RESUMO
The protein designated 7B2 is a recently discovered pituitary polypeptide which is selectively expressed in cells containing secretory granules, such as neurons and endocrine cells. Northern blot analysis of 7B2 gene expression in small cell lung carcinoma (SCLC) cell lines revealed that 7B2 was expressed in all nine cell lines of the classic type tested, but in six of seven SCLC cell lines of the variant type, 7B2 expression could not be detected. In only one of four non-SCLC cell lines tested, 7B2 was expressed. Furthermore, in 16 primary human non-SCLCs, no or only very low expression of 7B2 was found. In the eight primary human SCLCs tested, expression of 7B2 appeared variable: three exhibited a high level of expression; three a low level; while in two cases, expression was very low or not detectable at all. Finally, the three carcinoid tumors tested expressed very high levels of 7B2 mRNA. These data indicate that the 7B2 gene is a useful marker not only to discriminate between classic and variant types of SCLC cell lines, but also in human lung cancer diagnosis.
Assuntos
Neoplasias Pulmonares/análise , Proteínas do Tecido Nervoso , Hormônios Hipofisários/genética , RNA Mensageiro/análise , Carcinoma Pulmonar de Células não Pequenas/análise , Carcinoma de Células Pequenas/análise , DNA/análise , Humanos , Proteína Secretora Neuroendócrina 7B2 , Células Tumorais CultivadasRESUMO
Estramustine-binding protein has previously been demonstrated in normal rat prostatic tissue, in normal human prostate epithelium, and in prostatic carcinomas. It binds specifically estramustine and estromustine, the cytotoxic metabolites of estramustine phosphate (Estracyt), a drug which is used in the treatment of prostatic carcinoma. In this study we have examined the presence of an estramustine-binding associated protein in a panel of human cell lines, representing the major histopathological types of lung cancer. A mouse (murine) monoclonal antiserum developed against rat estramustine-binding protein was used for immunohistochemical detection. Fast protein liquid chromatography was used for biochemical characterization. As judged from the immunohistochemical investigation, estramustine-binding protein was present in large amounts in five of six non-small cell carcinoma cell lines, while seven of eight small cell carcinoma cell lines were essentially negative. Fast protein liquid chromatography analyses of lysated cells from the lung cancer cell lines, incubated with [3H]estromustine, concurred with the results from the immunohistochemical stainings. These data strongly indicate a convincing connection between the immunoreactivity and ligand-binding properties of estramustine-binding protein in the cell lines examined. The presence of an estramustine-binding associated protein in human lung cancer cell lines has implications for further investigations into the biological relevance and the potential for eventual therapeutic applications.
Assuntos
Proteínas de Transporte/análise , Estramustina/metabolismo , Neoplasias Pulmonares/análise , Compostos de Mostarda Nitrogenada/metabolismo , Proteínas Secretadas pela Próstata , Anticorpos Monoclonais , Carcinoma Pulmonar de Células não Pequenas/análise , Carcinoma de Células Pequenas/análise , Cromatografia Líquida , Humanos , Imuno-Histoquímica , Células Tumorais CultivadasRESUMO
Cell lines derived from human squamous lung carcinoma release large amounts of a soluble glycoprotein into the culture media, having very high molecular weight (greater than 2 X 10(6] and mucin-like properties. A monoclonal antibody called 43-9F has been generated that recognizes a carbohydrate epitope on the glycoconjugate. The epitope is also present on a diverse set of smaller glycoproteins (Mr 50,000-200,000) distributed primarily on the surface of the squamous lung carcinoma cells. A sensitive assay using the 43-9F antibody in a dot blot procedure has been devised that is able to detect an amount of antigen less than that possessed by a single squamous lung carcinoma cell. This assay, and also conventional immunofluorescence and immunohistochemical assay procedures, have been used to screen different normal cells, normal tissues, cancer cells, and tumor biopsy specimens for the antigen. In the normal lung the 43-9F antigen is found only on cells of some of the seromucous glands. In the normal digestive system it is associated in certain organs only with a limited population of mucosal epithelial cells. Other organ systems lack any reactive cells. The cells of most human non-small cell lung carcinomas and their released glycoconjugates have large amounts of the 43-9F epitope, while small cell lung carcinomas and the glycoconjugates released by small cell lung cancer cells lack the epitope. The oligosaccharide recognized by the 43-9F antibody may therefore provide a useful marker to distinguish the different lung carcinomas and for investigating the different cells of origin of these tumors.
Assuntos
Anticorpos Monoclonais , Carcinoma Pulmonar de Células não Pequenas/análise , Glicoproteínas/análise , Neoplasias Pulmonares/análise , Especificidade de Anticorpos , Carcinoma de Células Escamosas/análise , Carcinoma de Células Escamosas/imunologia , Linhagem Celular , Epitopos/análise , Glicoproteínas/imunologia , Humanos , Técnicas de Imunoadsorção , Peso Molecular , Neuraminidase/metabolismo , Ensaio RadioliganteRESUMO
Membrane preparations from 36 human non-small cell lung cancers were examined for the expression of epidermal growth factor (EGF) receptors, and comparisons were made between tumor types and stage. Eight normal lung membrane preparations were also examined. The concentrations of EGF receptors were assessed by ligand binding studies using 125I-radiolabeled EGF. In two point saturation experiments using 0.3 nM 125I-EGF incubated with membranes from 35 primary lung tumors, a median of 18 fmol/mg of protein (range, 1.1 to 530) was found. This was significantly greater than binding to eight lung membranes: median, 6.1 fmol/mg of protein (range, 1.0 to 14.5) (P less than 0.02). Scatchard binding curves obtained in 21 of the 36 tumors and seven of eight of the normal lung preparations showed high and low affinity sites for EGF receptors on all but two tumor membranes. The dissociation constant of the high affinity sites was similar on tumor and normal lung membranes: range, 0.75 to 30 x 10(-10) M/liter. However, the tumors had a significantly higher concentration of these receptor sites: median, 30.4 fmol/mg of protein versus a median of 6.2 fmol/mg of protein on normal lung membranes (P less than 0.01). Likewise, there were significantly more low affinity sites on tumors: median, 237 fmol/mg compared to 60.2 fmol/mg on normal lung (P less than 0.01). No differences were found in this analysis between tumors of different histological subtypes or clinical stage. It is possible that the high level of expression of high affinity sites on lung tumors could be used as a target for ligand-complexed drugs.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/análise , Receptores ErbB/análise , Neoplasias Pulmonares/análise , Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB/genética , Amplificação de Genes , Humanos , Imuno-Histoquímica , CinéticaRESUMO
The neu protooncogene is a recently described transforming gene originally isolated from ethylnitrosourea-induced rat neuroblastomas. We have examined the expression of the neu gene in human non-small cell lung carcinomas using immunoprecipitation and immunohistochemistry. The neu protein product (p185neu) was present in eight of 22 non-small cell carcinoma cell lines derived from human lung tumors. Expression of p185neu was found in all histological subtypes of non-small cell carcinomas including large cell carcinomas, squamous cell carcinomas, and adenocarcinomas. Extension of these data to biopsy specimens of human lung tumors demonstrated that normal ciliated bronchial epithelium of the peripheral airways expressed p185neu at low levels. Neoplastic cells in four of 12 adenocarcinomas and three of five squamous cell carcinomas also expressed p185neu at levels higher than the normal ciliated bronchial epithelium. Together these studies indicate that p185neu expression is a common feature of human lung tumors.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/análise , Neoplasias Pulmonares/análise , Proteínas Proto-Oncogênicas/análise , Proto-Oncogenes , Biópsia , Amplificação de Genes , Humanos , Imuno-Histoquímica , Pulmão/análise , Proteínas Proto-Oncogênicas/imunologia , Receptor ErbB-2 , Células Tumorais CultivadasRESUMO
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
A Phase Ia clinical trial was undertaken to evaluate and compare murine monoclonal antibody KS1/4 and KS1/4-methotrexate immunoconjugate in patients with Stage IIIB or IV non-small cell carcinoma of the lung. Six patients received KS1/4 alone and five patients received KS1/4-methotrexate conjugate. The maximal total dose received per patient in both groups was 1661 mg. Mild to moderate side effects in both groups included fever, chills, anorexia, nausea, vomiting, diarrhea, anemia, and brief transaminasemia. One patient who received antibody alone had an apparent acute immune complex-mediated reaction. Ten of 11 patients had a human anti-mouse response. Posttreatment carcinoma biopsies revealed binding of monoclonal antibody KS1/4 and deposition of C3d and C4c complement fragments. Monoclonal antibody binding and complement deposition correlated with increasing doses of infused antibody. There was one possible clinical response.
Assuntos
Antígenos de Neoplasias/imunologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Moléculas de Adesão Celular , Imunoglobulina G/uso terapêutico , Imunotoxinas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Metotrexato/uso terapêutico , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/sangue , Anticorpos Monoclonais/uso terapêutico , Antígenos de Neoplasias/análise , Carcinoma Pulmonar de Células não Pequenas/análise , Carcinoma Pulmonar de Células não Pequenas/sangue , Ensaios Clínicos como Assunto , Avaliação de Medicamentos , Molécula de Adesão da Célula Epitelial , Humanos , Técnicas Imunoenzimáticas , Imunoglobulina G/efeitos adversos , Imunoglobulina G/análise , Imunotoxinas/efeitos adversos , Neoplasias Pulmonares/análise , Neoplasias Pulmonares/sangue , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-IdadeRESUMO
Twelve human small cell lung cancer (SCLC) cell lines and 6 non-SCLC cell lines were analysed with respect to expression of the c-myc, c-myb, and c-raf1 protooncogenes at the protein level. Analysis of p64c-myc protein expression in 12 SCLC cell lines resulted in the observation that it is present at high levels not only in cells with low, but also in those with moderate neuroendocrine differentiation. Neuroendocrine differentiation was based on parameters such as growth rate, colony formation, L-Dopa decarboxylase (DDC) activity, bombesin, and neurotensin described before. Surprisingly, in two cell lines with low neuroendocrine differentiation but without c-myc protein expression (SCLC-86M1 and NCI-H526) p75c-myb expression was observed which may therefore be able to substitute for the p64c-myc protein. Analysis of p74c-raf1 expression did not result in correlation with any growth or differentiation parameter since it was expressed at low levels in 11 out of 12 cases. We conclude that SCLC in vitro can be classified in three rather than two previously defined subclasses. In addition to the classic subclass with slow growth, high neuroendocrine differentiation, and absent or very low p64c-myc expression and the variant subclass with fast growth, absent to very low neuroendocrine differentiation, and high p64c-myc expression, we suggest a third subclass designated as transitional with moderate growth, moderate neuroendocrine differentiation, and high p64c-myc expression. Data on a small number of non-SCLC cell lines tested showed that high levels of p64c-myc correlate with high in vitro growth rates. This indicates that high p64c-myc levels may be associated with high proliferative activity, and lack of differentiation in lung cancer in general. The p74c-raf1 protein was found in all non-SCLC cell lines. Whether this classification of SCLC cell lines is applicable to SCLC in vivo remains to be determined.
Assuntos
Biomarcadores Tumorais/biossíntese , Carcinoma de Células Pequenas/análise , Neoplasias Pulmonares/análise , Proteínas Proto-Oncogênicas/biossíntese , Bombesina/metabolismo , Carcinoma Pulmonar de Células não Pequenas/análise , Carcinoma Pulmonar de Células não Pequenas/classificação , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Pequenas/classificação , Carcinoma de Células Pequenas/genética , Divisão Celular , Linhagem Celular , Dopa Descarboxilase/metabolismo , Humanos , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/genética , Neurotensina/metabolismo , Oncogenes , Proteínas Proto-Oncogênicas c-myb , Proteínas Proto-Oncogênicas c-myc , Proteínas Proto-Oncogênicas c-rafRESUMO
Small-cell lung cancer (SCLC), a chemotherapy-responsive disease, is characterized by neuroendocrine properties. In contrast, non-small-cell lung cancer (NSCLC) is at best moderately responsive to chemotherapy, and only 10% to 20% of cases demonstrate neuroendocrine properties. The present study is a retrospective analysis of the use of immunoperoxidase markers for neuron-specific enolase (NSE), Leu-7, and chromogranin A in NSCLC patients treated with chemotherapy. It was designed to determine if the presence of neuroendocrine markers predict for response to chemotherapy. The diagnostic slides and blocks were obtained on 52 NSCLC patients who were treated with chemotherapy (26 responders and 26 nonresponders). Immunoperoxidase studies were performed, and slides were scored without knowledge of the patient's response. Markers were positive in responders and nonresponders, respectively, as follows: NSE, 14 of 26 (54%) versus seven of 26 (27%), P = .04; Leu-7, 11 of 25 (44%) versus five of 26 (19%), P = .08; and chromogranin A, three of 26 (12%) versus 0 of 26 (0%), P = .71. Two markers were positive in 10 of 26 responders (38%) and 0 of 26 nonresponders (0%), P less than .01. Responders with two or more positive markers showed superior survival (median, 79 weeks) compared with responders with fewer than two positive markers (median, 51 weeks) and nonresponders (median, 27 weeks). These data suggest that the presence of neuroendocrine markers in NSCLC is associated with an increased likelihood of response to chemotherapy and may add to the standard parameters (performance status, weight loss) used to select patients for chemotherapy.
Assuntos
Antígenos de Diferenciação/análise , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/análise , Cromograninas/análise , Neoplasias Pulmonares/análise , Proteínas do Tecido Nervoso/análise , Fosfopiruvato Hidratase/análise , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Cromogranina A , Feminino , Humanos , Técnicas Imunoenzimáticas , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Previous studies have described significant elevations in the concentrations of secretory immunoglobulin A (sIgA) in bronchial washings obtained from cancerous lungs. To date, there have been no prospective investigations examining the predictive value of sIgA measurements in clinically relevant settings. Our goal was to determine if measurement of sIgA in bronchoalveolar lavage (BAL) at the time of bronchoscopic evaluation of potentially malignant lung nodules might prospectively predict the presence of cancer. We observed no significant increase in the sIgA obtained from eight BALs obtained from cancerous lungs as compared with BALs taken from these same patients' contralateral cancer-free lungs. We also saw no significant difference in BAL (sIgA) obtained from patients eventually found to have cancer (N = 8) as compared with those found to have noncancer diagnoses (N = 6). In light of these findings, we think it unlikely that measurement of sIgA will be clinically useful in the diagnosis of pulmonary malignant neoplasms.
Assuntos
Líquido da Lavagem Broncoalveolar/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Imunoglobulina A Secretora/análise , Neoplasias Pulmonares/imunologia , Idoso , Albuminas/análise , Líquido da Lavagem Broncoalveolar/análise , Carcinoma Pulmonar de Células não Pequenas/análise , Estudos de Avaliação como Assunto , Seguimentos , Humanos , Neoplasias Pulmonares/análise , Estadiamento de Neoplasias , Projetos Piloto , Prognóstico , Estudos Prospectivos , Sensibilidade e Especificidade , Método Simples-Cego , Nódulo Pulmonar Solitário/imunologia , Nódulo Pulmonar Solitário/metabolismoRESUMO
Bronchial carcinoids and small cell lung cancer (SCLC) are currently recognized as neuroendocrine (NE) neoplasms. However, non-SCLC (NSCLC) may also express NE properties. Paraffin-embedded sections of a comprehensive panel of 113 lung carcinomas were analyzed for the expression of three general markers common to all NE cells, namely, chromogranin A, Leu-7 and neuron-specific enolase (NSE), five specific NE secretory products, and four other tumor markers by immunohistochemistry using the sensitive avidin-biotinylated peroxidase technique. The authors were able to demonstrate the following: (1) most, but not all carcinoids and SCLCs expressed multiple NE markers in a high percentage of tumor cells; (2) up to a half of NSCLC cases contained small subpopulations of cells expressing NE in a high percentage of tumor cells; (2) up to half of NSCLC cases contained small subpopulations of cells expressing NE markers; and (3) occasional NSCLCs showed staining patterns indistinguishable from SCLC. Specifically, 7 of 77 NSCLCs expressed four or more NE markers. NE markers in NSCLCs were more commonly expressed in adenocarcinomas and large cell carcinomas and rarely in squamous cell carcinomas. For comparison, the mean number of NE markers expressed by all cases of NSCLC was 1.5, carcinoids 6.0, and SCLCs 3.8. Individual "marker counts" were not useful in categorizing lung tumors as carcinoids and SCLC versus NSCLC. Instead, 95% of the tumors were correctly classified, applying a statistical model created from staining indices of the three general NE markers (chromogranin A, Leu-7, NSE) and three other tumor markers (carcinoembryonic antigen, keratin, vimentin). Because NSCLCs with NE features might have different clinical characteristics than other NSCLCs, immunohistochemistry provides an effective manner to identify this biologically interesting subset of NSCLCs in routine paraffin sections.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias Pulmonares/análise , Adenocarcinoma/análise , Adenocarcinoma/patologia , Antígeno Carcinoembrionário/análise , Tumor Carcinoide/análise , Tumor Carcinoide/patologia , Carcinoma Pulmonar de Células não Pequenas/análise , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Pequenas/análise , Carcinoma de Células Pequenas/patologia , Cromogranina A , Cromograninas/análise , Humanos , Leucina/análise , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/patologia , Fosfopiruvato Hidratase/análiseRESUMO
Detailed studies of both cell lines and fresh specimens of SCLC and NSCLC have demonstrated that considerable heterogeneity exists within each tumour with respect to morphology and the expression of a range of biomarkers. While retrospective studies suggest that the presence or absence of some of of some of these markers may be of clinical importance, future trials of lung cancer should assess these markers to determine their prospective value in predicting response to therapy, survival and cure from lung cancer.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Pequenas , Neoplasias Pulmonares , Antígenos de Neoplasias/imunologia , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/análise , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Pequenas/análise , Carcinoma de Células Pequenas/genética , Carcinoma de Células Pequenas/imunologia , Carcinoma de Células Pequenas/patologia , Linhagem Celular , Regulação da Expressão Gênica , Humanos , Neoplasias Pulmonares/análise , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Oncogenes , Peptídeos/análise , Fatores de Crescimento TransformadoresRESUMO
Six new non-small-cell lung cancer (NSCLC) cell lines were established directly from human tissue or indirectly via nude mouse xenografts in serum-supplemented media with success rates of 8% and 13%, respectively. They comprised one adenocarcinoma (ADLC-5M2), two squamous cell carcinomas (EPLC-32M1, EPLC-65H), two large cell carcinomas (LCLC-97TM1, LCLC-103H), and one malignant biphasic mesothelioma (MSTO-211H). All cell lines grew adherent to culture vessels with population doubling times (PDT) of 16-40 h, formed colonies in soft agarose with efficiencies of 0.1%-5.1%, and all grew in athymic nude mice. Xenograft histologies appeared as follows: (a) undifferentiated carcinomas with feeble resemblance to the original tumors in the case of adenocarcinomas and squamous cell carcinomas; (b) large cell carcinoma with high resemblance to the original tumor; (c) an undifferentiated tumor with predominance of large epithelial cells and few fibrous cells in the case of mesothelioma. Human chorionic gonadotropin (HCG) was found by radioimmunoassay and high-affinity binding sites for epidermal growth factor (EGF) by radio-receptor assay in 4/4 cell lines. A very low activity of L-DOPA decarboxylase (DDC) was detectable only in the adenocarcinoma cell line. All cell lines overexpressed the c-myc protooncogene, and no gene rearrangement or amplification was observed. Chromosome analysis revealed modal chromosome numbers of 70-73 in ADLC-5M2, EPLC-32M1, EPLC-65H, and MSTO-211H. Cell lines derived from large cell carcinoma had modal values of 65 and 170 and a wider chromosome distribution than all other cell lines. A NSCLC specific chromosomal aberration has been undetectable until now. These cell lines may aid in elucidating the biology of NSCLC and its interrelationship to other lung tumors.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Células Tumorais Cultivadas/citologia , Animais , Carcinoma Pulmonar de Células não Pequenas/análise , Diferenciação Celular , Divisão Celular , Meios de Cultura , DNA de Neoplasias/análise , Dopa Descarboxilase/análise , Humanos , Cariotipagem , Neoplasias Pulmonares/análise , Masculino , Camundongos , Camundongos Nus , Transplante de Neoplasias , RNA Neoplásico/análise , Células Tumorais Cultivadas/análiseRESUMO
To demonstrate unbalanced distribution of subunits of human chorionic gonadotropin (hCG) in the lung and lung tumors and to clarify its significance in differentiation and carcinogenesis of the lung, immunohistochemistry was performed on human fetus, infant, and adult lungs, and endocrine and nonendocrine tumors of the lung. Tissues were immunostained for alpha-subunits and for beta-subunits of glycoprotein hormones (hCG, luteinizing hormone, follicle stimulating hormone, and thyroid stimulating hormone), serotonin, and gastrin-releasing peptide. Immunoreactive alpha-subunit was first identified in endocrine-like cells at the 39th gestational week, and was found in all infant lungs and two-thirds of adult lungs. The hCG beta-immunoreactive cells were extremely rare in an adult lung, and were not found in fetus or infant lungs. The alpha-subunit-containing cells were present in neuroepithelial bodies, tumorlets, carcinoid tumors, and small cell carcinomas of the lung (SCCL). There were occasionally alpha-subunit-containing cells in non-SCCL but one of the carcinomas also contained many serotonin-positive and gastrin-releasing peptide-positive cells in the same region. All alpha-subunit-immunoreactive cells lacked immunoreactivity for beta-subunits of glycoprotein hormones, except some for hCG beta in one carcinoid tumor. Immunoreactive cells for isolated hCG beta appeared much more frequently in non-SCCL than in SCCL. Most non-SCCL containing hCG beta-positive cells did not show alpha-subunit-immunoreactivity. Thus, immunohistochemical distribution of hCG-subunits was unbalanced and hCG-subunits may be expressed through an independent mechanism, commonly in the lung and lung tumors. The significance of isolated alpha-subunit is further discussed in light of multidirectional differentiation of lung neoplasms (14, 17).
Assuntos
Gonadotropina Coriônica/análise , Neoplasias Pulmonares/análise , Pulmão/análise , Adulto , Carcinoma Pulmonar de Células não Pequenas/análise , Carcinoma de Células Pequenas/análise , Gonadotropina Coriônica/imunologia , Gonadotropina Coriônica Humana Subunidade beta , Feto/análise , Peptídeo Liberador de Gastrina , Histocitoquímica , Humanos , Recém-Nascido , Fragmentos de Peptídeos/análise , Peptídeos/análise , Serotonina/análiseRESUMO
A total of 152 non-small cell lung cancers (NSCLC) were studied retrospectively to determine the relationship between epidermal growth factor receptor (EGF-R) status and the histological type, tumour size, nodal status and prognosis. EGF-R status was assessed on routinely embedded paraffin sections with an antibody to the cytoplasmic domain of the tumour (F4 antibody). EGF was demonstrated in all tumour types and every squamous and large cell carcinoma was positive for the antibody. Most tumours showed heterogeneity of staining. EGF expression was seen statistically more frequently in well differentiated tumours. Patients with 50% or more tumour cells showing positivity tended to have an improved survival but this result failed to reach statistical significance. There was no relationship between the size of the primary tumour or the lymph node status. Other cells, such as mucinous glands, bronchial epithelial cells and macrophages stained positively with the monoclonal antibody. EGF receptor status, with the antibodies presently available, adds little to help in either diagnosis or prognosis. Interpretation of data has to be guarded since the antibody was seen in some normal cells.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/análise , Receptores ErbB/análise , Neoplasias Pulmonares/análise , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Metástase Linfática , Estadiamento de NeoplasiasRESUMO
To evaluate the effect of CDDP on bronchial arterial infusion (CDDP-BAI) for non-small cell lung cancer platinum (Pt.) was quantified both in the plasma and the lung including parenchyma, primary tumor and lymph nodes. These data were analyzed in comparison with those of patients treated with systemic chemotherapy of CDDP (CDDP-SC). Concentration of Pt. in the plasma was measured in 8 patients treated with 100-190 mg of CDDP-BAI and 3 with 125-140 mg of CDDP-SC. In consequence, rapid decrease in value of free Pt. was noted just after the administration of CDDP with reduction by 50% resulting in 42.1 minutes after CDDP-BAI and 35.0 minutes after CDDP-SC, on average. These suggested that CDDP-BAI was effective not only in the lesion infused but also in the others possibly-disseminated. Surgical specimens of the lung were removed to measure concentration of Pt. 10-48 days after CDDP-BAI and 20-62 days after CDDP-SC. It measured 1.33 micrograms/g after BAI and 0.46 microgram/g after CDDP-SC in the tumor tissue on the average respectively, and 0.73 microgram/g after BAI and 0.47 microgram/g after SC in the normal lung parenchyma. On the other hand the Pt. concentration in hilar nodes measured higher in value than the tumor, when given by BAI. However, CDDP-SC almost equally caused Pt. concentration lower in value in the tumor, lymph nodes and normal lung parenchyma. As to disappearance of Pt. from the tumor during the preoperative period, there was no difference between two methods of administering CDDP. Based on these data, CDDP-BAI provided higher concentration of Pt. in the tumor, and it appeared correlative to high density of staining on angiograms. In referring to Shimosato's Classification, histological effects of CDDP-BAI varied in grade not only in each tumor but also in the area within a tumor. The present histological-chemical analysis showed a significant relationship between histological effects and Pt. concentration, especially on CDDP-BAI.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Pulmão/análise , Platina/análise , Idoso , Artérias Brônquicas , Carcinoma Pulmonar de Células não Pequenas/análise , Cisplatino/administração & dosagem , Feminino , Humanos , Infusões Intra-Arteriais , Neoplasias Pulmonares/análise , Masculino , Pessoa de Meia-Idade , Platina/sangueRESUMO
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
A continuous cell line, NSCLCN6L2, was established in vitro from a human bronchopulmonary epidermoid carcinoma and then cloned on agar gel and by selective media. The DNA content of each sub-population was compared with that of the parent line by flow cytometry. This study showed the heterogeneity of the NSCLCN6L2 line and the possibility of selection by cloning distinct ploidy sub-populations (group 1: diploid lines; group 2: hypotetraploid lines; group 3: a diploid and tetraploid line); it also allowed the time-course of the evolving lines to be followed. Correlation of these results with other properties of the different sub-populations will provide a better understanding of their biological behavior, particularly of their chemosensitivity.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/análise , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/análise , Carcinoma de Células Escamosas/genética , DNA de Neoplasias/análise , Citometria de Fluxo , Humanos , Neoplasias Pulmonares/análise , Neoplasias Pulmonares/genética , Ploidias , Células Tumorais Cultivadas/análise , Células Tumorais Cultivadas/patologiaRESUMO
Investigations regarding the prognostic value of DNA content (ploidy) and proliferative characteristics [percentage of cells in S-phase or S-phase fraction (SPF)] have been greatly facilitated by the application of flow cytometry (FCM) using nuclei isolated from paraffin-embedded tissue. We have applied this technique to tumor sections from patients presenting with non-small-cell lung cancer (NSCLC) in 1980 and 1981. From 67 out of 115 patients material of sufficient quantity and quality was obtained to perform DNA-FCM. A multivariate analysis including stage of disease (UICC), age, tumor histology and treatment modality was performed to examine the prognostic significance of DNA-FCM in NSCLC. Aneuploidy was found in 65% of cases. In our study, the DNA content was not related to histology, stage of disease or treatment modality, nor to the length of survival (log rank test P = 0.62). Calculation of SPF was possible in 49/67 cases. The SPF was not related to histology, stage of disease or treatment modality, but a significant prognostic value was found for survival; patients with a high SPF died earlier (P = 0.04) and this was especially true for squamous cell carcinoma (P = 0.02). This study demonstrates the prognostic importance of DNA-FCM-derived information in NSCLC using a multivariate analysis; however further prospective studies in larger patient populations are needed.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/análise , DNA de Neoplasias/análise , Neoplasias Pulmonares/análise , Adenocarcinoma/análise , Aneuploidia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/análise , Contagem de Células , Citometria de Fluxo , Humanos , Interfase , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Prognóstico , Fatores de TempoRESUMO
The epidermal growth factor receptor is homologous to the oncogene erb-beta and is the receptor for a class of tumour growth factors (TGF-alpha). The clinical correlations with its expression were studied in 77 non-small cell lung cancers (NSCLC). They were stained for epidermal growth factor receptor (EGFr) by means of an indirect immunoperoxidase technique using a monoclonal antibody against the receptor. Normal lung tissue and normal bronchus were stained for comparison. Cancer tissue showed significantly increased staining compared to normal lung (P less than 0.05). Staining for EGFr in 40 squamous carcinomas was significantly stronger than in 37 specimens of other types of NSCLC (P less than 0.05), and staining in stage three NSCLC was stronger than in stage 1 and 2 (P less than 0.05). These results suggest that the presence of a high intensity of staining for EGF receptor is associated with spread of human non-small cell lung cancer and this receptor may be a suitable target for therapy.