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  • 1.
    Andersson, Charlotta
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Oji, Yusuke
    Ohlson, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wang, Sihan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Li, Xingru
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Sugiyama, Haruo
    Li, Aihong
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Prognostic significance of specific anti-WT1 IgG antibody level in plasma in patients with ovarian carcinoma2014Ingår i: Cancer Medicine, E-ISSN 2045-7634, Vol. 3, nr 4, s. 909-918Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Ovarian carcinoma (OC) has a poor prognosis and lack early effective screening markers. Wilm's tumor gene 1 (WT1) is overexpressed in OCs. Therefore, it is of great interest to investigate whether WT1-specific antibody (Ab) measurements in plasma can serve as a biomarker of anti-OC response, and is of importance in relation to patient prognosis. Peripheral blood samples were obtained from a total of 103 women with ovarian tumors with median being 1 day (range 0-48 days) before operation. WT1 IgG Ab levels were evaluated using enzyme-linked immunosorbent assay (ELISA). Immunohistochemical analysis of WT1 protein expression was performed on OC tissue samples. We found that low-WT1 Ab level in plasma was related to improved survival in patients diagnosed at stages III-IV and grade 3 carcinomas. Positive WT1 protein staining on OC tissue samples had a negative impact on survival in the entire cohort, both overall survival (OS) (P = 0.046) and progression-free survival (PFS) (P = 0.006), but not in the serous OC subtype. Combining WT1 IgG Ab levels and WT1 staining, patients with high-WT1 IgG Ab levels in plasma and positive WT1 protein staining in cancer tissues had shorter survival, with a significant association in PFS (P = 0.016). These results indicated that WT1 Ab measurements in plasma and WT1 staining in tissue specimens could be useful as biomarkers for patient outcome in the high-risk subtypes of OCs for postoperative individualized therapy.

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  • 2.
    Björk, Emma
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Division of Obstetrics and Gynecology, Örnsköldsvik Hospital, Örnsköldsvik, Sweden.
    Vinnars, Marie-Therese
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Division of Obstetrics and Gynecology, Örnsköldsvik Hospital, Örnsköldsvik, Sweden.
    Nagaev, Ivan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Nagaeva, Olga
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Mincheva-Nilsson, Lucia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Enhanced local and systemic inflammatory cytokine mRNA expression in women with endometriosis evokes compensatory adaptive regulatory mRNA response that mediates immune suppression and impairs cytotoxicity2020Ingår i: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 84, nr 4, artikel-id e13298Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Problem: Endometriosis is a disease characterized by ectopic implantation of endometrium and impaired immune responses. To explore its pathogenic mechanisms, we studied the local and systemic cytokine mRNA profiles and their role in the immunity of patients with endometriosis and healthy controls.

    Method of Study: mRNA for eleven cytokines defining cytotoxic Th1, humoral Th2, regulatory Tr1/Th3, and inflammatory cytokine profiles was characterized locally in endometriotic tissue and endometrium, and systemically in PBMCs from women with endometriosis and healthy controls, using real‐time qRT‐PCR. In addition, immunohistochemical stainings with monoclonal antibodies were performed looking for T regulatory cells in endometriotic lesions.

    Results: We found a downregulation of mRNA for cytokines mediating cytotoxicity and antibody response and an upregulation of inflammatory and T‐regulatory cytokines in the endometriotic tissues and endometrium from the patients with endometriosis, suggesting enhanced local inflammation and priming of an adaptive regulatory response. Consistent with those findings, there was an abundancy of T regulatory cells in the endometriotic lesions.

    Conclusions: The ectopic implantation seen in endometriosis could be possible as a consequence of increased inflammation and priming of adaptive T regulatory cells, resulting in impaired cytotoxicity and enhanced immune suppression.

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  • 3.
    Danielsson, Johanna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Professionell utveckling.
    Hadding, Cecilia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Professionell utveckling.
    Martin, Fahlström
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Professionell utveckling.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lindquist, David
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Professionell utveckling.
    Medical students’ experiences in learning to perform pelvic examinations: a mixed-methods study2021Ingår i: International Journal of Medical Education, E-ISSN 2042-6372, Vol. 12, s. 233-242Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: We aimed to explore learning experiences among medical students learning to perform pelvic examinations and to identify factors that facilitate their training.

    Methods: A mixed-methods study including a web-based survey and focus group discussions (FGDs) was conducted among medical students who had completed their obstetrics and gynaecology (ObGyn) clerkship. The FGDs were recorded, transcribed and analysed using qualitative content analysis with systematic text condensation. Survey factors were compared using the χ2 test or Fisher's exact test.

    Results: 160 students (97 female, 61 male, two other) at six universities in Sweden responded to the survey. Two mixed FGDs were conducted. The majority (87%) of the students experienced confidence in performing pelvic examinations, stating that sufficient, repeated training opportunities and support from a clinical tutor were crucial components of the learning experience. Prior to the ObGyn clerkship, negative expectations were more common among male students. The male participants experienced having a disadvantage because of their gender, while female students considered their gender an advantage (p<0.001, N=121, Fisher's Exact Test). The clinical tutor and the use of professional patients (PPs) had a fundamental role in providing learning opportunities by including the student in patient care activities.

    Conclusions: The importance of the clinical tutor, as well as the use of PPs, are important factors when planning education in pelvic examinations, and this knowledge could be used when educating other intimate examinations during medical school. In addition, similar investigations on students' experience in training other intimate examinations could be considered.

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  • 4. Falconer, Henrik
    et al.
    Palsdottir, Kolbrun
    Stalberg, Karin
    Dahm-Kahler, Pernilla
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lundin, Evelyn Serreyn
    Wijk, Lena
    Kimmig, Rainer
    Jensen, Pernille Tine
    Eriksson, Ane Gerda Zahl
    Maenpaa, Johanna
    Persson, Jan
    Salehi, Sahar
    Robot-assisted approach to cervical cancer (RACC): an international multi-center, open-label randomized controlled trial2019Ingår i: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 29, nr 6, s. 1072-1076Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Radical hysterectomy with pelvic lymphadenectomy represents the standard treatment for early-stage cervical cancer. Results from a recent randomized controlled trial demonstrate that minimally invasive surgery is inferior to laparotomy with regards to disease-free and overall survival. Primary Objective To investigate the oncologic safety of robot-assisted surgery for early-stage cervical cancer as compared with standard laparotomy. Study Hypothesis Robot-assisted laparoscopic radical hysterectomy is non-inferior to laparotomy in regards to recurrence-free survival with the advantage of fewer post-operative complications and superior patient-reported outcomes. Trial Design Prospective, multi-institutional, international, open-label randomized clinical trial. Consecutive women with early-stage cervical cancer will be assessed for eligibility and subsequently randomized 1:1 to either robot-assisted laparoscopic surgery or laparotomy. Institutional review board approval will be required from all participating institutions. The trial is coordinated from Karolinska University Hospital, Sweden. Major Inclusion/Exclusion Criteria Women over 18 with cervical cancer FIGO (2018) stages IB1, IB2, and IIA1 squamous, adenocarcinoma, or adenosquamous will be included. Women are not eligible if they have evidence of metastatic disease, serious co-morbidity, or a secondary invasive neoplasm in the past 5 years. Primary Endpoint Recurrence-free survival at 5 years between women who underwent robot-assisted laparoscopic surgery versus laparotomy for early-stage cervical cancer. Sample Size The clinical non-inferiority margin in this study is defined as a 5-year recurrence-free survival not worsened by >7.5%. With an expected recurrence-free survival of 85%, the study needs to observe 127 events with a one-sided level of significance (alpha) of 5% and a power (1-beta) of 80%. With 5 years of recruitment and 3 years of follow-up, the necessary number of events will be reached if the study can recruit a total of 768 patients. Estimated Dates for Completing Accrual and Presenting Results Trial launch is estimated to be May 2019 and the trial is estimated to close in May 2027 with presentation of data shortly thereafter.

  • 5.
    Gideonsson, Ida
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Center of Obstetrics and Gynecology, Umeå University Hospital, Umeå, Sweden.
    Israelsson, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Strandberg, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Long-term follow-up of tamoxifen treatment and the use of imaging in psammocarcinoma: a case report, review of the literature and discussion of diagnostic and therapeutic challenges2023Ingår i: Current Oncology, ISSN 1198-0052, E-ISSN 1718-7729, Vol. 30, nr 12, s. 10260-10271Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Psammocarcinoma (PsC) represents a rare form of low-grade serous tumor of the ovary or peritoneum. Although ovarian cancer generally has a poor prognosis in its late stages, PsC seems to have a more indolent course. We present a patient with a history of unspecific abdominal pain for more than a year, with sudden acute onset of severe inguinal pain. On admission to the hospital, a computed tomography (CT) revealed a pelvic mass of suspected ovarian origin. Radical surgery was attempted but not achieved due to widespread tumor growth. Histopathological evaluation revealed estrogen receptor-positive stage III PsC. Tamoxifen treatment was thus initiated, still maintaining stable disease 10 years later. The patient has undergone extensive radiological work-up, including CT, chest X-ray, 18F-fluoro-deoxy-glucose positron emission tomography (PET)/CT, 99mTc- hydroxymethylene diphosphonate (HDP) bone scintigraphy, 18F-fluoro-thymidine (FLT) PET/CT, Tc-99m depreotide scintigraphy and magnetic resonance imaging. In conclusion, we demonstrate that PsC has characteristic radiological features and different imaging modalities can be suitable in different clinical situations. In contrast to most other ovarian cancers, PsC does not always warrant adjuvant chemotherapy, even in advanced stages. This emphasizes the need for a deeper knowledge of the biological behavior of this rare tumor, to select the optimal treatment strategy.

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  • 6.
    Hosokawa, K
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Wahlberg, P
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Ny, Tor
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Cajander, S
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Olofsson, Jan I
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Dominant expression and distribution of oestrogen receptor beta over oestrogen receptor alpha in the human corpus luteum2001Ingår i: Molecular human reproduction, ISSN 1360-9947, E-ISSN 1460-2407, Vol. 7, nr 2, s. 137-145Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To investigate the potential importance of oestrogen as a local regulator of human corpus luteum function, the mRNA expression pattern and cellular localization of oestrogen receptors (ERs), ER-alpha and ER-beta, were studied in corpora lutea grouped according to age, where days 2-5 post-LH rise were designated as the early luteal phase, days 6-10 as mid-luteal and days 11-14 as the late luteal phase respectively. Northern blot analysis using an ER-beta probe in samples from whole ovarian tissue and isolated corpora lutea, revealed a major band at 7.5 kb and several minor bands between 4-10 kb, while no signals for ER-alpha mRNA were obtained. However, using a semi-quantitative reverse transcription-polymerase chain reaction followed by Southern blotting, ER-beta mRNA levels were found to be 63% lower (P: < 0.05, n = 39) in the mid-luteal phase compared with the early luteal phase, while ER-alpha mRNA expression showed no statistical differences between the different age groups. Using in-situ hybridization, ER-beta mRNA expression was localized to the steroidogenic luteal cells as well as perivascular cells and fibroblasts in the corpus luteum. Immunohistochemistry confirmed the localization of ER-beta protein, but no clear staining of luteal cells was found using antibodies against ER-alpha. Collectively, the findings of low to moderate expression of ER-beta mRNA and protein in the steroidogenic cells, and also in vascular endothelial cells of the corpus luteum, as opposed to diminutive amounts of ER-alpha mRNA, suggest that oestrogen activity is primarily transduced via ER-beta in the human corpus luteum.

  • 7.
    Idahl, Annika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Jurstrand, Margaretha
    Kliniskt forskingscentrum, Örebro universitetssjukhus.
    Møller, Jens K
    Klinisk mikrobiologi, Århus universitetssjukhus, Skejby, Danmark.
    Marklund, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Lindgren, Peter
    Inst för kvinnors och barns hälsa, obstetrik och gynekologi, Uppsala universitet.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Chlamydia trachomatis, Mycoplasma genitalium, Neisseria gonorrhoeae, human papillomavirus, and polyomavirus are not detectable in human tissue with epithelial ovarian cancer, borderline tumor, or benign conditions2010Ingår i: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 202, nr 1, s. 71.e1-71.e6Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    OBJECTIVE: We sought to analyze the presence of the microorganisms Chlamydia trachomatis, Mycoplasma genitalium, Neisseria gonorrhoeae, human papillomavirus (HPV), and the polyomaviruses BK virus (BKV) and JC virus (JCV) in ovarian tissues of women with ovarian carcinomas, borderline tumors, and benign conditions. STUDY DESIGN: Ovarian tissue, snap-frozen and stored at -80 degrees C, from 186 women with benign conditions, borderline tumors, and epithelial ovarian cancer, as well as tissue from the contralateral ovary of 126 of these women, were analyzed regarding presence of C trachomatis and N gonorrhoeae (transcription mediated amplification), M genitalium (real-time polymerase chain reaction [PCR]), HPV (PCR), and BKV and JCV (PCR). RESULTS: All the tissue samples studied were found negative for the microorganisms analyzed. CONCLUSION: C trachomatis, M genitalium, N gonorrhoeae, HPV, and the polyomaviruses BKV and JCV are not detectable in ovarian tissues either from women with benign conditions and borderline tumors or from women with ovarian cancer.

  • 8.
    Idahl, Annika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Jurstrand, Margaretha
    Clinical Research Centre, Örebro University Hospital, Örebro, Sweden.
    Kumlin, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Ohlson, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Chlamydia trachomatis and Mycoplasma genitalium plasma antibodies in relation to epithelial ovarian tumors2011Ingår i: Infectious diseases in obstetrics and gynecology, ISSN 1064-7449, E-ISSN 1098-0997, Vol. 2011, artikel-id 824627Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To assess associations of Chlamydia trachomatis and Mycoplasma genitalium antibodies with epithelial ovarian tumors.

    Methods: Plasma samples from 291 women, undergoing surgery due to suspected ovarian pathology, were analyzed with respect to C. trachomatis IgG and IgA, chlamydial Heat Shock Protein 60-1 (cHSP60-1) IgG and M. genitalium IgG antibodies. Women with borderline tumors (), ovarian carcinoma (), or other pelvic malignancies () were matched to four healthy controls each.

    Results: Overall, there were no associations of antibodies with EOC. However, chlamydial HSP60-1 IgG antibodies were associated with type II ovarian cancer () in women with plasma samples obtained >1 year prior to diagnosis (). M. genitalium IgG antibodies were associated with borderline ovarian tumors ().

    Conclusion: Chlamydial HSP60-1 IgG and M. genitalium IgG antibodies are in this study associated with epithelial ovarian tumors in some subsets, which support the hypothesis linking upper-genital tract infections and ovarian tumor development.

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  • 9.
    Israelsson, Pernilla
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Björk, Emma
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Nagaev, Ivan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Nagaeva, Olga
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Mincheva-Nilsson, Lucia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    NKG2D-mediated cytotoxicity improves after primary surgery for high-grade serous ovarian cancer2023Ingår i: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 89, nr 1, artikel-id e13647Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Problem: Tumors compromise the patients’ immune system to promote their own survival. We have previously reported that HGSC exosomes play a central role, downregulating NKG2D cytotoxicity. Primary surgery's effect on tumor exosomes and NKG2D cytotoxicity in HGSC patients has not been studied before. The overall objective of this study was to explore the effect of surgery on the exosome-induced impairment of NKG2D cytotoxicity in HGSC.

    Method of study: Paired pre- and post-operative blood samples were subjected to cell and exosome analyses regarding the NKG2D receptor and ligands, and NKG2D-mediated cytotoxicity. Lymphocytes were phenotyped by immunoflow cytometry. Exosomes, isolated by ultracentrifugation, and characterized by nanoparticle tracking analysis, transmission and immune electron microscopy and western blot were used in functional cytotoxic experiments. HGSC explant culture-derived exosomes, previously studied by us, were used for comparison.

    Results: HGSC exosomes from patients’ sera downregulated NKG2D-mediated cytotoxicity in NK cells of healthy donors. In a subgroup of subjects, NKG2D expression on CTLs and NK cells was upregulated after surgery, correlating to a decrease in the concentration of exosomes in postoperative sera. An overall significantly improved NKG2D-mediated cytotoxic response of the HGSC patients’ own NK cells in postoperative compared to preoperative samples was noted.

    Conclusions: Surgical removal of the primary tumor has a beneficial effect, relieving the exosome-mediated suppression of NKG2D cytotoxicity in HGSC patients, thus boostering their ability to combat cancer.

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  • 10.
    Israelsson, Pernilla
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Björk, Emma
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Nagaev, Ivan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Nagaeva, Olga
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Mincheva-Nilsson, Lucia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    The influence of surgery on circulating ovarian cancer exosomes and the NKG2D‐mediated cytotoxicityManuskript (preprint) (Övrigt vetenskapligt)
  • 11.
    Israelsson, Pernilla
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Dehlin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Nagaev, Ivan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Mincheva-Nilsson, Lucia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Cytokine mRNA and protein expression by cell cultures of epithelial ovarian cancer: Methodological considerations on the choice of analytical method for cytokine analyses2020Ingår i: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 84, nr 1, artikel-id e13249Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Problem: To get a comprehensive picture of cytokine expression in health and disease is difficult, cytokines are transiently and locally expressed, and protein analyses are burdened by biological modifications, technical issues, and sensitivity to handling of samples. Thus, alternative methods, based on molecular techniques for cytokine mRNA analyses, are often used. We compared cytokine mRNA and protein expression to evaluate whether cytokine mRNA profiles can be used instead of protein analyses.

    Method of study: In kinetic experiments, cytokine mRNA and protein expression of IL-1 beta, IL-6, IL-8, TNF-alpha, and TNF-beta/LTA were studied using real-time RT-qPCR and Luminex(R) microarrays in the ovarian cancer cell lines OVCAR-3, SKOV-3 and the T-cell line Jurkat, after activation of transcription by thermal stress. In addition, we analyzed IL-6 and IL-8 mRNA and protein in a small number of ovarian cancer patients.

    Results: Ovarian cancer cells can express cytokines on both mRNA and protein level, with 1-4 hours' time delay between the mRNA and protein peak and a negative Spearman correlation. The mRNA and protein expression in patient samples was poorly correlated, reflecting previous studies.

    Conclusion: Cytokine mRNA and protein expression levels show diverging results, depending on the material analyzed and the method used. Considering the high sensitivity and reproducibility of real-time RT-qPCR, we suggest that cytokine mRNA profiles could be used as a proxy for protein expression for some specific purposes, such as comparisons between different patient groups, and in defining mechanistic pathways involved in the pathogenesis of cancer and other pathological conditions.

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  • 12.
    Israelsson, Pernilla
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Labani-Motlagh, Alireza
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Nagaev, Ivan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Dehlin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Nagaeva, Olga
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Mincheva-Nilsson, Lucia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    Assessment of cytokine mRNA expression profiles in tumor microenvironment and peripheral blood mononuclear cells of patients with high-grade serous carcinoma of the ovary2019Ingår i: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 29, s. A138-A138Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction/Background Tumor establishment, metastatic spreading and poor survival in ovarian cancer is strongly associated with progressive derangement of the patient‘s immune system. Accumulating evidence suggests that immune impairment is influenced by the production and presence of cytokines in the tumor microenvironment.

    Methodology Cytokine mRNA profiles in tumor tissue and peripheral blood mononuclear cells (PBMC) were analyzed in patients with high grade serous carcinoma (HGSC) of the ovary and compared it to patients with benign ovarian conditions and controls with normal ovaries. Cytokine assessment was done by real-time quantitative RT-PCR and specific primers and probes for 12 cytokines-IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-15, TNF-α, TNF-β/LTA, TGF-β1, and GM-CSF chosen to distinguish between cytotoxic Th1, humoral Th2, regulatory Th3/Tr1 and inflammatory responses.

    Results The cytokine mRNA response in the HGSC patients was significantly up regulated compared to patients with benign ovarian conditions and normal ovary controls confirming the immunogenicity of HGSC and implying immune recognition and reaction locally in the tumor microenvironment and systemically in the peripheral blood.There was an up-regulation of inflammatory and inhibitory cytokine mRNA promoting tumor progression, T-regulatory cell priming and T-regulatory cell-mediated immune suppression. In contrast, there was an inability to mount the crucially important IFN gamma response needed for upregulation of the cytotoxic anti-tumor response in the local microenvironment. In addition, systemic IL-4- mediated Th2 response prevailed in the peripheral blood deviating the systemic defense towards humoral immunity.

    Conclusion Taken together, these results suggest local and systemic cytokine cooperation promoting tumor survival, progression and immune escape. Our study confirms and extends previous investigations and contributes to the evaluation of potential cytokine candidates for diagnostic cytokine mRNA profiles and for future therapeutic interventions based on cytokine inhibition.

  • 13.
    Israelsson, Pernilla
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Labani-Motlagh, Alireza
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Nagaev, Ivan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Dehlin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Nagaeva, Olga
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Mincheva-Nilsson, Lucia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Assessment of cytokine mRNA expression profiles in tumor microenvironment and peripheral blood mononuclear cells of patients with high-grade serous carcinoma of the ovary2017Ingår i: Journal of Cancer Science & Therapy, ISSN 1948-5956, Vol. 9, nr 5, s. 422-429Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Tumor establishment, metastatic spreading and poor survival in ovarian cancer is strongly associated with progressive derangement of the patient’s immune system. Accumulating evidence suggests that immune impairment is influenced by the production and presence of cytokines in the tumor microenvironment. Methods: Cytokine mRNA profiles in tumor tissue and peripheral blood mononuclear cells (PBMC) were analyzed in patients with high grade serous carcinoma (HGSC) of the ovary and compared it to patients with benign ovarian conditions and controls with normal ovaries. Cytokine assessment was done by real-time quantitative RT-PCR and specific primers and probes for 12 cytokines-IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-15, TNF-α, TNF-β/LTA, TGF-β1, and GM-CSF chosen to distinguish between cytotoxic Th1, humoral Th2, regulatory Th3/Tr1 and inflammatory responses. Results: The cytokine mRNA response in the HGSC patients was significantly up regulated compared to patients with benign ovarian conditions and normal ovary controls confirming the immunogenicity of HGSC and implying immune recognition and reaction locally in the tumor microenvironment and systemically in the peripheral blood.There was an up-regulation of inflammatory and inhibitory cytokine mRNA promoting tumor progression, T-regulatory cell priming and T-regulatory cell-mediated immune suppression. In contrast, there was an inability to mount the crucially important IFN gamma response needed for upregulation of the cytotoxic anti-tumor response in the local microenvironment. In addition, systemic IL-4- mediated Th2 response prevailed in the peripheral blood deviating the systemic defense towards humoral immunity. Conclusions: Taken together, these results suggest local and systemic cytokine cooperation promoting tumor survival, progression and immune escape. Our study confirms and extends previous investigations and contributes to the evaluation of potential cytokine candidates for diagnostic cytokine mRNA profiles and for future therapeutic interventions based on cytokine inhibition.

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  • 14.
    Jagarlamudi, Krishna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Liu, Lian
    Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan, China.
    Adhikari, Deepak
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Reddy, Pradeep
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Idahl, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Liu, Kui
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Oocyte-specific deletion of Pten in mice reveals a stage-specific function of PTEN/PI3K signaling in oocytes in controlling follicular activation2009Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 4, nr 7, s. e6186-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Immature ovarian primordial follicles are essential for maintenance of the reproductive lifespan of female mammals. Recently, it was found that overactivation of the phosphatidylinositol 3-kinase (PI3K) signaling in oocytes of primordial follicles by an oocyte-specific deletion of Pten (phosphatase and tensin homolog deleted on chromosome ten), the gene encoding PI3K negative regulator PTEN, results in premature activation of the entire pool of primordial follicles, indicating that activation of the PI3K pathway in oocytes is important for control of follicular activation. To investigate whether PI3K signaling in oocytes of primary and further developed follicles also plays a role at later stages in follicular development and ovulation, we conditionally deleted the Pten gene from oocytes of primary and further developed follicles by using transgenic mice expressing zona pellucida 3 (Zp3) promoter-mediated Cre recombinase. Our results show that Pten was efficiently deleted from oocytes of primary and further developed follicles, as indicated by the elevated phosphorylation of the major PI3K downstream component Akt. However, follicular development was not altered and oocyte maturation was also normal, which led to normal fertility with unaltered litter size in the mutant mice. Our data indicate that properly controlled PTEN/PI3K-Akt signaling in oocytes is essential for control of the development of primordial follicles whereas overactivation of PI3K signaling in oocytes does not appear to affect the development of growing follicles. This suggests that there is a stage-specific function of PTEN/PI3K signaling in mouse oocytes that controls follicular activation.

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  • 15.
    Jonsson, S.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Idahl, A.
    Chlamydia trachomatis and anti-MUC1 antibodies and subsequent risk of high grade serous ovarian cancer: a population-based case-control study in Northern Sweden2019Ingår i: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 29, s. A139-A139Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction/Background Chlamydia trachomatis (C. trachomatis) salpingitis causes inflammatory damage to the fallopian tube, the suggested origin of most high grade serous cancers (HGSC), and could thereby cause initiation and progression of ovarian cancer. Infection with C. trachomatis may stimulate production of MUC1 protein and potentially both increase or decrease anti-MUC1 antibody levels. The aim of this study was to examine if serology indicating past infection with C. trachomatis and anti-MUC1 antibodies in prospective blood samples were associated with HGSC.

    Methodology In a prospective nested case-control study within the Northern Sweden Health and Disease Study (NSHDS) and the Northern Sweden Maternity Cohort (NSMC), the prevalence of chlamydial and anti-MUC1 antibodies was analyzed in blood samples drawn more than one year prior to diagnosis from 92 women with HGSC and 363 matched controls. Matching factors were age and date at blood draw. Plasma C. trachomatis IgG was analyzed using a MIF-test (Focus Diagnostics), chlamydial HSP60 (cHSP60) and anti-MUC1 IgG were analyzed using ELISA serology (Medac; Thermo-Fisher Scientific). HGSC diagnosis was confirmed by pathology report review.

    Data were analyzed using Chi-square test, Fisher’s exact test and Mann-Whitney U test. Correlation analysis was done by Spearman’s correlation test. A two-sided P-value less than 0.05 was considered significant.

    Results The prevalence of C. trachomatis IgG and cHSP60 IgG antibodies, as well as the level of anti-MUC1 IgG in women with HGSC compared with controls were similar (16.3% vs. 17.0%, p=0.867; 27.3% vs 28.5%, p=0.802; median 0.24 vs 0.25, p=0.700). A significant correlation was found between anti-MUC1 IgG and cHSP60 IgG (r=0.169; p< 0.001).

    Conclusion There were no significant association between chlamydial or anti-MUC1 IgG antibodies and HGSC in this prospective nested case control study.

  • 16.
    Jonsson, Sarah
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Idahl, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Chlamydia trachomatis and Anti-MUC1 Serology and Subsequent Risk of High-Grade Serous Ovarian Cancer: A Population-Based Case-Control Study in Northern Sweden2020Ingår i: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 13, nr 1, s. 86-91Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Chlamydia trachomatis salpingitis causes inflammatory damage to the fallopian tube and could potentially cause initiation and progression of high-grade serous ovarian cancer (HGSC). Furthermore, C. trachomatis infection may stimulate mucin 1 (MUC1) protein production, possibly affecting anti-MUC1 antibody levels. The aim of this study was to examine if serology indicating past infection with C. trachomatis as well as anti-MUC1 production was associated with subsequent risk of HGSC.

    MATERIALS AND METHODS: In a prospective nested case-control study within the Northern Sweden Health and Disease Study and the Northern Sweden Maternity Cohort, the prevalence of chlamydial and anti-MUC1 antibodies was analyzed in blood samples drawn more than one year before diagnosis from 92 women with HGSC and 359 matched controls. Matching factors were age, date at blood draw, and sampling cohort. Plasma C. trachomatis IgG was analyzed using commercial micro-immunofluorescence test; chlamydial Heat Shock Protein 60 IgG (cHSP60) and anti-MUC1 IgG were analyzed with ELISA technique.

    RESULTS: The prevalence of C. trachomatis IgG and cHSP60 IgG antibodies, as well as the level of anti-MUC1 IgG was similar in women with HGSC and controls (16.3% vs. 17.0%, P = 0.87; 27.2% vs. 28.5%, P = 0.80; median 0.24 vs. 0.25, P = 0.70). Anti-MUC1 IgG and cHSP60 IgG levels were correlated (r = 0.169; P < 0.001).

    CONCLUSIONS: The findings of this prospective nested case-control study did not support an association between C. trachomatis infection, as measured by chlamydial serology, or anti-MUC1 IgG antibodies, and subsequent risk of HGSC.

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  • 17.
    Labani-Motlagh, Alireza
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Israelsson, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Nagaev, Ivan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Nagaeva, Olga
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Dehlin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Baranov, Vladimir
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Mincheva-Nilsson, Lucia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Differential expression of ligands for NKG2D and DNAM-1 receptors by epithelial ovarian cancer-derived exosomes and its influence on NK cell cytotoxicity2016Ingår i: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 37, nr 4, s. 5455-5466Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cancers constitutively produce and secrete into the blood and other biofluids 30-150 nm-sized endosomal vehicles called exosomes. Cancer-derived exosomes exhibit powerful influence on a variety of biological mechanisms to the benefit of the tumors that produce them. We studied the immunosuppressive ability of epithelial ovarian cancer (EOC) exosomes on two cytotoxic pathways of importance for anticancer immunity-the NKG2D receptor-ligand pathway and the DNAM-1-PVR/nectin-2 pathway. Using exosomes, isolated from EOC tumor explant and EOC cell-line culture supernatants, and ascitic fluid from EOC patients, we studied the expression of NKG2D and DNAM-1 ligands on EOC exosomes and their ability to downregulate the cognate receptors. Our results show that EOC exosomes differentially and constitutively express NKG2D ligands from both MICA/B and ULBP families on their surface, while DNAM-1 ligands are more seldom expressed and not associated with the exosomal membrane surface. Consequently, the NKG2D ligand-bearing EOC exosomes significantly downregulated the NKG2D receptor expression on peripheral blood mononuclear cells (PBMC) while the DNAM-1 receptor was unaffected. The downregulation of NKG2D receptor expression was coupled to inhibition of NKG2D receptor-ligand-mediated degranulation and cytotoxicity measured in vitro with OVCAR-3 and K562 cells as targets. The EOC exosomes acted as a decoy impairing the NKG2D mediated cytotoxicity while the DNAM-1 receptor-ligand system remained unchanged. Taken together, our results support and explain the mechanism behind the recently reported finding that in EOC, NK-cell recognition and killing of tumor cells was mainly dependent on DNAM-1 signaling while the contribution of the NKG2D receptor-ligand pathway was complementary and uncertain.

  • 18. Liu, Lian
    et al.
    Rajareddy, Singareddy
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Reddy, Pradeep
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Jagarlamudi, Krishna
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Du, Chun
    Shen, Yan
    Guo, Yongzhi
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Boman, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Lundin, Eva
    Patologi.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Selstam, Gunnar
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Liu, Kui
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Phosphorylation and inactivation of glycogen synthase kinase-3 by soluble kit ligand in mouse oocytes during early follicular development.2007Ingår i: Journal of Molecular Endocrinology, ISSN 0952-5041, E-ISSN 1479-6813, Vol. 38, nr 1-2, s. 137-146Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Communication between mammalian oocytes and their surrounding granulosa cells through the Kit-Kit ligand (KL, or stem cell factor, SCF) system has been shown to be crucial for follicular development. Our previous studies (Reddy et al. 2005, Liu et al. 2006) have indicated that the intra-oocyte KL-Kit-PI3 kinase (PI3K)-Akt-Foxo3a cascade may play an important role in follicular activation and early development. In the present study, using in situ hybridization and in vitro culture of growing oocytes from 8-day-old postnatal mice, we have demonstrated that another Akt substrate, glycogen synthase kinase-3 (GSK-3), is expressed in growing oocytes. Also, treatment of cultured mouse oocytes with soluble KL not only leads to increased Akt kinase activity in the oocytes, which can phosphorylate recombinant GSK-3 in vitro, but also leads to phosphorylation of oocyte GSK-3alpha and GSK-3beta, which can result in the inactivation of GSK-3 function in oocytes. In addition, we have shown that the regulation of GSK-3alpha and GSK-3beta in cultured oocytes by soluble KL is accomplished through PI3K, since the PI3K-specific inhibitor LY294002 completely abolished the KL-induced phosphorylation of GSK-3alpha and GSK-3beta. Moreover, blockage of the Kit signaling pathway by a Kit function-blocking antibody, ACK2, resulted in reduced phosphorylation of GSK-3. Taken together, our data suggest that the cascade from granulosa cell-derived KL to Kit-PI3K-Akt-GSK-3 in oocytes may take part in regulation of oocyte growth and early ovarian follicular development.

  • 19.
    Oda, Husam
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Öfverman, Charlotte
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Lindquist, David
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Stefansson, Kristina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    CD8, CD44, Ki-67, and p53 immunoreactivity in vulvar squamous cell carcinoma: correlation with prognosis in relation to HPV-DNA and p16ink4a statusManuskript (preprint) (Övrigt vetenskapligt)
  • 20.
    Ofverman, Charlotte
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Stefansson, Kristina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lindquist, David
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    CASE SERIES OF PATIENTS WITH LEIOMYOSARCOMA OF THE UTERUS TREATED WITH TRABECTEDIN IN NORTHERN SWEDEN2016Ingår i: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 26, nr Supplement 3, s. 1046-1046, artikel-id IGCS-0142Artikel i tidskrift (Refereegranskat)
  • 21.
    Olofsson, Jan I
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Poromaa, I S
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Kjellberg, Lennart
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Damber, M G
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Clinical and pregnancy outcome following ectopic pregnancy: a prospective study comparing expectancy, surgery and systemic methotrexate treatment2001Ingår i: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 80, nr 8, s. 744-749Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Systemic single-dose methotrexate treatment is a safe treatment option with a reasonably high success rate, with similar probability of a later intrauterine pregnancy as conventional surgical treatment.

  • 22.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Gynekologi2021Ingår i: Kliniska färdigheter: mötet mellan patient och läkare / [ed] Pontus Karling, Lund: Studentlitteratur AB, 2021, 4, s. 145-157Kapitel i bok, del av antologi (Övrigt vetenskapligt)
  • 23.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Intraovarian mechanisms influencing the human corpus luteum2000Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: The human corpus luteum (CL) is a transient endocrine gland, only functionally active for about 14 days. Its principal function is to produce and secrete progesterone and thereby support the endometrium for implantation of a blastocyst and prevent rejection of the developing embryo. In the event of a non-conceptive cycle, functional and structural demise of the CL follows and a new ovulatory cycle begins. The aims of the thesis were to study different mechanisms involved in the extrinsic and intrinsic regulation of the CL and correlate these findings to available clinical investigations tools.

    Materials and methods: Sixty women volunteered to donate their CL prior to scheduled surgery due to benign conditions. They were grouped according to CL-age, based on the occurrence of a preovulatory luteinizing hormone (LH) surge where days 2-5 post LH surge were designated as early luteal phase, days 6-9 as mid luteal phase and days 11-14 as late luteal phase. The CL bearing ovary was investigated using transvaginal ultrasonographical B-mode and color Doppler imaging prior to surgery. Following excision, the CL was further characterized using anatomical and morphological measurements, in vivo and in vitro hormone synthesis, isolation and cultures of steroidogenic luteal cells. Moreover, active transcription of putative regulatory genes of interest was targeted using semi-quantitative reverse-transcription polymerase chain reaction, in situ hybridization and Northern blots, and these genes' respective translation products were characterized by immunocytochemistry.

    Results: The bulk of progesterone is stimulated by human chorionic gonadotropin (hCG) in the peripheral (steroidogenic) layer of the CL, where the LH/hCG receptor, as well as progesterone receptor (PR) isoform A/B and estrogen receptor type β (ER-β), but not ER-α, was localized. The sesitivity towards hCG was highest during the mid luteal phase in concordance with the value of LH/hCG receptor coding mRNAs. During this phase, despite low levels of PR-B mRNA, hCG treatment initiated a significant rise in progesterone output which could be blunted by the PR antagonist mifepristone. Increased amounts of prostaglandin (PG) F and its respective receptor (FP) mRNA were detected during the later developmental stages of the CL. However, steroidogenic luteal cells were unresponsive to added PGF until late luteal phase, indicative of an acquisition of sensitivity to the proposed luteolytic signal during this stage. Intraluteal vascular density was highest in early luteal phase and dramatically decreased during the course of CL development, a finding which was inversely correlated to resistance to blood flow in intraovarian blood vessels supplying the CL. Furthermore, a high degree of agreement between ultrasonographical and anatomical measurements of the CL was found.

    Conclusions: Based on the novel findings herein, the hypothesis of steroid influence, acting within or near the steroidogenic luteal cells is confirmed. Alongside the classical extrinsic signals (e.g. hCG) and locally produced factors (e.g. PGF) these findings may further explain their modulatory roles during luteolysis or very early pregnancy. Furthermore, transvaginal ultrasonography in combination with color Doppler measurements may serve as a clinical tool to evaluate CL function.

  • 24.
    Ottander, Ulrika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Högberg, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Löfgren, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    [A case report. Sepsis in connection with levonorgestrel IUD]1995Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 92, nr 48, s. 4555-4557Artikel i tidskrift (Refereegranskat)
  • 25.
    Ottander, Ulrika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Dahlstrand, Hanna
    Karolinska Institutet, Stockholm, Sverige.
    Äggstockscancer2023Ingår i: Cancersjukdomar / [ed] Mikael Johansson; Roger Henriksson; Mef Nilbert, Lund: Studentlitteratur AB, 2023, 1:1, s. 369-377Kapitel i bok, del av antologi (Övrigt vetenskapligt)
  • 26.
    Ottander, Ulrika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Hosokawa, Kenichi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Liu, Kui
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Ny, Tor
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Olofsson, Jan I
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    A putative stimulatory role of progesterone acting via progesterone receptors in the steroidogenic cells of the human corpus luteum2000Ingår i: Biology of Reproduction, ISSN 0006-3363, E-ISSN 1529-7268, Vol. 62, nr 3, s. 655-663Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To further explore the proposed auto-regulatory role of progesterone action in the human corpus luteum (CL), the expression and functional roles of progesterone receptor (PR) isoforms A and B during the luteal phase (LP) of the menstrual cycle were investigated. A total of 27 otherwise healthy patients previously scheduled for surgery were recruited after informed consent. An LH rise was detected, and CL were grouped according to age (Days 2-5 post-LH-rise, early LP; Days 6-10, mid LP; Days 11-14, late LP). Using a semiquantitative reverse transcription-polymerase chain reaction assay, the PR-B mRNA levels, which were 100- to 1000-fold lower than PR-A/B mRNA, were 46% lower (P < 0.05, n = 24) in mid LP, compared to early and late LP. CL tissue levels of progesterone and PR-A/B protein levels were inversely correlated to increasing CL age; i.e., significantly reduced levels were observed in the late LP (r(2) = 0.34, P < 0.01, n = 23). Expression of PR-A/B mRNA as well as PR-A/B protein were detected by in situ hybridization and immunohistochemistry, respectively. Both methods revealed a clear and distinct localization to cells in the steroidogenic layer of the CL. Freshly obtained mid-luteal CL cells were cultured in vitro, and media were analyzed for progesterone concentrations after treatment by incremental doses of hCG and the stable PR antagonist mifepristone, alone or in combination. Mifepristone did not per se alter progesterone synthesis, but when it was added in conjunction with hCG, a dose-related inhibitory response was seen, with a maximal 47% reduction in progesterone output at a 10 microM addition (P < 0.05, n = 3). Collectively, these data implicate a stimulatory role of progesterone receptor-mediated action in the steroidogenic cells of the human CL, which may serve as an important pathway for maintaining functional homeostasis during early pregnancy.

  • 27.
    Ottander, Ulrika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Leung, Constant HB
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Olofsson, Jan I
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Functional evidence for divergent receptor activation mechanisms of luteotrophic and luteolytic events in the human corpus luteum1999Ingår i: Molecular human reproduction, ISSN 1360-9947, E-ISSN 1460-2407, Vol. 5, nr 5, s. 391-395Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Using a dispersed human luteal cell culture model, progesterone synthesis following treatment by incremental doses of human chorionic gonadotrophin (HCG) and the stable prostaglandin F2alpha (PGF2alpha) analogue cloprostenol, alone or in combination, was related to corpora lutea (CL) mRNA transcript abundance coding for the luteinizing hormone (LH)/HCG receptor (LH-R) and PGF2alpha-receptor (FP) by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) in 33 otherwise healthy women, scheduled for surgery due to benign conditions. CL were grouped according to age, based on the occurrence of a preovulatory LH surge where post-LH days 2-5 were designated as early luteal phase, days 6-10 as mid-luteal phase and days 11-14 as late luteal phase. When exposed to HCG, maximal progesterone output was raised 2.2-fold (P = 0.08, n = 5) compared with untreated controls in the early CL, while it increased 5.7- and 4.6-fold in the mid- and late groups respectively (P<0.05, n = 4 mid-luteal phase, n = 3 late luteal phase). This stimulation pattern was found to be concordant with the value of mRNA coding for LH-R in all groups (n = 6 early luteal phase, n = 5 mid-luteal phase, n = 6 late luteal phase). The integrated response to HCG and cloprostenol showed a dose-dependent 60% inhibition of progesterone production; but only in late luteal phase luteal cells (P<0.01, n = 3). FP mRNA values were lowest in early luteal phase, and increased with the age of the CL. Interestingly, lowest CL tissue concentrations of the natural FP agonist PGF2alpha were found during mid-luteal phase while it increased again 1.6-fold during late luteal phase (P<0.05, n = 8 versus mid-luteal phase, n = 6). Collectively, these data demonstrate that (i) the extrinsic functional control (or rescue of CL in the event of pregnancy) occurs when the sensitivity towards LH/HCG is maximal; and (ii) the demise of CL function is mediated via an acquisition of sensitivity towards the intrinsic luteolytic signal, PGF2alpha in the ageing CL.

  • 28.
    Ottander, Ulrika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Nakata, M
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Liu, K
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Ny, Tor
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Olofsson, J I
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Compartmentalization of human chorionic gonadotrophin sensitivity and luteinizing hormone receptor mRNA in different subtypes of the human corpus luteum1997Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 12, nr 5, s. 1037-1042Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The relationship was investigated between different ultrasonographically defined subtypes of the human corpus luteum and progesterone production. Twenty-one women in the mid-luteal phase who underwent laparotomy for benign uterine conditions volunteered for this study. The corpus luteum was identified by preoperative ultrasound and classified into four types according to earlier established criteria, where types a and c were centrally hypoechoic, types b and d were centrally echogenic, types a and b had thin surrounding 'walls' (<3 mm) and types c and d had thick walls (<3 mm). After luteectomy, the theca externa capsule was removed and tissue from directly beneath the surface ('peripheral region') and the layer immediately beneath ('inner region') minced into 4-6 mg pieces. Following preincubation, pieces were incubated for 3 h at 37 degrees C in HEPES-minimal essential medium buffer with or without human chorionic gonadotrophin (HCG; 10 IU/ml), and subsequently progesterone accumulation in the medium was determined by radioimmunoassay. The highest progesterone production was consistently seen in the peripheral region. Type a had a significantly (P > 0.01) lower progesterone production (3.2 +/- 1.5 nmol/g tissue wet weight, mean +/- SEM, n = 4) than that of types b, c and d (17.7 +/- 3.5 nmol/g tissue wet weight, n = 9). All types responded to HCG with an almost two-fold increase in progesterone production. However, the maximal progesterone produced following stimulation by HCG in the type a corpus luteum was <50% of the basal (unstimulated) progesterone synthesis of any other type of corpus luteum. Using in-situ hybridization, with a primate RNA probe complementary to the region coding the extracellular part of the luteinizing hormone (LH) receptor, a highly localized expression of LH receptor mRNA to the peripheral region was found. Negligible or low levels of expression were found in the theca externa capsule and the inner region. No obvious correlations between the different subtypes of corpora lutea and LH receptor mRNA expression were seen. Thus, the ultrasonographic detection of a thin-walled and centrally hypoechoic corpus luteum correlates well with reduced progesterone secretion. The underlying cellular mechanism does not appear to involve a diminished sensitivity to the gonadotrophic stimulation by LH or HCG.

  • 29.
    Ottander, Ulrika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Poromaa, Inger Sundström
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bjurulf, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Skytt, Asa
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Olofsson, Jan I
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Allopregnanolone and pregnanolone are produced by the human corpus luteum.2005Ingår i: Mol Cell Endocrinol, ISSN 0303-7207, Vol. 239, nr 1-2, s. 37-44Artikel i tidskrift (Refereegranskat)
  • 30.
    Ottander, Ulrika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Solensten, Nils Gunnar
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Olofsson, Jan I
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Intraovarian blood flow measured with color doppler ultrasonography inversely correlates with vascular density in the human corpus luteum of the menstrual cycle2004Ingår i: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 81, nr 1, s. 154-159Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective

    To evaluate the morphologic characteristics underlying the ultrasonographic appearance and blood flow dynamics in the human corpus luteum (CL) of the menstrual cycle.

    Design

    Cross-sectional study.

    Setting

    Umeå University Hospital, Umeå, Sweden.

    Patient(s)

    Twenty-six otherwise healthy women with proven fertility and a history of regular menstrual cycles, scheduled for elective hysterectomy or tubal sterilization.

    Intervention(s)

    An ovulatory LH rise in urine was established and the CL age was determined according to the day after the LH rise. Before surgery, a standardized ultrasonographic examination of the CL, including B-mode and color Doppler ultrasonography measurements, was performed. Upon commencing the minilaparotomy, the CL was excised and measured using a digital slide-caliper. The volume density (percentage of CL volume occupied by blood vessels) of factor VIII–related antigen immunostained endothelial cells was determined.

    Main outcome measure(s)

    Pulsatility index obtained from intraovarian blood vessels supplying the CL and volume density of blood vessels in CL tissue. The CL maximal and minimal outer and inner dimensions were measured in vivo by ultrasonography and ex vivo by a digital slide caliper.

    Result(s)

    A statistically significant decrease of blood vessel density and an increased resistance to blood flow, as indicated by pulsatility index, was established during the course of corpus luteum development. An inverse correlation between pulsatility index and volume density of blood vessels was found. A high degree of agreement between ultrasonographic and anatomic measurements of surgically removed CL was found.

    Conclusion(s)

    Transvaginal ultrasonography in combination with intraovarian color Doppler flow measurements is a simple and reliable method to evaluate the size and vascularization of the human CL.

  • 31.
    Reddy, Pradeep
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Liu, Lian
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Ren, Chong
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Lindgren, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Boman, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Shen, Yan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Rytinki, Miia
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Liu, Kui
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Formation of E-cadherin-mediated cell-cell adhesion activates AKT and mitogen activated protein kinase via phosphatidylinositol 3 kinase and ligand-independent activation of epidermal growth factor receptor in ovarian cancer cells2005Ingår i: Mol Endocrinol, ISSN 0888-8809, Vol. 19, nr 10, s. 2564-2578Artikel i tidskrift (Refereegranskat)
  • 32.
    Reddy, Pradeep
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Shen, Lijun
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Ren, Chong
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Boman, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lindgren, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Liu, Yi-Xun
    Sun, Qing-Yuan
    Liu, Kui
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Activation of Akt (PKB) and suppression of FKHRL1 in mouse and rat oocytes by stem cell factor during follicular activation and development2005Ingår i: Dev Biol, ISSN 0012-1606, Vol. 281, nr 2, s. 160-170Artikel i tidskrift (Refereegranskat)
  • 33.
    Rutegård, Martin
    et al.
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Moshtaghi-Svensson, John
    Weibull, Caroline E.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Nordenvall, Caroline
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Exposure to oestrogen and risk of anastomotic leakage after colorectal cancer surgery - A clue to the different leak rates in men and women.2023Ingår i: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 25, nr 1, s. 9-15Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Colorectal anastomotic leakage is consistently more common in men, regardless of tumour location. This fact is largely unexplained but might be a consequence of biological differences including hormonal exposure and not only related to anatomy.

    METHODS: This was a retrospective, nationwide registry-based observational study of post-menopausal women operated for colorectal cancer with an anastomosis between 2007 and 2016. Hormonal exposure before surgery, as defined by prescribed drugs affecting oestrogen levels, was related to postoperative anastomotic leakage, using mixed-effects logistic regression models with adjustment for confounding. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were derived. In addition, separate estimates according to tumour location were computed, and a sensitivity analysis excluding topical oestrogen hormone exposure was conducted.

    RESULTS: Some 16,535 post-menopausal women were included, of which 16.2% were exposed to drugs increasing oestrogen levels before surgery. In this exposed group compared to the unexposed, leak rates were 3.1 and 3.8%, respectively. After adjustment, a reduction of anastomotic leakage in the exposed group was detected (OR: 0.77; 95% CI: 0.59-0.99). This finding was largely attributed to the rectal cancer subgroup (OR: 0.55; 95% CI: 0.36-0.85), while the exclusion of topical oestrogen drugs further reduced the estimates of the main analysis (OR: 0.63; 95% CI: 0.38-1.02).

    CONCLUSIONS: Anastomotic leakage rates are lower in women exposed to hormone replacement therapy before surgery for colorectal cancer, which might explain some of the difference in leak rates between men and women, especially regarding rectal cancer.

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  • 34.
    Vaskivuo, Tommi E
    et al.
    Department of Obstetrics and Gynecology, University of Oulu, Oulu, Finland.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Oduwole, Olayiwola
    Research Center for Molecular Endocrinology, WHO Collaborating Center, University of Oulu, Oulu, Finland.
    Isomaa, Veli
    Research Center for Molecular Endocrinology, WHO Collaborating Center, University of Oulu, Oulu, Finland.
    Vihko, Pirkko
    Research Center for Molecular Endocrinology, WHO Collaborating Center, University of Oulu, Oulu, Finland.
    Olofsson, Jan I
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Tapanainen, Juha S
    Department of Obstetrics and Gynecology, University of Oulu, Oulu, Finland.
    Role of apoptosis, apoptosis-related factors and 17beta-hydroxysteroid dehydrogenases in human corpus luteum regression2002Ingår i: Molecular and Cellular Endocrinology, ISSN 0303-7207, E-ISSN 1872-8057, Vol. 194, nr 1-2, s. 191-200Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The human corpus luteum (CL) is a transient endocrine organ with a life span of 14-16 days. Apoptosis has been suggested to be the mechanism of CL regression and the possible regulatory role of the bcl-2 family in this process has been studied in animals and, to some extent, in humans. In the present study, apoptosis was studied in the human CL and in luteinised granulosa cells by in situ 3'-end labelling and gel electrophoretic DNA fragmentation analysis. The apoptosis-regulating factors Bcl-2, Bax and TNF-alpha, transcription factor NF-kappaB and Caspase-3, a key executioner protein in apoptotic cell death, were studied by immunohistochemistry and in situ hybridisation. Furthermore, we analysed expression of 17beta hydroxysteroid dehydrogenase (17HSD) type 1 and 2, key enzymes in the estrogen metabolism. Apoptosis was found in the CL throughout the luteal phase, but a marked increase of apoptotic luteal cells was observed during the late luteal phase (CL day 11-14). This was preceded by a clear increase of 17HSD type 1 expression. The apoptosis-regulating proteins Bcl-2 and Bax were expressed constantly in the CL throughout the luteal phase. TNF-alpha expression was constant during the early and mid-luteal phases, but in the late luteal phase, some specimens showed increased immunostaining. NF-kappaB and Caspase-3 were present in the CL throughout the luteal phase and in individual specimens, the expression of Caspase-3 was associated with a high rate of apoptosis in the late luteal phase. In conclusion, apoptosis is involved in human luteal regression and estradiol (E(2)) may function as a trigger for this process. The expression of the pro- and anti-apoptotic factors studied in the CL suggest their part in this process, but the conclusive evidence for the exact molecular mechanisms remains open.

  • 35.
    Vinnars, Marie-Therese
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Björk, Emma
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Nagaev, Ivan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bremme, Katarina
    Holmlund, Ulrika
    Sverremark-Ekström, Eva
    Mincheva-Nilsson, Lucia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Enhanced Th1 and inflammatory mRNA responses upregulate NK cell cytotoxicity and NKG2D ligand expression in human pre-eclamptic placenta and target it for NK cell attack2018Ingår i: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 80, nr 1, artikel-id e12969Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Problem: Pre-eclampsia (PE), a severe human pregnancy disorder, is associated with exaggerated systemic inflammation, enhanced cytokine production, and increased shedding of microvesicles leading to endothelial dysfunction, coagulopathy, and extensive placenta destruction. The cause of PE is still unclear. Evidence suggests that its origin lies in the placenta and that the maternal immune system is involved. A shift in cytokine production in PE pregnancy promotes NK cell activation, suggested to be important in PE pathogenesis. In line with this suggestion, we studied NK cell cytotoxicity in peripheral blood of PE patients and controls and the mRNA expression of cytokines and of the NKG2D receptor and its ligands MICA/B and ULBP1-3 in PE- and normal placenta.

    Method of study: The cytotoxic capacity of peripheral blood NK cells was analyzed using K562 target cells. The cytokine mRNA profiles and the mRNA expression of the NKG2D receptor and its ligands MICA/B and ULBP 1-3 in PE placenta were assessed and compared to those in normal placenta using real-time quantitative RT-PCR.

    Results: The cytotoxicity of peripheral blood NK cells was upregulated in PE cases. Further, we found an enhanced inflammatory cytokine mRNA response combined with a dysregulated regulatory response and a significant mRNA overexpression of NKG2D receptor and its ligands MICA/B and ULBP in PE placenta.

    Conclusion: The destruction of chorionic villi observed in PE placenta might be conveyed by an enhanced local cytotoxic response through the NKG2D receptor-ligand pathway, which in turn might be promoted by an intense inflammatory response not counteracted by regulatory cytokine responses.

  • 36.
    Wedin, Madelene
    et al.
    biomedical and clinical science, Linköping University, Linkoping, Sweden.
    Stalberg, Karin
    Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
    Marcickiewicz, Janusz
    Department of Obstetrics and Gynecology, Varberg Hospital, Varberg, Sweden.
    Ahlner, Eva
    Department of Oncology, Department of Biomedical and Clinical Science, Linköping University Hospital, Linkoping, Sweden.
    Ottander, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Åkesson, Åsa
    Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, Institute of clinical sciences, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
    Lindahl, Gabriel
    Department of Oncology, Department of Biomedical and Clinical Scienses, Linköping University, Linköping, Sweden.
    Wodlin, Ninnie Borendal
    Department of Obstetrics and Gynecology in Linköping and Department of Biomedical and Clinical Science, Linköping University, Linköping, Sweden.
    Kjølhede, Preben
    Department of Obstetrics and Gynecology in Linköping and Department of Biomedical and Clinical Science, Linköping University, Linköping, Sweden.
    Risk factors for lymphedema and method of assessment in endometrial cancer: a prospective longitudinal multicenter study2021Ingår i: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 31, nr 11, s. 1416-1427Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: The aim of the study was to determine risk factors for lymphedema of the lower limbs, assessed by four methods, 1 year after surgery for endometrial cancer.

    METHODS: A prospective longitudinal multicenter study was conducted in 14 Swedish hospitals. 235 women with endometrial cancer were included; 116 underwent surgery including lymphadenectomy, and 119 had surgery without lymphadenectomy. Lymphedema was assessed preoperatively and 1 year postoperatively objectively by systematic circumferential measurements of the legs, enabling volume estimation addressed as (1) crude volume and (2) body mass index-standardized volume, or (3) clinical grading, and (4) subjectively by patient-reported perception of leg swelling. In volume estimation, lymphedema was defined as a volume increase ≥10%. Risk factors were analyzed using forward stepwise logistic regression models and presented as adjusted odds ratio (aOR) and 95% confidence interval (95% CI).

    RESULTS: Risk factors varied substantially, depending on the method of determining lymphedema. Lymphadenectomy was a risk factor for lymphedema when assessed by body mass index-standardized volume (aOR 14.42, 95% CI 3.49 to 59.62), clinical grading (aOR 2.11, 95% CI 1.04 to 4.29), and patient-perceived swelling (aOR 2.51, 95% CI 1.33 to 4.73), but not when evaluated by crude volume. Adjuvant radiotherapy was only a risk factor for lymphedema when assessed by body mass index-standardized volume (aOR 15.02, 95% CI 2.34 to 96.57). Aging was a risk factor for lymphedema when assessed by body mass index-standardized volume (aOR 1.07, 95% CI 1.00 to 1.15) and patient-perceived swelling (aOR 1.06, 95% CI 1.02 to 1.10), but not when assessed by crude volume or clinical grading. Increase in body mass index was a risk factor for lymphedema when estimated by crude volume (aOR 1.92, 95% CI 1.36 to 2.71) and patient-perceived swelling (aOR 1.36, 95% CI 1.11 to 1.66), but not by body mass index-standardized volume or clinical grading. The extent of lymphadenectomy was strongly predictive for the development of lymphedema when assessed by body mass index-standardized volume and patient-perceived swelling, but not by crude volume or clinical grading.

    CONCLUSION: Apparent risk factors for lymphedema differed considerably depending on the method used to determine lymphedema. This highlights the need for a 'gold standard' method when addressing lymphedema for determining risk factors.

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