Recurrent amplification of RTEL1 and ABCA13 and its synergistic effect associated with clinicopathological data of gastric adenocarcinoma.

BACKGROUND: Despite progression in treatment of gastric cancer, prognosis of patients remains poor, in part due to the low rate of diagnosis during its early stages. This paradigm implies the necessity to identify molecular biomarkers for early gastric cancer diagnosis, as well as for disease monitoring, thus contributing to the development of new therapeutic approaches. In a previous study, performed by array-Comparative Genomic Hybridization, we described for the first time in literature recurrent amplification of RTEL1 and ABCA13 genes in gastric cancer. Thus, the aim of the present study was to validate recurrent amplification of RTEL1 and ABCA13 genes and associate CNV status with clinicopathological data. FINDINGS: Results showed RTEL1 and ABCA13 amplification in 38 % of samples. Statistical analysis demonstrated that RTEL amplification is more common in older patients and more associated with intestinal type and ABCA13 amplification increases the risk of lymph node metastasis and is more common in men. Co-amplification of these genes showed a significant association with advanced staging. CONCLUSIONS: aCGH is a very useful tool for investigating novel genes associated with carcinogenesis and RTEL1 amplification may be important for the development of gastric cancer in older patients, besides being a probable event contributing for chromosomal instability in intestinal gastric carcinogenesis. ABCA13 amplification may have age-specific function and could be considered a useful marker for predicting lymph node metastasis in resected gastric cancer patients in early stage. Lastly, RTEL1 and ABCA13 synergistic effect may be considered as a putative marker for advanced staging in gastric cancer patients.

Conventional cytogenetic characterization of a new cell line, ACP01, established from a primary human gastric tumor.

Gastric cancer is the second most frequent type of neoplasia and also the second most important cause of death in the world. Virtually all the established cell lines of gastric neoplasia were developed in Asian countries, and western countries have contributed very little to this area. In the present study we describe the establishment of the cell line ACP01 and characterize it cytogenetically by means of in vitro immortalization. Cells were transformed from an intestinal-type gastric adenocarcinoma (T4N2M0) originating from a 48-year-old male patient. This is the first gastric adenocarcinoma cell line established in Brazil. The most powerful application of the cell line ACP01 is in the assessment of cytotoxicity. Solid tumor cell lines from different origins have been treated with several conventional and investigational anticancer drugs. The ACP01 cell line is triploid, grows as a single, non-organized layer, similar to fibroblasts, with focus formation, heterogeneous division, and a cell cycle of approximately 40 h. Chromosome 8 trisomy, present in 60% of the cells, was the most frequent cytogenetic alteration. These data lead us to propose a multifactorial triggering of gastric cancer which evolves over multiple stages involving progressive genetic changes and clonal expansion.

[Paracoccidioidomycosis in a patient with human immunodeficiency virus infection. A necropsy case]. / Paracoccidioidomicose em paciente com a infecção pelo vírus da imunodeficiência humana. Relato de necrópsia.

This is a case report of the association of Paracoccidioidomycosis and Acquired Immunodeficiency Syndrome (AIDS) occurring in a 43-year old male. This is, to the best of our knowledge, the first detailed pathological account of that association. Also discussed are the low rates of that association, its natural history and treatment results. It is emphasised the importance of the associations of AIDS and tropical infectious diseases in this country.

Aging And Environmental Enrichment Exacerbate Inflammatory Response On Antibody-Enhanced Dengue Disease In Immunocompetent Murine Model

We previously demonstrated in young mice that in comparison with animals raised in an impoverished environment (IE), animals from an enriched environment (EE) show more severe dengue disease, associated with an increased expansion of memory T target cells. Because active older adults show less functional decline in T-cell adaptive immunity, we hypothesized that aged mice from EE would show higher mortality and T-lymphocyte expansion than mice from IE. To test this hypothesis, we administered serial i.p. injections of anti-DENV2 hyperimmune serum, followed 24 h later by DENV3 (genotype III)-infected brain homogenate. Control mice received equal volumes of serum but received uninfected brain homogenate. The presence of virus or viral antigens was indirectly detected by real-time quantitative RT-PCR and immunohistochemistry. Compared to infected IE animals, EE mice, independent of age, showed higher mortality and more intense clinical signs. Compared to young mice, the higher mortality of aged mice was associated with a higher degree of T lymphocytic hyperplasia in the spleen and infiltration in kidneys, liver, and lungs, but less viral antigen immunolabeling. We propose that a higher expansion of T cells and serotype cross-reactive antibodies are associated with disease severity in aged mice (AU)

In situ apoptosis of adaptive immune cells and the cellular escape of rabies virus in CNS from patients with human rabies transmitted by Desmodus rotundus

The aim of the current study was to investigate the apoptosis of neurons, astrocytes and immune cells from human patients that were infected with rabies virus by vampire bats bite. Apoptotic neurons were identified by their morphology and immune cells were identified using double immunostaining. There were very few apoptotic neurons present in infected tissue samples, but there was an increase of apoptotic infiltrating CD4+ and TCD8+ adaptive immune cells in the rabies infected tissue. No apoptosis was present in NK, macrophage and astrocytes. The dissemination of the human rabies virus within an infected host may be mediated by viral escape of the virus from an infected cell and may involve an anti-apoptotic mechanism, which does not kill the neuron or pro-apoptosis of TCD4+ and TCD8+ lymphocytes and which allows for increased proliferation of the virus within the CNS by attenuation of the adaptive immune response.(AU)

Conventional cytogenetic characterization of a new cell line, ACP01, established from a primary human gastric tumor

Gastric cancer is the second most frequent type of neoplasia and also the second most important cause of death in the world. Virtually all the established cell lines of gastric neoplasia were developed in Asian countries, and western countries have contributed very little to this area. In the present study we describe the establishment of the cell line ACP01 and characterize it cytogenetically by means of in vitro immortalization. Cells were transformed from an intestinal-type gastric adenocarcinoma (T4N2M0) originating from a 48-year-old male patient. This is the first gastric adenocarcinoma cell line established in Brazil. The most powerful application of the cell line ACP01 is in the assessment of cytotoxicity. Solid tumor cell lines from different origins have been treated with several conventional and investigational anticancer drugs. The ACP01 cell line is triploid, grows as a single, non-organized layer, similar to fibroblasts, with focus formation, heterogeneous division, and a cell cycle of approximately 40 h. Chromosome 8 trisomy, present in 60 percent of the cells, was the most frequent cytogenetic alteration. These data lead us to propose a multifactorial triggering of gastric cancer which evolves over multiple stages involving progressive genetic changes and clonal expansion.