Epstein-Barr virus-positive gastric cancer: a distinct molecular subtype of the disease?

Abstract: Approximately 90% of the world population is infected by Epstein-Barr virus (EBV). Usually, it infects B lymphocytes, predisposing them to malignant transformation. Infection of epithelial cells occurs rarely, and it is estimated that about to 10% of gastric cancer patients harbor EBV in their malignant cells. Given that gastric cancer is the third leading cause of cancer-related mortality worldwide, with a global annual incidence of over 950,000 cases, EBV-positive gastric cancer is the largest group of EBV-associated malignancies. Based on gene expression profile studies, gastric cancer was recently categorized into four subtypes; EBV-positive, microsatellite unstable, genomically stable and chromosomal instability. Together with previous studies, this report provided a more detailed molecular characterization of gastric cancer, demonstrating that EBV-positive gastric cancer is a distinct molecular subtype of the disease, with unique genetic and epigenetic abnormalities, reflected in a specific phenotype. The recognition of characteristic molecular alterations in gastric cancer allows the identification of molecular pathways involved in cell proliferation and survival, with the potential to identify therapeutic targets. These findings highlight the enormous heterogeneity of gastric cancer, and the complex interplay between genetic and epigenetic alterations in the disease, and provide a roadmap to implementation of genome-guided personalized therapy in gastric cancer. The present review discusses the initial studies describing EBV-positive gastric cancer as a distinct clinical entity, presents recently described genetic and epigenetic alterations, and considers potential therapeutic insights derived from the recognition of this new molecular subtype of gastric adenocarcinoma.

Evaluation of human T-lymphotropic virus prevalence/co-infection rates for a four-year period in a non-metropolitan blood center in Southeast Brazil

Abstract: INTRODUCTION: Human T-lymphotropic virus types 1/2 (HTLV-1/2) are distributed worldwide and are endemic in specific regions. METHODS: Serological evaluation of the HTLV-1/2 prevalence and co-infection rate [human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), Chagas disease, and syphilis)] for 2011-2014 was performed with volunteer blood donors from the western part of São Paulo State. RESULTS: Serrana and Araçatuba had higher HTLV seroprevalence rates (0.1%); while Franca, Olimpia, and Bebedouro had lower seroprevalences (0.04%). Co-infection (HBV and syphilis) was present in 12.3% of HTLV-infected blood donors. CONCLUSIONS: Our findings provide data for the prevalence of HTLV in Brazil and demonstrate the importance of regional and global hemovigilance.

Prevention of respiratory syncytial virus infections

Respiratory syncytial virus is the most important cause of viral lower respiratory illness in infants and children worldwide. By the age of 2 years, nearly every child has become infected with respiratory syncytial virus and re-infections are common throughout life. Most infections are mild and can be managed at home, but this virus causes serious diseases in preterm children, especially those with bronchopulmonary dysplasia. Respiratory syncytial virus has also been recognized as an important pathogen in people with immunossupressive and other underlying medical problems and institutionalizated elderly, causing thousands of hospitalizations and deaths every year. The burden of these infections makes the development of vaccines for respiratory syncytial virus highly desirable, but the insuccess of a respiratory syncytial virus formalin-inactivated vaccine hampered the progress in this field. To date, there is no vaccine available for preventing respiratory syncytial virus infections, however, in the last years, there has been much progress in the understanding of immunology and immunopathologic mechanisms of respiratory syncytial virus diseases, which has allowed the development of new strategies for passive and active prophylaxis. In this article, the author presents a review about novel approaches to the prevention of respiratory syncytial virus infections, such as: passive immunization with human polyclonal intravenous immune globulin and humanized monoclonal antibodies (both already licensed for use in premature infants and children with bronchopulmonary dysplasia), and many different vaccines that are potential candidates for active immunization against respiratory syncytial virus.

Bronchiolitis, respiratory syncytial virus, and recurrent wheezing: what is the relationship?

Various follow-up studies of children hospitalized with bronchiolitis caused by respiratory syncytial virus have demonstrated that a significant proportion of infants (50%) have recurrent wheezing during childhood. Nevertheless, the relationship between these two entities, if any, has not been established. In order to explain this observation, several hypotheses have been proposed. The first suggests that some children could have an individual predisposition to bronchiolitis caused by respiratory syncytial virus and recurrent wheezing. The virus could be a marker of this condition, and the individual predisposition could in turn be related to an individual hypersensitivity to common allergens (atopy), airway hyperreactivity, or to some disorder related to pulmonary anatomy or physiology that was present before the acute episode of bronchiolitis. Another hypothesis proposes that respiratory syncytial virus could be directly responsible for recurrent wheezing. During an episode of bronchiolitis, the damage in the airway mucosa caused by the vital inflammatory response to infection contributes to sensitivity to other allergens or exposes irritant receptors, resulting in recurrent wheezing. For this review, we analyzed the studies that discuss these hypotheses with the purpose of clarifying the mechanisms for the important issue of recurrent wheezing in childhood.

Alterações nucleares das cellulas do figado nas infecções de Macacus Rhesus e M. Cynomolgus pelo virus da febre amarella

No figado de um Macacus rhesus inoculado por BEAUREPAIRE ARAGÃO com sangue deum caso benigno de febre amarella e no qual elle descreveu symptomas e lesões typicas semelhantes ás obidas por STOKES, BAUER e HUDSON pela inoculação com o virus africano no mesmo animal, encontrámos alterações nucleares da mesma natureza das assignaladas, no herpes zoster, herpes symptomatico, varicella e virus III do coelho e descriptas ora sob o nome de "inclusões acidophilas intranucleares" (LIPSCHÜTZ, GOODPASTURE), ora sob o de "degeneração oxychromatica" (LAUDA e LUGER). Alterações nucleares semelhantes da cellula hepatica encontrámos, posteriormente em 13 M. rhesus e 2 M. cynomolgus inoculados com e virus brasileiro da febre amarella o qual fôra isolado independentemente por BEAUREPAIRE ARAGÂO e depois por A. MARQUES DA CUNHA e J. MUNIZ de dois casos benignos de febre amarella, tendo sido um dos macacos injectado directamente com o sangue do doente; dois macacos foram inoculados com Aedes aegypti infectados em homem e em macaco; os animais foram anímaes empregados em passagens em serie do virus pelo macaco, e talvez esse facto explique até certo ponto, as notaveis differenças por vezes encontradas nas alterações histopathologicas do figado, visto como, em condições naturaes, o virus nunca passa directamente de homem para homem. A intensidade com que se apresenta a degeneração oxychromatica de modo algum está na dependencia das alterações do conteúdo gorduroso, necrose e necrobiose encontradas; em um caso, ella era a unica alteração presente no figado, sendo então particularmente intensa. As inclusões acidophilas intranucleares (degeneração oxychromatica) não foram encontradas em diversos M. rhesus não inoculados e mortos por causas obscuras; no entanto, em taes figados eram presentes infiltração e degeneração gordurosas associadas a alterações de necrose e necrobiose. Alguns estadios (figuras intranucleares "em borboleta" e "em ameba", v. fig. g e h, Est. colorida) sendo abundantes, facilitam, em virtude de sua configuração especial, o reconhecimento da degeneração oxychromatica em córtes feitos segundo uma technica rapida (pequenos fragmentos de figado fixados em formol aquecido a 60°C.-trinta minutos, córtes em congelação, hematoxylina, eosina, alcool absoluto, phenol-xylol-creosoto, xylol, balsamo), não tendo, afóra isso, importancia especial. Ao passo que a degeneração e infiltração gordurosa, bem como a necrose e a necrobiose da cellula hepatica apresentam variações consideraveis em sua intensidade de um para outro animal em uma passagem em serie não interrompida do virus pelo M. rhesus, chegando mesmo a faltar interamente em dois animaes cujo figado, no entanto, mostrou-se capaz de reproduzir symptomas e lesões typicas na passagem seguinte, as inclusões acidophilas intranucleares (degeneração oxychromatica), de regra, se encontram com muito maior regularidade...

Febre maculosa das Montanhas Rochosas: ensaios negativos de transmissão experimental do virus por Triatomideos

1. - As seguintes especies de Triatomideos não puderam transmitir pela picada o virus da febre maculosa das Montanhas Rochosas a cobayas normaes, nos seguintes prazos após a sucção de animal infectado: Eutriatoma uhleri, 33, 47, 75 e 141 dias (1 exemplar); Triatoma protracta, 15 e 37 dias (1 exemplar), Triatoma infestans, 8 dias (15 exemplares), e Rhodnius prolixus, 2 dias (1 exemplar). Foi demonstrado por inoculaçao que o ultimo insecto ainda continha o virus vivo. 2. - Experiencias de transmissão mechanica, por picada interrompida em animal infectado e continuada immediatamente em animal são, foram tambem negativas, com as especies T. protracta e R. prolixus. Um unico insecto da primeira especie picou 2 vezes cada animal, emquanto que 22 exemplares da segunda especie picaram de 1 a 3 vezes cada cobaya. 3. - A inoculação de gottas de dejecções de um R. prolixus eliminadas 2 dias depois de sugar animal infectado, não produziu a infecção em cobaya normal, não obstante ter sido demonstrada a presença do virus no organismo do barbeiro, por inoculação do conteúdo estomacal em outra cobaya. 4. - Foram feitas experiencias para determinar o tempo de sobrevivencia do virus nos barbeiros, inoculando-se conteúdo intestinal a diversos intervallos depois da sucção de cobayas infectadas, com os seguintes resultados: T. infestans: positivo 1 vez em 24 horas e 2 vezes em 48 horas; negativo 2 vezes em 72. 96, 120 e 192 horas. P. megistus: positivo 3 vezes em 24 horas, 2 vezes em 48 horas e 1 vez em 72 horas; negativo 1 vez em 72 e 96 horas; resultado duvidoso ou sem valor (infecção intercorrente) 1 vez em 48 horas e 2 vezes a 72, 96 e 144 horas cada um. R. prolixus: positivo 1 vez em 24, 48 e 72 horas e negativo em 96 horas. 5. - Em vista dos resultados destas experiencias, feitas com 5 especies pertecentes a 4 generos de Triatomideos, torna-se muito pouco provavel que estes Hemipteros possam transmitir pela picada o virus da febre maculosa das Montanhas Rochosas, ou retel-o em seu organismo, em estado virulento, por mais de 2 a 4 dias.