Infeção por citomegalovirus e cancro do cólo do útero: de dúvidas passadas a questões presentes

Background: Since early 60's that Cytomegalovirus was studied for its possible role in cervical cancer development. Despite several decades of studies and the description of CMV DNA in cervical samples, it is still doubtful what is the prevalence of Cytomegalovirus in cervix and if CMV can act as a co-factor in cervical carcinogenesis. Methods: In this Systematic Review we intend to summarize the frequency of Cytomegalovirus in cervical samples by revising all published studies between 1980 and 2011 regarding the detection of Cytomegalovirus in cervical samples and the development of lesions/ invasive cervical cancer. Crude and adjusted frequencies of Cytomegalovirus infection were calculated according to country and world region. Results: This study revealed that the worldwide crude frequency of Cytomegalovirus infection in the cervix was 18.9% in all cervical samples and 36.5% in HPV positive women. Cytomegalovirus infection was present in all different types of lesions: 17.4% in normal/cervicitis, 28.0% in LSIL, 19.7% in HSIL and 44.4% in CIS/ICC. The overall rate of Cytomegalovirus infection varied from 1.58% to 61.0% with an increased incidence in less developed countries. Conclusion: In this study we described a high frequency of positive Cytomegalovirus cases in all types of cervical samples, with increased incidence in both HPV-infected women and CIS/ICC cases. Hence, despite results showed that Cytomegalovirus shedding in cervical samples is frequent more studies should be performed to clarify if Cytomegalovirus infection is an opportunistic infection in HPV-infected cases, or if it contributes for cervical immunosuppression that will favor HPV-associated carcinogenesis.RESUMO Introdução: Desde os anos 60 que o Citomegalovírus tem sido estudado pelo potencial papel no desenvolvimento de cancro do colo do útero. Após várias décadas de estudos e relatos da presença de DNA viral em amostras cervico-vaginais, ainda permanecem dúvidas sobre qual a prevalência do Citomegalovírus no cólo do útero e se este pode ser um cofator da carcinogénese. Métodos: Nesta Revisão Sistemática pretendemos descrever a prevalência de Citomegalovírus em amostras cervicais, revendo todos os estudos publicados entre 1980 e 2011 que descrevem a infecção por Citomegalovírus em amostras cervicais e o desenvolvimento de lesões/carcinoma invasor. As frequências da infecção por Citomegalovírus foram calculadas de acordo com a região no mundo. Resultados: Este estudo revelou que a frequência bruta da infecção por Citomegalovírus no cólo do útero foi de 18,9% em todas as amostras e 36,5% em mulheres HPV positivas. A infecção por Citomegalovírus está presente em todas as diferentes lesões: 17,4% em normais/cervicite, 28,0% em LSIL, 19,7% em HSIL e 44,4% em CIS/ICC. A frequência global variou de 1,58% a 61,0%, com uma maior incidência em países menos desenvolvidos. Conclusão: Neste estudo, verificou-se uma elevada frequência de casos positivos para Citomegalovírus em todos os tipos de amostras cervico-vaginais, com maior incidência em mulheres infectadas por HPV e em casos de cancro. Assim, são necessários mais estudos para esclarecer se a infecção por Citomegalovírus é uma infecção oportunista ou se contribui para a imunossupressão favorecendo a carcinogénese associada ao HPV.info:eu-repo/semantics/publishedVersio

Characterization of herpesvirus infection in cervico-vaginal samples : role in cervical cancer

Introdução: O cancro do cólo do útero é o terceiro cancro mais comum no sexo feminino em todo o mundo. A infeção persistente por HPV de alto risco é considerado o agente etiológico necessário, mas não suficiente, para o seu desenvolvimento. Vários estudos sugerem a interação de outros agentes patogénicos, como o vírus de Epstein-Barr (EBV) e o Citomegalovírus (CMV). Objectivos: O objectivo deste estudo consistiu em caracterizar a prevalência/frequência de infeção por EBV e CMV em amostras cervico-vaginais e tentar estabelecer uma correlação entre estes vírus e o desenvolvimento de cancro do cólo do útero. Material e Métodos: Este estudo foi realizado em 89 amostras cervico-vaginais de mulheres com diferentes lesões, recolhidas no Serviço de Ginecologia do Instituto Português de Oncologia do Porto. A frequência das infecções por CMV e EBV foi avaliada por PCR em tempo real com sondas específicas para genes virais. Resultados: O nosso estudo revelou uma frequência de 10.1% para a infeção por EBV e de 5.20% para o CMV. O DNA de CMV foi detetado em: normais (1.20%), lesão de baixo grau (8.20%), lesão de alto grau (6.80%), carcinoma in situ/carcinoma cervical invasor (13.3%); a infeção por EBV foi detetada em todos os tipos de lesões: normais (16.7%), com inflamação (5.26%), lesão de baixo grau (9.52%), lesão de alto grau (4.50%) e com carcinoma in situ/carcinoma cervical invasor (22.2%). Tanto na infeção por CMV como EBV a infeção encontrava-se em todas as faixas etárias, sem predominância em nenhuma destas. Na análise de risco, apenas a infeção por CMV revelou um aumento do risco para o desenvolvimento de carcinoma lesões de baixo grau (OR=7.73, =0.043) e todo o tipo de lesões e in situ/carcinoma invasor (OR=7.73, p=0.021). Na correlação entre a infeção por CMV/ EBV e HPV não se obtiveram resultados estatisticamente significativos que indiciassem um aumento do risco no desenvolvimento de lesões. Conclusão: O estudo realizado demonstrou uma prevalência baixa para ambos os vírus em estudo (EBV e CMV) relativamente a estudos realizados anteriormente. Os resultados revelaram: 1) distribuição ubíqua de CMV e EBV em mulheres com diferentes lesões; e 2) A infeção por CMV deve representar um risco aumentado no desenvolvimento de carcinoma in situ/carcinoma cervical invasor.Introduction: Cervical cancer is the third most common cancer in women worldwide. A persistent infection by high-risk HPV is considered the etiological agent necessary but not sufficient for its development. Several studies suggest an interaction of other pathogens, such as Epstein-Barr virus (EBV) and Cytomegalovirus (CMV). Aims of the study: The aim of this study was to establish a correlation between EBV and CMV infection in the development of cervical cancer by studying its prevalence in different lesions. Materials and Methods: This study was performed in 89 cervico-vaginal samples of women with different cervical lesions, who attended the Department of Gynecology at the Portuguese Institute of Oncology of Porto. The frequency of EBV and CMV infections was evaluated by real time PCR with specific probes for the viral genes. Results: Our study revealed a frequency of 10.1% women with EBV infection and 5.20% with CMV infection. The CMV DNA was detected on: normal (1.20%), low-grade lesion (8.20%), high-grade lesion (6.80%), in situ/invasive cervical carcinoma (13.3%); EBV infection was detected in all types of lesions: normal (16.7%), with inflammation (5.26%), low-grade lesion (9.52%), high-grade lesion (4.50%) and in situ/invasive cervical carcinoma (22.2%). Both CMV and EBV infection were present in all age groups, with no predominance in any of these. In risk analysis, only CMV infection revealed an increased risk for the development of low-grade lesions (OR=7.73, p=0.043) and all kinds of lesions plus in situ/invasive carcinoma (OR=7.73, p= 0.021). In the correlation between CMV/EBV and HPV infection no statistically significant results were obtained that would indicate an increased risk in the development of lesions. Conclusion: This study demonstrated a low prevalence for both viruses under study (EBV and CMV) relative to previous studies. The results showed: 1) ubiquitous distribution of CMV and EBV in women with different lesions; and 2) CMV infection should indicate an increased risk in the development of carcinoma in situ/invasive cervical carcinoma

miR-34a and miR-125b Expression in HPV Infection and Cervical Cancer Development

We aimed to characterize miR-125b and miR-34a expression in 114 women with different cervical lesions: normal epithelium with (n = 20) and without (n = 29) HPV infection; LSIL (n = 28); HSIL (n = 29); and ICC (n = 8). miRNA expression analysis was performed by comparing the distinct groups with the reference group (women with normal epithelium without HPV). For miR-125b, we observed a twofold (2-ΔΔCt = 2.11; P = 0.038) increased expression among women with normal epithelium with HPV infection and a trend of downregulation in different cervical lesions including an 80% reduction (2-ΔΔCt = 0.21; P = 0.004) in ICC. Similarly, miR-34a expression analysis revealed an increased expression (2-ΔΔCt = 1.69; P = 0.049) among women with normal cervix and HPV infection, and despite no significant correlation with cervical lesions, its expression was increased by twofold (2-ΔΔCt = 2.08; P = 0.042) in ICC. Moreover, miR-125b levels were able to predict invasive cancers with 88% sensitivity and 69% specificity. Results showed that while miR-34a expression seems to be correlated with invasive cervical cancer, miR-125b expression is significantly changed within the different cervical lesions and their levels should be further investigated as possible predictive/prognostic biomarkers using a noninvasive approach

Mechanisms underlying the association between obesity and Hodgkin lymphoma

© International Society of Oncology and BioMarkers (ISOBM) 2016A solid body of knowledge indicates that overweight and obese subjects are prone to develop cancer, aggressive disease, and death more than their lean counterparts. While obesity has been causally associated with various cancers, only a limited number of studies beheld the link with classical Hodgkin lymphoma (HL). Contemporary metaanalysis and prospective studies confirmed the association of body mass index with HL. Besides epidemiological evidence, excess adiposity is known to influence tumor behavior through adipokines, adipose-derived stem cell migration, and metabolism regulation, and by modulating immunoinflammatory response. Nevertheless, the obesity paradox has been described in few cancers. Considering that adipose tissue is an immunomodulatory organ, and that inflammation is the cornerstone of HL pathophysiology, the rationale for being causally related due to endocrine/paracrine interactions cannot be negligible. In this hypothesis-generating review, we explore the biologically plausible links between excess adiposity and HL in light of recent basic and clinical data, in order to create a basis for understanding the underlying mechanisms and foster applied research. The establishment of an association of excess adiposity with HL will determine public health preventive measures to fight obesity and eventually novel therapeutic approaches in HL patients.The authors acknowledge the support from Instituto de Investigação Bento da Rocha Cabral. This work was supported by the RayBiotech grant (RayBiotech 2013 Innovative Research Grant Award). MJ Oliveira is a recipient of a Portuguese Science Foundation Investigator FCT2012 position. RayBiotech’s 2013 Innovative Research Grant program supports the proposal entitled BGenetic, molecular and cellular determinants of the causal association between obesity and Hodgkin Lymphoma,^ which focuses in the comprehension of pathophysiological mechanisms behind this unexplored association.info:eu-repo/semantics/publishedVersio

Effect of the cryopreservation method used, the embryonic stage and the use of conjugated linoleic acid isomers on the cryotolerance of in vitro-produced bovine embryos

Conjugated linoleic acid (CLA) might be able to improve the cryotolerance of in vitro-produced (IVP) embryos. The effect of two CLA isomers on the cryotolerance of bovine IVP embryos, as well as that of the stage of embryonic development and the method used for cryopreservation was evaluated by three experiments. In Experiment 1, oocytes (n = 3,917) were fertilized in vitro and cultured with 0, 50, 100, or 200 ?M trans-10, cis-12 (t10, c12 CLA). In Experiment 2, fertilized oocytes (n = 2,131) were cultured with 100 ?M t10, c12 or cis-9, trans-11 (c9, t11 CLA), or a combination of both isomers. The embryos were vitrified at the blastocyst (BL) or the expanded blastocyst (EB) stage. In Experiment 3, oocytes (n = 1,720) were fertilized and cultured with or without 100 ?M t10, c12 CLA, and the blastocysts were vitrified or frozen. Blastocyst development rate as well as the rates of re-expansion and hatching after thawing was recorded. Moreover, the mean cell number and mRNA expression of acetyl-CoA carboxylase (ACC1) and stearoyl-CoA desaturase (SCD1) as well as fatty acid synthase (FASN) multienzyme complex were determined. In Experiment 1, the highest concentration of t10, c12 CLA that did not reduce blastocyst development rate was 100 ?M. In Experiment 2, the rates of re-expansion and hatching among the EBs obtained through IVP after supplementation with t10, c12 CLA (73.1% and 57.7%), with c9, t11 CLA (80.0% and 68.6%), with the combination (78.3% and 52.2%), and with the control group (85.4% and 58.3%) were similar. At the BL stage, the rates of re-expansion and hatching were lower than those at the EB stage, and CLA combination allowed a hatching rate (8.0%) lower than that observed in the control group (40.0%). In Experiment 3, the hatching rates for vitrified EBs (vitrified control; 67.4%) and vitrified CLA EBs (65.8%) were higher than those obtained for frozen EBs, exposed (13.3%) or not exposed (28.6%) to CLA. In addition, in Experiment 3, the hatching rate was higher at the EB stage in vitrified groups, while the rates of BL and EB were similar in frozen groups, thus proving that vitrification was more efficient than freezing for IVP bovine embryos. In Experiment 3, CLA isomer t10, C12 did not influence the embryonic cell number or mRNA expression of ACC1 and SCD1 enzymes, but decreased the mRNA expression of FASN. In conclusion, 100 ?M CLA did not affect subsequent embryonic development. However, neither CLA isomer improved the cryotolerance of IVP bovine embryos.</p

Hepatic steatosis and patients with inflammatory bowel disease: when transient elastography makes the difference

Recent studies suggest an increased prevalence of hepatic steatosis (HS) in patients with inflammatory bowel disease (IBD). Features such as chronic inflammation, previous surgeries, drug-induced hepatotoxicity, malnutrition, and intestinal dysbiosis seem to be involved in its pathogenesis. Background Recent studies suggest an increased prevalence of hepatic steatosis (HS) in patients with inflammatory bowel disease (IBD). Features such as chronic inflammation, previous surgeries, drug-induced hepatotoxicity, malnutrition, and intestinal dysbiosis seem to be involved in its pathogenesis. Aims The aim of this study was to assess the frequency of HS in patients with IBD quantified by controlled attenuation parameter (CAP) and by clinical–analytical scores: Hepatic Steatosis Index (HSI) and Fatty Liver Index (FLI). The secondary aim was to investigate risk factors associated with HS in patients with IBD. Patients and methods A cross-sectional study was carried out including consecutive outpatients observed in our department between January and March 2017. HS was defined as HSI of at least 36 or FLI of at least 60 or CAP of greater than 248. Results A total of 161 patients were included, with a mean age of 40.6±12.8 years. There were 86 (53.4%) female patients. Overall, 62.7% had Crohn’s disease and 37.1% had ulcerative colitis. Moreover, 73 (45.3%) patients had CAP greater than 248, 27 (16.8%) had FLI greater than 60, and 46 (28.6%) had HSI greater than 36. We found that patients with CAP of greater than 248 were more frequently obese (28.8 vs. 0.0% P<0.001), male (57.5 vs. 37.5% P=0.011), and presented more frequently with metabolic syndrome (23.9 vs. 4.5% P <0.001). With regard to IBD factors, patients with HS had a higher frequency of previous surgeries (31.5 vs. 12.5% P=0.003). In multivariate analysis, only male sex [odds ratio: 5.7 (95% confidence interval: 2.0–15.9); P=0.001] and previous surgeries [odds ratio: 5.9 (95% confidence interval: 1.5–22.9); P=0.011] were independent risk factors of HS. Conclusion In our cohort, the frequency of HS varied between 16.8 and 45.3% defined by noninvasive methods. We found that male sex and previous history of surgery were the independent risk factors of HS when quantified by transient elastography