RESUMO
Although patients diagnosed with melanoma of = 1.00 mm thickness have a relatively good cure rate, the prognosis for patients with locally advanced and metastatic melanoma is grave. The discovery of new and effective therapies for this disease depends in large part on molecular studies that will resolve why advanced-stage melanoma is refractory to conventional chemotherapy and radiation therapy. To identify genes that have important functions in advanced-stage melanomas, in particular, in melanoma-infiltrated lymph nodes, which are not well characterized at the molecular level, we generated a LongSAGE library from a melanoma-positive lymph node, and subjected melanoma-infiltrated lymph nodes to protein expression profiling. The data document that the molecular signature of melanoma, which has spread to regional lymph nodes, is very similar to the molecular signature of primary melanomas. Equally important, we provide evidence that the ubiquitin-conjugating enzyme, Ubc9, is expressed at high levels in melanoma-positive lymph nodes, and that it plays a crucial role in preventing advanced-stage melanomas from undergoing chemotherapy-induced apoptosis.
Assuntos
Anticorpos Antineoplásicos , Antígenos de Neoplasias/biossíntese , Linfonodos/imunologia , Linfonodos/patologia , Melanoma/enzimologia , Melanoma/patologia , Análise Serial de Proteínas , Enzimas de Conjugação de Ubiquitina/imunologia , Antígenos de Neoplasias/genética , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Resistencia a Medicamentos Antineoplásicos , Humanos , Melanoma/diagnóstico , Melanoma/tratamento farmacológico , Invasividade Neoplásica , Estadiamento de Neoplasias , Biblioteca de Peptídeos , Células Tumorais Cultivadas , Enzimas de Conjugação de Ubiquitina/análise , Enzimas de Conjugação de Ubiquitina/biossíntese , Enzimas de Conjugação de Ubiquitina/genéticaRESUMO
BACKGROUND: Pemphigoides gestationis (PG) is a blistering disorder of pregnancy caused by antibodies against basement membrane proteins. They are directed against the 180 kD bullous pemphigoid antigen (BPAg2), towards the epitopes within the NC 16A domain. There are many similarities between pemphigoid gestationis and bullous pemphigoid (BP), but the literature so far indicated different immunofluorescence results in regards with C3 and IgG, and IgG subclasses (IgG4 vs. IgG1). METHODS: We evaluated staining patterns and IgG subclasses, as well as C5b-9 membrane attack complex (MAC) in 10 pregnant patients with PG, using sandwich double antibody immunofluorescence (SDAI) and direct immunofluorescence (DIF). RESULTS: All ten specimens stained with C3 by DIF, but only five had trace amount of IgG reactants by this method. By SDAI, 100% were positive for the IgG4 and C5b-9 MAC, 70% for IgG2, 50% for IgG1, and 40% for IgG3. CONCLUSION: IgG4 was the predominant IgG subtype identified. This finding has not been reported for PG, but it mimics results reported for BP. One explanation is prolonged disease course, as well as blocking of antigenic domains by IgG4. Understanding this completely will help develop therapies and prevention strategies for immunobullous and other autoimmune diseases, and perhaps aid in an exact classification.
Assuntos
Imunoglobulina G/metabolismo , Penfigoide Gestacional/imunologia , Complexo de Ataque à Membrana do Sistema Complemento/análise , Feminino , Técnica Direta de Fluorescência para Anticorpo , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Penfigoide Gestacional/metabolismo , Penfigoide Gestacional/patologia , Gravidez , Coloração e RotulagemRESUMO
Telepathology is probably the latest addition to the world of pathology. The costs of pathologic tests have increased, the requirements for shortened turnaround time are omnipresent and we are all aware of the current litigious environment. Telepathology is one of the answers to at least some of these requests. Here we review the current status of telepathology in the world of telemedicine; compare differences, similarities and applications of static and dynamic telepathology; and give a short introduction to the basic setup of a telepathology laboratory.