Browsing by Author "Alves, H."
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- Angiogenesis in Schistosoma haematobium-associated urinary bladder cancerPublication . Dematei, A.; Fernandes, R.; Soares, R.; Alves, H.; Richter, J.; Botelho, M.C.Schistosoma haematobium, a parasitic flatworm that infects more than 100 million people, mostly in the developing world, is the causative agent of urogenital schistosomiasis, and is associated with a high incidence of squamous cell carcinoma (SCC) of the bladder. During infection, eggs are deposited in the bladder causing an intense inflammatory reaction. Angiogenesis is defined as the formation of new blood vessels from preexisting ones and is recognized as a key event in cell proliferation and carcinogenesis and spread of malignant lesions. A growing amount of evidence points to angiogenesis playing a key role in schistosomiasis-associated bladder cancer. Thus, identifying biomarkers of this process plays an important role in the study of cancer. Here, we review recent findings on the role of angiogenesis in bladder cancer and the growth factors that induce and assist in their development, particularly SCC of the bladder associated to urogenital schistosomiasis.
- Annexin A11 gene polymorphism (R230C variant) and sarcoidosis in a Portuguese populationPublication . Morais, A.; Lima, B.; Peixoto, M.; Melo, N.; Alves, H.; Marques, J.A.; Delgado, L.A recent genome-wide association study detected a protective effect for the annexin A11 rs1049550*T allele (R230Cvariant) in susceptibility to sarcoidosis. We evaluated the association between rs1049550 C/T and sarcoidosis susceptibility, distinct disease phenotypes and evolution in a Portuguese population. We performed a case-control study of 208 patients and 197 healthy controls. Samples were genotyped for rs1049550 C/T using real-time polymerase chain reaction. The frequency of the annexin A11 rs1049550*T allele was significantly lower in patients than in controls (33.2 vs 44.9%, P < 0.001). Odds ratio of 0.52 and 0.44 were obtained, respectively for carriers of one (CT) and two (TT) copies normalized to the CC wild-type genotype (P < 0.001). There were no significant differences in patients with and without Löfgren syndrome. A significant increase in the frequency of the T allele was observed in patients with bronchoalveolar lavage (BAL) fluid neutrophilia (P = 0.04). No significant associations were seen for lung function pattern, radiological stages or different forms of disease evolution. Our study confirms that rs1049550*T allele exerts a significant protective effect on sarcoidosis susceptibility. Given the role of annexin A11 in cell division, apoptosis and neutrophil function, this polymorphism may affect key elements of granulomatous and interstitial inflammation in sarcoidosis.
- Anti-cancer potential of Fasciola hepatica extractsPublication . Ferreira, S.; Fernandes, R.; Alves, H.; Richter, J.; Botelho, M.C.Fascioliasis is a food borne disease caused by infection with a liver fluke termed Fasciola (F.) hepatica. Fascioliasis, as a neglected tropical disease, commonly affects poor people from developing countries. It has been estimated that at least 2.6 million people are infected with fascioliasis worldwide. According to the International Agency for Research on Cancer, two other liver flukes Opistorchis viverrini and Clonorchis sinensis) have been recognized as definitive causes of cancer (IARC, 2012). On the other hand even long-lasting and/ or repeated F. hepatica infections have not been associated with cancer, so far. There are any known causative associations between this parasite and cholangiocarcinoma or liver cancer.
- Association study of the platelet collagen receptor glycoprotein VI gene with rheumatoid arthritisPublication . Michou, L.; Cornélis, F.; Baron, M.; Bombardieri, S.; Balsa, A.; Westhovens, R.; Barrera, P.; Alves, H.; Radstake, T.R.; Migliorini, P.; Bardin, T.; Petit-Teixeira, E.; Boilard, E.Beyond their role in haemostasis, platelets can actively contribute to immunity. The activation of the platelet collagen receptor glycoprotein VI (GPVI) promotes the release of small extracellular vesicles called microparticles. These microparticles are found in the joint bathing fluid of patients with rheumatoid arthritis (RA) and are thought to amplify inflammation. The gene coding for GPVI is localised on chromosome 19q13.4 and contains different single nucleotide polymorphisms (SNPs). Five non-synonymous SNPs define the major and minor haplotypes of GPVI. The minor haplotype is associated with higher risk of cardiovascular incidents. In this study, we examined whether this minor haplotype is also associated with RA.
- Associations between sarcoidosis clinical course and ANXA11 rs1049550 C/T, BTNL2 rs2076530 G/A, and HLA class I and II allelesPublication . Morais, A.; Lima, B.; Alves, H.; Melo, N.; Mota, P.C.; Marques, A.; Delgado, L.Background: A genetic background may be responsible for the different clinical courses in sarcoidosis. We analyzed associations between sarcoidosis clinical course and HLA class I/II alleles and susceptibility gene SNPs ANXA11 rs1049550 C/T and BTNL2 rs2076530 G/A in a Portuguese population, investigating possible gene–gene interactions. Methods: We studied 138 unrelated Caucasian sarcoidosis patients (78 women, 56.5%; mean age, 37.2 ± 12.1 years). Disease that persisted after 2 years was considered chronic. Samples were genotyped for ANXA11 rs1049550 C/T and BTNL2 rs2076530 G/A SNPs using TaqMan Real-Time PCR Assays. HLA class I/II alleles were typed using PCR sequence-specific primers. Results: Sixty-six patients experienced disease resolution and 72 (52%) developed chronic disease. Comparison of rs1049550 and rs2076530 allele frequencies showed no significant differences. Only the HLA DRB1*03 allele was significantly associated with disease resolution (21.2% vs 4.9% for chronic disease; RR = 0.35; P < .01 after Bonferroni correction). In the logistic regression models evaluating the association between HLA alleles and chronic sarcoidosis adjusted for rs1049550 and rs2076530, only DRB1*03 was significantly associated with disease resolution. No significant interactions were found in any of the logistic regression analyses. Conclusions: In this population of Caucasian patients with sarcoidosis, only DRB1*03 was associated with disease resolution after 2 years’ follow-up, with no significant interactions found for susceptibility gene SNPs ANXA11 rs1049550 or BTNL2 rs2076530.
- Bladder cancer and urinary Schistosomiasis in AngolaPublication . Botelho, M.C.; Figueiredo, J.; Alves, H.Schistosomiasis haematobia is among the most prevalent parasitosis in Angola. The pathology is characterized by serious and irreversible lesions in the urogenital tract induced by chronic infection with the parasite that can eventually lead to squamous cell carcinoma of the bladder. Considering the frequency and severe morbidity observed, even in younger ages, the purpose of this study was to assess the prevalence and morbidity of S. haematobium infection in Angola. A baseline survey was conducted between November 2007 and February 2008. A randomly sample of 300 inhabitants aged 15 to 75 years old participated in this study. Prevalence of S. haematobium infection was 71.7 % (215/300). Infection was higher in females (56.3 %) but no significant difference was found in prevalence and intensity between gender and age groups. The predominant selfreported symptoms were dysuria (91.2 %), hypogastralgia (88.7 %) and haematuria (87.1%) and these symptoms were strongly associated with S. haematobium infection (p<0.05). Ultrasound and cystoscopy examinations performed in a sub-sample of 29 individuals revealed pathological conditions at the urinary tract in all examined. Considering the high prevalence of S. haematobium infections in Angola and schistosomiasis-associated bladder cancer, our results indicate that this population should be targeted for follow up and implementation of measures for treatment and control of schistosomiasis.
- Cellular adhesion gene SELP is associated with rheumatoid arthritis and displays differential allelic expressionPublication . Burkhardt, J.; Blume, M.; Petit-Teixeira, E.; Hugo Teixeira, V.; Steiner, A.; Quente, E.; Wolfram, G.; Scholz, M.; Pierlot, C.; Migliorini, P.; Bombardieri, S.; Balsa, A.; Westhovens, R.; Barrera, P.; Radstake, T.R.; Alves, H.; Bardin, T.; Prum, B.; Emmrich, F.; Cornelis, F.; Ahnert, P.; Kirsten, H.In rheumatoid arthritis (RA), a key event is infiltration of inflammatory immune cells into the synovial lining, possibly aggravated by dysregulation of cellular adhesion molecules. Therefore, single nucleotide polymorphisms of 14 genes involved in cellular adhesion processes (CAST, ITGA4, ITGB1, ITGB2, PECAM1, PTEN, PTPN11, PTPRC, PXN, SELE, SELP, SRC, TYK2, and VCAM1) were analyzed for association with RA. Association analysis was performed consecutively in three European RA family sample groups (Nfamilies = 407). Additionally, we investigated differential allelic expression, a possible functional consequence of genetic variants. SELP (selectin P, CD62P) SNP-allele rs6136-T was associated with risk for RA in two RA family sample groups as well as in global analysis of all three groups (ptotal = 0.003). This allele was also expressed preferentially (p<10-6) with a two- fold average increase in regulated samples. Differential expression is supported by data from Genevar MuTHER (p1 = 0.004; p2 = 0.0177). Evidence for influence of rs6136 on transcription factor binding was also found in silico and in public datasets reporting in vitro data. In summary, we found SELP rs6136-T to be associated with RA and with increased expression of SELP mRNA. SELP is located on the surface of endothelial cells and crucial for recruitment, adhesion, and migration of inflammatory cells into the joint. Genetically determined increased SELP expression levels might thus be a novel additional risk factor for RA.
- Could Estradiol be used as a biomarker of infection in Schistosoma haematobium infected patients?Publication . Botelho, M.C; Cardoso, R.; Bordalo, A.; Alves, H.; Richter, J.Urogenital schistosomiasis is a chronic infection caused by the human blood fluke Schistosoma haematobium. Schistosomiasis haematobia is a known risk factor for cancer leading to squamous cell carcinoma of the urinary bladder (SCC). This is a neglected tropical disease endemic in many countries of Africa and the Middle East. Schistosome eggs produce catechol-estrogens. These estrogenic molecules are metabolized to active quinones that cause alterations in DNA (leading in other contexts to breast or thyroid cancer). Our group has shown that schistosome egg associated catechol estrogens induce tumor-like phenotypes in urothelial cells, originated from parasite estrogen-host cell chromosomal DNA adducts and mutations. Also we have demonstrated that these molecules are detected as Estradiol in sera of infected patients.
- CYP2D6 and IL-6 C-174G variants in schistosomiasis haematobiaPublication . Cardoso, R.; Alves, H.; Bordalo, A.; Richter, J.; Botelho, M.C.Aim: Study polymorphic variants in CYP2D6 and the C-174G promoter polymorphism of the IL-6 gene on S. haematobium infected patients from and endemic area of Guinea Bissau. Background: - Schistosome egg associated catechol estrogens induce tumor-like phenotypes in urothelial cells and might cause schistosomiasis associated infertility (Botelho et al, Trends in Parasitol, 2015); - The cytochrome P450 (CYP) genes are involved in estrogen biosynthesis and metabolism and generation of DNA damaging procarcinogens (Blackburn et al, Cancer Causes and Control, 2015); - Very high or very low levels of IL-6 are associated with estrogen metabolism imbalance.
- CYP2D6 and IL-6 c-174G variants in schistosomiasis haematobiaPublication . Cordeiro, R.; Alves, H.; Bordalo, A.; Richter, J; Botelho, M.C.AIM: To study the polymorphic variants in CYP2D6 and the C-174G promoter polymorphism of the IL-6 gene on S. haematobium infected patients from an endemic area of Guinea Bissau. BACKGROUND: - Our group has shown that schistosome egg associated catechol estrogens induce tumor-like phenotypes in urothelial cells. These estrogen metabolites might also be the cause of schistosomiasis associated infertility; - The cytochrome P450 (CYP) genes are oxygenases involved in estrogen biosynthesis and metabolism, generation of DNA damaging procarcinogens, and response to anti-estrogen therapies; - IL6 Interleukin-6 (IL-6) is a pleiotropic cytokine expressed in many tissues. These cytokine is largely expressed in female urogenital tract as well as reproduction organs. Very high or very low levels of IL-6 are associated with estrogen metabolism imbalance.
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