scholarly journals The effects of ergot and non-ergot-derived dopamine agonists in an experimental mouse model of endometriosis

Reproduction ◽  
2011 ◽  
Vol 142 (5) ◽  
pp. 745-755 ◽  
Author(s):  
Francisco Delgado-Rosas ◽  
Raúl Gómez ◽  
Hortensia Ferrero ◽  
Francisco Gaytan ◽  
Juan Garcia-Velasco ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Dopamine Agonists ◽  
Cellular Proliferation ◽  
Lesion Size ◽  
Proliferation Index ◽  
Pilot Studies ◽  
Cardiac Valve Regurgitation ◽  
Angiogenic Gene ◽  
Endothelial Growth Factor

Implantation of a retrogradely shed endometrium during menstruation requires an adequate blood supply, which allows the growth of endometriotic lesions. This suggests that the development of endometriosis can be impaired by inhibiting angiogenesis. The growth of endometriotic foci is impaired by commercial oncological antiangiogenic drugs used to block vascular endothelial growth factor (VEGF) signaling. The dopamine agonist cabergoline (Cb2) inhibits the growth of established endometriosis lesions by exerting antiangiogenic effects through VEGFR2 inactivation. However, the use of ergot-derived Cb2 is associated with an increased incidence of cardiac valve regurgitation. To evaluate the potential usage of non-ergot-derived dopamine agonists for the treatment of human endometriosis, we compared the efficacy of quinagolide with that of Cb2 in preventing angiogenesis and vascularization in a heterologous mouse model of endometriosis. Nude mice whose peritoneum had been implanted with eutopic human endometrial fragments were treated with vehicle, 50 μg/kg per day oral Cb2, or 50 or 200 μg/kg per day quinagolide during a 14-day period. At the end of the treatment period, the implants were excised in order to assess lesion size, cell proliferation, degree of vascularization, and angiogenic gene expression. Neoangiogenesis was inhibited and the size of active endometriotic lesions, cellular proliferation index, and angiogenic gene expression were significantly reduced by both dopamine agonists when compared with the placebo. Given that Cb2 and quinagolide were equally effective in inhibiting angiogenesis and reducing lesion size, these experiments provide the rationale for pilot studies to explore the use of non-ergot-derived dopamine agonists for the treatment of endometriosis in humans.

Wnt5a Expression Is Associated With the Tumor Proliferation and the Stromal Vascular Endothelial Growth Factor—An Expression in Non–Small-Cell Lung Cancer

2005 ◽  
Vol 23 (34) ◽  
pp. 8765-8773 ◽  
Author(s):  
Cheng-long Huang ◽  
Dage Liu ◽  
Jun Nakano ◽  
Shinya Ishikawa ◽  
Keiichi Kontani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell ◽  
Squamous Cell Carcinomas ◽  
Proliferation Index ◽  
Beta Catenin ◽  
Vascular Endothelial ◽  
Small Cell Lung ◽  
Ki 67 ◽  
Wnt5a Expression ◽  
Endothelial Growth Factor

Purpose The Wnt gene family encodes the multifunctional signaling glycoproteins. We performed the present study to investigate the clinical significance of Wnt5a expression in non–small-cell lung cancer (NSCLC). Patients and Methods One hundred twenty-three patients with NSCLC who had undergone resection were investigated. Real-time quantitative reverse transcriptase polymerase chain reaction was performed to evaluate the Wnt5a gene expression. Immunohistochemistry was performed to investigate the Wnt5a protein expression, the Ki-67 proliferation index, tumor angiogenesis, and the expression of beta-catenin and vascular endothelial growth factor-A (VEGF-A). Results Wnt5a gene expression in squamous cell carcinoma was significantly higher than that in adenocarcinoma (P < .0001). There was a significant correlation between the normalized Wnt5a gene expression ratio and the intratumoral Wnt5a protein expression (r = 0.729; P < .0001). The intratumoral Wnt5a expression was significantly correlated with the Ki-67 proliferation index (r = 0.708; P < .0001). In contrast, no correlation was observed between the intratumoral Wnt5a expression and tumor angiogenesis. Furthermore, the intratumoral Wnt5a expression was significantly correlated with the stromal expression of beta-catenin (r = 0.729; P < .0001) and VEGF-A (r = 0.661; P < .0001). In addition, the stromal VEGF-A expression was also correlated with Ki-67 proliferation (r = 0.627; P < .0001). Cox regression analyses demonstrated Wnt5a status to be a significant prognostic factor for NSCLC patients (P = .0193), especially for patients with squamous cell carcinomas (P = .0491). Conclusion The present study revealed that an overexpression of Wnt5a could produce more aggressive NSCLC, especially in squamous cell carcinomas, during tumor progression.

scholarly journals Clinicopathological and Molecular Characteristics of Pleomorphic Invasive Lobular Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Jennifer M. Segar ◽  
Ritu Pandey ◽  
Kiah J. Farr ◽  
Raymond Nagle ◽  
Lauren LeBeau ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Expression Analysis ◽  
Invasive Lobular Carcinoma ◽  
Gene Expression Analysis ◽  
Cellular Proliferation ◽  
Lobular Carcinoma ◽  
Mtor Pathway ◽  
Proliferation Index ◽  
Molecular Characteristics

Pleomorphic invasive lobular carcinoma (PILC) is a distinct morphological and biologically aggressive variant of invasive lobular carcinoma (ILC). We hypothesized that was due to de novo activation of PI3K/Akt/mTOR pathway in PILC resulting in higher proliferation rate and markers of cell cycle activation. We identified PILC and ILC tumors and tested for PI3K/Akt/mTOR pathway activation by immunohistochemistry (PTEN and pS6K1) and gene expression analysis (by Nanostring nCounter system). Proliferation index (Ki67) was elevated in 85% of PILCs compared to 20% of ILCs ( p < 0.007 ). PTEN expression was high in all while pS6K1 was high in 8/9 PILCs compared to 3/9 ILCs ( p < 0.007 ). Gene expression analysis shows that PILCs have overexpression of genes involved in cell cycle proliferation, cellular proliferation, DNA damage, and repair genes but no difference in PI3K/Akt/mTOR pathway genes. PILCs are a biologically distinct group of ILC, and clinicopathological characteristics suggest they would have a more clinically aggressive behavior. In addition, our results indicate that PI3k/Akt/mTOR pathway and cell cycle proliferation are activated in majority of these tumors. Further studies are needed to investigate these mechanisms as there are approved therapies available that may benefit PILCs.

Use of dopamine agonists to target angiogenesis in women with endometriosis

2020 ◽  
Author(s):  
Nuria Pellicer ◽  
Daniela Galliano ◽  
Sonia Herraiz ◽  
Yu Z Bagger ◽  
Joan-Carles Arce ◽  
...  
Keyword(s):  
Medical Management ◽  
Dopamine Agonists ◽  
Cellular Proliferation ◽  
Ovarian Function ◽  
Lesion Size ◽  
Experimental Models ◽  
Plasminogen Activator Inhibitor 1 ◽  
Fiber Density ◽  
Endometrial Cells ◽  
Pai 1

Abstract Endometriosis requires medical management during a woman’s reproductive years. Most treatments aim to create a hypoestrogenic milieu, but for patients wishing to conceive, drugs that allow normal ovarian function are needed. Targeting angiogenesis, a hallmark of the disease, using dopamine agonists (DAs) is a promising strategy for endometriosis treatment. Herein, we review experimental and clinical data that investigate this concept. In experimental models of endometriosis, DAs (bromocriptine, cabergoline, quinagolide) downregulate proangiogenic and upregulate antiangiogenic pathways in inflammatory, endothelial and endometrial cells, blocking cellular proliferation and reducing lesion size. Impaired secretion of vascular endothelial growth factor (VEGF) and inactivation of its receptor type-2 are key events. VEGF inhibition also reduces nerve fiber density in lesions. In humans, quinagolide shows similar effects on lesions, and DAs reduce pain and endometrioma size. Moreover, a 20-fold downregulation of Serpin-1, the gene that encodes for plasminogen activator inhibitor 1 (PAI-1), has been observed after DAs treatment. Pentoxifylline, a PAI-1, increases pregnancy rates in women with endometriosis. Thus, the data support the use of DAs in the medical management of endometriosis to reduce lesion size and pain while maintaining ovulation. A combined approach of DAs and pentoxifylline is perhaps a smart way of targeting the disease from a completely different angle than current medical treatments.

Treatment of a burn animal model with functionalized tridimensional electrospun biomaterials

2017 ◽  
Vol 32 (5) ◽  
pp. 663-676 ◽  
Author(s):  
Daniela Steffens ◽  
Monica Beatriz Mathor ◽  
Paula Rigon da Luz Soster ◽  
Gustavo Vergani ◽  
Dayane Piffer Luco ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lactic Acid ◽  
Growth Factor ◽  
Lesion Size ◽  
Lesion Group ◽  
In Vivo Experiments ◽  
Tumor Growth Factor ◽  
Mean Size ◽  
Endothelial Growth Factor

Laminin-functionalized poly-d,l-lactic acid scaffolds were produced. Following this, mesenchymal stem cells and keratinocytes were seeded on biomaterials for the in vivo experiments, where the biomaterials with or without cells were implanted. The analysis is comprised of the visual aspect and mean size of the lesion plus the histology and gene expression. The results showed that the cells occupied all the structure of the scaffolds in all the groups. After nine days of in vivo experiments, the defect size did not show statistical difference among the groups, although the groups with the poly-d,l-lactic acid/Lam biomaterial had the lowest lesion size and presented the best visual aspect of the wound. Gene expression analysis showed considerable increase of tumor growth factor beta 1 expression, increased vascular endothelial growth factor and balance of the BAX/Bcl-2 ratio when compared to the lesion group. Histological analysis showed well-formed tissue in the groups where the biomaterials and biomaterials plus cells were used. In some animals, in which biomaterials and cells were used, the epidermis was formed throughout the length of the wound. In conclusion, these biomaterials were found to be capable of providing support for the growth of cells and stimulated the healing of the skin, which was improved by the use of cells.

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