RESUMO
BACKGROUND: Src is a non-receptor tyrosine kinase involved in signalling and crosstalk between growth-promoting pathways. We aim to investigate the relationship of active Src in response to trastuzumab of HER2-positive breast carcinomas. METHODS: We selected 278 HER2-positive breast cancer patients with (n=154) and without (n=124) trastuzumab treatment. We performed immunohistochemistry on paraffin-embedded tissue microarrays of active Src and several proteins involved in the PI3K/Akt/mTOR pathway, PIK3CA mutational analysis and in vitro studies (SKBR3 and BT474 cancer cells). The results were correlated with clinicopathological factors and patients' outcome. RESULTS: Increased pSrc-Y416 was demonstrated in trastuzumab-resistant cells and in 37.8% of tumours that correlated positively with tumour size, necrosis, mitosis, metastasis to the central nervous system, p53 overexpression and MAPK activation but inversely with EGFR and p27. Univariate analyses showed an association of increased active Src with shorter survival in patients at early stage with HER2/hormone receptor-negative tumours treated with trastuzumab. CONCLUSIONS: Src activation participates in trastuzumab mechanisms of resistance and indicates poor prognosis, mainly in HER2/hormone receptor-negative breast cancer. Therefore, blocking this axis may be beneficial in those patients.
Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Antineoplásicos/farmacologia , Neoplasias da Mama/enzimologia , Neoplasias do Sistema Nervoso Central/enzimologia , Receptor ErbB-2/metabolismo , Quinases da Família src/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/secundário , Quimioterapia Adjuvante , Classe I de Fosfatidilinositol 3-Quinases , Análise Mutacional de DNA , Resistencia a Medicamentos Antineoplásicos , Ativação Enzimática , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Fosfatidilinositol 3-Quinases/genética , Transdução de Sinais , Trastuzumab , Quinases da Família src/antagonistas & inibidoresRESUMO
The blue rubber bleb nevus syndrome is a rare entity characterized by the presence of cavernous hemangiomas in the skin and gastrointestinal tract with frequent digestive hemorrhages. Different therapeutic modalities exist: medical treatment, surgical resection; and most recently, endoscopic therapy has been described. We present a patient with blue rubber bleb nevus syndrome treated with combined endoscopic therapy: sclerosis and band ligation.
Assuntos
Hemorragia Gastrointestinal/terapia , Neoplasias Gastrointestinais/terapia , Hemangioma Cavernoso/terapia , Nevo Azul/terapia , Neoplasias Cutâneas/terapia , Adulto , Endoscopia Gastrointestinal , Hemorragia Gastrointestinal/diagnóstico , Neoplasias Gastrointestinais/diagnóstico , Hemangioma Cavernoso/diagnóstico , Humanos , Ligadura , Nevo Azul/diagnóstico , Escleroterapia , Neoplasias Cutâneas/diagnóstico , SíndromeRESUMO
Acute post traumatic pancreatitis is an infrequent disease representing 0.4% of the acute pancreatitis with pseudocyst formation. Few data have been reported in the literature with regard to response to treatment, particularly in cases of small or multiple pseudocysts. Internal surgical drainage is the usual treatment. Different therapeutic alternatives have been proposed among which conservative treatment with total parenteral nutrition, somatostatin or octreotide, or more recently, endoscopy may be included. We herein present one case of acute post traumatic pancreatitis initially treated with conservative treatment which evolved to the formation of pseudocysts which were satisfactorily drained by endoscopic cystogastrostomy.