Gastroesophageal cancer (GEC) is an aggressive disease characterized by a high frequency of metastasis and poor overall survival rates. GEC presents HER2 overexpression in 5 to 25% of tumors eligible for HER2-targeted therapy. HER2 evaluation requires protein levels and copy number alteration analyses by immunohistochemistry (IHC) and in situ hybridization (FISH or SISH), respectively. These are semiquantitative methodologies that need an expert and well-trained pathologist. Therefore, the use of new surrogate methods for HER2 evaluation in cancer, such as gene expression analysis, might improve GEC HER2 classification. We evaluated HER2 positivity in GEC through conventional IHC and SISH analyses and investigated the potential application of HER2 mRNA expression by quantitative PCR to categorize GEC samples as HER2-positive or HER2-negative. Among 270 GEC samples, 10.9% were HER2-positive by IHC and SISH analyses. HER2 mRNA was overexpressed in HER2-positive GEC samples and presented high accuracy in distinguishing those tumors from HER2-negative GEC. Nevertheless, HER2 mRNA analysis was not capable of classifying HER2-equivocal GEC samples into HER2-positive or -negative according to SISH data. Quantitative PCR analysis showed HER2 overexpression in HER2-positive GEC samples. Nevertheless, HER2 mRNA analysis failed to classify HER2-equivocal GEC according to SISH data.

Esophageal squamous cell carcinoma (ESCC) is among the ten most frequent and deadly cancers, without effective therapies for most patients. More recently, drugs targeting deregulated growth factor signaling receptors have been developed, such as HGF-MET targeted therapy. We assessed MET and HGF genetic alterations and gene and protein expression profiles in ESCC patients from the Brazilian National Cancer Institute and publicly available datasets, as well as the intratumor heterogeneity of the alterations found. Our analyses showed that HGF and MET genetic alterations, both copy number and mutations, are not common in ESCC, affecting 5 and 6% of the cases, respectively. HGF showed a variable mRNA expression profile between datasets, with no alterations (GSE20347), downregulation (GSE45670), and upregulation in ESCC (our dataset and GSE75241). On the other hand, MET was found consistently upregulated in ESCC compared to non-tumor surrounding tissue, with median fold-changes of 5.96 (GSE20347), 3.83 (GSE45670), 6.02 (GSE75241), and 5.0 (our dataset). Among our patients, 84% of the tumors showed at least a two-fold increase in MET expression. This observation was corroborated by protein levels, with 55% of cases exhibiting positivity in 100% of the tumor cells. Intratumor heterogeneity was evaluated in at least four tumor biopsies from five patients and two cases showed a consistent increase in MET expression (at least two-fold) in all tumor samples. Our data suggested that HGF-MET signaling pathway was likely to be overactivated in ESCC, representing a potential therapeutic target, but eligibility for this therapy should consider intratumor heterogeneity.

ABSTRACT The organic extracts from stems, roots and leaves of Tephrosia egregia Sandwith, Fabaceae, provided a new flavone, 5-hydroxy-8-(1",2"-epoxy-3"-hydroxy-3"-methylbutyl)-7-methoxyflavone (1), in addition to eleven known compounds: pongaflavone (2), praecansone B (3), 12a-hydroxyrotenone (4), praecansone A, 2',6'-dimethoxy-4',5'-(2",2"-dimethyl)-pyranochalcone, pongachalcone, maackiain, β-sistosterol and its glucoside, p-cumaric acid and cinnamic acid. The structures of all compounds were established on the basis of spectroscopic methods, mainly 1D and 2D NMR and HRESIMS, involving comparison with literature data. Cytotoxicity of compounds 1–4 was evaluated against AGP-01 (cancerous ascitic fluid), HCT-116 (colon adenocarcinoma), HL-60 (leukemia), PC-3 (prostate carcinoma), SF-295 (glioblastoma) and SKMEL 28 (melanoma) cell lines.

ABSTRACT Phytochemical investigation of Bauhinia acuruana Moric., Fabaceae, resulted in the isolation of sixteen constituents, including two new compounds 2'-hydroxy-2,3,5-trimethoxybibenzyl (1), (2R,3S)-2-(3,4'-dihydroxyphenyl)-5-methoxy-6-methylchroman-3,7-diol (2), together with fourteen known ones (3–16). The structures of the compounds were established by spectroscopic analysis including HR-ESI-MS, 1D and 2D NMR data, followed by comparison with previously reported data from the literature. Compounds 1, 2, 6, 7, 8 and 9 were evaluated for their cytotoxicity, which turned out to be marginal in a panel of six human cancer cell lines.

RESUMO A urolitíase obstrutiva em pequenos ruminantes é uma doença metabólica de etiologia multifatorial com distribuição mundial. A elevação da concentração urinária de solutos, minerais ionizados (cristaloides) que formam cristais insolúveis é citada por alguns autores como o fator mais importante. Assim, o conhecimento do perfil mineral dos animais submetidos a dietas calculogênicas e a composição química dos urólitos tornam-se ferramentas eficazes na prevenção da doença. Neste estudo, foram utilizados 14 ovinos hígidos, machos (não castrados), da raça Santa Inês, com idade aproximada de 90 dias, distribuídos em dois grupos (G1 - sem vitamina C e G2 - com vitamina C) e alimentados com dieta calculogênica. A análise dos perfis minerais, séricos e urinários revelou completo desbalanceamento na relação entre concentrações de cálcio, fósforo e magnésio, havendo elevação expressiva do fósforo e do magnésio e diminuição substancial do cálcio. Com isso, a análise bioquímica dos urólitos demonstrou que o cálcio esteve presente em 50% das amostras analisadas.

ABSTRACT Urolithiasis in small ruminants is a metabolic disease of multifactorial etiology with worldwide distribution. Increased urinary concentration of solutes, ionized minerals (crystalloid) that form insoluble crystals is cited by some authors as the most important factor. Thus, knowledge of mineral profile of the animals fed calculogenic diets and chemical composition of uroliths becomes an effective tool in preventing the disease. In this study, we used 14 healthy, male, non-neutered sheep, of the Santa Ines breed, aged approximately 90 days, divided into two groups (G1-without vitamin C and G2-with vitamin C) fed calculogenic diet. Analysis of mineral profiles in serum and urine revealed complete imbalance in the relationship between concentrations of calcium, phosphorus and magnesium, with significant increase of phosphorus and magnesium and substantial reduction of calcium. Thus, biochemical analysis of uroliths showed that calcium was present in 50% of samples.

Few studies have reported the molecular epidemiological characterization of HIV-1 in the Northern region of Brazil. The present study reports the molecular and epidemiological characterization of 31 HIV-1 isolates from blood donors from the State of Amazonas who donated blood between April 2006 and March 2007. Serum/plasma samples from all donors were screened for HIV antibodies by ELISA and the results confirmed by Western blot analysis. Genomic DNA was extracted from the buffy coat using the Super Quik-Gene-DNA Isolation kit. Nested PCR was performed on the env, gag, and pol regions of HIV-1 using the Gene Amp PCR System 9700. Sequencing reactions were performed using the inner PCR primers and the DYEnamic™ ET Dye Terminator Kit, and phylogenetic analysis was performed using the gag, pol, and env gene sequences. We collected samples from 31 blood donors who tested positive for HIV-1 in confirmatory experiments. The male:female ratio of blood donors was 3.4:1, and the mean age was 32.4 years (range: 19 to 61 years). Phylogenetic analysis showed that subtype B is the most prevalent among Northern Brazilian HIV-1-seropositive blood donors. One HIV-1 subtype C and one circulating recombinant form (CRF_BF) of HIV-1 were identified in the State of Amazonas. This is the first study showing the occurrence of a possible "homogenous" subtype C in this region of Brazil. This finding could contribute to a better characterization of the HIV-1 strains that circulate in the country.