RESUMO
Tissue inhibitor of metalloprotease 4 (TIMP4) contributes to poor prognosis in breast and other tumours. However, the mechanisms of how TIMP4 influences breast cancer cell behaviour are unknown. Our aim was to explore the signalling pathways modulated by TIMP4 in breast cancer cells. Human recombinant TIMP4 was added to MCF7 breast cancer cells and RNASeq was performed. TIMP4 RNASeq results were validated by RT-PCR. Network analyses of TIMP4-exposed cells showed that ER-α, HIF1A and TGF-ß signalling were activated, whereas FOXO3 signalling was downregulated. ER-α protein levels were increased and concordantly, promoters of TIMP4-upregulated genes were significantly enriched in oestrogen-binding sites. We concluded that TIMP4 modulates multiple signalling pathways relevant in cancer in MCF7 cells, including the ER-α cascade.
Assuntos
Receptor alfa de Estrogênio/metabolismo , Transdução de Sinais , Inibidores Teciduais de Metaloproteinases/metabolismo , Western Blotting , Neoplasias da Mama/fisiopatologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Células MCF-7 , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Recombinantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Inibidores Teciduais de Metaloproteinases/genética , Inibidores Teciduais de Metaloproteinases/farmacologia , Inibidor Tecidual 4 de MetaloproteinaseRESUMO
Two cases are presented in which conventional approaches did not permit dilation of and stent placement in obstructed ureters. In patients with iatrogenic ureteral laceration or rigid ureteral kinking, direct percutaneous translumbar puncture may provide a safe alternative. The authors' technique is described.
Assuntos
Punções , Stents , Ureter , Obstrução Ureteral/terapia , Adulto , Idoso , Feminino , HumanosRESUMO
From 1982 to 1989, 18 eligible patients (median age 50.5 years, range 30-72 years) with inflammatory breast carcinoma have been treated with neoadjuvant intra-arterial (IA) chemotherapy. The treatment regimen includes IA cisplatin, adriamycin, mytomycin C and thiotepa on Day 1 and intravenous 5-fluorouracil on Days 1 and 2. An objective clinical response rate of 100% (eight complete and 10 partial) has been observed. The median disease-free and overall survivals are 27 months (range 5-85+ months) and 33 months (range 8-85+ months), respectively. With a median follow-up of 21.5 months, six (33.3%) patients remain alive and free of disease and 12 patients have died because of distant metastases. No local recurrences have been observed. Intra-arterial chemotherapy is an attractive technique for the treatment of locally advanced breast carcinoma with mild toxicity and high local control rate.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Infusões Intra-Arteriais , Artéria Torácica Interna , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Tiotepa/administração & dosagemRESUMO
The tumor registry (TR) of the Clinica Universitaria de Navarra is a hospital based registry which includes all patients with a diagnosis of neoplastic disease diagnosed and/or treated in the different departments of the hospital. The incidence of different tumors from January 1981 to December 1986, has been studied based on the following parameters: sex, age, diagnosis and tumor site. It is concluded that the results of 6 years indicate a specialised care in oncologic patients of different tumor sites, which represents an adequate volume of patients for a university oriented program of training and research, at the level of pregraduate and specialised postgrade cycles.
