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Sökning: WFRF:(Mints Miriam)

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  • Mints, Miriam (författare)
  • Idiopathic menorrhagia : Studies of angiogenesis and surgical therapy
  • 2003
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Background Excessive menstrual bleeding, menorrhagia (i.e. > 80 nil loss of blood) is a com-mon gynecological problem in women of reproductive age, accounting for over 20% of visits to gynecology outpatient clinics. The disorder may not only cause iron deficiency anemia but also considerable social discomfort and reduction in the quality of life. Although commonly associated with fibroids and carcinoma, approximately 50% of patients with menorrhagia do not show any evidence of uterine pathology. This suggests a defect in the cellular processes and regulatory mechanisms of menstruation. Historically, many women with heavy menstrual bleeding were advised to undergo hysterectomy, which was the only way of enduring a "cure". Hysterectomy is an effective treatment of menorrhagia, but it is associated with substantial postoperative morbidity and convalescence. In the early 1990s, endometrial resection or ablation became a well-established outpatient alternative for the surgical treatment of menorrhagia. The aim of this thesis This work has mainly been focused on two aspects: firstly, the analysis of transcervical resection of the endometrium (TCRE) as a surgical option for treatment of menorrhagia and, secondly, on the involvement of the vascular endothelial growth factor (VEGF) family in the regulation of anglogenesis in the human endometrium in healthy women and those with idiopathic menorrhagia. In particular, we investigated if the vessel wall anatomy was abnormal and related findings to the expression of VEGF and VEGF receptors in the blood vessels. Results The general clinical outcome in the present studies (papers I and II) showed favorable results with low peroperative and postoperative complication rates: fluid overload occurred in 4% and perforation in 1% of the patients. Most of women who underwent TCRE found this surgery acceptable and approximately 80% of these women have avoided hysterectomy. Second-look hysteroscopy in women after TCRE showed signs of regenerative endometrium. In order to determine why the endometrium regenerates and what regulates this process, we have investigated the expression and distribution of VEGF and its receptors as well as vessel morphology in normal and menorrhagic endometrium (papers III- V). Our data suggest an up-regulation of the agonist-receptor pathway of VEGF in idiopathic menorrhagia: the vascular expression of VEGF-A, VEGFR1, -2, -3 in capillaries was 1.8-, 1.8-, 2.0-, and 1. 6-fold higher, respectively, in the menorrhagia group. Since VEGF-A not only stimulates migration and survival of endothelial cells but also induces vascular permeability, we have addressed this aspect by analyzing of vessel morphology. We found that vessels in patients with menorrhagia displayed an unusual morphology with focal regions, gaps. The relative size of the gaps was significantly larger in menorrhagia samples than in controls (P=0.000002). Moreover, the sizes of the gaps correlated positively to the number of endometrial blood vessels expressing VEGF-A (P=0.0002) and VEGFR1 (P=0.03). To our knowledge, this is the first study that demonstrates the presence of endothelial gaps in menorrhagic endometrium and as a part of a specific disease process. Conclusions TCRE provides a minimally invasive technique for treatment of menorrhagia with good clinical results: about 80% of women have the possibility of avoiding hysterectomy. Therefore, endometrial resection/ablation should be offered as a surgical option to all women with idiopathic menorrhagia who have completed their families. Normal endometrial angiogenesis is perturbed in idiopathic menorrhagia with an up-regulation of the agonist-receptor pathway of VEGF-A, which leads to anatomical differences in blood vessels, manifested inter alia as gaps. Our novel observations may be of significance in order to explain some of the underlying mechanisms that contribute to idiopathic menorrhagia and will provide novel opportunities for therapeutic intervention in the future.
  • Razumova, Zoia, et al. (författare)
  • The prognostic role of lrig proteins in endometrial cancer
  • 2021
  • Ingår i: Cancers. - : MDPI. - 2072-6694. ; 13:6, s. 1-12
  • Tidskriftsartikel (refereegranskat)abstract
    • Endometrial cancer (EC) is the most common gynecologic malignancy in Sweden and it has various prognostic factors. The LRIG family is a group of three integral surface proteins with a similar domain organization. The study aimed to explore LRIG family as prognostic factor proteins in EC. The initial study cohort included 100 women with EC who were treated at the Department of Women’s and Children’s Health, Karolinska University Hospital Solna, between 2007 and 2012. We assessed the associations between LRIG protein expression and type, grade, and stage of EC, as well as progression‐free and overall survival. Immunohistochemistry results revealed that most women in the analytical sample had >50% LRIG1‐, LRIG2‐ and LRIG3‐positive cells. A statistically significant association was observed between having a high number of LRIG3‐positive cells and superior overall survival (incidence rate ratio = 0.977; 95% confidence interval: 0.958–0.996, p = 0.019). Moreover, positive LRIG3 staining of the cell membrane was associated with reducing in the risk of death (hazard ratio = 0.23; 95% confidence interval: 0.09–0.57). Our results show that LRIG3 expression might be a prognostic factor in EC. The role of LRIG1 and LRIG2 expression remains to be further investigated.
  • Wersäll, Ofra Castro, et al. (författare)
  • PGC1α and VDAC1 expression in endometrial cancer
  • 2021
  • Ingår i: Molecular and clinical oncology. - : Spandidos Publications. - 2049-9450 .- 2049-9469. ; 14:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Endometrial cancer (EC) is one of the ten most common gynecological cancers. As in most cancers, EC tumour progression involves alterations in cellular metabolism and can be associated with, for instance, altered levels of glycolytic enzymes. Mitochondrial functions and proteins are known to serve key roles in tumour metabolism and progression. The transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1α) is a major regulator of mitochondrial biogenesis and function, albeit of varying prognostic value in different cancers. The voltage-dependent anion channel type 1 (VDAC1) regulates apoptosis as well as metabolite import and export over the mitochondrial outer membrane, and is often used for comparative quantification of mitochondrial content. Using immunohistochemistry, the present study examined protein expression levels of PGC1α and VDAC1 in tumour and paired benign tissue samples from 148 patients with EC, in order to examine associations with clinical data, such as stage and grade, Ki-67, p53 status, clinical resistance and overall survival. The expression levels of both PGC1α and VDAC1, as well as a PGC1α downstream effector, were significantly lower in tumor tissues than in benign tissues, suggesting altered mitochondrial function in EC. However, Kaplan-Meier, log rank and Spearman's rank correlation tests revealed that their expression was not correlated with survival and clinical data. Therefore, PGC1α and VDAC1 are not of major prognostic value in EC.
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  • Föregående 12[3]
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