RESUMO
Activation of the receptor for epidermal growth factor (EGFR) in some testicular tumors activates several signaling pathways. Some components of these pathways are phosphorylated or mutated in testicular germ tumors (TCGT), including EGFR, Kirstein ras oncogen (KRAS) and cell surface protein of the germ cell (KIT). The latter two activate RAF /MEK/ERK and PI3 K/AKT, and interconnect with the EGFR/pI3 k/Akt pathway. We investigated the expression of EGFR/pI3 k/Akt pathway proteins in seminomas and in their precursor lesion, germinal cell neoplasia in situ (GCNIS) and related genetic mutations. We used immunohistochemistry for pEGFR, pI3 k and pAkt expression with a scoring system for 46 seminoma surgical specimens: 36 classical and 10 GCNIS. In 17 samples, the mutations of EGFR (exons 19 - 21), KIT (exons 11, 17) and KRAS (exons 2, 3) were investigated using qPCR and sequencing. Of the 36 seminomas studied, 22 (61%) expressed pEGFR. Ten samples exhibited high scores for pEGFR, pI3 k and pAkt. In 5 of 17 cases (33%) some mutation was exhibited in the exons studied: 21 of EGFR (2), 17 of EGFR (1), 3 of KRAS (1) and 11 of KIT (1). Six cases exhibited nuclear translocation of EGFR; of these, four exhibited mutations of EGFR, KRAS and KIT. Eight of ten of the GCNIS expressed a high pEGFR score (80%). In 2 of 6 cases (33%), mutation was detected in exon 21 of EGFR and one smear showed EGFR translocation to the nucleus. The translocation represents a subpopulation with worse prognosis for TCGT. The EGFR/pI3 k/Akt signaling pathway is linked to TDRG1, which regulates chemosensitivity to cisplatin; this is a mechanism of resistance to treatment. TDRG1 and the EGFR/pI3 k/pAkt pathway could be therapeutic targets for seminomas resistant to cisplatin.
Assuntos
Fosfatidilinositol 3-Quinases , Seminoma , Fator de Crescimento Epidérmico , Receptores ErbB/genética , Humanos , Masculino , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Seminoma/genética , Transdução de SinaisRESUMO
Liver biopsies were analyzed in 21 patients with chronic renal failure (CRF) who tested positive for Hepatitis C Virus (HCV), using Elisa II and/ or PCR. The study included 14 men and 7 women, the average age being 41 years old (range: 20-65). The average span of time under dialysis was 64 months (range: 12-192). Hbs ag. was positive in six patients. Patients underwent biopsy for showing persistent rise of transaminase for more than 6 months. The modified Knodell Index was used to grade hepatic lesions. All biopsies showed chronic hepatitis, of which 2 were associated with cirrhosis. Eight patients were infected with mild chronic hepatitis, ten were infected with moderate chronic hepatitis, and only three patients had a severe lesion. Fibrosis was mild in 13 cases, moderate in 6, and 2 had cirrhosis. Chronic Hepatitis C characteristic lesions analysis showed lymphoid nodules in 6 cases (29%), ductal epithelium lesions in 7 (33%), and steatosis in 7 (33%). Chronic HCV infection in our patients seems to have histologic characteristics similar to those reported in HCV positive non CRF patients.
Assuntos
Hepatite C/patologia , Falência Renal Crônica/terapia , Fígado/patologia , Diálise Renal/efeitos adversos , Adulto , Idoso , Biópsia por Agulha , Feminino , Fibrose/patologia , Hepatite C/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
The gastrin-producing G-cells of the antropyloric mucosa are affected by a variety of disorders. By immunoperoxidase methods, employing a specific anti-gastrin I and II antibody, we demonstrated G cells in antropyloric biopsies of 15 patients with chronic gastritis, 6 of them with gastric ulcer and 1 with duodenal ulcer disease. As controls we studied 5 biopsies of histologically normal antropyloric mucosa. We correlated the numbers of G cells per gland with the histological, clinical and endoscopic findings. Normal antropyloric mucosa contained a mean of 2.11 G cells per gland. Patients with chronic gastritis had decreased numbers of G cells (mean 0.75) The difference was statistically significant. The cases with chronic gastritis and intestinal metaplasia had lower numbers of G cells (mean 0.38). The case with duodenal ulcer had a number of G-cells similar of normal cases (1.57). This finding give a morphologic basis for the low gastrin serum levels usually present in these entities.
Assuntos
Mucosa Gástrica/patologia , Gastrinas/metabolismo , Gastrite/patologia , Adulto , Mucosa Gástrica/citologia , Gastrinas/sangue , Gastrite/metabolismo , Humanos , Pessoa de Meia-IdadeRESUMO
En un grupo de 15 pacientes con gastritis cronica antral se observo una disminucion estadisticamente significativa de celulas G (productoras de gastrina) por seccion glandular en comparacion con los controles normales. Esta disminucion fue todavia mas acentuada en aquellos que presentaban metaplasia intestinal o ulcera peptica activa. La disminucion de celulas G seria el sustrato morfologico de los bajos niveles sericos de gastrina que presentan estos pacientes en respuesta a una ingesta proteica
Assuntos
Gastrinas , Gastrite , Técnicas ImunoenzimáticasRESUMO
En un grupo de 15 pacientes con gastritis cronica antral se observo una disminucion estadisticamente significativa de celulas G (productoras de gastrina) por seccion glandular en comparacion con los controles normales. Esta disminucion fue todavia mas acentuada en aquellos que presentaban metaplasia intestinal o ulcera peptica activa. La disminucion de celulas G seria el sustrato morfologico de los bajos niveles sericos de gastrina que presentan estos pacientes en respuesta a una ingesta proteica
Assuntos
Gastrinas , Gastrite , Técnicas ImunoenzimáticasRESUMO
The gastrin-producing G-cells of the antropyloric mucosa are affected by a variety of disorders. By immunoperoxidase methods, employing a specific anti-gastrin I and II antibody, we demonstrated G cells in antropyloric biopsies of 15 patients with chronic gastritis, 6 of them with gastric ulcer and 1 with duodenal ulcer disease. As controls we studied 5 biopsies of histologically normal antropyloric mucosa. We correlated the numbers of G cells per gland with the histological, clinical and endoscopic findings. Normal antropyloric mucosa contained a mean of 2.11 G cells per gland. Patients with chronic gastritis had decreased numbers of G cells (mean 0.75) The difference was statistically significant. The cases with chronic gastritis and intestinal metaplasia had lower numbers of G cells (mean 0.38). The case with duodenal ulcer had a number of G-cells similar of normal cases (1.57). This finding give a morphologic basis for the low gastrin serum levels usually present in these entities.