ABSTRACT
Epithelial intercellular cohesion, mainly mediated by E-cadherin (CDH1) expression and function, may be deregulated during cancer cell invasion of adjacent tissues and lymphatic and vascular channels. CDH1 expression is down-modulated in invasive lobular breast carcinomas but its regulation in invasive ductal carcinomas (IDC) is less clear. CDH1 expression is repressed by transcription factors such as Snail (SNAI1) and its product is degraded after Hakai ubiquitination. We compared CDH1, SNAI1 and HAKAI mRNA expression in IDC and paired adjacent normal breast tissue and evaluated its relation with node metastasis and circulating tumor cells. Matched tumor/peritumoral and blood samples were collected from 30 patients with early IDC. Epithelial cells from each compartment (tumor/peritumoral) were recovered by an immunomagnetic method and gene expression was determined by real time RT-PCR. There were no differences in CDH1, SNAI1 and HAKAI mRNA expression between tumor and corresponding peritumoral samples and no differential tumoral gene expression according to nodal involvement. Another 30 patients with a long-term follow-up (at least 5 years) and a differential prognosis (good or poor, as defined by breast cancer death) had E-cadherin and Snail protein detected by immunohistochemistry in tumor samples. In this group, E-cadherin-positive expression, but not Snail, may be associated with a better prognosis. This is the first report simultaneously analyzing CDH1, SNAI1 and HAKAI mRNA expression in matched tumor and peritumoral samples from patients with IDC. However, no clear pattern of their expression could distinguish the invasive tumor compartment from its adjacent normal tissue.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Breast Neoplasms/metabolism , Cadherins/metabolism , Carcinoma, Ductal, Breast/metabolism , Transcription Factors/metabolism , Ubiquitin-Protein Ligases/metabolism , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cadherins/genetics , Carcinoma, Ductal, Breast/genetics , Carcinoma, Ductal, Breast/pathology , Epithelial Cells/chemistry , Gene Expression Regulation, Neoplastic , Immunohistochemistry , Lymphatic Metastasis , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Reverse Transcriptase Polymerase Chain Reaction , RNA, Messenger/genetics , RNA, Messenger/metabolism , Transcription Factors/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Ubiquitin-Protein Ligases/geneticsABSTRACT
Neste estudo avaliou-se a acao terapeutica de ketoconazole por via sistemica em 105 pacientes com candidiase vulvovaginal, nas formas aguda e cronica. O ketoconazole foi administrado na dose de dois comprimidos de 200 mg por dia, durante cinco dias consecutivos. Realizou-se exame micologico a fresco (microscopia) e cultura em meio de Nickerson, antes do tratamento (para confirmacao diagnostica) e sete e trinta dias apos o termino do mesmo (para comprovacao da cura). Foi observado um percentual de cura micologica da ordem de 75,5%. Ocorreram efeitos colaterais em 19 pacientes (18,1%), tornando necessaria a interrupcao do tratamento em tres pacientes, sendo em um caso por cefaleia, vomitos e astenia moderados, e em dois casos por nausea e mal-estar tambem de grau moderado. Os investigadores consideraram o tratamento da candidiase vulvovaginal entre bom e excelente em 78,4% dos casos, enquanto que para as pacientes tal conceito situou-se em 81,2% dos casos