 publications

(13 citation statements)

References 56 publications

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“…On the other hand, pituitary tumors are usually less vascularized than the normal pituitary tissue, as suggested by Schechter [2], and later confirmed by other authors [3][4][5]. Differences in the angiogenic pattern of pituitary adenomas have yielded highly controversial results concerning hormonal phenotypes, size, or invasion [6][7][8]. In most studies, immunohistochemistry evaluation of different markers of microvascular density (MVD) such as endothelial cluster differentiation molecules CD31 and CD34, factor eightrelated antigen, and ulex europaeus agglutinin I have been used.…”

Section: Introductionmentioning

confidence: 84%

VEGF and CD31 Association in Pituitary Adenomas

et al. 2010

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Pituitary tumors are usually less vascularized than the normal pituitary, and the role of angiogenesis in these adenomas is contentious. Appraisal of microvascular density and expression of the potent angiogenic vascular endothelial growth factor (VEGF) by immunohistochemistry has yielded controversial results, as a broad spectrum of immunostaining can be found. We determined the protein expression of VEGF and CD31, an endothelial marker, in a series of 56 surgically removed pituitary adenomas using Western blot assay. Prolactinomas had higher VEGF protein expression compared to nonfunctioning or ACTH- and GH-secreting adenomas, while CD31 was similar in the different adenoma histotypes. VEGF and CD31 were not affected by sex, age, years of adenoma evolution, or proliferation rate (Ki67 and PCNA) for all adenoma types. Only in nonfunctioning adenomas CD31 concentration increased significantly with age. There was a positive correlation between CD31 and VEGF expression when all adenoma histotypes were considered, or when prolactinomas and nonfunctioning adenomas were evaluated separately. The positive association of VEGF and CD31 expression suggests the participation of angiogenesis in adenoma development, while epithelial cell proliferation in pituitary tumors is not directly related to VEGF or CD31 expression, and other factors, such as primary genetic alterations may be involved.

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Section: Introductionmentioning

confidence: 84%

VEGF and CD31 Association in Pituitary Adenomas

et al. 2010

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“…Lacunarity relates to texture, it quantifies the distribution and size of gaps within an image 23 . Fractal dimension and lacunarity have previously been utilized to quantify complex morphologies and patterns in a range of biological settings including cell shape, chromatin texture, retinal angiogenesis, neuronal growth and physiological measurements 33 46 47 48 49 50 . We observed a significant difference in the fractal dimension and lacunarity of hyperplastic compared to malignant mesothelial tissue samples ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Unique fractal evaluation and therapeutic implications of mitochondrial morphology in malignant mesothelioma

Lennon

Cianci

Kanteti

et al. 2016

Sci Rep

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Malignant mesothelioma (MM), is an intractable disease with limited therapeutic options and grim survival rates. Altered metabolic and mitochondrial functions are hallmarks of MM and most other cancers. Mitochondria exist as a dynamic network, playing a central role in cellular metabolism. MM cell lines display a spectrum of altered mitochondrial morphologies and function compared to control mesothelial cells. Fractal dimension and lacunarity measurements are a sensitive and objective method to quantify mitochondrial morphology and most importantly are a promising predictor of response to mitochondrial inhibition. Control cells have high fractal dimension and low lacunarity and are relatively insensitive to mitochondrial inhibition. MM cells exhibit a spectrum of sensitivities to mitochondrial inhibitors. Low mitochondrial fractal dimension and high lacunarity correlates with increased sensitivity to the mitochondrial inhibitor metformin. Lacunarity also correlates with sensitivity to Mdivi-1, a mitochondrial fission inhibitor. MM and control cells have similar sensitivities to cisplatin, a chemotherapeutic agent used in the treatment of MM. Neither oxidative phosphorylation nor glycolytic activity, correlated with sensitivity to either metformin or mdivi-1. Our results suggest that mitochondrial inhibition may be an effective and selective therapeutic strategy in mesothelioma, and identifies mitochondrial morphology as a possible predictor of response to targeted mitochondrial inhibition.

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“…On the other hand, the role of angiogenesis in pituitary tumor development has been questioned, because the normal pituitary is a highly vascularized gland, reflecting the need to respond to regulatory feedbacks and rapidly deliver hormones into circulation. Differences in the angiogenic pattern of pituitary tumors have yielded highly controversial results concerning hormonal phenotypes, size, or invasion (Turner et al, 2003;Di Ieva et al, 2008;Pizarro et al, 2009). Some data point to increased angiogenesis, whereas others have described that pituitary tumors are usually less vascularized than normal pituitary tissue (Schechter, 1972;Jugenburg et al, 1995;Turner et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Inhibitory Effects of Antivascular Endothelial Growth Factor Strategies in Experimental Dopamine-Resistant Prolactinomas

Luque

Pérez-Millán²,

Ornstein³

et al. 2011

J Pharmacol Exp Ther

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Prolactin-secreting adenomas are the most frequent type among pituitary tumors, and pharmacological therapy with dopamine agonists remains the mainstay of treatment. But some adenomas are resistant, and a decrease in the number or function of dopamine D2 receptors (D2Rs) has been described in these cases. D2R knockout [Drd2(Ϫ/Ϫ)] mice have chronic hyperprolactinemia and pituitary hyperplasia and provide an experimental model for dopamine agonist-resistant prolactinomas. We described previously that disruption of D2Rs increases vascular endothelial growth factor (VEGF) expression. We therefore designed two strategies of antiangiogenesis using prolactinomas generated in Drd2(Ϫ/Ϫ) female mice: direct intra-adenoma mVEGF R1 (Flt-1)/Fc chimera (VEGF-TRAP) injection for 3 weeks [into subcutaneously transplanted pituitaries from Drd2(Ϫ/Ϫ) mice] and systemic VEGF neutralization with the specific monoclonal antibody G6-31. Both strategies resulted in substantial decrease of prolactin content and lactotrope area, and a reduction in tumor size was observed in in situ prolactinomas. There were significant decreases in vascularity, evaluated by cluster of differentiation molecule 31 vessel staining, and proliferation (proliferating cell nuclear antigen staining) in response to both anti-VEGF treatments. These data demonstrate that the antiangiogenic approach was effective in inhibiting the growth of in situ dopamine-resistant prolactinomas as well as in the transplanted adenomas. No differences in VEGF protein expression were observed after either anti-VEGF treatment, and, although serum VEGF was increased in G6-31-treated mice, pituitary activation of the VEGF receptor 2 signaling pathway was reduced. Our results indicate that, even though the role of angiogenesis in pituitary adenomas is contentious, VEGF might contribute to adequate vascular supply and represent a supplementary therapeutic target in dopamine agonist-resistant prolactinomas.

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Euclidean and fractal geometry of microvascular networks in normal and neoplastic pituitary tissue

Cited by 29 publications

References 56 publications

VEGF and CD31 Association in Pituitary Adenomas

VEGF and CD31 Association in Pituitary Adenomas

Unique fractal evaluation and therapeutic implications of mitochondrial morphology in malignant mesothelioma

Inhibitory Effects of Antivascular Endothelial Growth Factor Strategies in Experimental Dopamine-Resistant Prolactinomas

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