| 11. |
- Gideonsson, Ida, et al.
(författare)
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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 challenges
- 2023
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Ingår i: Current Oncology. - : MDPI. - 1198-0052 .- 1718-7729. ; 30:12, s. 10260-10271
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 12. |
- Hosokawa, K, et al.
(författare)
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Dominant expression and distribution of oestrogen receptor beta over oestrogen receptor alpha in the human corpus luteum
- 2001
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Ingår i: Molecular human reproduction. - : Oxford University Press (OUP). - 1360-9947 .- 1460-2407. ; 7:2, s. 137-145
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 13. |
- Idahl, Annika, 1965-, et al.
(författare)
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Chlamydia trachomatis and Mycoplasma genitalium plasma antibodies in relation to epithelial ovarian tumors
- 2011
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Ingår i: Infectious diseases in obstetrics and gynecology. - : Hindawi Publishing Corporation. - 1064-7449 .- 1098-0997. ; 2011
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 14. |
- Idahl, Annika, 1965-
(författare)
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Chlamydia trachomatis as a risk factor for infertility in women and men, and ovarian tumor development
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Chlamydia trachomatis in women is a risk factor for tubal factor infertility and extra uterine pregnancies, but the impact of a C. trachomatis infection on male fertility is unclear. It is also hypothesized that persistent infection with C. trachomatis, or other microorganisms, might initiate/promote ovarian tumor development. The aims of the thesis were to study whether C. trachomatis serum antibodies in women and men had an impact on infertility diagnoses, semen characteristics, pregnancy rates and pregnancy outcomes; furthermore, to explore associations of C. trachomatis, and Mycoplasma genitalium, plasma antibodies with epithelial ovarian cancer and borderline ovarian tumors, as well as the presence of C. trachomatis bacteria, and other microorganisms, in ovarian tissues. Materials and methods: Papers I and II: 244/226 infertile couples were tested for serum C. trachomatis IgG, IgA, IgM and chlamydial Heat Shock Protein 60 (cHSP60) IgG antibodies. C. trachomatis IgG positive couples were also tested for C. trachomatis DNA in a urine sample. The follow-up period was 14-54 months. 244 spontaneously pregnant women were also tested for serum C. trachomatis IgG antibodies. Papers III and IV: Plasma samples from 291 women with epithelial ovarian cancer, borderline ovarian tumors and benign conditions, and plasma samples from 271 healthy controls, were analyzed for C. trachomatis IgG, IgA and cHSP60-1 IgG and M. genitalium IgG antibodies. Ovarian tissues from 186 women with benign ovaries, borderline ovarian tumors and epithelial ovarian cancer, as well as tissues from the contra lateral ovary in 126 women, were analyzed for the presence of C. trachomatis, M. genitalium, Neisseria gonorrhoeae, HPV and the polyoma viruses BKV and JCV with nucleic acid amplification tests. Results: Papers I and II: The prevalence of C. trachomatis IgG antibodies was higher among infertile than fertile women, and there were 9 couples with ongoing C. trachomatis infections. In men, C. trachomatis IgG and IgA antibodies were associated with a reduced likelihood to achieve pregnancy for the couple, as well as lower sperm concentration, reduced sperm motility and vitality, increased teratozoospermia index and the occurrence of leukocytes. C. trachomatis IgG and cHSP60 IgG antibodies in infertile women were associated with tubal factor infertility, but not with reduced pregnancy rates or outcomes. Paper III: cHSP60-1 IgG antibodies were associated with ovarian cancer belonging to the postulated type II pathogenetic pathway when plasma samples obtained more than one year prior to diagnosis were analyzed. M. genitalium IgG antibodies were associated with borderline ovarian tumors; however a statistical type 1 error cannot be excluded. Paper IV: None of the microorganisms studied were found in the ovarian tissue samples. Conclusions: C. trachomatis IgG and IgA antibodies in the man substantially decreases the chances of the infertile couple to achieve pregnancy, and are associated with subtle negative changes in semen characteristics. C. trachomatis IgG and cHSP60 IgG antibodies in the woman are risk factors for tubal factor infertility. Prospective plasma cHSP60-1 IgG antibodies are associated with type II ovarian carcinomas, but C. trachomatis bacteria, or the other microorganisms studied, could not be detected in benign, borderline or malignant ovarian tissues.
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| 15. |
- Idahl, Annika, 1965-, et al.
(författare)
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Chlamydia trachomatis, Mycoplasma genitalium, Neisseria gonorrhoeae, human papillomavirus, and polyomavirus are not detectable in human tissue with epithelial ovarian cancer, borderline tumor, or benign conditions
- 2010
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 202:1, s. 71.e1-71.e6
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 16. |
- Israelsson, Pernilla, et al.
(författare)
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Assessment of cytokine mRNA expression profiles in tumor microenvironment and peripheral blood mononuclear cells of patients with high-grade serous carcinoma of the ovary
- 2017
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Ingår i: Journal of Cancer Science & Therapy. - : OMICS Publishing Group. - 1948-5956. ; 9:5, s. 422-429
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 17. |
- Israelsson, Pernilla, et al.
(författare)
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Assessment of cytokine mRNA expression profiles in tumor microenvironment and peripheral blood mononuclear cells of patients with high-grade serous carcinoma of the ovary
- 2019
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Ingår i: International Journal of Gynecological Cancer. - : BMJ Publishing Group Ltd. - 1048-891X .- 1525-1438. ; 29, s. A138-A138
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 18. |
- Israelsson, Pernilla, et al.
(författare)
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Cytokine mRNA and protein expression by cell cultures of epithelial ovarian cancer : Methodological considerations on the choice of analytical method for cytokine analyses
- 2020
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Ingår i: American Journal of Reproductive Immunology. - : John Wiley & Sons. - 1046-7408 .- 1600-0897. ; 84:1
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 19. |
- Israelsson, Pernilla, 1984-
(författare)
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Mechanisms for immune escape in epithelial ovarian cancer
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tumors develop mechanisms to subvert the immune system, constituting immune escape. Epithelial ovarian cancer (EOC), the deadliest of all gynecological malignancies, uses a variety of mechanisms to undermine immune surveillance, aiding its establishment and metastatic spreading. Despite progress in oncoimmunology, a lot remains unknown about the cancer-immune system interplay. The aim of this thesis was to study tumor-mediated mechanisms for immune escape in EOC patients, focusing on the role of cytokines and EOC- derived exosomes. Cytokines are key molecules regulating immune effector functions in health and disease. We used real-time RT-qPCR and a set of primers and probes for 12 cytokines, discriminating between different immune responses and compared the cytokine mRNA expression profiles locally in the TME and systemically in peripheral blood immune cells of EOC patients, to women with benign ovarian conditions and women with normal ovaries. The cytokine mRNA expression was in general most prominent in EOC patients, confirming the immunogenicity of EOC. We found significant dominance of inflammatory and immunosuppressive/ regulatory cytokines, known to promote tumor progression by priming and activating T regulatory cell-mediated immune suppression. In contrast, IFN-γ, crucially important for evoking a cytotoxic anti-tumor response, was not upregulated. Instead, a systemic increase of IL-4 prevailed, deviating the immune defense towards humoral immunity. With regard to our cytokine study, we performed comparative analyses of cytokine mRNA versus protein expression in the EOC cell lines OVCAR-3 and SKOV-3. We found that cytokine mRNA signals were universally detected, and in some instances translated into proteins, but the protein expression levels depended on the material analyzed and the method used. Due to the high sensitivity of real-time RT-qPCR, we suggest that cytokine mRNA expression profiles can be used for some instances, such as in studies of mechanistic pathways and in comparisons between patient groups, but cannot replace expression at the protein level. Exosomes are nanometer-sized vesicles of endosomal origin, released by virtually all cells, participating in normal and pathological processes. Like many tumors, EOC is a great exosome producer. We isolated exosomes from EOC ascitic fluid and supernatant from tumor explant cultures to study their effect on the NK cell receptors NKG2D and DNAM-1, involved in tumor killing. We found that EOC exosomes constitutively expressed NKG2D ligands on their surface while DNAM-1 ligand expression was rare and not associated with the exosomal membrane. Consistently, the major cytotoxic pathway of NKG2D-mediated killing was dysregulated by EOC exosomes while the accessory DNAM-1- mediated pathway remained unchanged. Our results provide a mechanistic explanation to the previously made observation that in EOC patients, tumor killing is only dependent on the accessory DNAM-1 pathway. Following these iii iv results, we studied NKG2D-mediated cytotoxicity in vivo in EOC patients before and after surgery. We found that the serum exosomes isolated from EOC patients were able to downregulate the NKG2D receptor and suppress NKG2D-mediated cytotoxicity in NK cells from healthy donors, in a similar way as exosomes from EOC ascites. We also found that surgery of the primary EOC tumor has a beneficial effect on the patients’ anti-tumor cytotoxic immune response. One mechanistic explanation could be a decrease in circulating NKG2D ligand- expressing exosomes, thus improving the cytotoxic NK cell function. In conclusion, our results contribute to the understanding of the mechanisms responsible for tumor immune escape in general, and in EOC patients in particular, and might be useful in developing novel antitumor therapies. Our studies highlight the prevailing immunosuppression in the local TME and the immunosuppressive role of EOC exosomes. Furthermore, they support the notion that cancer surgery is also a way of removing exosome-producing cells and reducing the serum concentration of immunosuppressive exosomes, thus boosting the patients’ cytotoxic anti-tumor response.
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| 20. |
- Israelsson, Pernilla, et al.
(författare)
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NKG2D-mediated cytotoxicity improves after primary surgery for high-grade serous ovarian cancer
- 2023
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Ingår i: American Journal of Reproductive Immunology. - : John Wiley & Sons. - 1046-7408 .- 1600-0897. ; 89:1
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Tidskriftsartikel (refereegranskat)abstract
- 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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