| 1. |
- Castro, Felipe A, et al.
(författare)
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Association of HLA-DRB1, interleukin-6 and cyclin D1 polymorphisms with cervical cancer in the Swedish population-A candidate gene approach.
- 2009
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 125:8, s. 1851-1858
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Tidskriftsartikel (refereegranskat)abstract
- High-risk human papillomavirus (hrHPV) infection is the major risk factor for cervical cancer (CxCa). The role of genetic susceptibility in the disease has been suggested, but the existing data lack consistency. We conducted a nested case-control study on 973 CxCa cases and 1,763 matched controls, from two Swedish population-based cohorts to examine the association of common genetic variants with CxCa risk. Human leukocyte antigen (HLA) alleles and 24 other polymorphisms in 14 genes were selected on the basis of reported association or mechanistic plausibility with an HPV infection or cervical cancer development. Genotyping was conducted using multiplex PCR and Luminex technology. A significant association of CxCa with various polymorphisms was observed: rs1800797 in the IL-6 gene (odds ratio [OR] = 0.88, 95% confidence intervals [CI]: 0.79-0.99); rs1041981 in the LTA gene (OR = 0.87, 95% CI: 0.78-0.98), and rs9344 in the CCND1 gene (OR = 1.14, 95% CI: 1.02-1.27), for those individuals carrying the rare allele. Additionally, the alleles 0401 and 1501 of the HLA class II DRB1 locus were associated with an increased risk (OR = 1.23, 95% CI: 1.04-1.45 and OR = 1.29, 95% CI: 1.11-1.50, respectively), and allele 1301 was associated with decreased risk (OR = 0.59, 95% CI: 0.47-0.73). The effects of CCND1 and the HLA*DRB1 alleles were independent of the effect of smoking. We did not find any association of risk with polymorphisms in genes related to the innate immune system. In conclusion, our study provides evidence for genetic susceptibility to CxCa due to variations in genes involved in the immune system and in cell cycle. (c) 2009 UICC.
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| 2. |
- Castro, Felipe A, et al.
(författare)
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Contribution of TMC6 and TMC8 (EVER1 and EVER2) variants to cervical cancer susceptibility
- 2012
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 130:2, s. 349-355
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Tidskriftsartikel (refereegranskat)abstract
- Cervical cancer (CxCa) is caused by persistent human papillomavirus (HPV) infection; genetic predisposition is also suspected to play a role. Our study is a targeted candidate gene follow-up based on: (i) strong clinical evidence demonstrating that mutations in the TMC6 and TMC8 (EVER1 and EVER2) genes associate with the HPV-associated disease epidermodysplasia verruciformis (EV) and (ii) recent epidemiological data suggesting a genetic susceptibility conferred by polymorphisms in such genes for skin and CxCa. Clarifying the association of the TMC6/8 genes with risk of CxCa will help in understanding why some HPV-infected women develop persistent infection, cervical lesions and eventually cancer while others do not. Twenty-two single nucleotide polymorphisms (SNPs) harboring the TMC6/8 genes were genotyped in 2,989 cases with cervical intraepithelial neoplasia grade III or invasive CxCa and 2,281 controls from the Swedish population. Association was evaluated in logistic regression models. Two SNPs displayed association with cervical disease: rs2290907 [odds ratio (OR)(GGvsAA) = 0.6, 95% confidence interval (95% CI): 0.3-0.9, p = 0.02)] and rs16970849 (OR(AGvsGG) = 0.8, 95% CI: 0.66-0.98, p = 0.03). The present data support the involvement of the TMC6/8 region in CxCa susceptibility but further analyses are needed to replicate our findings, fully characterize the region and understand the function of the genetic variants involved.
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| 3. |
- Dimova, Tanya, et al.
(författare)
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Maternal Foxp3 expressing CD4+ CD25+ and CD4+ CD25- regulatory T-cell populations are enriched in human early normal pregnancy decidua : a phenotypic study of paired decidual and peripheral blood samples.
- 2011
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Ingår i: American Journal of Reproductive Immunology and Microbiology. - : John Wiley & Sons. - 8755-8920 .- 1046-7408. ; 66:Suppl 1, s. 44-56
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Tidskriftsartikel (refereegranskat)abstract
- PROBLEM: Regulatory T cells (Treg cells), a small subset of CD4(+) T cells maintaining tolerance by immunosuppression, are proposed contributors to the survival of the fetal semiallograft. We investigated Treg cells in paired decidual and peripheral blood (PB) samples from healthy women in early pregnancy and PB samples from non-pregnant women.METHOD OF STUDY: Distribution, location, cytokine mRNA, and phenotype were assessed in CD4(+) CD25(+) Treg cells from paired samples using immunohistochemistry, immunofluorescence, flow cytometry, and real-time quantitative RT-PCR.RESULTS: The presence and in situ distribution of CD4(+) Foxp3(+) Treg cells in decidua are hereby demonstrated for the first time. Three Foxp3(+) cell populations, CD4(+) CD25(++) Foxp3(+), CD4(+) CD25(+) Foxp3(+), and CD4(+) CD25(-) Foxp3(+), were enriched locally in decidua. In contrast, no statistically significant difference in numbers of circulating Treg cells between pregnant and non-pregnant women was found. The Foxp3(+) cells expressed the surface molecules CD45RO, CTLA-4, CD103, Neuropilin-1, LAG-3, CD62L, and TGFβ1 mRNA consistent with Treg phenotype. The population of CD4(+) CD25(-) Foxp3(+) cells, not described in human decidua before, was enriched 10-fold compared with PB in paired samples. Their cytokine expression was often similar to Th3 profile, and the Foxp3 mRNA expression level in CD4(+) CD25(-) cells was stable and comparable to that of CD4(+) CD25(+) Treg cells implying that the majority of CD4(+) CD25(-) Foxp3(+) cells might be naïve Treg cells.CONCLUSION: (i) There is a local enrichment of Treg cells in decidua (ii) The exclusive accumulation of decidual CD4(+) CD25(-) Foxp3(+) cells suggests an additional reservoir of Foxp3(+) naïve Treg cells that can be converted to 'classical' Treg cells in uterus.
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| 4. |
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| 5. |
- González, Carlos A, et al.
(författare)
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Dietary factors and in situ and invasive cervical cancer risk in the European prospective investigation into cancer and nutrition study.
- 2011
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Ingår i: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 129:2, s. 449-459
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Tidskriftsartikel (refereegranskat)abstract
- Some dietary factors could be involved as cofactors in cervical carcinogenesis, but evidence is inconclusive. There are no data about the effect of fruits and vegetables intake (F&V) on cervical cancer from cohort studies. We examined the association between the intake of F&V and selected nutrients and the incidence of carcinoma in situ (CIS) and invasive squamous cervical cancer (ISC) in a prospective study of 299,649 women, participating in the European Prospective Investigation into Cancer and Nutrition study. Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CI). A calibration study was used to control measurement errors in the dietary questionnaire. After a mean of 9 years of follow-up, 253 ISC and 817 CIS cases were diagnosed. In the calibrated model, we observed a statistically significant inverse association of ISC with a daily increase in intake of 100 g of total fruits (HR 0.83; 95% CI 0.72-0.98) and a statistically nonsignificant inverse association with a daily increase in intake of 100 g of total vegetables (HR 0.85: 95% CI 0.65-1.10). Statistically nonsignificant inverse associations were also observed for leafy vegetables, root vegetables, garlic and onions, citrus fruits, vitamin C, vitamin E and retinol for ISC. No association was found regarding beta-carotene, vitamin D and folic acid for ISC. None of the dietary factors examined was associated with CIS. Our study suggests a possible protective role of fruit intake and other dietary factors on ISC that need to be confirmed on a larger number of ISC cases.
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| 6. |
- Hedlund, Malin, 1981-, et al.
(författare)
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Human placenta expresses and secretes NKG2D ligands via exosomes that down-modulate the cognate receptor expression : evidence for immunosuppressive function
- 2009
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 183:1, s. 340-351
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Tidskriftsartikel (refereegranskat)abstract
- During mammalian pregnancy maternal-fetal tolerance involves a number of immunosuppressive factors produced by placenta. Recently, placenta-derived exosomes have emerged as new immune regulators in the maternal immune tolerance. Exosomes are membrane nanovesicles with defined morphology, which are secreted from endosomal multivesicular bodies (MVB) upon fusion with the plasma membrane. Previously, we reported that the MHC class I chain-related (MIC) proteins A and B, human ligands of the activating NK cell receptor NKG2D, are expressed by placenta, sorted to MVB of syncytiotrophoblast and probably released via MIC-bearing exosomes. In this report, we show that the second family of human NKG2D ligands, the UL-16 binding proteins (ULBP), is also expressed by placenta. Importantly, this expression was not due to placental CMV infection. Immunoelectron microscopy disclosed that ULBP1-5 are produced and retained in MVB of the syncytiotrophoblast on microvesicles/exosomes. Using human placenta explant cultures and different assays, we demonstrate that exosomes bearing NKG2D ligands are released by human placenta. Isolated placental exosomes carried ULBP1-5 and MIC on their surface and induced down-regulation of the NKG2D receptor on NK, CD8(+), and gammadelta T cells, leading to reduction of their in vitro cytotoxicity without affecting the perforin-mediated lytic pathway. Release of placental NKG2D ligands via exosomes is an alternative mechanism for generation of bioactive soluble form of these ligands. These findings highlight a role for NKG2D ligand-bearing placental exosomes in the fetal immune escape and support the view of placenta as a unique immunosuppressive organ.
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| 7. |
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| 8. |
- Kjellberg, Lennart
(författare)
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Att tolka Pan Tadeusz
- 1991
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Ingår i: Slovo. - 0348-744X .- 2001-7359. ; :40, s. 5-12
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 9. |
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| 10. |
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