The expression of monocarboxylate transporters in thyroid carcinoma can be associated with the morphological features of BRAF (V600E) mutation

BRAF (V600E) mutation, usually performed by DNA techniques, is one of the most common diagnostic markers in papillary thyroid carcinoma. Few papers have demonstrated that plump cells (eosinophilic cytoplasms and papillary thyroid carcinoma nuclei) and peculiar sickle-shaped nuclei represent morphological features of BRAF (V600E) on papillary thyroid carcinomas. These features seem to be linked to glycolytic phenotype whereby monocarboxylate transporters 1-4 are hypothesized to have a dominant role as lactate transporters. We investigated the association between these morphological features and monocarboxylate transporters 1 and 4 in 48 cyto-histological samples diagnosed as "positive for malignancy-favoring papillary thyroid carcinoma". These cases were processed with liquid-based cytology and underwent BRAF (V600E) mutational analysis (pyrosequencing) on liquid-based cytology and monocarboxylate transporters immunostaining on histology. The expression of monocarboxylate transporter 1, monocarboxylate transporter 4, glucose trasporter-1 and carbonic anhidrase were scored semi-quantitatively with expression from 0 to 3+ (strong positivity). The 33 mutated and 15 wild type cases showed 100 % cyto-histological concordance. The cytological evaluation revealed plump cells and sickle nuclear shape in 100 % mutated cases. Monocarboxylate transporter 1 yielded 76 % positivity in the mutated cases especially in both the plump cells and sickle-shaped nuclei, whereas the wild types showed 13.3 % positive monocarboxylate transporter 1 (p = 0.00013). Monocarboxylate transporter 4 resulted in 100 % positivity in mutated and 40 % in wild types (p 0.05). This is the first report analyzing the association between monocarboxylate transporter expression and the morphological features of BRAF (V600E) mutated papillary thyroid carcinomas suggesting the possible involvement of lactate in the morphological features.info:eu-repo/semantics/publishedVersio

Reactivation of epigenetically silenced HER4/ERBB4 results in apoptosis of breast tumor cells

Experimental and clinical data support a growth inhibitory role for HER4 in breast cancer. Clinically HER4 expression is extinguished during breast tumorigenesis supporting a tumor suppressor function for HER4, however, a molecular mechanism to explain the selective loss of HER4 expression has remained elusive. Epigenetic mechanisms, for example, aberrant gene promoter hypermethylation, have been shown to ablate tumor suppressor gene expression in breast carcinomas. We identified a CpG island within the HER4 promoter and show by pyrosequencing of bisulfite-treated DNA an inverse correlation between HER4 expression and the extent of promoter methylation. Treatment of the HER4-negative BT20 cell line with the DNA demethylating agent 5-aza-2′-deoxycytidine (DAC)-enhanced HER4 expression, confirming a role for DNA methylation in suppressed HER4 expression. DAC treatment to reactive HER4 expression in combination with the HER4 ligand heregulin-β1 (HRG) resulted in apoptosis of BT20 cells providing a novel therapeutic strategy for triple-negative tumors. The BT20 cells were rescued from apoptosis when preincubated with HER4 small interfering RNA, thereby confirming a role for HER4 in DAC/HRG-induced apoptosis. We verified HER4 promoter methylation in primary breast carcinomas and detected a significant increase in HER4 promoter methylation in HER4-negative breast tumors (P<0.001). Furthermore, increased levels of HER4 promoter methylation were significantly associated with worse patient prognosis (P=0.0234). Taken together, our data support a tumor suppressor function for HER4, which is epigenetically suppressed in breast tumors through promoter hypermethylation

Quality of fresh-cut strawberry

The aim of this work was to study the physical, chemical, physiological and microbiological changes during the flow chart of fresh-cut strawberry. Strawberry cvs. Camarosa, Dover and Tudla, derived from experimental area of the Universidade Federal de Viçosa, were selected by color (red ¾) and absence of wound. Afterwards, the minimal processing was evaluated, as follows: fast cooling, water and ice, removal of the calyx followed by conservation at 5±0.5°C and 90-95% RH for 13 days, sanitation, drainage, cut in halves. Removal of the calyx did not result significant difference for fresh weight, total soluble solids, total titratable acidity, pH and ratio TSS/TTA. The rapid cooling resulted in lower electrolyte leakage and respiratory rate, especially sanitized fruits. Sanitization by immersion in chlorine solution slowed the growth of fungi and yeast. Drainage for 20 minutes eliminated practically all water on the surface of the fruits. The fresh-cutting did not affect the visual and nutritional quality of strawberries like appearance, microbiot, vitamin C, anthocyanins and phenolic compounds, consisting of alternative market potential economically viable.O objetivo deste trabalho foi estudar mudanças físicas, químicas, fisiológicas e microbiológicas durante o fluxograma de processamento mínimo de morango. Morangos das cultivares Camarosa, Dover e Tudla oriundos de área experimental da Universidade Federal de Viçosa, foram selecionados por cor (¾ vermelho) e ausência de danos. Posteriormente, foi avaliado o fluxograma de processamento mínimo: resfriamento rápido, água e gelo; remoção do cálice acompanhado de conservação a 5±0,5ºC e 90-95% UR, por 13 dias; sanitização; drenagem; corte, em metades. A remoção do cálice não resultou diferença significativa para massa fresca, sólidos solúveis totais, acidez total titulável, pH e razão SST/ATT. O resfriamento rápido ocasionou menores extravasamentos de eletrólitos e taxa respiratória, sobretudo nos frutos sanitizados. A sanitização por imersão em solução de cloro retardou o crescimento de fungos e levedura. A drenagem por 20 minutos eliminou praticamente toda a água na superfície dos frutos. O processamento mínimo não afetou a qualidade visual e nutricional dos morangos como aparência, microbiota, vitamina C, antocianinas e compostos fenólicos, consistindo em alternativa de mercado potencial economicamente viável