Gerasimos Tzortzatos

Karolinska University Hospital, Tukholma, Stockholm, Sweden

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Publications (6)21.28 Total impact

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    ABSTRACT: 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 Compre¬hensive 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.
    Oncology letters 01/2015; 9(4):1782-1786. DOI:10.3892/ol.2015.2890 · 0.99 Impact Factor
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    ABSTRACT: Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1,184 genotyped and imputed SNPs in 6,608 Caucasian cases and 37,925 controls, and 895 Asian cases and 1,968 controls, revealed the best signal of association for SNP rs11263763 (P=8.4×10(-14), OR=0.86, 95% CI=0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumour samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high to moderate LD as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression.
    Human Molecular Genetics 11/2014; DOI:10.1093/hmg/ddu552 · 6.68 Impact Factor
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    ABSTRACT: Uterine cancer (UC) represents 5.1% of all female malignancies in Sweden. Accumulation of UC in families occurs in around 5% of cases. We wanted to identify any familial association between UC and other selected cancers and to study the frequency of Lynch,Cowden and cancer syndromes among consecutive UC patients in Sweden.
    Hereditary Cancer in Clinical Practice 05/2014; 12(1):14. DOI:10.1186/1897-4287-12-14 · 1.71 Impact Factor
  • Gerasimos Tzortzatos, Angelos Sioutas, Mats O Beckman
    Thrombosis and Haemostasis 10/2009; 102(3):601-2. DOI:10.1160/TH09-03-0167 · 5.76 Impact Factor
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    ABSTRACT: The low molecular weight heparin, Dalteparin, shortens human labor time. The aim of this study was to investigate if the mechanism behind this effect involves myometrial contractility and cervical ripening and if the anticoagulative activity is necessary for its effect. Experimental in vitro study. Lund University and Karolinska Institute, Sweden. The effect of low molecular weight heparins with or without anticoagulative properties on myometrial contractility was measured in vitro on smooth muscle strips from biopsies obtained at elective cesarean sections. The effects on cervical ripening were assessed in cervical fibroblasts cultured from explants of cervical biopsies obtained at delivery. Mean force and number of contractions in uterine smooth muscle strips and interleukin-8 (IL-8) secretion in cervical fibroblasts. Myometrial smooth muscle strips pretreated with low molecular weight heparins showed increased contractile activity compared to untreated smooth muscle strips. Secretion of IL-8 from cultured cervical fibroblasts was significantly increased after treatment with low molecular weight heparin. Both these effects were independent of anticoagulative activity of the low molecular weight heparin. A possible underlying mechanism for the shortened labor time after low molecular weight heparin treatment is enhanced myometrial contractility and an increased IL-8 secretion in cervical fibroblast, mimicking the final cervical ripening in vivo. Our data support the notion that anticoagulant activity is not required to promote labor.
    Acta Obstetricia Et Gynecologica Scandinavica 09/2009; 88(9):984-9. DOI:10.1080/00016340903176818 · 1.85 Impact Factor
  • Gerasimos Tzortzatos, Angelos Sioutas, Kjell Schedvins
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    ABSTRACT: To report a case of successful IVF-pregnancy after treatment for ovarian growing teratoma syndrome. Case report. Gynecologic department at a university hospital. A 20-year-old woman, gravida 0 para 0, was diagnosed with malignant teratoma of the ovary. She was treated by unilateral salpingo-oophorectomy and chemotherapy. A couple of years later she was diagnosed with growing teratoma syndrome. Fertility-preserving surgery with unilateral salpingo-oophorectomy and chemotherapy. In vitro fertilization. Disease free, successful pregnancy. After treatment for ovarian immature teratoma and growing teratoma syndrome the patient was free of the disease. She underwent in vitro fertilization treatment with autologous embryo transfer and gave birth to a healthy child. Growing teratoma syndrome is an extremely rare metastatic complication of a malignant germ cell tumor after a combination treatment with surgery and adjuvant chemotherapy. This case shows that successful pregnancy outcome is possible after effective treatment for ovarian growing teratoma syndrome.
    Fertility and sterility 02/2009; 91(3):936.e1-3. DOI:10.1016/j.fertnstert.2008.12.004 · 4.30 Impact Factor