RESUMO
Superior vena cava syndrome (SVCS) is considered one of the telltale signs of a terminal malignant process. We describe a successful endovascular desobliteration of a subtotal occluded SVC and the left innominate vein using a Y-stent technique in a 46-year-old female with a mediastinal nodal metastasis of a relapsing renal cell carcinoma. Complete clinical improvement in the symptoms within the first 24 hours of the procedure and no complication were observed. This report describes endovascular stenting of the SVC as a palliation therapy to overcome the severe clinical symptoms of SVCS besides surgical or chemotherapy in mediastinal malignancy masses.
Assuntos
Veias Braquiocefálicas , Carcinoma de Células Renais/complicações , Procedimentos Endovasculares/instrumentação , Neoplasias Renais/complicações , Stents , Síndrome da Veia Cava Superior/terapia , Veias Braquiocefálicas/diagnóstico por imagem , Carcinoma de Células Renais/secundário , Feminino , Humanos , Neoplasias Renais/patologia , Metástase Linfática , Pessoa de Meia-Idade , Flebografia/métodos , Síndrome da Veia Cava Superior/diagnóstico , Síndrome da Veia Cava Superior/etiologia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Despite considerable interest in the isolation of mAbs with potent neutralization activity against primary HIV-1 isolates, both for identifying useful targets for vaccine development and for the development of therapeutically useful reagents against HIV-1 infection, a relatively limited number of such reagents have been isolated to date. Human mAbs (hu-mAbs) are preferable to rodent mAbs for treatment of humans, but isolation of hu-mAbs from HIV-infected subjects by standard methods of EBV transformation of B cells or phage display of Ig libraries is inefficient and limited by the inability to control or define the original immunogen. An alternative approach for the isolation of hu-mAbs has been provided by the development of transgenic mice that produce fully hu-mAbs. In this report, we show that immunizing the XenoMouse G2 strain with native recombinant gp120 derived from HIV(SF162) resulted in robust humoral Ab responses against gp120 and allowed the efficient isolation of hybridomas producing specific hu-mAbs directed against multiple regions and epitopes of gp120. hu-mAbs possessing strong neutralizing activity against the autologous HIV(SF162) strain were obtained. The epitopes recognized were located in three previously described neutralization domains, the V2-, V3- and CD4-binding domains, and in a novel neutralization domain, the highly variable C-terminal region of the V1 loop. This is the first report of neutralizing mAbs directed at targets in the V1 region. Furthermore, the V2 and V3 epitopes recognized by neutralizing hu-mAbs were distinct from those of previously described human and rodent mAbs and included an epitope requiring a full length V3 loop peptide for effective presentation. These results further our understanding of neutralization targets for primary, R5 HIV-1 viruses and demonstrate the utility of the XenoMouse system for identifying new and interesting epitopes on HIV-1.
Assuntos
Fármacos Anti-HIV/isolamento & purificação , Fármacos Anti-HIV/farmacologia , Anticorpos Monoclonais/isolamento & purificação , Anticorpos Monoclonais/farmacologia , Genes de Imunoglobulinas , Anticorpos Anti-HIV/isolamento & purificação , Anticorpos Anti-HIV/farmacologia , HIV-1/imunologia , Sequência de Aminoácidos , Animais , Fármacos Anti-HIV/química , Anticorpos Heterófilos/química , Anticorpos Heterófilos/genética , Anticorpos Heterófilos/isolamento & purificação , Anticorpos Heterófilos/farmacologia , Anticorpos Monoclonais/biossíntese , Anticorpos Monoclonais/genética , Especificidade de Anticorpos/genética , Ligação Competitiva/genética , Ligação Competitiva/imunologia , Sequência Conservada/imunologia , Mapeamento de Epitopos , Epitopos/química , Epitopos/imunologia , Regulação da Expressão Gênica/imunologia , Marcadores Genéticos/imunologia , Anticorpos Anti-HIV/biossíntese , Anticorpos Anti-HIV/genética , Proteína gp120 do Envelope de HIV/imunologia , Humanos , Hibridomas , Região Variável de Imunoglobulina/química , Região Variável de Imunoglobulina/genética , Camundongos , Camundongos Transgênicos , Dados de Sequência Molecular , Testes de Neutralização/métodos , Estrutura Terciária de Proteína/genéticaRESUMO
Platelet-derived growth factor (PDGF) has been directly implicated in developmental and physiological processes, as well as in human cancer and other proliferative disorders. We have recently isolated and characterized a novel protease-activated member of the PDGF family, PDGF D. PDGF D has been shown to be proliferative for cells of mesenchymal origin, signaling through PDGF receptors. Comprehensive and systematic PDGF D transcript analysis revealed expression in many cell lines derived from ovarian, renal, and lung cancers, as well as from astrocytomas and medulloblastomas. beta PDGF receptor profiling further suggested autocrine signaling in several brain tumor cell lines. PDGF D transforming ability and tumor formation in SCID mice was further demonstrated. Exploiting a sensitive PDGF D sandwich ELISA using fully human monoclonal antibodies, PDGF D was detected at elevated levels in the sera of ovarian, renal, lung, and brain cancer patients. Immunohistochemical analysis confirmed PDGF D localization to ovarian and lung tumor tissues. Together, these data demonstrate that PDGF D plays a role in certain human cancers.
