Em roedores, o aumento da permeabilidade vascular, a transformação decidual, e angiogênese são eventos cruciais para o sucesso da gestação. O fator endotelial vascular (VEGF) é um mitogênico para células endoteliais e um indutor de angiogênese. O VEGF age via dois receptores da família das tirosina quinases: VEGFR1 e VEGFR2. O objetivo deste estudo foi investigar usando o método imunohistoquímico, a expressão espacial e temporal do VEGF e os receptores VEGFR1 e VEGFR2 em células endometriais de camundongo entre o 4º e 8º dias de gestação. No 4º dia de gestação, VEGF, VEGFR1 e VEGFR2 foram expressos pelo epitélio luminal e glandular e fracamente pelo estroma endometrial. Do 5º ao 8º dias de gestação, o VEGF foi expresso nas células deciduais mesometriais. VEGFR1 e VEGFR2 foram expresso pelas células do epitélio luminal e glandular e mostraram uma marcação diferencial na decídua mesometrial e antimesometrial. Os receptores VEGFR1 e VEGFR2 foram intensamente expressos pelas células endoteliais dos capilares sinusóides mesometriais e pelas células Nk uterinas. / In rodents, increase of vascular permeability, decidual cell transformation, and uterine angiogenesis are crucial events for the success of pregnancy. Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells and an inducer of angiogenesis. VEGF acts via two tyrosine kinase family receptors: VEGFR1 and VEGFR2. The aim of this study was to investigate using the immunohistochemical method, the spatiotemporal expression of VEGF and its receptors VEGFR1 e VEGFR2 by mouse endometrial cells on days 4 to 8 of pregnancy. On day 4, VEGF, VEGFR1 and VEGFR2 were expressed mostly by the luminal and glandular epithelium. Stromal cells showed a very weak labeling. On days 5-8, VEGF and its receptors showed an increased labeling throughout the mesometrial decidua. The expression of VEGF, VEGFR1, and VEGFR2 were differentially expressed in the mesometrial cells and in the predecidual cells of the antimesometrial decidua. VEGFR1 and VEGF R2 were highly expressed by endothelial cells of the mesometrial sinusoids, and Nk uterine cells.

Em roedores, o aumento da permeabilidade vascular, a transformação decidual, e angiogênese são eventos cruciais para o sucesso da gestação. O fator endotelial vascular (VEGF) é um mitogênico para células endoteliais e um indutor de angiogênese. O VEGF age via dois receptores da família das tirosina quinases: VEGFR1 e VEGFR2. O objetivo deste estudo foi investigar usando o método imunohistoquímico, a expressão espacial e temporal do VEGF e os receptores VEGFR1 e VEGFR2 em células endometriais de camundongo entre o 4º e 8º dias de gestação. No 4º dia de gestação, VEGF, VEGFR1 e VEGFR2 foram expressos pelo epitélio luminal e glandular e fracamente pelo estroma endometrial. Do 5º ao 8º dias de gestação, o VEGF foi expresso nas células deciduais mesometriais. VEGFR1 e VEGFR2 foram expresso pelas células do epitélio luminal e glandular e mostraram uma marcação diferencial na decídua mesometrial e antimesometrial. Os receptores VEGFR1 e VEGFR2 foram intensamente expressos pelas células endoteliais dos capilares sinusóides mesometriais e pelas células Nk uterinas. / In rodents, increase of vascular permeability, decidual cell transformation, and uterine angiogenesis are crucial events for the success of pregnancy. Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells and an inducer of angiogenesis. VEGF acts via two tyrosine kinase family receptors: VEGFR1 and VEGFR2. The aim of this study was to investigate using the immunohistochemical method, the spatiotemporal expression of VEGF and its receptors VEGFR1 e VEGFR2 by mouse endometrial cells on days 4 to 8 of pregnancy. On day 4, VEGF, VEGFR1 and VEGFR2 were expressed mostly by the luminal and glandular epithelium. Stromal cells showed a very weak labeling. On days 5-8, VEGF and its receptors showed an increased labeling throughout the mesometrial decidua. The expression of VEGF, VEGFR1, and VEGFR2 were differentially expressed in the mesometrial cells and in the predecidual cells of the antimesometrial decidua. VEGFR1 and VEGF R2 were highly expressed by endothelial cells of the mesometrial sinusoids, and Nk uterine cells.

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Background: Renal cell carcinoma (RCC) is most lethal of the urological cancers, with more than 40% dying of the disease. About 30% of the patients have metastases at initial diagnosis and up to 40% undergoing nephrectomy for localized RCC develop metastasis. A follow-up protocol based on accurate prognostic variables allows identification of low and high risk patients and selection of those most likely to benefit from adjuvant therapy. I have studied a number of prognostic patient-related factors, including tumour stage and grade, angiogenetic factors and tumour markers, in order to improve follow-up guideline as well as to try to predict prognosis and clinical outcome for individual patients. Material and Methods: The studies are based on patients treated for RCC between 1982 and 2002. All patients eligible for surgery with or without metastasis were treated with nephrectomy and were followed according to a scheduled follow-up programme. Serum samples were collected after obtained informed consent. Multiple clinicopathological, laboratory variables and preoperative radiological examinations were analyzed. Results: Study I- After nephrectomy in 187 patients with non-metastatic RCC, 30% developed metastases during the follow-up. The risk for metastases was greater for more advanced stage and was adjusted by size and DNA ploidy. The median time to the diagnosis of metastases was 14.5 months. Metastases occurred in 43% of the patients within one year, within 2 years in 70% and 80% in 3 years. Patients with tumours less than 5 cm and diploid pT1>5cm and pT2 tumours survived longer than those with larger and aneuploid tumours. The 5-years survival rate for pT1, pT2, pT3 tumours were 95%, 87%, and 37% respectively. In pT3 tumours DNA ploidy had no relation to survival time. Study II and IV- The median survival time for patients with metastatic RCC was 7 months. Cytoreductive nephrectomy was associated with longer survival time. Factors including performance status (PS), number of metastatic sites, erythrocyte sedimentation rate (ESR), calcium in serum, vein invasion, capsule invasion had independent prognostic value with Cox multivariate analysis. Study III- The incidence of adrenal tumour involvement was 5.3 %, unaffected of RCC type, tumour location or side. Gender (male) and locally advanced tumours (pT3 > 5cm) were factors predicting adrenal involvement. The presence of adrenal involvement was a significant adverse prognostic variable, indicating a significantly shorter survival in patients both with and without distant metastases. Conclusion: Optimal follow-up guidelines are important from both medical and economic perspectives. The risk for progression depends mainly on stage, which in combination with other prognostic factors may allow more individualized and cost effective follow-up, in some cases by avoiding unnecessary examinations in a third of the patients. Cytoreductive nephrectomy in patients with good PS, metastases limited to one organ, low ESR, normal calcium and no vein invasion were factors associated to long survival time. Soluble angiogenic factors in serum gave no prognostic information. Ipsilateral adrenalectomy in conjunction with radical nephrectomy should be performed if an adrenal lesion cannot be cleared of suspicion during preoperative work up. Ipsilateral adrenal involvement is a highly adverse prognostic factor and should be staged as M1a in the TNM staging system.