Publications by authors named "Katrin Kristjansdottir"

5 Publications

  • Page 1 of 1

Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits.

Nat Commun 2018 09 7;9(1):3636. Epub 2018 Sep 7.

deCODE Genetics/Amgen, Sturlugata 8, 101, Reykjavik, Iceland.

Uterine leiomyomas are common benign tumors of the myometrium. We performed a meta-analysis of two genome-wide association studies of leiomyoma in European women (16,595 cases and 523,330 controls), uncovering 21 variants at 16 loci that associate with the disease. Five variants were previously reported to confer risk of various malignant or benign tumors (rs78378222 in TP53, rs10069690 in TERT, rs1800057 and rs1801516 in ATM, and rs7907606 at OBFC1) and four signals are located at established risk loci for hormone-related traits (endometriosis and breast cancer) at 1q36.12 (CDC42/WNT4), 2p25.1 (GREB1), 20p12.3 (MCM8), and 6q26.2 (SYNE1/ESR1). Polygenic score for leiomyoma, computed using UKB data, is significantly correlated with risk of cancer in the Icelandic population. Functional annotation suggests that the non-coding risk variants affect multiple genes, including ESR1. Our results provide insights into the genetic background of leiomyoma that are shared by other benign and malignant tumors and highlight the role of hormones in leiomyoma growth.
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http://dx.doi.org/10.1038/s41467-018-05428-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128903PMC
September 2018

Maternal deaths in Iceland over 25 years.

Acta Obstet Gynecol Scand 2016 Jan 14;95(1):74-8. Epub 2015 Nov 14.

Faculty of Medicine, University of Iceland, Reykjavík, Iceland.

Introduction: Maternal death, during pregnancy or within 42 and 365 days from the end of pregnancy, was evaluated for a small high-income nation with comprehensive healthcare.

Material And Methods: Cases were identified using record linkage by running national census information on all deaths of women aged 15-49 years during 1985-2009 against the national birth register and computerized hospital admission files for pregnancy-related diagnoses as well as actual case records where needed. Death certificates and hospital records were reviewed.

Results: Thirty deaths were identified; 26 at ≥ 22 weeks (= birth) and four earlier in pregnancy. For 107,871 deliveries, the overall mortality was 27.8/100,000. There were five direct deaths (4.6/100,000 deliveries), five indirect deaths (4.6/100,000 deliveries) and 19 coincidental deaths (17.6/100,000 deliveries). Using WHO criteria (direct and indirect in pregnancy or at ≤ 42 days postpartum) the ratio was 5.6/100,000 deliveries (95% confidence interval 1.1-10.1) and 5.5/100,000 live births (maternal mortality ratio, based on six deaths). Direct deaths were caused by sepsis, severe preeclampsia and choriocarcinoma, indirect by suicide, pre-existing cardiac and diabetic illness. No woman died of postpartum hemorrhage, anesthesia or ectopic pregnancy. Suboptimal care occurred.

Conclusion: Maternal mortality in Iceland over a 25-year period up to the end of year 2010 was low, between 5 and 6/100,000 births. A comprehensive national healthcare system with accessible antenatal care in a society with good general living conditions and universal education probably contributed to this.
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http://dx.doi.org/10.1111/aogs.12797DOI Listing
January 2016

7 Methyl indole ethyl isothiocyanate causes ROS mediated apoptosis and cell cycle arrest in endometrial cancer cells.

Gynecol Oncol 2012 Aug 2;126(2):252-8. Epub 2012 May 2.

Molecular Therapeutics Laboratory, Program in Women's Oncology, Department of Obstetrics and Gynecology, Women and Infants Hospital of Rhode Island, Alpert Medical School, Brown University, Providence, RI 02905, USA.

Objective: Chemotherapy options for advanced endometrial cancer are limited and newer therapeutic agents are urgently needed. This study describes the therapeutic potential of 7 Methyl-indole ethyl isothiocyanate (7Me-IEITC) in endometrial cancer cell lines.

Methods: 7Me-IEITC was synthesized in our laboratory. The cell viability of 7Me-IEITC treated ECC-1 and KLE endometrial cancer cell was determined by MTS assay. Morphology and apoptosis were further confirmed by DAPI-staining and TUNEL assay. The measurement of reactive oxygen species (ROS), mitochondrial transmembrane depolarization potential (ΔΨm) and cell cycle phase was determined by FACS analysis. Expression of proteins involved in apoptosis, survival and cell-cycle progression was analyzed by Western blotting.

Results: 7Me-IEITC reduced the viability of the ECC-1 and KLE cancer cell-lines (IC(50)~2.5-10 μM) in a dose dependent fashion. 7Me-IEITC treatment caused mitochondrial transmembrane potential reduction, elevated the production of ROS, leading to activation of apoptosis in endometrial cancer KLE and ECC-1 cells. 7Me-IEITC treatment activated Bad, suppressed Bcl2 phosphorylation followed by PARP-1 deactivation and caspase 3 and 7 activation. 7Me-IEITC treatment arrested the progression of KLE cells in S-phase and caused CDC25 and cyclin-D1 downregulation. Pre-treatment with ascorbic acid abrogated 7Me-IEITC induced apoptosis in ECC-1 and KLE cells, suggesting that 7Me-IEITC mediated cytotoxicity is primarily through ROS production.

Conclusion: 7Me-IEITC demonstrated promising cytotoxic effects in endometrial cancer cell line model.
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http://dx.doi.org/10.1016/j.ygyno.2012.04.041DOI Listing
August 2012

Chemotherapeutic effect of calcidiol derivative B3CD in a neuroblastoma xenograft model.

Chem Biol Drug Des 2010 Aug 11;76(2):164-73. Epub 2010 May 11.

Molecular Therapeutics Laboratory, Program in Women's Oncology, Department of Obstetrics and Gynecology, Women and Infants' Hospital of RI, Warren Alpert Medical School of Brown University, Providence, RI 02905, USA.

Bromoacetoxy-calcidiol (B3CD), a pro-apoptotic and cytotoxic agent in neuroblastoma (NB) cell lines, displayed therapeutic potential in vivo as an anticancer drug in a NB xenograft mouse model. Tumors of all animals treated intraperitoneally with B3CD went into regression within 10-30 days of treatment, while tumors in control animals grew aggressively. The response mechanisms of NB cells to B3CD in vitro were studied and included differential targeting of cell cycle key regulators p21 and cyclin D1 on the transcriptional and expression level leading to arrest in G0/G1 phase. In contrast to the effect in ovarian cancer cells, B3CD-induced cell death in SMS-KCNR NB cells was only marginally mediated by the p38 MAPK signaling pathway. Signaling induced by exogenous recombinant EGF leads to a partial restoration of the negative effects of B3CD on SMS-KCNR cell proliferation and survival. Upon combinational treatment of SMS-KCNR cells with B3CD and recombinant EGF, the EGF receptor (EGF-R) was highly activated. We suggest future studies to include analysis of the effects of B3CD in combination therapy with pharmacological inhibitors of cell cycle regulators or with EGF-R-targeting inhibitors, -toxins or -antibodies in vitro and their translation into in vivo models of tumor development.
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http://dx.doi.org/10.1111/j.1747-0285.2010.00988.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024052PMC
August 2010

HER-dimerization inhibitors: evaluating pertuzumab in women's cancers.

Expert Opin Biol Ther 2010 Feb;10(2):243-50

Warren Alpert Medical School of Brown University, Women and Infants Hospital of Rhode Island - Program in Women's Oncology, 101 Dudley Street, Providence, Rhode Island, USA.

Importance Of The Field: Pertuzumab is a human EGF receptor (HER)-dimerization inhibitor that represent a novel class of agents aimed at blocking HER2 from pairing with other receptors of the HER family. In this review, we discuss the background and scientific rationale, related to pertuzumab as it has undergone development for women's cancers.

Areas Covered In This Review: Pre-clinical and clinical trials, published or presented at national meetings from 1995 to the present, are included in this review.

What The Reader Will Gain: A Phase II trial in HER2-positive metastatic breast cancer showed promising activity of pertuzumab when it was combined with trastuzumab and a randomized Phase III trial is now underway. Pertuzumab, when evaluated in recurrent ovarian cancer showed limited activity when combined with chemotherapy in platinum-sensitive and platinum-resistant disease. However, a recent subset analysis suggests that HER3 mRNA levels may predict response to pertuzumab in ovarian cancer.

Take Home Message: HER-dimerization inhibitors represent a novel mechanism of inhibition of HER pathways. Pertuzumab may play a role in the management of HER2-positive breast cancer. The potential benefit of pertuzumab in ovarian cancer is unclear, but low HER3 levels may suggest a sub-group of patients that can benefit from pertuzumab.
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http://dx.doi.org/10.1517/14712590903514090DOI Listing
February 2010