| 11. |
- Castro Wersäll, Ofra, et al.
(author)
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Dietary Habits and Daily Routines as Prognostic Factors in Endometrial Cancer : A Machine Learning Approach
- 2023
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In: Nutrition and Cancer. - : Routledge. - 0163-5581 .- 1532-7914. ; 75:1, s. 310-319
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Journal article (peer-reviewed)abstract
- Endometrial cancer (EC) is becoming more common worldwide, primarily due to an increase in life expectancy and obesity. As several modifiable factors may affect EC incidence and progression, we aimed to elucidate how dietary habits and daily routines influence recurrence and survival among women with EC, using a Random Survival Forest (RSF) approach. 481 women who previously underwent hysterectomy due to EC completed two extensive questionnaires on dietary habits and daily routines, and we used RSF to identify risky or protective variables. Among the 186 variables considered, consumption of sugar-sweetened beverages and fried potatoes increased the risk of EC recurrence and death, while physical activity decreased the risk of death. We conclude that RSF is a suitable approach to study survival in multivariable datasets.
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| 12. |
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| 13. |
- Govorov, Igor, et al.
(author)
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Blood inflammatory and endothelial markers in women with von Willebrand disease
- 2019
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:1
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Journal article (peer-reviewed)abstract
- Introduction: VWD-affected females often experience menorrhagia. Periodical fluctuations of the sex steroids during the menstrual cycle cause changes both in the coagulation and immune system. The aim of the current study was to assess the changes in selected inflammatory and endothelial markers in women with VWD during two phases of the menstrual cycle (follicular and luteal) and to compare it with corresponding data from healthy controls.Materials and methods: The study group included 12 VWD-affected females with regular menstrual cycle, with none of them being prescribed hormone treatment. They were not pregnant or breastfeeding. The control group consisted of 102 healthy females, matched for age and BMI.Results: Within the VWD group, endostatin was higher during the follicular phase, compared to the luteal phase, although the difference was not significant (p = 0.062). sICAM-1 and IL-6 were higher in VWD-affected females, compared to the controls, sVCAM-1, cathepsin S and sP-selectin were lower (p<0.003 for all cases). The pattern was constant throughout the menstrual cycle.Conclusions: Higher levels of endostatin during early follicular phase could potentially predispose women with VWD to the development of heavy menstrual bleeding, due to antiangiogenic properties and ability to suppress several coagulation factors. Lower p-selectin levels in VWD group, compared to controls, may also contribute to the bleeding tendency. Changes in other proteins, involved in angiogenesis are hypothetically related to the formation of angiodysplasia—common complication of VWF deficiency. The latter statement requires confirmation in larger studies.
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| 14. |
- Govorov, Igor, et al.
(author)
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STK4 protein expression pattern follows different trends in endometrioid and serous endometrial adenocarcinoma upon tumor progression
- 2022
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 12:1
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Journal article (peer-reviewed)abstract
- In a previous study, we showed that serine/threonine-protein kinase 4 (STK4) is involved in the control on proliferation and migration of endometrial cancer (EC) cells in vitro. In the present paper, we studied STK4 expression in EC tissues from a large cohort of patients to determine whether STK4 can serve as a marker for the aggressiveness and prognosis of EC. Tissue samples from patients with EC were examined for tumor type, grade, and stage. The STK4 protein expression in EC cells was assessed by immunohistochemistry and related to clinicopathological data of patients, such as progression and patient survival rate. The STK4 mRNA levels and its relation to the survival rate were analyzed also in publicly available databases. The STK4 gene expression was low at both, the mRNA and protein levels in EC, especially in serous tumors. Comparison of STK4 expression with the patient survival rate shows that the higher expression is associated with worse prognosis in serous EC, while no such dependence was found in endometrioid EC. Hence, the determination of the SKT4 expression pattern could be used as a putative prognostic marker for serous EC.
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| 15. |
- Govorov, Igor, et al.
(author)
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Upregulation of PKN1 as a Prognosis Biomarker for Endometrial Cancer
- 2022
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In: Cancer Control. - : Sage Publications. - 1073-2748 .- 1526-2359. ; 29
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Journal article (peer-reviewed)abstract
- BACKGROUND: Several markers of survival among endometrial cancer (EC) patients have been proposed, namely, the oncoprotein stathmin, RAF kinase inhibitor (RKIP), Cyclin A, GATA-binding protein 3 (GATA3), and growth and differentiation factor-15 (GDF-15). Their elevated expression correlated significantly with a high stage, serous papillary/clear cell subtypes, and aneuploidy. In a previous study, we reported the elevated expression of the serine/threonine protein kinase N1 (PKN1) in cancerous cells. In the present paper, we studied PKN1 expression in EC tissues from a large cohort of patients, to determine whether PKN1 can serve as a marker for the aggressiveness and prognosis of EC, and/or as a marker of survival among EC patients.METHODS: Tissue samples from EC patients were examined retrospectively for tumor type, tumor size, FIGO stage and grade, depth of invasion in the myometrium, and presence of lymph node metastasis. The PKN1 protein expression in EC cells was assessed by immunohistochemistry. PKN1 mRNA levels were analyzed in publicly available databases, using bioinformatic tools.RESULTS: We found that expression of PKN1 at the mRNA and proteins levels tended to increase in high-grade EC samples (P = .0001 and P = .06, respectively). In addition, patients with metastatic disease had higher PKN1 mRNA levels (P = .02). Moreover, patients with high PKN1 expression could be characterized by poorer survival.CONCLUSIONS: We have shown a trend of the higher PKN1 expression levels in EC patients with poor prognosis. Therefore, PKN1 might be considered as a candidate prognostic marker for EC.
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| 16. |
- Ha, Chunfang, et al.
(author)
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Adrenomedullin and its receptor, calcitonin receptor-like receptor, are aberrantly expressed in women with idiopathic menorrhagia
- 2009
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In: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997. ; 2:1, s. 7-11
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Journal article (peer-reviewed)abstract
- The human endometrium undergoes a unique process of benign angiogenesis under the control of ovarian steroids during reproductive life. Aberrant angiogenesis has been implicated in idiopathic menorrhagia, a common gynaecological complaint. One of the key factors involved in endometrial angiogenesis is adrenomedullin (AM), a multifunctional 52-amino acid peptide. AM mediates the activities of endometrial angiogenesis via calcitonin receptor-like receptor (CLR). The objective of the present study was to compare the endometrial expression of AM and CRL in women with and without idiopathic menorrhagia. Endometrial biopsies were obtained from 9 women with menorrhagia (>= 80 ml per menstruation) and 12 women with normal blood loss (<80 ml per menstruation). Protein and mRNA expression levels of AM and CLR were determined using immunohistochemistry and real-time PCR. Compared to the controls, patients with menorrhagia exhibited low immunostaining intensity of AM, while high CLR staining was observed in the epithelium (p<0.05). No difference in mRNA expression was observed between the groups. These data suggest that an imbalance in the AM/CLR system might alter endometrial angiogenesis in menorrhagia.
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| 17. |
- Hildenbrand, Anna, et al.
(author)
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Aquaporin 1 is expressed in the human endometrium during normal cycle and increases after mifepristone treatment.
- 2008
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In: International Journal of Molecular Medicine. - 1107-3756 .- 1791-244X. ; 22:1, s. 49-53
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Journal article (peer-reviewed)abstract
- Aquaporin-1 (AQP1) is involved in the angiogenesis and structural modifications of microvessels and possibly also in the pathogenesis of idiopathic menhorrhagia, where a reduced AQP1 expression is seen in the endometrium. Mifepristone treatment induces reduced menstrual bleeding and amenorrhea and also has a direct effect on endometrial arterioles. Administered with gestagen-only contraceptive methods, antiprogestins improve the bleeding pattern. The objective of this study was to evaluate the AQP1 expression in endometrial blood vessels during normal cycle and after mifepristone treatment. Localization and expression of AQP1 was determined using immunohistochemistry and reverse transcriptase chain reaction (RT-PCR) in 43 biopsies from human endometrium taken during a normal cycle and after mifepristone treatment. AQP1 expression in human endometrial vessels is not cycle dependent and is stronger in capillaries and arteries than in veins. After mifepristone treatment the staining intensity was increased, but not the number of stained vessels. The presence of AQP1 was also confirmed using RT-PCR. The changes in AQP1 expression could contribute to the reduced bleeding seen following mifepristone treatment and could be an effect of either antagonizing progesterone or cortisol.
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| 18. |
- Lomnytska, Marta I, et al.
(author)
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Diagnostic protein marker patterns in squamous cervicalcancer
- 2010
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In: Proteomics - Clinical Applications. - Weinheim : WILEY-VCH Verlag GmbH & Co. KGaA. - 1862-8346 .- 1862-8354. ; 4:1, s. 17-31
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Journal article (peer-reviewed)abstract
- Purpose: Cervical cancer is the second most prevalent malignancy of women. Our aim was toidentify additional marker protein patterns for objective diagnosis of squamous cervical cancer(SCC).Experimental design: Collected tissue biopsies of SCC, squamous vaginal cancer (SVC), normalcervical and vaginal mucosa were subjected to 2-DE, SameSpot analysis, MALDI-TOF-MSprotein identification, and analysis of the expression of selected proteins by immunohistochemistry.Results: In 148 protein spots selected by the difference in expression 99 proteins were identified.A differential protein pattern for SCC was, e.g. over-expressed (OE) eukaryotic translationinitiation factor 3-2b, neutrophil cytosolic factor 2, annexin A6 (ANXA6), for SVC it was OEcathepsin D, g-catenin, RAB2A, for both cancers it was OE apolipoprotein E, tropomyosin 3,HSPA8, and underexpressed cytokeratin 13, osteoglycin. In SCC nuclear expression ofneutrophil cytosolic factor 2, PRDX2, HSP27 (nine of ten cases), ANXA6 (nine of ten cases) wasobserved while tropomyosin 4 was expressed only in two of ten cases. There was 81.1% (43/53)agreement between the expression of protein spots and the immune expression of proteins(www.proteinatlas.org).Conclusions and clinical relevance: SCC is characterized by specific tissue marker proteinpatterns that allow objective detection of the disease. They can become a basis for objectiveautomated cytology-based screening and improve current diagnostics of SCC.
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| 19. |
- Mints, Miriam
(author)
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Idiopathic menorrhagia : studies of angiogenesis and surgical therapy
- 2003
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Doctoral thesis (other academic/artistic)abstract
- Background: Excessive menstrual bleeding, menorrhagia (i.e. > 80 nil loss of blood) is a com-mon gynecological problem in women of reproductive age, accounting for over 20% of visits to gynecology outpatient clinics. The disorder may not only cause iron deficiency anemia but also considerable social discomfort and reduction in the quality of life. Although commonly associated with fibroids and carcinoma, approximately 50% of patients with menorrhagia do not show any evidence of uterine pathology. This suggests a defect in the cellular processes and regulatory mechanisms of menstruation. Historically, many women with heavy menstrual bleeding were advised to undergo hysterectomy, which was the only way of enduring a "cure". Hysterectomy is an effective treatment of menorrhagia, but it is associated with substantial postoperative morbidity and convalescence. In the early 1990s, endometrial resection or ablation became a well-established outpatient alternative for the surgical treatment of menorrhagia. The aim of this thesis: This work has mainly been focused on two aspects: firstly, the analysis of transcervical resection of the endometrium (TCRE) as a surgical option for treatment of menorrhagia and, secondly, on the involvement of the vascular endothelial growth factor (VEGF) family in the regulation of anglogenesis in the human endometrium in healthy women and those with idiopathic menorrhagia. In particular, we investigated if the vessel wall anatomy was abnormal and related findings to the expression of VEGF and VEGF receptors in the blood vessels. Results The general clinical outcome in the present studies (papers I and II) showed favorable results with low peroperative and postoperative complication rates: fluid overload occurred in 4% and perforation in 1% of the patients. Most of women who underwent TCRE found this surgery acceptable and approximately 80% of these women have avoided hysterectomy. Second-look hysteroscopy in women after TCRE showed signs of regenerative endometrium. In order to determine why the endometrium regenerates and what regulates this process, we have investigated the expression and distribution of VEGF and its receptors as well as vessel morphology in normal and menorrhagic endometrium (papers III-V). Our data suggest an up-regulation of the agonist-receptor pathway of VEGF in idiopathic menorrhagia: the vascular expression of VEGF-A, VEGFR1, -2, -3 in capillaries was 1.8-, 1.8-, 2.0-, and 1.6-fold higher, respectively, in the menorrhagia group. Since VEGF-A not only stimulates migration and survival of endothelial cells but also induces vascular permeability, we have addressed this aspect by analyzing of vessel morphology. We found that vessels in patients with menorrhagia displayed an unusual morphology with focal regions, gaps. The relative size of the gaps was significantly larger in menorrhagia samples than in controls (P=0.000002). Moreover, the sizes of the gaps correlated positively to the number of endometrial blood vessels expressing VEGF-A (P=0.0002) and VEGFR1 (P=0.03). To our knowledge, this is the first study that demonstrates the presence of endothelial gaps in menorrhagic endometrium and as a part of a specific disease process. Conclusions: TCRE provides a minimally invasive technique for treatment of menorrhagia with good clinical results: about 80% of women have the possibility of avoiding hysterectomy. Therefore, endometrial resection/ablation should be offered as a surgical option to all women with idiopathic menorrhagia who have completed their families. Normal endometrial angiogenesis is perturbed in idiopathic menorrhagia with an up-regulation of the agonist-receptor pathway of VEGF-A, which leads to anatomical differences in blood vessels, manifested inter alia as gaps. Our novel observations may be of significance in order to explain some of the underlying mechanisms that contribute to idiopathic menorrhagia and will provide novel opportunities for therapeutic intervention in the future.
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| 20. |
- Razumova, Zoia, et al.
(author)
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Cadmium intake as a prognostic factor in endometrial cancer : a Swedish cohort-based study
- 2022
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In: Nutrition and Cancer. - Stockholm : Karolinska Institutet, Dept of Women's and Children's Health. - 0163-5581 .- 1532-7914.
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Journal article (peer-reviewed)abstract
- Metalloendocrinology is a new interdisciplinary field, which was established due to the importance of connections between inorganic chemicals and hormonal mechanisms. The role of cadmium in hormone-related tumors is an excellent example of this connection, as cadmium mimics estrogen in the human body. Since endometrial cancer (EC) is hormonerelated, it is well-suited for assessing the estrogenic effects of cadmium. Therefore, the present study aims to explore the role of dietary cadmium intake in the progression-free survival (PFS) and overall survival (OS) in women with EC. Dietary cadmium intake was estimated based on a large cohort of Swedish women (n ¼ 416) with EC. Median dietary cadmium intake was then analyzed in relation to different tumor characteristics and clinical outcomes. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Median daily dietary cadmium intake in the cohort was 13.1 lg (interquartile range 25%-75%¼6.4). High dietary cadmium intake (lg/day) was associated with significantly decreased OS in the study cohort (HR ¼ 0.956, 95% CI ¼ 0.914- 1.001, p ¼ 0.05). Dietary cadmium intake was not associated with PFS (HR ¼ 0.975, 95% CI ¼ 0.924-1.028, p ¼ 0.348). Therefore, our results indicate that high dietary cadmium intake could be associated with poor outcome in women with EC.
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