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Sökning: WFRF:(Mints Miriam)

  • Resultat 11-17 av 17
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11.
  • Lomnytska, Marta I, et al. (författare)
  • Diagnostic protein marker patterns in squamous cervicalcancer
  • 2010
  • Ingår i: Proteomics - Clinical Applications. - Weinheim : WILEY-VCH Verlag GmbH & Co. KGaA. - 1862-8346. ; 4:1, s. 17-31
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Purpose: Cervical cancer is the second most prevalent malignancy of women. Our aim was toidentify additional marker protein patterns for objective diagnosis of squamous cervical cancer(SCC).Experimental design: Collected tissue biopsies of SCC, squamous vaginal cancer (SVC), normalcervical and vaginal mucosa were subjected to 2-DE, SameSpot analysis, MALDI-TOF-MSprotein identification, and analysis of the expression of selected proteins by immunohistochemistry.Results: In 148 protein spots selected by the difference in expression 99 proteins were identified.A differential protein pattern for SCC was, e.g. over-expressed (OE) eukaryotic translationinitiation factor 3-2b, neutrophil cytosolic factor 2, annexin A6 (ANXA6), for SVC it was OEcathepsin D, g-catenin, RAB2A, for both cancers it was OE apolipoprotein E, tropomyosin 3,HSPA8, and underexpressed cytokeratin 13, osteoglycin. In SCC nuclear expression ofneutrophil cytosolic factor 2, PRDX2, HSP27 (nine of ten cases), ANXA6 (nine of ten cases) wasobserved while tropomyosin 4 was expressed only in two of ten cases. There was 81.1% (43/53)agreement between the expression of protein spots and the immune expression of proteins(www.proteinatlas.org).Conclusions and clinical relevance: SCC is characterized by specific tissue marker proteinpatterns that allow objective detection of the disease. They can become a basis for objectiveautomated cytology-based screening and improve current diagnostics of SCC.</p>
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12.
  • 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.
13.
  • O'Mara, Tracy A, et al. (författare)
  • Identification of nine new susceptibility loci for endometrial cancer.
  • 2018
  • Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.</p>
14.
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15.
  • Tzortzatos, Gerasimos, et al. (författare)
  • Screening for germline phosphatase and tensin homolog-mutations in suspected Cowden syndrome and Cowden syndrome-like families among uterine cancer patients
  • 2015
  • Ingår i: Oncology Letters. - 1792-1074 .- 1792-1082. ; 9:4, s. 1782-1786
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Cowden syndrome (CS) is an autosomal dominant disorder characterized by multiple hamartomas in the breast, thyroid and endometrium, with a prevalence of 1 per 250,000. Females with CS have a 21-28% lifetime risk of developing uterine cancer. Germline mutations in the phosphatase and tensin homolog (PTEN) gene, a tumor suppressor gene, are responsible for 30-80% of CS cases. PTEN is a nine-exon gene, located on chromosome 10q23.3, which encodes the 403 amino acid PTEN protein. It negatively regulates the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathway, affecting various cellular processes and signaling pathways. The present study examined whether PTEN mutations are present in CS-like families with uterine cancer (UC). UC patients underwent surgery at Karolinska University Hospital, Stockholm, Sweden (2008-2012). Pedigrees were analyzed and 54 unrelated CS-like families were identified. CS-like families were defined as having at least one occurrence of uterine cancer and one of breast cancer, as well as at least one additional Cowden-associated tumor (uterine, breast, thyroid, colon or kidney cancer) in the same individual or in first-degree relatives. Genomic DNA was amplified using polymerase chain reaction, and DNA sequencing analysis of all nine exons of the PTEN gene was conducted. No germline PTEN mutations or polymorphisms were identified. Germline PTEN mutations are rare in CS-like families with uterine cancer, therefore, genetic screening must be restricted to patients that meet the strict National Comprehensive Cancer Network criteria. Gynecologists must be aware of the CS criteria and identify potential cases of CS in females where uterine cancer is the sentinel cancer.</p>
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16.
  • Tzortzatos, Gerasimos, et al. (författare)
  • The gynecological surveillance of women with Lynch Syndrome in Sweden
  • 2015
  • Ingår i: Gynecologic Oncology. - 0090-8258. ; 138:3, s. 717-722
  • Tidskriftsartikel (refereegranskat)abstract
    • Women with Lynch syndrome (LS) have up to a 60% lifetime risk of endometrial cancer (EC) and up to a 24% risk of ovarian cancer (OC). Gynecological surveillance is recommended, but the benefit and how it should be performed remain unclear. The purpose of this study was to assess diagnostic modalities for gynecological screening of LS patients in Sweden and clinical outcome.
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17.
  • Tzortzatos, Gerasimos, et al. (författare)
  • The gynecological surveillance of women with Lynch Syndrome in Sweden
  • 2015
  • Ingår i: Gynecologic Oncology. - ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0090-8258 .- 1095-6859. ; 138:3, s. 717-722
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Objective. Women with Lynch syndrome (LS) have up to a 60% lifetime risk of endometrial cancer (EC) and up to a 24% risk of ovarian cancer (OC). Gynecological surveillance is recommended, but the benefit and how it should be performed remain unclear. The purpose of this study was to assess diagnostic modalities for gynecological screening of LS patients in Sweden and clinical outcome. Methods. A retrospective nationwide study of 170 women with molecularly confirmed LS. Data including gynecological LS screening history, biopsy results (if any), genetic records, number of screening visits, results from screening including transvaginal ultrasound (TVUS), endometrial biopsy (EB), blood test for tumor marker cancer antigen (CA) 125, prophylactic surgery including age at procedure, and setting from which screening data were obtained from medical records. Results. A total of 117 women were eligible for gynecological screening and of these, 86 patients attended screening visits. Of these, 41 underwent prophylactic hysterectomy and/or bilateral salpingo-oophorectomy. Two patients (4.9%) were diagnosed with EC and two (4.9%) with precancerous lesions in conjunction with prophylactic surgery. Total incidence of gynecological cancer in the surveillance group (45 women) was 20% EC, 4% OC. Five patients had endometrial cancer or complex hyperplasia with atypia (n = 2) detected by endometrial biopsy. Four additional cases were detected due to interval bleeding. Both cases of ovarian cancer were detected by transvaginal ultrasound in patients with ovarian cysts under surveillance. The youngest woman with endometrial cancer was diagnosed at 35 years of age, before she was aware of her diagnosis of Lynch syndrome. Conclusions. Gynecological surveillance of women with Lynch syndrome may lead to earlier detection of precancerous lesions, which might have some impact on the morbidity from endometrial cancer although further studies are needed to prove this. Prophylactic hysterectomy with or without bilateral salpingo-oophorectomy reduces the cancer incidence. A practical approach to surveillance in Lynch syndrome women would be to offer annual surveillance beginning at age 30 years including probably both TVUS and EB in order to increase diagnostic yield with prospective data registry for follow-up studies. Prophylactic surgery could be performed at a suitable age after childbearing to obtain a balance between reducing the risk of cancer and minimizing long-term complications from premature menopause. (C) 2015 Elsevier Inc. All rights reserved.</p>
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