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| 2. |
- Ebefors, Kerstin, 1977, et al.
(författare)
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Mesangial cells from patients with IgA nephropathy have increased susceptibility to galactose-deficient IgA1
- 2016
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Ingår i: Bmc Nephrology. - : Springer Science and Business Media LLC. - 1471-2369. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: IgA nephropathy (IgAN) is the most common glomerulonephritis in the world, affecting close to a million people. Circulating galactose-deficient IgA (gd-IgA), present in patients with IgAN, form immune complex deposits in the glomerular mesangium causing local proliferation and matrix expansion. Intriguing though, individuals having gd-IgA deposits in the kidneys do not necessarily have signs of glomerular disease. Recurrence of IgAN only occurs in less than half of transplanted patients with IgAN, indicating that gd-IgA is not the only factor driving the disease. We hypothesize that, in addition to IgA complexes, patients with IgAN possess a subtype of mesangial cells highly susceptible to gd-IgA induced cell proliferation. Methods: To test the hypothesis, we designed a technique to culture primary mesangial cells from renal biopsies obtained from IgAN patients and controls. The cell response to gd-IgA treatment was then measured both on gene and protein level and the proliferation rate of the cells in response to PDGF was investigated. Results: When treated with gd-IgA, mesangial cells from patients with IgAN express and release more PDGF compared to controls. In addition, the mesangial cells from patients with IgAN were more responsive to treatment with PDGF resulting in an increased proliferation rate of the cells compared to control. Mesangial cells cultured from patients with IgAN expressed and released more IL-6 than controls and had a higher expression of matrix genes. Both mesangial cells derived from patients with IgAN and controls increased their expressed TGF beta 1 and CCL5 when treated with gd-IgA. Conclusion: We conclude that mesangial cells derived from IgAN patients have a mesangioproliferative phenotype with increased reactivity to IgA and that these cellular intrinsic properties may be important for the development of IgA nephropathy.
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| 3. |
- Kristjansdottir, Björg, et al.
(författare)
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Diagnostic performance of the biomarkers HE4 and CA125 in type I and type II epithelial ovarian cancer.
- 2013
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Ingår i: Gynecologic oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 131:1, s. 52-58
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the diagnostic performance of HE4 and CA125 in patients presenting with suspicious malignant ovarian cysts. We especially wanted to investigate the levels of HE4 and CA125 with regard to the gene and histology-unifying model of type I and type II epithelial ovarian cancer (EOC).
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| 4. |
- Kristjansdottir, Björg, et al.
(författare)
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Early inflammatory response in epithelial ovarian tumor cyst fluids.
- 2014
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Ingår i: Cancer medicine. - : Wiley. - 2045-7634. ; 3:5, s. 1302-1312
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Tidskriftsartikel (refereegranskat)abstract
- Mortality rates for epithelial ovarian cancer (EOC) are high, mainly due to late-stage diagnosis. The identification of biomarkers for this cancer could contribute to earlier diagnosis and increased survival rates. Given that chronic inflammation plays a central role in cancer initiation and progression, we selected and tested 15 cancer-related cytokines and growth factors in 38 ovarian cyst fluid samples. We used ovarian cyst fluid since it is found in proximity to the pathology and mined it for inflammatory biomarkers suitable for early detection of EOC. Immunoprecipitation and high-throughput sample fractionation were obtained by using tandem antibody libraries bead and mass spectrometry. Two proteins, monocyte chemoattractant protein-1 (MCP-1/CCL2) and interleucin-8 (IL-8/CXCL8), were significantly (P<0.0001) higher in the malignant (n=16) versus benign (n=22) tumor cysts. Validation of MCP-1, IL-8, and growth-regulated protein-α (GROα/CXCL1) was performed with ELISA in benign, borderline, and malignant cyst fluids (n=256) and corresponding serum (n=256). CA125 was measured in serum from all patients and used in the algorithms performed. MCP-1, IL-8, and GROα are proinflammatory cytokines and promoters of tumor growth. From 5- to 100-fold higher concentrations of MCP-1, IL-8 and GROα were detected in the cyst fluids compared to the serum. Significant (P<0.001) cytokine response was already established in borderline cyst fluids and stage I EOC. In serum a significant (P<0.01) increase of IL-8 and GROα was found, but not until stage I and stage III EOC, respectively. These findings confirm that early events in tumorigenesis can be analyzed and detected in the tumor environment and we conclude that ovarian cyst fluid is a promising source in the search for new biomarkers for early ovarian tumors.
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| 5. |
- Kristjansdottir, Björg, et al.
(författare)
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Potential tumor biomarkers identified in ovarian cyst fluid by quantitative proteomic analysis, iTRAQ.
- 2013
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Ingår i: Clinical proteomics. - : Springer Science and Business Media LLC. - 1542-6416 .- 1559-0275. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Epithelial-derived ovarian adenocarcinoma (EOC) is the most deadly gynecologic tumor, and the principle cause of the poor survival rate is diagnosis at a late stage. Screening and diagnostic biomarkers with acceptable specificity and sensitivity are lacking. Ovarian cyst fluid should harbor early ovarian cancer biomarkers because of its closeness to the tumor. We investigated ovarian cyst fluid as a source for discovering biomarkers for use in the diagnosis of EOC.
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| 6. |
- Levan, Kristina, 1974, et al.
(författare)
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Chromosomal alterations in 98 endometrioid adenocarcinomas analyzed with comparative genomic hybridization.
- 2006
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Ingår i: Cytogenetic and genome research. - : S. Karger AG. - 1424-859X .- 1424-8581. ; 115:1, s. 16-22
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to investigate chromosomal alterations in a large set of homogeneous tumors, 98 endometrioid adenocarcinomas. We also wanted to evaluate differences in chromosomal alterations in the different groups of tumors in relation to stage, survival and invasive or metastatic properties of the tumors. Comparative genomic hybridization (CGH) was used to detect chromosomal alterations in tissue samples from 98 endometrioid adenocarcinomas. All chromosomes were involved in DNA copy number variations at least once in the tumor material, but certain changes were recurrent and rather specific. Among the specific changes, it was possible to identify 39 chromosomal regions displaying frequent DNA copy number alterations. The most frequent alteration was detected at 1q25-->q42, in which gains were found in 30 cases (30%). Gains at 19pter-->p13.1 were detected in 26 tumors (26%) and at 19q13.1-->q13.3 in 19 tumors (19%). Increased copy numbers were also detected at 8q (8q21-->q22 and 8q22-->qter), at a relatively high rate, in 17 cases (17%). Furthermore, gains at 10q21-->q23 and 10p were found in 14 (14%) and 13 cases (13%), respectively. The most common losses were found in the three regions 4q22-->qter, 16q21-->qter and 18q21-->qter, all of which were detected in eight of the 98 tumors (8%). We also detected differences between the tumors from deceased patients and from survivors. Gain at 1q25-->q42 was more commonly detected in the tumors from patients who died of cancer. We noted that the regions most affected differed in the different surgical stages (I-IV). The results of the CGH analysis identify specific chromosomal regions affected by copy number changes, appropriate objects for further genetic studies.
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| 8. |
- Levan, Kristina, 1974, et al.
(författare)
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Immunohistochemical evaluation of epithelial ovarian carcinomas identifies three different expression patterns of the MX35 antigen, NaPi2b
- 2017
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Ingår i: Bmc Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: To characterize the expression of the membrane transporter NaPi2b and antigen targeted by the MX35 antibody in ovarian tumor samples. The current interest to develop monoclonal antibody based therapy of ovarian cancer by targeting NaPi2b emphasizes the need for detailed knowledge and characterization of the expression pattern of this protein. For the majority of patients with ovarian carcinoma the risk of being diagnosed in late stages with extensive loco-regional spread disease is substantial, which stresses the need to develop improved therapeutic agents. Methods: The gene and protein expression of SLC34A2/NaPi2b were analyzed in ovarian carcinoma tissues by QPCR (n = 73) and immunohistochemistry (n = 136). The expression levels and antigen localization were established and compared to the tumor characteristics and clinical data. Results: Positive staining for the target protein, NaPi2b was detected for 93% of the malignant samples, and we identified three separate distribution patterns of the antigen within the tumors, based on the localization of NaPi2b. There were differences in the staining intensity as well as the distribution pattern when comparing the tumor grade and histology, the mucinous tumors presented a significantly lower expression of both the targeted protein and its related gene. Conclusion: Our study identified differences regarding the level of the antigen expression between tumor grade and histology. We have identified differences in the antigen localization between borderline tumors, type 1 and type 2 tumors, and suggest that a pathological evaluation of NaPi2b in the tumors would be helpful in order to know which patients that would benefit from this targeted therapy.
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| 9. |
- Levan, Kristina, 1974
(författare)
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Molecular characterization of type I endometrial carcinomas
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Endometrial carcinoma is the most common malignancy in the female reproductive tract. In Sweden over 1300 women are diagnosed every year, and although the prognosis is favourable in the majority of cases, about 160 patients die of the disease every year. Since the clinical outcome may be quite different for patients with the same diagnosis, indications are that there may be important differences among the tumours at the molecular level. The overall goal of our research was to contribute to the understanding in the molecular biology underlying endometrioid adenocarcinomas. In total, 124 type I endometrial carcinoma patients were included in the study. Methods such as CGH, FISH, expression array analysis and QPCR were applied to investigate molecular specificities among the tumours. In particular, we were looking for biomarkers useful in distinguishing more aggressive tumours that might require special therapy. Thus, we submitted the data to extensive statistical treatment, comparing molecular data from aggressive tumours (tumours that killed the patient, tumours that metastasized) with those less aggressive. In the CGH analysis of 98 tumours, we found that tumours from survivors on average had fewer chromosome aberrations than those from nonsurvivors. In fact, 33% of the non-metastatic tumours displayed no detectable aberrations, clearly a marker for good prognosis. However, we could not find any aberration that was entirely specific for non-survivors. A subset of 13 tumours was analyzed for gene amplification in a set of 15 cancer-related genes on chromosomes 2 and 7 by FISH in tumour imprints. The findings corresponded quite well with findings in inbred BDII rats, which are known to be genetically predisposed for endometrial carcinoma. These results suggest that the BDII rat provides a useful model for analyzing the genetic background of at least a subgroup of human endometrial carcinomas. The expression array analysis of 45 tumours generated a set of 218 genes that were differentially expressed between survivors and non-survivors. Using this set of 218 genes in a cross validation test 89% of the tumours were classified correctly, and in hierarchical clustering, two clusters were formed, both with over 80% homogeneity with respect to survival. In the latter analysis it was noted that five out of six stage I tumours from non-survivors, clustered in the nonsurvivor fraction. The gene expression analysis indicated dysfunction of the Rb/E2F pathway involved in the tumour progression. To investigate the potential involvement of this well-known pathway we aimed to characterize the protein expression of a selection of the proteins involved. Significant differences in protein expression of pRb in combination with E2F-1 were clearly related to survival. In particular, these molecular tools helped us to identify a subset of non-survivors among tumours classified as stage I tumours. If more aggressive malignancies can be identified at an early stage, the indicated adjuvant treatments may dramatically improve the disease course for these individuals. Increased knowledge about the biological differences among individual tumours will provide the basis of a more accurate prognosis. In the future extended molecular information should also contribute to the development of improved and individually tailored treatment protocols.
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| 10. |
- Partheen, Karolina, 1976, et al.
(författare)
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Analysis of cytogenetic alterations in stage III serous ovarian adenocarcinoma reveals a heterogeneous group regarding survival, surgical outcome, and substage
- 2004
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Ingår i: Genes Chromosomes Cancer. ; 40:4, s. 342-8
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Tidskriftsartikel (refereegranskat)abstract
- Ovarian cancer is the leading cause of death among patients with gynecological cancers, but the biology of these tumors is still among the least understood of all major human malignancies. In this study, comparative genomic hybridization was used to determine chromosomal alterations in 98 stage III serous papillary adenocarcinomas. The tumors were grouped according to survival and the main prognostic factors stage and surgical outcome. There were chromosomal imbalances that were significantly more common in tumors from patients who died than in tumors from patients who survived: gains of 1q24-qter and losses of 4p, 4q31.1-qter, 5q12-q22, 8p, 16q, and X. Furthermore, we observed that gains of 8q23-8q24.2 and losses of 4p, 4q13-4q26, 4q31.1-qter, 5q12-q22, 8p, and 16q were significantly more common in tumors from patients with macroscopic residual tumor after primary surgery, compared to tumors from those who had undergone radical surgery. Gains of 3q13.3-qter, 6p, 7q21-q31, and 11q13-q23 and losses of 4q31.1-qter and 16q were more common in stage IIIc tumors than in stage IIIa+b tumors. On the basis of our results, we suggest that there are biological differences among the groups mentioned above and that absence of chromosomal aberrations in specific regions predicts a good clinical outcome for individual patients.
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