RESUMO
Synaptophysin is a Mr 38,000 integral membrane glycoprotein expressed by a variety of normal and neoplastic neuroendocrine cells. We studied synaptophysin as an immunocytochemical marker for neuroendocrine differentiation in lung cancer and compared it to the immunocytochemical expression of chromogranin A, a marker for dense core (endocrine) granules, and the biochemical activity of L-dopa decarboxylase (DDC), the key amine-handling enzyme. Of the 250 cell lines available to us, we selected examples representative of the following cell types: bronchial carcinoids (n = 4), small cell lung cancer (SCLC) (n = 7), extrapulmonary small cell carcinomas (n = 4), and non-small cell lung cancers (n = 18) whose neuroendocrine status had been previously determined on the basis of electron microscopy and DDC activity. We demonstrated (a) there was a higher incidence of synaptophysin than chromogranin A immunoreactivity in carcinoid (100 versus 75%), classic SCLC (70 versus 50%), and variant SCLC (57 versus 29%) cell lines; (b) 3 of the 4 (75%) extrapulmonary small cell lung cancer cell lines expressed synaptophysin and chromogranin A; (c) 5 of the 7 (71%) non-small cell lung cancer cell lines previously shown to express multiple neuroendocrine markers were positive for synaptophysin, chromogranin A, and DDC activity; (d) none of the other 11 non-small cell lung cancer cell lines expressed synaptophysin or chromogranin A; and (e) formalin fixation and paraffin embedding reduced synaptophysin immunoreactivity in 11 of 14 (79%) of the cell lines, as compared to freshly prepared specimens fixed in 95% ethanol. Western blot analysis using the synaptophysin antibody (SY38) demonstrated immunoreactive proteins ranging from Mr 43,000 to 45,000 in five representative cell lines. The concordance of expression of all three neuroendocrine markers was statistically significant when values for all cell lines were totalled. Synaptophysin was a more commonly expressed marker for variant SCLC cell lines, which rarely showed DDC activity. We conclude that synaptophysin may be a more sensitive and specific marker for neuroendocrine differentiation, when compared to chromogranin A and DDC in lung cancer cell lines which express only part of the neuroendocrine program.
Assuntos
Descarboxilases de Aminoácido-L-Aromático/análise , Cromograninas/análise , Dopa Descarboxilase/análise , Neoplasias Pulmonares/análise , Proteínas de Membrana/análise , Proteínas do Tecido Nervoso/análise , Sistemas Neurossecretores/análise , Tumor Carcinoide/análise , Carcinoma Pulmonar de Células não Pequenas/análise , Carcinoma de Células Pequenas/análise , Diferenciação Celular , Humanos , Neoplasias Pulmonares/patologia , Proteínas de Membrana/imunologia , Peso Molecular , Sinaptofisina , Células Tumorais CultivadasRESUMO
Different subtypes of voltage-operated calcium channels (VOCCs) are expressed in different tissues and can be distinguished by functional and pharmacological criteria. One type of high voltage-activated calcium channel, specifically recognized by the peptide neurotoxin omega-conotoxin (omega CTx), is expressed only in neurons. Seven different human small cell lung carcinoma (SCC) cell lines were also found to bind 125I-omega CTx. The binding was specific, saturable, and of high affinity. 125I-omega CTx binding was not antagonized by the calcium channel ligands verapamil, nitrendipine, and diltiazem. There was a correlation between the amount of toxin binding and the detection of depolarization-induced calcium fluxes studied with the fluorimetric probe Fura2. Fura2 experiments also demonstrated that, in addition to omega CTx-sensitive calcium channels, SCC cell lines also expressed omega CTx-insensitive calcium channels, which were antagonized by nitrendipine and verapamil. 125I-omega CTx-labeled VOCCs from SCC cells were, furthermore, precipitated by anti-VOCC autoantibodies obtained from patients affected by the Lambert-Eaton myasthenic syndrome, a neuromuscular disease often associated with SCC. The present findings further indicate the presence of neuronal molecules with important biological function on SCC plasma membrane and add new insights into the pathogenetic mechanism of autoimmune neurological paraneoplastic diseases, like Lambert-Eaton myasthenic syndrome.
Assuntos
Canais de Cálcio/metabolismo , Carcinoma de Células Pequenas/metabolismo , Conotoxinas , Neoplasias Pulmonares/metabolismo , Peptídeos Cíclicos/metabolismo , Sítios de Ligação , Ligação Competitiva , Canais de Cálcio/análise , Canais de Cálcio/efeitos dos fármacos , Carcinoma de Células Pequenas/análise , Humanos , Neoplasias Pulmonares/análise , Nitrendipino/farmacologia , Células Tumorais Cultivadas , Verapamil/farmacologiaRESUMO
Immunocytochemical and immunochemical techniques were used to study the expression of the neural cell adhesion molecule (NCAM) by human lung cancer cell lines. Intense surface staining for NCAM was found at light and electron microscopic levels on small cell lung cancer cells. The NCAM polypeptide of Mr 140,000 (NCAM 140) was detected by immunoblotting in all of 7 small cell lung cancer cell lines examined and in one out of two of the closely related large cell cancer cell lines: it was not detected in cell lines obtained from one patient with a mesothelioma, in two cases of adenocarcinoma, nor in two cases of squamous cell cancer. In contrast, neuron-specific enolase was found by immunoblotting in all the lung cancer cell lines tested and synaptophysin in all but the adenocarcinoma cell lines. These antigens were localized intracellularly. The specific expression of NCAM 140 by human small and large cell lung carcinomas suggests its potential as a diagnostic marker.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Pequenas/análise , Moléculas de Adesão Celular Neuronais/análise , Neoplasias Pulmonares/análise , Moléculas de Adesão Celular Neuronais/ultraestrutura , Humanos , Técnicas Imunoenzimáticas , Microscopia Eletrônica , Células Tumorais CultivadasRESUMO
The cisplatin(CDDP)-resistant cell line GLC4-CDDP shows a variety of differences from the parent line GLC4. The aim of this study was to determine which of the observed changes correlated with the degree of resistance and was therefore relevant to the phenomenon of CDDP resistance. For these experiments we used cells of the sensitive hSCLC cell line GLC4 and the in vitro-acquired CDDP-resistant sublines GLC4-CDDP3 and GLC4-CDDP11, with a resistance factor (RF) of 3 and 11 respectively for CDDP and of 1.8 and 7.4 respectively for carboplatin. Carboplatin was used, in addition to CDDP in seeking relevant mechanisms. No consistency was found between the RF and the growth pattern or antigen expression, cellular volume, doubling time, cellular or nuclear platinum (Pt) content or the level of Pt-non-histone chromatin protein (NHCP) binding. A correlation was found between the RF and the level of glutathione (GSH), and a trend was found for the level of Pt-DNA binding, Pt-GG adduct content and the amount of interstrand cross-links (ISC). These changes might therefore be relevant for the development of resistance. These findings are compatible with a GSH-induced reduction of the amount of reactive Pt in the resistant cell, resulting in a lower net platination and toxic Pt-DNA adduct formation.
Assuntos
Carcinoma de Células Pequenas/tratamento farmacológico , Cisplatino/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Anticorpos Monoclonais , Antígenos CD/imunologia , Antígenos de Neoplasias/imunologia , Antineoplásicos/antagonistas & inibidores , Carboplatina , Carcinoma de Células Pequenas/análise , Carcinoma de Células Pequenas/imunologia , Carcinoma de Células Pequenas/patologia , Linhagem Celular , Corantes , Resistência a Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Glutationa/análise , Humanos , Neoplasias Pulmonares/análise , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Compostos Organoplatínicos/antagonistas & inibidores , Platina/análise , Sais de Tetrazólio , Tiazóis , Células Tumorais Cultivadas/análise , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/imunologiaRESUMO
By flow cytometry, cellular DNA-RNA content was analyzed with Acridine Orange staining for primary tumor and the metastatic foci in 12 cases of primary lung carcinoma. Five (42%) of the primary and metastatic foci showed heterogeneous cellular DNA content, with high cellular DNA content of metastatic foci in all cases. Cellular RNA content was significantly higher in metastatic foci than in primary foci, indicating possible higher proliferative activity of the former foci. Three different metastatic foci in one patient showed essentially the same cellular DNA content. From the above it is evident that primary and metastatic foci of lung carcinoma show considerable heterogeneity not only in cellular DNA content but RNA content as well, thus indicating proliferative activity of the metastatic focus. It is consequently advisable to use a combination of various supplementary medications differing in cytocidal effect. Cases with higher cellular DNA content may likely have higher metastatic potential.
Assuntos
DNA de Neoplasias/análise , Neoplasias Pulmonares/patologia , RNA Neoplásico/análise , Adenocarcinoma/análise , Adenocarcinoma/patologia , Idoso , Carcinoma de Células Pequenas/análise , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Escamosas/análise , Carcinoma de Células Escamosas/patologia , Feminino , Citometria de Fluxo , Humanos , Neoplasias Pulmonares/análise , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Metástase NeoplásicaRESUMO
We have studied the pattern of chromogranin A (CgA)-related species in different human endocrine cells that produce CgA and also express the calcitonin gene. Antibodies against CgA peptides that span its linear sequence were used in Western analysis of cell lines derived from medullary thyroid carcinoma (MTC), small cell lung cancers (SCLC), epidermoid cell lung cancer (ECLC) and a pulmonary carcinoid tumor (CRND). Each of the cell lines demonstrated a distinct pattern of CgA-related species. Gel filtration studies also revealed multiple and different forms of immunoreactive CgA in the cell lines. Although proteolysis may contribute to our results, these observations suggest that native CgA is processed to smaller species in a tissue-specific pattern by different endocrine cells. More conclusive studies, however, are necessary to establish that cell processing leads to the specific CgA moieties that we have observed.
Assuntos
Cromograninas/análise , Proteínas do Tecido Nervoso/análise , Western Blotting , Tumor Carcinoide/análise , Carcinoma/análise , Carcinoma de Células Pequenas/análise , Carcinoma de Células Escamosas/análise , Cromatografia em Gel , Cromogranina A , Cromograninas/metabolismo , Humanos , Neoplasias Pulmonares/análise , Neoplasias da Glândula Tireoide/análise , Células Tumorais CultivadasRESUMO
Primary small cell carcinoma of the oesophagus (SCCO), histologically indistinguishable from its counterpart of the lung, is a rare tumour. Less than 100 cases are reported. A review of 558 consecutive patients with oesophageal carcinomas referred to our department revealed seven cases. These were studied and compared to a survey of 80 cases collected from 24 reports. The present results, as well as the survey, indicate a poor prognosis with rapid and widespread dissemination, and that death is attributed to distant metastases rather than local failure. Freedom from local symptoms was achieved in all seven patients, regardless of therapy modalities employed. A complete response of the primary lesion was observed in three patients after chemo- and subsequent radiotherapy. According to these findings the most suitable treatment approach seems to be the same as for small cell carcinoma of the lung. A detailed immunohistochemical analysis revealed more characteristics similar to small cell carcinoma of the lung than that of the skin, viz 'Merkel cell carcinoma'.
Assuntos
Carcinoma de Células Pequenas/patologia , Neoplasias Esofágicas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Pequenas/análise , Carcinoma de Células Pequenas/terapia , Terapia Combinada , Neoplasias Esofágicas/análise , Neoplasias Esofágicas/terapia , Feminino , Humanos , Imuno-Histoquímica , Queratinas/análise , Masculino , Glicoproteínas de Membrana/análise , Mucina-1 , Metástase Neoplásica , Prognóstico , Indução de Remissão , Estudos RetrospectivosRESUMO
Primary lung cancer samples of the major histological types were examined for expression of the tumor suppressor gene p53 by immunohistochemistry. Abnormalities in p53 expression were found in 28 of 40 carcinomas, 14 of 17 squamous tumours showing abnormal p53 expression, whereas no expression of p53 was detectable in 7 carcinoid tumours or in 10 normal lung samples. Direct evidence for homozygous expression of mutant p53 mRNA in representative carcinomas was obtained by means of an asymmetric polymerase chain reaction mRNA sequencing strategy, which allowed sequencing without any cloning step. All the mutations were G to T transversions resulting in mis-sense mutations in aminoacids highly conserved in evolution. Mutation of the p53 gene is the most frequently identified genetic change in human lung cancer; these findings suggest that simple immunohistological methods can provide strong evidence of such mutation.
Assuntos
Adenocarcinoma/análise , Tumor Carcinoide/análise , Carcinoma de Células Pequenas/análise , Carcinoma de Células Escamosas/análise , Cromossomos Humanos Par 17 , Neoplasias Pulmonares/análise , Mutação , Proteínas Oncogênicas/análise , Fosfoproteínas/análise , Adenocarcinoma/genética , Alelos , Sequência de Aminoácidos , Autorradiografia , Tumor Carcinoide/genética , Carcinoma de Células Pequenas/genética , Carcinoma de Células Escamosas/genética , DNA de Neoplasias/análise , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/genética , Dados de Sequência Molecular , Sondas de Oligonucleotídeos , Proteínas Oncogênicas/genética , Fosfoproteínas/genética , Reação em Cadeia da Polimerase , RNA Mensageiro/análise , Proteína Supressora de Tumor p53RESUMO
Thymic carcinoma (TCA) is a thymic epithelial neoplasm with obvious cytologic atypia. We studied 13 cases of TCA by light microscopy, immunohistochemistry, and electron microscopy and correlated the findings with clinical features. The patients' mean age was 54.2 years (range 30-74); the male/female ratio was 7/6. Twelve of the 13 patients presented with signs and symptoms caused by compression of mediastinal organs; the other patient was asymptomatic. Paraneoplastic syndromes were never seen. At thoracotomy, 11 tumors invaded or adhered to surrounding structures; the other two were encapsulated. The histologic types include squamous carcinoma including the lymphoepithelioma-like subtype (seven cases), small cell carcinoma (four cases), clear cell carcinoma (one case), and adenosquamous carcinoma (one case). Positive immunoperoxidase studies were as follows: keratin (13 cases), epithelial membrane antigen (EMA) (13 cases), leukocyte common antigen (none), carcinoembryonic antigen (CEA) (five cases), B72.3 (seven cases), Leu 7 (two cases), human placental alkaline phosphatase (none), vimentin (none), and chromogranin (one case). This profile is similar to those of normal thymus and thymoma except for the absence of CEA, B72.3, EMA in normal thymus, and the absence of CEA and B72.3 in thymoma. Electron-microscopic studies performed on eight cases showed glandular and squamous differentiation in one adenosquamous carcinoma, squamous differentiation in five squamous carcinomas, and neuroendocrine differentiation in one small-cell carcinoma. Nine patients died (three due to postoperative complications and six due to recurrences or metastasis at 3-36 months). Four patients (all with squamous carcinoma) were alive without disease at 2-60 months. The clinical and pathologic features were comparable with those of approximately 62 other cases of TCA previously reported. There are a number of well-defined histologic types of TCA that allow the pathologist to make a differential diagnosis of TCA from tumors extending or metastatic to thymus or other primary mediastinal tumors. Although neither asymptomatic presentation nor encapsulation improves the poor prognosis of TCA, the squamous carcinoma subtype is associated with a better outcome than the other subtypes. Based on the electronmicroscopic and immunohistochemical findings, the presence of normal thymic tissue at the periphery of several tumors, and the observation that several TCA arose from preexisting thymomas or thymic cysts, we conclude that TCA is derived from thymic epithelium.
Assuntos
Adenocarcinoma/patologia , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias do Timo/patologia , Adenocarcinoma/análise , Adulto , Idoso , Fosfatase Alcalina/análise , Antígeno Carcinoembrionário/análise , Carcinoma de Células Pequenas/análise , Carcinoma de Células Escamosas/análise , Feminino , Humanos , Imuno-Histoquímica , Isoenzimas/análise , Queratinas/análise , Masculino , Glicoproteínas de Membrana/análise , Pessoa de Meia-Idade , Mucina-1 , Neoplasias do Timo/análiseRESUMO
Sixteen primary human lung tumours were analysed for their content of somatostatin receptors using receptor autoradiography with somatostatin-28 and somatostatin octapeptide analogues as radio-ligands. Two out of 4 small-cell lung carcinomas were somatostatin receptor-positive, with a high density of homogeneously distributed receptors on tumour tissue only. Somatostatin receptors were characterized in one of the tumours in homogenate binding assay as saturable, high-affinity binding sites (KD = 0.53 nM) with a number of sites (Bmax) equivalent to 189 fmoles/mg protein. These sites were specific for somatostatin, since only biologically active somatostatin analogues but not unrelated peptides showed high-affinity binding. Both receptor-positive patients had limited disease; furthermore, the small-cell lung carcinoma patient with the longest survival was receptor-positive, while the one with the shortest survival was receptor-negative. None of the 12 non-small-cell lung carcinomas (5 squamous carcinomas, 7 adenocarcinomas) contained somatostatin receptors. For comparison, epidermal growth factor receptors were found in all non-small-cell lung carcinomas. Neuroendocrine features (synaptophysin, chromogranin, neuron-specific enolase, protein gene product 9.5) were present in all small-cell lung carcinomas but absent in non-small-cell lung carcinomas. Given the receptor-mediated action of somatostatin in other neuroendocrine tumours, these data may have a bearing on the clinical application of somatostatin analogues in patients with small-cell lung carcinomas.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/análise , Carcinoma de Células Pequenas/análise , Receptores ErbB/análise , Neoplasias Pulmonares/análise , Receptores de Neurotransmissores/análise , Somatostatina/metabolismo , Adulto , Idoso , Autorradiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de SomatostatinaRESUMO
Lung cancer has considerable treatment problems, with a poor 5-yr survival rate after surgery. Application of histopathological and immunohistopathological subtyping have proven to be powerful tools for the assessment of prognosis. Results in 33 patients with small cell carcinoma, 44 with large cell carcinoma, and five with adenoid cystic carcinoma of the lung are discussed. The 5-yr survival rates in patients with small cell carcinoma of the oat cell type and intermediate type were 24 and 44%, respectively. Argyrophilic granules and neuron-specific enolase, neuroendocrine markers, were detected more frequently in the oat cell type rather than in the intermediate type. In contrast, keratin, epithelial membrane antigen, and carcinoembryonic antigen, epithelial origin markers, were present more frequently in the intermediate type than in the oat cell type. The 5-yr survival rates with large cell carcinoma of the compact growth type and the loose structure type were 46 and 28%, respectively, based on evidence of morphologically intercellular cohesion. The epithelial origin markers were detectable and more frequent in the compact growth type than in the loose structure type. The growth patterns of adenoid cystic carcinoma are classified as tubular, cribriform, and solid. The solid pattern was the most aggressive with extensive perineural invasion. We propose that the pathological properties of lung cancer should be examined as a prognostic implication of subtyping.
Assuntos
Carcinoma Adenoide Cístico/patologia , Carcinoma de Células Pequenas/patologia , Carcinoma/patologia , Neoplasias Pulmonares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma/análise , Carcinoma/mortalidade , Carcinoma Adenoide Cístico/análise , Carcinoma Adenoide Cístico/mortalidade , Carcinoma de Células Pequenas/análise , Carcinoma de Células Pequenas/mortalidade , Feminino , Humanos , Técnicas Imunoenzimáticas , Neoplasias Pulmonares/análise , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de SobrevidaRESUMO
In this study antibodies specific for different intermediate-sized proteins (cytokeratins and neurofilaments) have been tested on a series of neuroendocrine (NE) lung tumors in order to evaluate their diagnostic validity. In particular we used a panel of polyclonal anti-neurofilament 200-kilodalton subunits whose reactivity against phospho-dependent epitopes was known. At least one NF subunit was constantly present and in all cases coexpression of cytokeratins and neurofilaments was confirmed. However, in cases of carcinoid tumor (CT) the results were homogeneous, while the cases of small cell lung carcinoma (SCLC) showed a much wider range of immunostaining. Our investigation confirms the hypothesis that the phosphorylation state is a significant determinant of immunohistochemical properties of neurofilaments. This might explain the large number of negative results obtained in previous investigations on NE tumors. The phosphorylation of neurofilaments may also be considered an indication of the degree of differentiation of the tumor.
Assuntos
Carcinoma de Células Pequenas/metabolismo , Carcinoma/metabolismo , Proteínas de Filamentos Intermediários/metabolismo , Queratinas/metabolismo , Neoplasias Pulmonares/metabolismo , Biomarcadores Tumorais/análise , Carcinoma/análise , Carcinoma/patologia , Carcinoma de Células Pequenas/análise , Carcinoma de Células Pequenas/patologia , Humanos , Imuno-Histoquímica , Proteínas de Filamentos Intermediários/análise , Queratinas/análise , Neoplasias Pulmonares/análise , Neoplasias Pulmonares/patologia , FosforilaçãoRESUMO
The sensitivity of eight cell lines established from treated and untreated patients with small cell carcinoma of the lung (SCCL) was tested in the clonogenic assay with 1 h and continuous exposure to aclarubicin (ACLA), adriamycin (ADR), daunorubicin (DAU) and mitoxantrone (MITO). The sensitivity to ADR, DAU and MITO covariated, and varied with a factor of five. The sensitivity to ACLA was independent of the sensitivity to ADR and varied only within a factor of two. Only ACLA showed pronounced increased potency with continuous incubation, and ACLA was the most potent drug in the three cell lines least sensitive to ADR. Two resistant cell lines were selected by treating NCI-H69 in vitro with DAU. One cell line (9-fold resistant to DAU) expressed large amounts of P-glycoprotein, the other cell line (4-fold resistant to DAU) had barely detectable glycoprotein. Both lines acquired resistance to ADR, ACLA and MITO. The cross-resistance to ACLA and MITO was only partial and ACLA was still the most potent drug on these lines. The sensitivity to ACLA of the cell lines least sensitive to ADR suggest that ACLA partially circumvents mechanisms of multidrug resistance. Together with the pronounced increase in potency with prolonged exposure, these results suggest that ACLA has a mechanism of action different from the 'classical' anthracyclines. In this context mitoxantrone is more similar to the classical anthracyclines although its structure is more dissimilar.
Assuntos
Aclarubicina/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Proteínas Sanguíneas/análise , Carcinoma de Células Pequenas/análise , Daunorrubicina/uso terapêutico , Doxorrubicina/uso terapêutico , Resistência a Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Técnicas In Vitro , Glicoproteínas de Membrana/análise , Mitoxantrona/uso terapêutico , Ensaio Tumoral de Célula-TroncoRESUMO
Patient suffering from vesical carcinoma, which is identified as small cells (oat cells) carcinoma. We carried out a histochemical study with H.C.G. and C.E.A. and analyse the results obtained.
Assuntos
Biomarcadores Tumorais/análise , Antígeno Carcinoembrionário/análise , Carcinoma de Células Pequenas/análise , Gonadotropina Coriônica/análise , Neoplasias da Bexiga Urinária/análise , Idoso , Carcinoma de Células Pequenas/patologia , Humanos , Masculino , Neoplasias da Bexiga Urinária/patologiaRESUMO
Selected neoplastic markers (NSE, gastrin, CEA, calcitonin, keratin) were studied in pulmonary specimens from 5 patients with bronchial carcinoid, 20--with small cell lung cancer (SCLC), and 2 with solid tumors. In patients with carcinoid and SCLC NSE and gastrin markers were found--characteristic for neuroendocrine neoplasia. The author discuss the usefulness of immunohistochemistry in differential diagnostics of pulmonary malignancy.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias Brônquicas/análise , Tumor Carcinoide/análise , Carcinoma de Células Pequenas/análise , Neoplasias Pulmonares/análise , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-IdadeRESUMO
We have studied the effects of two human pancreatic cancer and two human small cell lung cancer cell lines on clotting and platelet aggregation. Both pancreatic lines markedly shortened recalcification times and induced platelet aggregation. The lung cancer lines produced little shortening of recalcification times and no platelet aggregation. The clotting and aggregation activities of the pancreatic lines were further characterized. Recalcification times following the addition of cancer cell line material to plasmas deficient in factors VII and X were markedly prolonged, suggesting that the activity is due to tissue factor. Hirudin, an inhibitor of thrombin from the saliva of leeches, and rabbit polyclonal immunoglobulin G anti-bovine brain tissue factor inhibited both procoagulant and aggregation activities. Apyrase (an enzyme degrading ADP), diisopropylfluorophosphate (a serine protease inhibitor) and L-trans-epoxysuccinylleucylamido(4-guanidino)butane (a cysteine protease inhibitor) failed to inhibit these activities. Increasing concentrations of heparin inhibited platelet aggregation. Subcellular fractionation studies showed these activities to be localized to the plasma membrane. The association between mucin and the acceleration of clotting has been well described. The absence of mucin in electron micrographs of these pancreatic whole cells, membrane fractions, and shed microvesicles, as well as the failure of chaotropic agents (i.e., agents stripping material extrinsic to the cell membrane such as mucin) to abrogate this activity support these activities being intrinsic to the plasma membrane. These data strongly suggest that these activities are due to tissue factor which appears to be released as microvesicles in vitro. The release of tissue factor via microvesicles in vivo is one possible mechanism for the coagulopathy sometimes seen in patients with pancreatic carcinoma.
Assuntos
Adenocarcinoma/análise , Neoplasias Pancreáticas/análise , Tromboplastina/análise , Coagulação Sanguínea , Cálcio , Carcinoma de Células Pequenas/análise , Membrana Celular/análise , Humanos , Neoplasias Pulmonares/análise , Microscopia Eletrônica , Ductos Pancreáticos , Agregação Plaquetária , Células Tumorais Cultivadas/análiseRESUMO
In order to validate xenografted small cell lung carcinomas (SCLC) for biological studies, the authors established 12 lung neuroendocrine (NE) tumors (eight typical SCLC and four atypical NE tumors [ANE]) by heterotransplantation onto nude mice. Their characterization was performed using serial ultrastructural, enzymatic, and immunohistochemical methods on primary tumors and after xenografts. These were subclassified into epithelial (one), neuroendocrine (three), and multidifferenciated (eight) types. The phenotypic characters (cytokeratins, neurofilaments, neurone-specific enolase) and the proliferative rate (Ki 67 labelling) of original tumor were maintained until the last passage studied. Although further acquisition of subsets of cytokeratin or neurofilaments was observed in some cases, the authors could not detect any morphologic and/or biological spontaneous change comparable to those described in in vitro cell lines. In addition, ANE are not quite identical to variant subclasses described in vitro. The authors conclude that the stability of heterotransplanted SCLC is an advantage in further biological studies.
Assuntos
Carcinoma de Células Pequenas/patologia , Neoplasias Pulmonares/patologia , Animais , Anticorpos Monoclonais , Biomarcadores Tumorais/análise , Carcinoma de Células Pequenas/análise , Carcinoma de Células Pequenas/genética , Citoplasma/ultraestrutura , Feminino , Humanos , Técnicas Imunoenzimáticas , Proteínas de Filamentos Intermediários/análise , Queratinas/análise , Neoplasias Pulmonares/análise , Neoplasias Pulmonares/genética , Camundongos , Camundongos Nus , Peso Molecular , Transplante de Neoplasias , Proteínas de Neurofilamentos , Fenótipo , Fosfopiruvato Hidratase/análiseRESUMO
Lung cancer tissues from 68 patients were examined for epidermal growth factor (EGF) receptor levels and EGF receptor gene copy numbers. Histologic cell types of these lung cancer tissues included squamous-cell carcinoma (n = 30), adenocarcinoma (n = 28), large-cell carcinoma (n = 4), and small-cell carcinoma (n = 6). Tissues of squamous-cell carcinoma exhibited exceptionally high 125I-EGF binding activity, and those of small-cell carcinoma showed no EGF binding activity. Southern blot hybridization analysis revealed EGF receptor gene amplification in the squamous-cell carcinomas with high EGF binding activity. The EGF receptor levels in squamous-cell carcinomas and adenocarcinomas were compared with their pathological staging grouping and pathological findings, including degree of differentiation, diameter of tumor, and lymph node metastasis. However, unlike previous reports on breast and bladder cancers, there was no obvious correlation between these pathological characteristics and the EGF receptor levels of lung cancer.
Assuntos
Receptores ErbB/análise , Neoplasias Pulmonares/análise , Adenocarcinoma/análise , Southern Blotting , Carcinoma/análise , Carcinoma de Células Pequenas/análise , Carcinoma de Células Escamosas/análise , Fator de Crescimento Epidérmico/metabolismo , Humanos , Neoplasias Pulmonares/patologiaRESUMO
A multiinstitutional review of 3778 patients with a primary malignancy of the urinary bladder revealed 18 cases (0.48%) of small cell carcinoma which were histologically and morphometrically identical to pulmonary small cell undifferentiated carcinoma. Age, sex, and symptoms at first presentation were comparable to that known in transitional cell carcinoma. Sixteen patients (89%) developed metastatic disease, with most frequent involvement of regional lymph nodes, liver, skeleton, and abdominal cavity. The unfavorable clinical outcome was worse as compared with that reported in advanced stage poorly differentiated transitional cell carcinoma, and was similar to the rapidly fatal outcome of pulmonary small cell undifferentiated carcinoma. Fourteen patients (78%) died by tumor at a mean follow-up period of 9.4 months, and only one patient was free of recurrent disease more than 5 years after cystectomy. This apparent aggressive tumor behavior was independent of the presence of neuroendocrine differentiation characteristics at immunohistochemical (13 cases, 72%) or electron microscopic study (eight cases, 44%). The prolonged survival periods (15-38 months) of the five patients who received combination chemotherapy suggested that, just as in small cell lung carcinoma, chemotherapy may be profitable. A unified concept of histogenesis of bladder cancer with a common origin from a multipotent mucosal stem cell is proposed.
Assuntos
Carcinoma de Células Pequenas/patologia , Neoplasias da Bexiga Urinária/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Pequenas/análise , Carcinoma de Células Pequenas/mortalidade , Carcinoma de Células Pequenas/secundário , Membrana Celular/ultraestrutura , Citoplasma/ultraestrutura , Grânulos Citoplasmáticos/ultraestrutura , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Organelas/ultraestrutura , Neoplasias da Bexiga Urinária/análise , Neoplasias da Bexiga Urinária/mortalidadeRESUMO
Out of 16 cases involving a cervical carcinoma that were investigated by Southern blot hybridization, found were human papilloma virus (HPV) types 16 and 18 DNA sequences in 8 (50%) and in one (6.3%), respectively. Six out of the 8 HPV 16-positive specimens were from squamous cell carcinomas, one was from an adenocarcinoma, and the remaining specimen was from an argyrophil small cell carcinoma. In 7 out of 9 HPV-positive specimens, the viral sequences were integrated in the tumor cell genome, whereas in the remaining two they were not integrated and remained circular and/or oligomeric in form.