Common NOD2/CARD15 and TLR4 Polymorphisms Are Associated with Crohn's Disease Phenotypes in Southeastern Brazilians.

AIM: To investigate whether variants in NOD2/CARD15 and TLR4 are associated with CD and ulcerative colitis (UC) in a genetically admixed population of Rio de Janeiro, where IBD has continued to rise. METHODS: We recruited 67 consecutive patients with CD, 61 patients with UC, and 86 healthy and ethnically matched individuals as controls. DNA was extracted from buccal brush samples and genotyped by PCR with restriction enzymes for G908R and L1007finsC NOD2/CARD15 single-nucleotide polymorphisms (SNPs) and for T399I and D299G TLR4 SNPs. Clinical data were registered for subsequent analysis with multivariate models. RESULTS: NOD2/CARD15 G908R and L1007finsC SNPs were found in one and three patients, respectively, with CD. NOD2/CARD15 G908R and L1007finsC SNPs were not found in any patients with UC, but were found in three and three controls, respectively. With regard to the TLR4 gene, no significant difference was detected among the groups. Overall, none of the SNPs investigated determined a differential risk for a specific diagnosis. Genotype-phenotype associations were found in only CD, where L1007finsC was associated with colonic localization; however, TLR4 T399I SNP was associated with male gender, and D299G SNP was associated with colonic involvement, chronic corticosteroid use, and the need for anti-TNF-alpha therapy. CONCLUSION: Variants of NOD2/CARD15 and TLR4 do not confer susceptibility to IBD, but appear to determine CD phenotypes in this southeastern Brazilian population.

Proteome analysis of formalin-fixed paraffin-embedded tissues from a primary gastric melanoma and its meningeal metastasis: a case report.

Melanoma is the third most common brain metastasis cause in the United States as it has a relatively high susceptibility to metastasize to the central nervous system. Among the different origins for brain metastasis, those originating from primary gastric melanomas are extremely rare. Here, we compare protein profiles obtained from formalin-fixed paraffin- embedded (FFPE) tissues of a primary gastric melanoma with its meningeal metastasis. For this, the contents of a microscope slide were scraped and ultimately analyzed by nano-chromatography coupled online with tandem mass spectrometry using an Orbitrap XL. Our results disclose 184 proteins uniquely identified in the primary gastric melanoma, 304 in the meningeal metastasis, and 177 in common. Notably, we identified several enzymes related to changes in the metabolism that are linked to producing energy by elevated rates of glycolysis in a process called the Warburg effect. Moreover, we show that our FFPE proteomic approach allowed identification of key biological markers such as the S100 protein that we further validated by immunohistochemistry for both, the primary and metastatic tumor samples. That said, we demonstrated a powerful strategy to retrospectively mine data for aiding in the understanding of metastasis, biomarker discovery, and ultimately, diseases. To our knowledge, these results disclose for the first time a comparison of the proteomic profiles of gastric melanoma and its corresponding meningeal metastasis.

O papel do gene p16 e do gene Dapk no controle do ciclo celular e na via carcinogênese vulvar / The role of p16 and Dark genes in cell cycle control and in the pathways of vulvar carcinogenesis

O câncer vulvar é o quarto tipo de câncer mais comum nas mulheres e representa 4,8% dos cânceres do trato genital inferior. O carcinoma de células escamosas é responsável por 80 a 90% de todos os cânceres de vulva. O carcinoma escamoso vulvar e suas lesões pré-malignas parecem desenvolver-se por dois caminhos distintos, baseados em características etiológicas e histopatológicas, tendo assim uma etiologia heterogênea. Um dos caminhos está relacionado com a infecção pelo HPV, e o outro, com as desordens epiteliais, tais como líquen escleroso e hiperplasia epitelial. O HPV é um importante fator causal das neoplasias do trato genital inferior. Ele está presente em cerca de 90% dos cânceres do colo uterino e 30 a 40% dos cânceres de vulva. O tipo mais prevalente é o 16, seguido pelos tipos 18, 45, 31 e 33. O estudo das alterações genéticas e epigenéticas, por meio da análise de metilação e imunoexpressão gênica, tem demonstrado uma grande versatilidade para o monitoramento molecular de pacientes com câncer, o que impulsiona pesquisas de métodos diagnósticos e terapêuticos do câncer. Nesta atualização pretendeu-se demonstrar as funções dos genes p16 e DAPK e as recentes pesquisas sobre a expressão destes genes nas vias da carcinogênse vulvar.

Vulvar cancer is the fourth commonest kind of cancer in women and it represents 4.8% of cancers in the lower genital tract squamous cell carcinoma is responsible for 80-90% of all vulvar cancers. Squamous cell carcinoma and it's premalignant lesions seem to develop in two distinct pathways, based on etiological and histopathological characteristics, thus forming a heterogeneous etiology. Whereas one of the pathways is related to HPV infection, the other is related to epithelial disorders such as: lichen sclerousus and epithelial hyperplasia. HPV is an important contributing factor of neoplasia in the lower genital tract. It is found in 90% of cervical cancers and in 30-40 % of vulvar cancers. The most prevalent kind is 16, followed by 18, 45, 31, and 33. The study of genetic and epigenetic alterations by means of methylation and genic immunoexpression has demonstrated great versatility to the monitoring ofpatients with cancer, which boosts researches of diagnostic and therapeutic methods for cancer. This update intends to demonstrate the role of p16 and DAPK genes as well as the recent researches regarding the expression of these genes in the pathways of vulvar carcinogenesis.