RESUMO
Amyloid light chain (AL) amyloidosis is a rare hematologic disorder characterized by the accumulation of a misfolded monoclonal immunoglobulin (Ig) light chain (LC) as fibrillar protein deposits. Current treatments, including cytotoxic chemotherapy and immunomodulatory therapy, are directed at killing the plasma cells that produce the LCs, but have significant toxicity for other cell types. We have designed small interfering RNAs (siRNAs) targeting the amyloidogenic LC messenger RNA (mRNA) in order to reduce expression of the amyloid precursor protein. Using nanomolar concentrations of siRNAs, we have inhibited synthesis of LC in transfected cells in vitro in a dose-dependent fashion. Furthermore, in an in vivo plasmacytoma mouse model of AL amyloidosis, we have demonstrated that these siRNAs can significantly reduce local production and circulating levels of LC. This model system highlights the therapeutic potential of siRNA for AL amyloidosis.
Assuntos
Amiloidose/terapia , Cadeias Leves de Imunoglobulina/metabolismo , RNA Interferente Pequeno/uso terapêutico , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Cadeias Leves de Imunoglobulina/genética , Camundongos , Nanopartículas/administração & dosagem , Plasmocitoma/terapia , RNA Mensageiro , TransfecçãoRESUMO
Unexplained debilitating dementia or encephalopathy occurs frequently in adults and children with the acquired immune deficiency syndrome (AIDS). Brains from 15 individuals with AIDS and encephalopathy were examined by Southern analysis and in situ hybridization for the presence of human T-cell leukemia (lymphotropic) virus type III (HTLV-III), the virus believed to be the causative agent of AIDS. HTLV-III DNA was detected in the brains of five patients, and viral-specific RNA was detected in four of these. In view of these findings and the recent demonstration of morphologic and genetic relatedness between HTLV-III and visna virus, a lentivirus that causes a chronic degenerative neurologic disease in sheep, HTLV-III should be evaluated further as a possible cause of AIDS encephalopathy.
Assuntos
Encefalopatias/microbiologia , Córtex Cerebral/microbiologia , Deltaretrovirus/isolamento & purificação , Síndrome da Imunodeficiência Adquirida/microbiologia , Adulto , Anticorpos Antivirais/análise , Córtex Cerebral/análise , Criança , Demência/microbiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Hibridização de Ácido Nucleico , RNA Viral/análiseRESUMO
The small cell carcinoma (SCC) antigens recognized by LAM2 and LAM8 antibody were characterized by comparison of their tissue expression and analysis of their biochemical composition. LAM2, but not LAM8 antigen could be demonstrated in lipid extracts of SCC cells. By immunohistochemical staining the SCC antigen LAM2 was shown to be an epithelial type membrane antigen. Immunoblotting experiments and competition solid phase radioimmunoassays showed LAM2 antigen to be a native conformation of a glycoprotein with major bands at Mr 100,000-120,000 and a minor band at Mr 210,000. L-Fucose was a dominant part of the epitope which appeared to be closely related to the carbohydrate epitope of the blood group antigen H(O). The tumor-associated membrane antigen LAM8 was shown to be a glycoprotein with major bands at Mr 90,000-135,000 and a minor band at Mr 200,000. Neuraminic acid was the predominant part of the carbohydrate epitope. LAM8 antibody recognized a structure in the saliva of Lea positive probands, but untreated and neuraminidase-treated SCC extracts were unreactive with anti-Lea antibody. Anti CA 19-9 (sialo-Lea antigen) and LAM2 antibodies did not compete for LAM8 binding in direct radioimmunoassays. The sialo-GP90-135 antigen recognized by LAM8 antibody therefore is likely to represent a novel tumor antigen.
Assuntos
Anticorpos Monoclonais , Antígenos de Neoplasias/análise , Carcinoma de Células Pequenas/imunologia , Glicoproteínas/imunologia , Neoplasias Pulmonares/imunologia , Antígenos de Superfície/análise , Epitélio/análise , Epitopos/análise , Humanos , Técnicas de Imunoadsorção , Peso Molecular , RadioimunoensaioRESUMO
A mouse IgG2a monoclonal antibody, SWA20, defining a tumor-associated cell surface antigen on small cell carcinoma of the lung (SCC) was generated. The reactivity of the antibody with cell lines was examined by indirect immunofluorescence staining and solid phase radioimmunoassay and the reactivity with tissues by immunoperoxidase staining. The antibody reacts with a proportion of small cell carcinoma cell lines (4 of 8) and tissues (7 of 12), but not with other pulmonary or extrapulmonary cell lines (0 of 30) or tumor tissues (0 of 78). The antibody was unreactive with primary cultures of normal bronchial epithelial cells, RBC, and WBC. Immunoperoxidase staining of normal tissues showed rare antigen-positive cells in suprabasal layers of bronchial epithelium and less than 10% of positive cells in colon epithelium. Immunoblots of SCC extracts demonstrated antibody reactivity with a doublet band at Mr 40,000, a broader band at Mr 100,000, and a band at Mr 180,000. The antigen was not present in crude lipid extracts of SCC cells. Solid phase radioimmunoassays and immunoblots showed binding competition with the lectin Triticum vulgaris, sensitivity of the antigen to neuraminidase, and a partial sensitivity to treatment with periodate. The antigen was coexpressed on SCC cell lines with the antigen sGP90-135 defined first by antibody LAM8 (R. Waibel, C. J. O'Hara, and R. A. Stahel. Cancer Res., 47:3766-3770, 1987) but differed from it by lack of reactivity with Lea-positive saliva and partial resistance to periodate treatment. There was no binding competition between radiolabeled antibodies SWA20 and LAM8 to SCC target cells. The IgG2a antibody SWA20 identifies a previously undescribed tumor-associated surface membrane antigen, sGP100, expressed selectively on a proportion of SCC.
Assuntos
Anticorpos Monoclonais , Antígenos de Neoplasias/análise , Antígenos de Superfície/análise , Carcinoma de Células Pequenas/análise , Imunoglobulina G , Neoplasias Pulmonares/análise , Sialoglicoproteínas/análise , Linhagem Celular , Humanos , Imuno-Histoquímica , Peso MolecularRESUMO
The reactivity of the murine immunoglobulin monoclonal antibody LAM8 directed against a membrane antigen of human small cell carcinoma (SCC) of the lung was investigated on human cell lines and tissues. Indirect immunofluorescence staining, radioimmunoassays, and cytotoxicity assays showed LAM8 antibody to selectively react with SCC but not with non-SCC lung cancer cell lines and extrapulmonary tumor cell lines. Unlike other SCC antibodies, including those we have previously described, highly preferential reactivity with SCC tissues was also demonstrated by immunoperoxidase staining of deparaffinized formalin-fixed tissue sections. Membrane and cytoplasmic staining was seen in of 9 of 12 SCC tissues. No significant staining was seen in non-SCC lung cancer and a wide range of other tumors, including mesothelioma and bronchial carcinoids. Significant LAM8 reactivity was also absent in normal tissues of all major organs. Few tumors and epithelial tissues, including bronchial epithelium had rare LAM8 positive cells which were always less than 2% of the entire cell population. In vitro treatment with antibody and human complement was highly cytotoxic to SCC cells, but had not effect on bone marrow progenitor cells. Immunoblotting of membrane extracts separated on sodium dodecyl sulfate-polyacrylamide gels showed the LAM8 antigen to have a band of an approximate molecular weight of 135,000 and a cluster of bands with approximate molecular weights of 90,000. This reactivity was lost after incubation of the extracts with periodate. LAM8 antibody shows a highly preferential reactivity with SCC cell lines and formalin-fixed paraffin-embedded SCC tissues and is selectively cytotoxic to cells expressing LAM8 antigen.
Assuntos
Anticorpos Monoclonais/imunologia , Carcinoma de Células Pequenas/imunologia , Neoplasias Pulmonares/imunologia , Antígenos de Neoplasias/análise , Linhagem Celular , Citotoxicidade Imunológica , Imunofluorescência , Histocitoquímica , Humanos , Técnicas Imunoenzimáticas , Imunoglobulina M/imunologia , Peso Molecular , RadioimunoensaioRESUMO
In our continuing attempt to select monoclonal antibodies for immunotargeting of small cell lung carcinoma (SCLC) we have developed the IgG1 murine antibody SEN7 which by immunofluorescence stained all SCLC cell lines tested. On frozen tumor section six of seven SCLCs were positively stained. The reactivity of this antibody in a series of lung tumors and on normal tissues has some similarities with cluster 1 antibodies and cluster w4 antibodies, as defined by the First and Second International Workshop on Lung Cancer Antigens [P.C.L. Beverley, Y. Olabrian, J.A. Ledermann, L.G. Bobrow, and R.L. Souhami, Br. J. Cancer, 63 (Suppl): 10-19, 1991], particularly with regard to staining of neuroendocrine tissues. The similarities in staining of neuroendocrine tissues between antibody SEN7 and cluster 1 and cluster w4 antibodies prompted us to examine the binding of SEN7 with transfectants expressing the respective antigens. On the murine lymphoma cells B-9, stably transfected with a complementary DNA clone coding for an M(r) 140,000 isoform of human SCLC neural cell adhesion molecule (NCAM), antibody SEN7 reacted positively whereas the cluster w4 antibody was negative. The reaction of antibody SEN7 with the NCAM transfected murine lymphoma cells was unexpected in view of its lack of binding to peripheral blood mononuclear cells which regularly stain positive with NCAM antibodies. Western blotting of a renatured SCLC extract revealed a strong band around M(r) 180,000 in contrast to other cluster 1 antibodies which recognized a broad polydisperse band with a molecular weight of 140,000 to 210,000. Antibody binding was sensitive to tunicamycin treatment, suggesting the epitope to reside on an N-linked carbohydrate structure. No significant competition for SEN7 binding on SCLC cells was seen with other NCAM antibodies against the three distinct epitopes described on SCLC. This finding together with the lack of staining of peripheral blood mononuclear cells and the selected reactivity with the M(r) 180,000 band of NCAM indicate the antibody SEN7 recognizes an epitope on NCAM which has not been described previously. Biodistribution studies with radiolabeled SEN7 in nude mice bearing s.c. SCLC xenografts demonstrated the selective localization of more than 30% of the total injected dose per g tissue at day 4 following i.v. injection. The homogeneous binding to SCLC, the lack of binding to peripheral blood mononuclear cells, and the favorable tumor localization in a xenograft model indicates that SEN7 is a good antibody for immunotargeting of SCLC.
Assuntos
Anticorpos Monoclonais , Antígenos de Neoplasias/análise , Carcinoma de Células Pequenas/diagnóstico , Moléculas de Adesão Celular Neuronais/análise , Epitopos/análise , Imunoglobulina G , Neoplasias Pulmonares/diagnóstico , Animais , Afinidade de Anticorpos , Antígenos de Neoplasias/química , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/metabolismo , Carcinoma de Células Pequenas/imunologia , Carcinoma de Células Pequenas/metabolismo , Moléculas de Adesão Celular Neuronais/química , Moléculas de Adesão Celular Neuronais/imunologia , Epitopos/química , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Linfócitos/imunologia , Camundongos , Camundongos Nus , Monócitos/imunologia , Células Tumorais CultivadasRESUMO
The human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATLL), a disorder in which peripheral blood and multiple organs are infiltrated by malignantly transformed T lymphocytes. We investigated the nature of pulmonary disease in a patient with serologic evidence of HTLV-1 infection. In this case, endobronchial biopsy specimens showed infiltration of the bronchial mucosa by pleomorphic cells exhibiting a high degree of nuclear irregularity. These cells were morphologically identical in appearance to malignant cells found in peripheral blood and infiltrating the dermis, expressed the OKT4/Leu3 phenotype and the receptor for interleukin 2, and, by analogy to gene rearrangement studies on leukemic blood cells, were monoclonal in origin. However, in situ hybridization of endobronchial biopsy specimens with full-length HTLV-1 probes failed to detect retroviral RNA or proviral DNA. These studies indicate that T lymphocytic involvement of the lower respiratory tract in HTLV-1-associated ATLL is characterized by expression of a malignant phenotype despite the inability to document actual cellular infection with this retrovirus by a molecular hybridization technique.
Assuntos
Leucemia-Linfoma de Células T do Adulto/patologia , Pulmão/patologia , Linfócitos T Auxiliares-Indutores/patologia , Adulto , Brônquios/patologia , Antígenos CD4/análise , DNA Viral/análise , Feminino , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Leucemia-Linfoma de Células T do Adulto/genética , Leucemia-Linfoma de Células T do Adulto/imunologia , Mucosa/patologia , Hibridização de Ácido Nucleico , RNA Viral/análise , Receptores de Interleucina-2/análise , Linfócitos T/imunologiaRESUMO
Epithelioid hemangioendothelioma (EH) is a vascular neoplasm that occurs predominantly in soft tissue and is not infrequently misdiagnosed as an epithelial neoplasm or angiosarcoma. Only a few cases of hepatic EH have been described, and a relationship to oral contraceptive (OC) use in patients with the hepatic lesions has not generally been recognized. We present a series of five patients with malignant epithelioid hemangioendothelioma of the liver. Confirmation of the endothelial origin of these tumors was provided by positive immunoperoxidase staining for Factor-VIII-related antigen in the four cases studied by that technique, and by the demonstration of Weibel-Palade bodies in two tumors examined by electron microscopy. All five patients were young women (mean age 33 years) and all five gave a history of OC use of 4-7 years' duration. The clinical course varied from indolent but progressive to rapid death. One patient who underwent resection of the primary tumor has survived 3 years without evidence of disease, and one patient with metastatic disease who was treated with radiation and chemotherapy has survived for 8 years with disease. Three patients with extrahepatic spread have died of the tumor. Early diagnosis of this distinctive tumor might offer the hope of salvage by resection or liver transplantation.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Anticoncepcionais Orais Hormonais/efeitos adversos , Hemangioendotelioma/induzido quimicamente , Adulto , Biópsia , Feminino , Hemangioendotelioma/metabolismo , Hemangioendotelioma/patologia , Histocitoquímica , Humanos , Técnicas Imunoenzimáticas , Fígado/metabolismo , Fígado/patologia , Hepatopatias/metabolismo , Hepatopatias/patologia , Linfonodos/metabolismo , Linfonodos/patologia , Metástase Linfática , Fatores de TempoRESUMO
A rare spindle-cell pseudotumor caused by Mycobacterium avium-intracellulare (MAI) that mimics a mesenchymal tumor, was recently reported (7,14). We report on three such pseudotumors in patients with the acquired immunodeficiency syndrome (AIDS), two involving lymph nodes and one involving the bone marrow. In the course of investigating the first-encountered example of this tumor for evidence of smooth-muscle origin of the spindle cells, it was noted that these cells stained positively for desmin by immunoperoxidase techniques (IPX), as did a variety of other cytoskeleton filaments of all sizes. Electron microscopic examination of one of these lesions revealed spindle cells containing lysosomes and large numbers of microorganisms compatible with MAI but no filaments or organelles suggestive of smooth-muscle cells. Further studies revealed that the typical lesions produced by MAI in patients with AIDS, namely aggregates of histiocytes or individual histiocytes laden with organisms, rather than the expansile spindle-cell pseudotumor, also strain strongly for cytoskeleton filaments, as do M. tuberculosis and Mycobacterium leprae. Awareness of the existence of this unusual manifestation of MAI infection in AIDS patients and its desmin positivity can avoid misdiagnosis of a primary or metastatic smooth-muscle neoplasm. The cell of origin appears to be the histiocyte.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Citoesqueleto , Complexo Mycobacterium avium/isolamento & purificação , Infecção por Mycobacterium avium-intracellulare/patologia , Adulto , Citoesqueleto/ultraestrutura , Diagnóstico Diferencial , Humanos , Técnicas Imunoenzimáticas , Masculino , Músculo Liso , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Infecção por Mycobacterium avium-intracellulare/microbiologia , Neoplasias de Tecido Muscular/diagnóstico , Coloração e RotulagemRESUMO
Pancreatic distension with collagenase solution followed by stationary in vitro digestion yields large numbers of intact islets. We compared in rats two routes of collagenase injection, pancreatic ductal (PD) and portal venous (PV), for islet yield, in vitro insulin secretory capacities, and in vivo functional viability. The islet yield in the PD method (n = 11) was greater than that in the PV method (n = 8) (682 +/- 27 vs. 417 +/- 39 per pancreas, P less than 0.025). The insulin release from the PD islets in response to 16.7 mM glucose increased gradually following culture, 3.2 +/- 0.8 ng/10 islets/30 min (fresh) to 12.3 +/- 2.1 (24-hr culture). In contrast, insulin release from the PV islets increased during the first 6 hr of culture, but decreased after 24 hr in culture. Under electronmicroscopic examination, the PD islets revealed a well preserved structure with healthy endocrine cells, while the PV islets showed a dilated capillary network and distorted endocrine cell continuity. When 100 PD islets were transplanted into streptozotocin-induced diabetic B6AF1 mice (n = 8), all the recipient mice restored normoglycemia (less than 200 mg/dl) within 1-4 days following transplantation and maintained it until rejection. However, the recipient mice given 100 PV islets showed a significant delay in restoring normoglycemia, and 3 of 8 mice given 100 PV islets were still hyperglycemic on day 4 postgrafting. In summary, pancreatic ductal collagenase injection followed by stationary in vitro digestion reproducibly yields higher numbers of intact and viable islets when compared with portal venous collagenase injection, indicating the superiority of this method to portal venous injection.
Assuntos
Colagenase Microbiana/metabolismo , Pâncreas/irrigação sanguínea , Animais , Glicemia/análise , Injeções Intravenosas , Insulina/análise , Transplante das Ilhotas Pancreáticas , Colagenase Microbiana/administração & dosagem , Pâncreas/patologia , Ratos , Ratos Endogâmicos , Veias/efeitos dos fármacosRESUMO
We have described a monoclonal antibody with specificity for permeability-altered drug-resistant cells. This gamma G2b antibody was characterized by antibody-mediated complement-dependent cytotoxicity and by immunofluorescence analysis using a flow cytometer-cell sorter. Further experiments with the flow cytometer showed that vinblastine=resistant cells exposed to that drug had a wider range of fluorescence intensity and had a modal channel 4 times as bright as the same cells cultured in growth medium. We believe that this monoclonal antibody recognizes part of the "P' glycoprotein found on drug-resistant Chinese hamster ovary cells.
Assuntos
Anticorpos Monoclonais , Resistência a Medicamentos , Animais , Linhagem Celular , Epitopos , Feminino , Imunofluorescência , Hibridomas/imunologia , Camundongos , Fenótipo , Coloração e RotulagemRESUMO
Viral particles have been demonstrated by electron microscopy in lymph nodes from patients with acquired immune deficiency syndrome AIDS-related persistent generalized lymphadenopathy (PGL) syndrome. Immunohistochemical and in situ hybridization studies have identified these viruses as the human immunodeficiency virus (HIV). In this study, we examined 20 PGL lymph nodes and found viral particles in 18 cases. Immunohistochemical studies on these cases revealed positive staining for the HIV core protein P24 within germinal centers of secondary follicles. In addition we found viral particles, morphologically indistinguishable from those observed in PGL lymph nodes, in 13 of 15 non-HIV related reactive lymph nodes. Immunohistochemical staining of these lymph nodes for the P24 core protein was negative. None of the patients in this group had risk factors for developing AIDS and none exhibited clinical evidence of immune deficiency. We conclude that the viral particles observed in PGL lymph nodes are most likely HIV, but similar particles can be seen in reactive lymph nodes not associated with HIV infection. The discrete localization of these particles within germinal centers has been observed for other viruses and immune complexes and a possible mechanism of this antigen deposition is discussed.
Assuntos
Complexo Relacionado com a AIDS/patologia , Síndrome da Imunodeficiência Adquirida/complicações , Linfonodos/ultraestrutura , Vírion/ultraestrutura , Humanos , Imuno-Histoquímica , Microscopia EletrônicaRESUMO
The clinical, pathologic, and immunologic features in nine cases of non-Hodgkin's lymphoma of the multilobated B-cell type are described. Clinical and phenotypic heterogeneity was observed in these B-cell neoplasms. A probable follicular center cell derivation for these cytologically unusual B-cell lymphomas is supported by antecedent histories of follicular center cell neoplasms in three cases; a focal nodular pattern in one case; the demonstration of peanut lectin (PNA) receptors, a marker for follicular center cells, on neoplastic multilobated B cells; and immunoultrastructural studies of nonneoplastic tonsillar cells that identified and characterized rare multilobated cells, immunoreactive for B1, B2, and Ia membrane antigens, a phenotype consistent with follicular center-type cells. Comparison of B- and T-cell multilobated lymphomas revealed that only immunologic studies accurately discriminated between these neoplasms.
Assuntos
Linfoma/patologia , Adolescente , Adulto , Idoso , Antígenos de Neoplasias/análise , Antígenos de Superfície/análise , Linfócitos B , Feminino , Histocitoquímica , Humanos , Imunoquímica , Linfoma/classificação , Linfoma/metabolismo , Linfoma/ultraestrutura , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Receptores Mitogênicos/análiseRESUMO
Sucrase-isomaltase (SI) is a mucosal disaccharidase that is present in normal small intestine and fetal colon. It also has been noted in colonic adenomas and adenocarcinomas. We used a polyclonal antibody to human SI to investigate enzyme presence and utility in detecting dysplastic changes in chronic ulcerative colitis. Sections from 32 cases were reviewed for the presence or absence of active colitis and dysplasia. Immunostaining of these cases for SI was performed and the results were reported based on location of immunoreactivity (ie, membrane and cytoplasmic staining in superficial and crypt epithelial cells) and percentage of positivity. Of 81 sections examined, 48 were rated negative for dysplasia (23 inactive colitis, 20 active, and five probably negative) and 28 were rated positive (eight low grade and 20 high grade). Surface membrane staining of epithelial cells was noted in all 28 dysplastic slides and positive cases (sensitivity, 100%) but also in 29 of 48 negative sections (P less than .001). In contrast, cytoplasmic positivity was present in 25 of 28 dysplastic and in only two of 48 negative slides (P less than .0001). The presence of cytoplasmic staining of SI in the superficial or crypt cells revealed a sensitivity of 92% and a specificity of 94%. There were five additional sections rated as indefinite for dysplasia (probably positive or unknown); two showed staining patterns typical of negative slides and three showed positive staining patterns. Of the 18 samples of transitional mucosa next to areas of dysplasia, surface membrane staining of SI was seen in all samples and cytoplasmic staining was seen in 15. We conclude that membrane staining of SI can be detected in inflammatory, regenerative, and dysplastic mucosa in ulcerative colitis. Cytoplasmic staining, however, correlates strongly with the presence of dysplastic change and may help in its detection.
Assuntos
Colite Ulcerativa/enzimologia , Colite Ulcerativa/patologia , Complexo Sacarase-Isomaltase/análise , Adulto , Idoso , Feminino , Humanos , Doenças Inflamatórias Intestinais/enzimologia , Doenças Inflamatórias Intestinais/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
Adenocarcinomas of the colon arise from adenomatous polyps. We hypothesized that sucrase-isomaltase (SI), a glycoprotein hydrolase, found in normal small intestine, fetal colon, and colon carcinomas is a marker associated with progression of adenomatous polyps with dysplasia to adenocarcinomas. To examine this hypothesis, we performed immunostaining using a polyclonal antihuman SI antibody in 32 adenomatous polyps with varying degrees of dysplasia. In addition, sucrase enzyme activity was determined in three sets of simultaneously harvested polyps, cancer, and adjacent normal mucosa from the same patient. All severely dysplastic polyps (6/6) exhibited SI staining. Most polyps (85%) with 3+ staining (i.e., greater than 10% of polyp positive for SI) had severe dysplasia, whereas those with mild dysplasia had either 1% to 5% staining or no staining in 95% of the cases. These data indicate that the extent of SI immunostaining in polyps correlates with the degree of dysplasia (p = 0.0001). Sucrase-isomaltase activity in the polyps was 18.1 +/- 1.8 mU/mg (mean +/- SD); in adjacent carcinoma SI activity was 29.1 +/- 1.8 mU/mg. Adjacent mucosa showed no activity in all cases. In summary, our results suggest that SI expression correlates with the progression of dysplastic adenomatous polyps to carcinoma. Sucrase-isomaltase expression may be useful as a clinical marker to improve our prognostic capabilities in patients with dysplastic lesions of the colon, that is, inflammatory bowel disease.
Assuntos
Adenocarcinoma/metabolismo , Biomarcadores Tumorais , Neoplasias do Colo/metabolismo , Pólipos Intestinais/metabolismo , Complexos Multienzimáticos/metabolismo , Complexo Sacarase-Isomaltase/metabolismo , Adenocarcinoma/patologia , Neoplasias do Colo/patologia , Humanos , Mucosa Intestinal/enzimologia , Pólipos Intestinais/patologia , Coloração e RotulagemRESUMO
Cathepsin B (CB) is involved in the hydrolysis of thyroglobulin (Tg) and thought to be regulated by thyroid stimulating hormone (TSH) in the normal thyroid. Our analyses of 91 thyroid tissues from 71 patients with Graves' disease (GD), multinodular goiter (MNG), papillary carcinoma (PC), or follicular carcinoma (FC), demonstrated a 2-fold increase in expression of CB in GD and an average increase of 1.5-fold in MNG (varying from 10-fold below normal to 6-fold above normal in MNG nodules), as might be predicted by the altered functional status of thyroid follicular cells in those diseases. However, CB activity was not downregulated in conjunction with the known "blocking effect" of malignancy on many thyroid functions, but rather increased on average 9-fold in papillary carcinomas (n = 33), and also showed a marked increase in 2 follicular carcinomas. Activity measurements were confirmed by CB protein detection on Western blot with moderately increased CB protein levels demonstrated in GD, variable expression in nodules of MNG, and markedly increased protein expression in carcinomas. In all diseased states, increased protein was detected primarily as overexpression of the 27 kd heavy chain of 2-chain mature CB and less frequently as overexpression of 31 kd single-chain mature CB. However, an additional 35 kd protein form was noted in 3 of 9 PCs, 1 of 2 FCs, and 1 of 4 GD cases but in none of 10 MNG cases. In conjunction with elevated CB activity plus additional protein bands on Western blots, altered patterns of CB immunohistochemical staining were observed, irrespective of the type of thyroid disease, suggesting certain common changes in CB expression, posttranslational processing, and vesicular trafficking. In summary, GD and MNG thyroid tissues demonstrated altered CB expression in keeping with predicted functional changes in thyroid follicular cells, while increased CB expression in carcinomas indicated a more pathological role for CB in thyroid cancers, possibly related to the processes of invasion or metastasis.
Assuntos
Catepsina B/metabolismo , Bócio Nodular/enzimologia , Doença de Graves/enzimologia , Proteínas/metabolismo , Neoplasias da Glândula Tireoide/enzimologia , Western Blotting , Bócio Nodular/metabolismo , Bócio Nodular/patologia , Doença de Graves/metabolismo , Doença de Graves/patologia , Humanos , Imuno-Histoquímica , Frações Subcelulares/enzimologia , Frações Subcelulares/metabolismo , Hormônios Tireóideos/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologiaRESUMO
Elevated serum levels of alpha-fetoprotein (AFP) (100-1,000 ng/ml) were found in three patients with islet cell tumors. Serial levels correlated with progression of disease, suggesting that AFP could be a useful tumor marker substance for islet cell tumors. Survey sera from an expanded pool of 23 patients with islet cell tumors and nine with carcinoid tumors did not identify additional cases, however, suggesting that elevated AFP levels in these classes of Apudomas are uncommon. Nonetheless, the distinction from other AFP-producing tumors such as hepatocellular carcinoma is clinically important and warrants an awareness of the rare association of AFP with these tumors.
Assuntos
Adenoma de Células das Ilhotas Pancreáticas/sangue , Neoplasias Pancreáticas/sangue , alfa-Fetoproteínas/análise , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/secundário , Humanos , Técnicas Imunoenzimáticas , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Radioimunoensaio/métodosRESUMO
We describe an unusual type of carcinoma of the parotid gland in a 67-year-old man. Because of rapid tumor growth, radical parotidectomy was done. Light microscopic study of the tumor revealed focal gland formation with transition to anaplastic carcinoma. Among the undifferentiated mononuclear cells and bizarre large cells were scattered many osteoclastlike multinucleated giant cells. Immunohistochemical studies on paraffin sections revealed positive staining for epithelial membrane antigen in the epithelial component; however, the multinucleated giant cells were clearly negative for this antigen. Reactions for other cell constituents (carcinoembryonic antigen, alpha 1-antitrypsin, alpha-1-antichymotrypsin, Leu-M1, Leu-M3, lysozyme, and factor VIII-related antigen) were negative in both epithelial and giant cell components of the tumor. Electron microscopy revealed poorly formed cell junctions and numerous microvilli on the surface of the mononuclear tumor cells and multinucleated giant cells, features considered not of diagnostic significance. Similar to carcinomas with osteoclastlike multinucleated giant cells in other organs, this parotid gland tumor has shown clinical and morphologic evidence of aggressive growth; pulmonary metastases developed and the patient died 28 months after radical surgery.
Assuntos
Carcinoma/patologia , Osteoclastos/patologia , Neoplasias Parotídeas/patologia , Idoso , Carcinoma/ultraestrutura , Histocitoquímica , Humanos , Imunoquímica , Masculino , Microscopia Eletrônica , Osteoclastos/ultraestrutura , Neoplasias Parotídeas/ultraestruturaRESUMO
A case of malignant hemangioendothelioma of the spleen is reported. Light and electron microscopic evidence suggests that the tumor is a neoplastic proliferation of the two cell types, one resembling the "sinus endothelial" cell of the normal spleen, and the other resembling the "fixed reticular cell" of splenic red pulp.