umu.sePublications
Change search
Link to record
Permanent link

Direct link
BETA
Öfverman, Charlotte
Alternative names
Publications (10 of 13) Show all publications
Stefansson, K., Oda, H., Öfverman, C., Lundin, E., Hedman, H. & Lindquist, D. (2019). LRIG1‑2 and LMO7 immunoreactivity in vulvar squamous cell carcinoma: association with prognosis in relation to HPV‑DNA and p16INK4a status. Oncology Reports, 42(1), 142-150
Open this publication in new window or tab >>LRIG1‑2 and LMO7 immunoreactivity in vulvar squamous cell carcinoma: association with prognosis in relation to HPV‑DNA and p16INK4a status
Show others...
2019 (English)In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 42, no 1, p. 142-150Article in journal (Refereed) Published
Abstract [en]

The present study was conducted to investigate the possible prognostic value of molecular markers LRIG1‑2 and LIM domain 7 protein (LMO7) in vulvar squamous cell carcinoma (VSCC) and their possible correlation to human papilloma virus (HPV)‑ and p16INK4a‑status of the tumors. Patients diagnosed with VSCC at the University Hospital of Umeå, Sweden, during the years 1990‑2013 were selected. Tumor blocks were retrieved from tissue archives and clinical data were collected from the records of patients. HPV‑PCR analysis, HPV genotyping and immunohistochemistry were performed. In total, 112 patients were included. Forty percent of the tumors were HPV‑positive, 27% were p16INK4a‑positive and 23% were positive for both HPV and p16INK4a (considered HPV‑driven). HPV‑positivity and p16INK4a‑positivity were associated with prolonged disease‑free survival (DFS) in Kaplan‑Meier survival analysis. Leucine‑rich repeats and immunoglobulin‑like domains 1 (LRIG1) immunoreactivity was not significantly associated with survival. High leucine‑rich repeats and immunoglobulin‑like domains 2 (LRIG2) immunoreactivity was associated with a prolonged overall survival (OS) (P=0.001). By analyzing HPV‑negative cases only, it was determined that high LRIG2 immunoreactivity was associated with both favorable OS (P=0.008) and DFS (P=0.031). LRIG2 immunoreactivity was also an independent prognostic factor in multivariate analysis of OS (P=0.002, HR=0.41; 95% CI, 0.24‑0.71). High immunoreactivity with LMO7‑1250 antibody was associated with survival benefits in the whole cohort (OS; P=0.011) although DFS was only prolonged in HPV‑negative and not HPV‑driven tumors (P=0.038 and 0.042, respectively). The present study indicated that LRIG2 and LMO7 may be useful prognostic markers in VSCC, particularly for patients without HPV‑driven tumors or with advanced tumors at diagnosis. In contrast to earlier observations regarding other types of squamous cell carcinoma, LRIG1 was not a significant prognostic factor in VSCC.

Place, publisher, year, edition, pages
Spandidos Publications, 2019
Keywords
vulvar squamous cell carcinoma, leucine‑rich repeats and immunoglobulin‑like domains, human papillomavirus, p16INK4a, survival
National Category
Cancer and Oncology
Research subject
health services research
Identifiers
urn:nbn:se:umu:diva-159681 (URN)10.3892/or.2019.7138 (DOI)31059071 (PubMedID)
Available from: 2019-06-03 Created: 2019-06-03 Last updated: 2019-06-05Bibliographically approved
Ofverman, C., Stefansson, K., Ottander, U. & Lindquist, D. (2016). CASE SERIES OF PATIENTS WITH LEIOMYOSARCOMA OF THE UTERUS TREATED WITH TRABECTEDIN IN NORTHERN SWEDEN. International Journal of Gynecological Cancer, 26(Supplement 3), 1046-1046, Article ID IGCS-0142.
Open this publication in new window or tab >>CASE SERIES OF PATIENTS WITH LEIOMYOSARCOMA OF THE UTERUS TREATED WITH TRABECTEDIN IN NORTHERN SWEDEN
2016 (English)In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 26, no Supplement 3, p. 1046-1046, article id IGCS-0142Article in journal, Meeting abstract (Refereed) Published
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-128468 (URN)000387109100886 ()
Available from: 2017-06-22 Created: 2017-06-22 Last updated: 2018-06-09Bibliographically approved
Loizou, C., Laurell, G., Lindquist, D., Öfverman, C., Stefansson, K., Nylander, K. & Olofsson, K. (2015). Incidence of tonsillar cancer in northern Sweden: Impact of human papilloma virus. Oncology Letters, 10(6), 3565-3572
Open this publication in new window or tab >>Incidence of tonsillar cancer in northern Sweden: Impact of human papilloma virus
Show others...
2015 (English)In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 10, no 6, p. 3565-3572Article in journal (Refereed) Published
Abstract [en]

The incidence rate of tonsillar cancer is increasing worldwide. The current study identifies a parallel increase in the incidence of tonsillar cancer, human papilloma virus (HPV) and p16 expression among a population from northern Sweden, a sparsely populated area, confirming the strong association between p16 and HPV infection in tonsillar tissue. Data from the Swedish Cancer Registry was assessed to identify cases of tonsillar cancer in the northern territorial area of Sweden. HPV DNA was extracted from paraffin embedded diagnostic biopsies and detected by polymerase chain reaction using general primers Gp5+/6+ and CpI/IIG. Expression of p16 was identified by immunochemistry. Patients were grouped into urban or rural residence categories. A total of 214 cases were identified, comprising 155 (72.4%) men and 59 (27.6%) women, and 65 of these patients, who presented between 2000 and 2012, were analyzed. The overall median age for the analyzed patients was 58 years; 48 (74%) were males (median age, 57.5 years) and 17 (26%) were females (median age, 65 years). Of the 65 specimens, 59 (91%) were positive for HPV, and 62 (95%) expressed p16. The incidence of tonsillar cancer in the cohort demonstrated a 2-fold increase between 1990 and 2013; specifically, a 2.7-fold increase was observed in men whilst the female group exhibited only a small increase. These findings demonstrate a strong association between p16 expression and HPV infection in tonsillar malignancies. The incidence of HPV-positive tonsillar cancer has increased in recent years, even in sparsely populated regions, as demonstrated in northern Sweden.

Place, publisher, year, edition, pages
Spandidos Publications, 2015
Keywords
head and neck cancer, human papilloma virus, immunohistochemistry, incidence, p16, tonsillar cancer
National Category
Cancer and Oncology Otorhinolaryngology
Identifiers
urn:nbn:se:umu:diva-114586 (URN)10.3892/ol.2015.3775 (DOI)000367232600038 ()
Available from: 2016-02-16 Created: 2016-01-25 Last updated: 2018-06-07Bibliographically approved
Stefansson, K., Oda, H., Öfverman, C., Lundin, E., Hedman, H. & Lindquist, D. (2015). LRIG protein expression and HPV prevalence in vulvar cancer patients in northern Sweden. International Journal of Gynecological Cancer, 25(9), 684-684
Open this publication in new window or tab >>LRIG protein expression and HPV prevalence in vulvar cancer patients in northern Sweden
Show others...
2015 (English)In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 25, no 9, p. 684-684Article in journal, Meeting abstract (Other academic) Published
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-123480 (URN)000377145702004 ()
Available from: 2016-07-06 Created: 2016-07-04 Last updated: 2018-06-07Bibliographically approved
Lindquist, D., Öfverman, C., Stefansson, K. & Aglund, K. (2015). Survival-data for endometrial cancer patients in northern Sweden 2010-2011. International Journal of Gynecological Cancer, 25(9), 1100-1100
Open this publication in new window or tab >>Survival-data for endometrial cancer patients in northern Sweden 2010-2011
2015 (English)In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 25, no 9, p. 1100-1100Article in journal, Meeting abstract (Other academic) Published
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-123479 (URN)000377145703060 ()
Available from: 2016-07-06 Created: 2016-07-04 Last updated: 2018-06-07Bibliographically approved
Öfverman, C. (2009). Progesterone metabolites: learning, tolerance, antagonism & metabolism. (Doctoral dissertation). Umeå: Umeå university
Open this publication in new window or tab >>Progesterone metabolites: learning, tolerance, antagonism & metabolism
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Progesterone metabolites as allopregnanolone, isoallopregnanolone and tetrahydrodeoxy-corticosterone (THDOC) are increased in the luteal phase of the menstrual cycle, throughout pregnancy and during stress. Allopregnanolone and THDOC are neurosteroids with 3α-hydroxy, 5α-configurations and positive modulating effect on the GABAA receptor. They have similar properties and effect, and share the same binding sites on the GABAA receptor. Isoallopregnanolone has a 3β-hydroxy, 5α-configuration and a diverse effect as a proposed antagonist to both allopregnanolone and THDOC. Neurosteroids are thought to exert their effect predominantly at extrasynaptic GABAA receptors, containing for example α4- or α5-subunits. Such receptors are involved in the tonic response. Different subunits have diverse distribution pattern in the brain and are involved in different functions. The α5-subunit, mainly expressed in the hippocampus, is involved in learning, while α4 is more widespread and involved in e.g. anxiety and anaesthesia.

The aim of the present thesis was to contribute to the knowledge about selected progesterone metabolites and their effects on learning and tolerance development, as well as their metabolism. Also basic characteristics between different α-subunits of the GABAA receptor were evaluated.

The thesis shows that the effect of bicuculline and pentobarbital is not dependent on the α-subunit isoform of the GABAA receptor expressed in oocytes. Acute tolerance developed after allopregnanolone-induced anaesthesia with a decrease at both mRNA and protein levels of the GABAA receptor α4-subunit in the thalamus VPM nucleus. A negative correlation between the α4 mRNA and the increased dose of allopregnanolone needed to maintain the anaesthesia level was also shown. In addition, allopregnanolone induces a learning impairment in the Morris water maze test, when high concentrations of allopregnanolone are present in the brain. This impairment is not possible to reverse by isoallopregnanolone. In α5β3γ2L-transfected HEK-293 cells THDOC induces a baseline shift of its own and also potentiate the GABA-current. Neither of those THDOC effects can be inhibited by isoallopregnanolone. Instead isoallopregnanolone shows an agonistic effect on the THDOC-potentiation of the GABA-response. The main allopregnanolone metabolites identified, 5α-DHP and isoallopregnanolone, as well as allopregnanolone itself are mainly localized to the brain after an i.v. injection. After an isoallopregnanolone injection there is a more even distribution of the given steroid and the metabolites between plasma and brain. There is an epimerisation between isoallopregnanolone and allopregnanolone and vice versa.

In conclusion, the present thesis shows that the α4-subunit in the thalamus VPM nucleus is likely to be involved in the acute tolerance development against allopregnanolone and that allopregnanolone-induced learning impairment is likely to be hippocampus dependent. The lack of antagonistic effect of isoallopregnanolone on the THDOC-induced α5β3γ2L-GABAA response, together with epimerisation of isoallopregnanolone to allopregnanolone, could explain why isoallopregnanolone does not work as an antagonist to the allopregnanolone-induced learning impairment in a hippocampus dependent learning task.

Place, publisher, year, edition, pages
Umeå: Umeå university, 2009. p. 73
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1306
Keywords
allopregnanolone, isoallopregnanolone, THDOC, learning, tolerance, antagonism, inhibition, patch clamp, Morris water maze, metabolism, epimerization
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
urn:nbn:se:umu:diva-27064 (URN)978-91-7264-888-3 (ISBN)
Public defence
2009-12-05, Sal 914, By 1, 9 tr, NUS, Norrlands Universitetssjukhus, Umeå, 10:00 (English)
Opponent
Supervisors
Available from: 2009-11-16 Created: 2009-11-09 Last updated: 2018-06-08Bibliographically approved
Birzniece, V., Türkmen, S., Lindblad, C., Zhu, D., Johansson, I.-M., Bäckström, T. & Wahlström, G. (2006). GABA(A) receptor changes in acute allopregnanolone tolerance. European Journal of Pharmacology, 535(1-3), 125-134
Open this publication in new window or tab >>GABA(A) receptor changes in acute allopregnanolone tolerance
Show others...
2006 (English)In: European Journal of Pharmacology, ISSN 0014-2999, E-ISSN 1879-0712, Vol. 535, no 1-3, p. 125-134Article in journal (Refereed) Published
Abstract [en]

To study acute tolerance, rats were anesthetized with interrupted i.v. allopregnanolone infusions where the "silent second" in the electroencephalogram (EEG) was the target. Animals were killed either directly at the first silent second or at the silent second level after 30 or 90 min of anaesthesia. Acute tolerance was demonstrated at 90 min of anaesthesia as earlier shown. In situ hybridization showed a decreased expression of the gamma-aminobutyric acid(A) (GABA(A)) receptor subunit alpha4mRNA amount in the thalamus ventral-posteriomedial nucleus of the tolerant rats. A parallel change in the abundance of the alpha4 subunit was detected with immunohistochemistry. The increase in maintenance dose rate (MDR) was significantly negatively correlated with the alpha4mRNA in the thalamus ventral-posteriomedial nucleus, and positively correlated with alpha2mRNA in different hippocampal subregions. There was also a positive relationship between the alpha1mRNA amounts in the different hippocampal subregions, with significant differences between groups. These changes in GABA(A) receptor subunits mRNA expression and protein (alpha4) might be of importance for the development of acute tolerance to allopregnanolone.

Keywords
Anesthetics/administration & dosage/blood/pharmacokinetics, Animals, Brain/*drug effects/metabolism, Brain Chemistry/drug effects, Dentate Gyrus/chemistry/drug effects/metabolism, Dose-Response Relationship; Drug, Drug Tolerance, Gene Expression/drug effects, Immunohistochemistry, In Situ Hybridization, Infusions; Intravenous, Male, Pregnanolone/*administration & dosage/blood/pharmacokinetics, Protein Subunits/analysis/genetics, RNA; Messenger/genetics/metabolism, Rats, Rats; Sprague-Dawley, Receptors; GABA-A/analysis/*genetics, Receptors; GABA-B/analysis/genetics, Ventral Thalamic Nuclei/chemistry/drug effects/metabolism
Identifiers
urn:nbn:se:umu:diva-16927 (URN)10.1016/j.ejphar.2006.01.059 (DOI)16513107 (PubMedID)
Available from: 2007-12-02 Created: 2007-12-02 Last updated: 2018-06-09Bibliographically approved
Birzniece, V., Bäckström, T., Johansson, I.-M., Lindblad, C., Lundgren, P., Löfgren, M., . . . Zhu, D. (2006). Neuroactive steroid effects on cognitive functions with a focus on the serotonin and GABA systems.. Brain Research Reviews, 51(2), 212-239
Open this publication in new window or tab >>Neuroactive steroid effects on cognitive functions with a focus on the serotonin and GABA systems.
Show others...
2006 (English)In: Brain Research Reviews, ISSN 0165-0173, E-ISSN 1872-6321, Vol. 51, no 2, p. 212-239Article in journal (Refereed) Published
Keywords
Animals, Brain/drug effects/*metabolism/physiopathology, Cognition/drug effects, Cognition Disorders/chemically induced/*metabolism/physiopathology, Gonadal Steroid Hormones/adverse effects/*metabolism, Humans, Learning/drug effects, Neural Pathways/drug effects/metabolism/physiopathology, Receptors; GABA-A/metabolism, Serotonin/*metabolism, gamma-Aminobutyric Acid/*metabolism
Identifiers
urn:nbn:se:umu:diva-15313 (URN)doi:10.1016/j.brainresrev.2005.11.001 (DOI)16368148 (PubMedID)
Available from: 2008-01-04 Created: 2008-01-04 Last updated: 2018-06-09Bibliographically approved
Rahman, M., Lindblad, C., Johansson, I.-M., Bäckström, T. & Wang, M.-D. (2006). Neurosteroid modulation of recombinant rat alpha5beta2gamma2L and alpha1beta2gamma2L GABA(A) receptors in Xenopus oocyte.. Eur J Pharmacol, 547(1-3), 37-44
Open this publication in new window or tab >>Neurosteroid modulation of recombinant rat alpha5beta2gamma2L and alpha1beta2gamma2L GABA(A) receptors in Xenopus oocyte.
Show others...
2006 (English)In: Eur J Pharmacol, ISSN 0014-2999, Vol. 547, no 1-3, p. 37-44Article in journal (Refereed) Published
Keywords
Androstane-3;17-diol/pharmacology, Animals, Desoxycorticosterone/analogs & derivatives/pharmacology, Dose-Response Relationship; Drug, Female, GABA Agonists/pharmacology, GABA Antagonists/pharmacology, GABA Modulators/*pharmacology, Male, Membrane Potentials/drug effects, Microinjections, Oocytes/*drug effects/metabolism/physiology, Patch-Clamp Techniques/instrumentation/methods, Pregnanediol/pharmacology, Pregnanes/pharmacology, Pregnenolone/pharmacology, Protein Subunits/genetics/physiology, Pyridines/pharmacology, RNA; Messenger/administration & dosage/genetics, Rats, Rats; Wistar, Receptors; GABA-A/genetics/*physiology, Steroids/*pharmacology, Xenopus laevis, gamma-Aminobutyric Acid/pharmacology
Identifiers
urn:nbn:se:umu:diva-16917 (URN)10.1016/j.ejphar.2006.07.039 (DOI)16934248 (PubMedID)
Available from: 2007-10-19 Created: 2007-10-19 Last updated: 2018-06-09Bibliographically approved
Bäckström, T., Andersson, A., Andreén, L., Birzniece, V., Bixo, M., Björn, I., . . . Zingmark, E. (2003). Pathogenesis in menstrual cycle-linked CNS disorders.. Annals of the New York Academy of Sciences, 1007, 42-53
Open this publication in new window or tab >>Pathogenesis in menstrual cycle-linked CNS disorders.
Show others...
2003 (English)In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1007, p. 42-53Article, review/survey (Other academic) Published
Keywords
Affect/physiology, Animals, Female, Humans, Menstrual Cycle/*physiology, Mood Disorders/*etiology/physiopathology/psychology, Pregnanolone/physiology, Premenstrual Syndrome/*etiology/physiopathology/psychology, Receptors; GABA-A/physiology
Identifiers
urn:nbn:se:umu:diva-16450 (URN)10.1196/annals.1286.005 (DOI)14993039 (PubMedID)
Available from: 2007-09-28 Created: 2007-09-28 Last updated: 2018-06-09Bibliographically approved
Organisations

Search in DiVA

Show all publications