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Lambert-Eaton myasthenic syndrome: Immunoglobulin G inhibition of Ca2+ flux in tumor cells correlates with disease severity
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19 patients with non-small cell lung cancer (enolase: 29-Z U/1, NSE: 7-l %) (p-zO.001) at the time of diagnosis. Mean enolase and NSE levels m patients with SCLC were seen to differ significantly according to the clinical stage. The results of those patients with ED differed from those of patients with LD (pxO.001). The results of the group of patients that achieved remission differed from that of patients during relapse (p
“Co-bleomycin scintigraphy for the staging of lung cancer Nieweg OE, Piers DA, Beekhuis H, Sluiter HJ, Van Der Wal AM, WoldringMG.DeportmentofSurgery. UniversilyHospital.Groningen. Cancer 1989;63: 1119-22. The value of Cobalt-57 bleomycin (“Co-BLM) scintigraphy in the detection of lymph node metastases in the hilum and mediastinum waS investigatedin 132patientswithperipherallylocatedlungcancer.Inone half of the patients with metastases, these were visualized. Specificity was 98%. These results were better than those obtained with chest radiography and conventional roentgen tomography. “Co-BLM scintigmphy is routinely used in the staging of patients with lung cancer, obviating the need for mediastinoscopy.
This was significantly greater than binding to eight lung membranes:median, 6.1 fmol/mg of protein (range, 1 .O to 14.5) (P < 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 lo-l0 M/liter. However, the tumors had a signiftcantly higher concentration of these receptor sites: median, 30.4 fmol/mg of protein versus a median of 6.2 fmollmg of protein on normal lung membranes (P < 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 < 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 ligandcomplexed drugs. Elevation of sialyl stage-specific moose embryonic antigen levels in pleural effusion in patients with adenocarcinoma of the lung. IguchiH,HaraN,MiyazakiK,OhtsuY,SonodaF,OhtaM.Deparhent ofBiochemisrry, Nadomd Kyushu Cancer Center, Minomi-ku, Fukwka 815. Cancer 1989;63:1327-30. Sialyl stage-specific mouse embryonic antigen (SSEA-1) levels were measured in pleural effusions obtained from patients with lung cancer and benign pulmonary disease, using a solid-phase immunoradiometric sandwich assay. The mean (- SEM) levels (unit/ml) of pleural fluid sialyl SSEA-1 were 3620 - 1419 in adenocarcinoma (n = 25). 123 30 in nonadenocarcinoma (n = 13) and 95 * 19 in benign pulmonary disease (n = 13). respectively. The positive rate was 64% in adenocarcinoma, 7.7% in nonadenocarcinoma, and 0% in benign pulmonary disease, respectively, when a cutoff level was defined as the mean +3 SD value (300 unit/ml) based on pleural fluid sialyl SSEA- 1 levels in benign pulmonary disease. There wasa significantpositive correlation between pleural fluid levels of sialyl SSEA-1 and those of carcinoembryonic antigen in adenocarcinoma patients (r = 0.8246, Pi 0.01). Pleural fluid sialyl SSEA-I levels correlated with cytologic findings in adenocarcinema patients. These observations suggest that sialyl SSEA-1 in pleural effusion is a useful marker to discriminate malignant from nonmalignant and adenocarcinoma from nonadenccarcinoma of the lung. ??
Neuron-specific enohw and tbymidine kinase as an aid to the diagnosis and treatment monitoring of small cell lung caacer. Fischbach W, Schwarz-Wallrauch C, Jany B. Medizinische Poliklinik, Universily of Wwzburg. D-8700 Wwzburg. Cancer 1989;63: 1143-9. The serum levels of newon specific enolase. (s-NSE) and thymidine kinase (s-n<) were studied in detail in patients with small cell lung cancer (SCLC) to evaluate as to whether their combined use may aid to diagnosis and follow-up of this particular tumor. Only s-NSE could differentiate between SCLC and non-small cell lung cancer (NSCLC) or benign pulmonary diseases (BPD) to some extent, pathologic serum concentrations occurring in 81%, 17%. and 0%. respectively. The comparable figures for s-TK were 62%. 24%. and 28%. respectively. Serum NSE decreased and increased parallelling tumor regression and progression, respectively, except when brain metastases were present. Alterations of s-TK, in contrast, did not usually mirror the coarse of disease.Duringinitialchemotherapy(CT)atransitoryincreaseofserum levels was observed for both NSE and TK. Monitoring, based on daily blood samples, showed comparable peaks only for s-TK during the following CTcycles, whereas s-NSE was within the normal range even when tumor mass was still present. Those subsequent s-TKpeaks under CTmaybedueto tumorcell IysisasaresultofCTindicatingtheefficacy of treatment by this way. Rapidly prolifemting tissues such as bone marrow or bowel mucosa, however, have also to be considered as possible sources of s-TK.
Characterization of epidermal growth factor receptor ia primary human non-small cell lung cancer. Veale D, Kerr N, Gibson GJ, Harris AL. Deparmwnr of Respirarory Medicine, Freeman Hospital, Newcasrle upon Tyne NE7 7DN. Cancer Res 1989;49:1313-7. 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 ConcentrationsofEGFreceptors wereassessedbyligandbindingstudies using ‘=I-radiolabeled EGF. In two point saturation experiments using 0.3 nM ‘=I-EGF incubated with membranes from 35 primary lung tumors,amedian of 18 fmol/mg ofprotein (range, 1 .l to530) was found.
Lambert-Eaton myasthenic syndrome: Immanoglobulin G iahibition of Ca” flux ia tumor cells correlates with disease severity. Lang B, Vincent A, Murray NMF, Newsom-Davis J. Deparrmenz of Neurological Science, Royal Free Hospital School of Medicine, Hampslead, L.ondon. Ann Neural 1989;25:265-71. We compared the effects of Lambert-Eaton myasthenic syndrome (LEMS) immunoglobulin G (IgG) obtained from patients with and without small-cell lung carcinoma (XIX) on voltage-gated (K+stimulated) ‘sCa2+ flux in cell lines derived from a human SCLC (MARIO) and from a ratphecchromccytoma (X12) and related these to electromyographic indexes of clinical severity. Control IgG was obtained from patients with other neurological disorders or healthy individuals. Inhibition of Ca2* flux by LEMS IgG was time and dose dependent. The flux was significantly reduced in MAR10 cells grown in either SCLC-LEMS IgG (0.38 nmol/l06 cells; p < 0.001) or nonSCLC-LEMS IgG (0.35 nmol/106 cells; p < 0.001). compared with that in MARIO cells grown in control IgG (0.7 nmol/lt? cells). Similar significant reductions were also observed in PC12 cells. The reduction in amplitude of the resting compound muscle action potential in the LEMS patients correlated positively (r = 0.70; p = 0.007) with the inhibition of Ca*+ flux in MARIO cells by their IgG. These results strongly support the view that IgG autoantibodies that can inhibit CaZ+ flux in SCLCcellsareresponsibleforthedisorderoftransmitterrelease at motor nerves in SCLC-associated LEMS.
19 patients with non-small cell lung cancer (enolase: 29-Z U/1, NSE: 7-l %) (p-zO.001) at the time of diagnosis. Mean enolase and NSE levels m patients with SCLC were seen to differ significantly according to the clinical stage. The results of those patients with ED differed from those of patients with LD (pxO.001). The results of the group of patients that achieved remission differed from that of patients during relapse (p
“Co-bleomycin scintigraphy for the staging of lung cancer Nieweg OE, Piers DA, Beekhuis H, Sluiter HJ, Van Der Wal AM, WoldringMG.DeportmentofSurgery. UniversilyHospital.Groningen. Cancer 1989;63: 1119-22. The value of Cobalt-57 bleomycin (“Co-BLM) scintigraphy in the detection of lymph node metastases in the hilum and mediastinum waS investigatedin 132patientswithperipherallylocatedlungcancer.Inone half of the patients with metastases, these were visualized. Specificity was 98%. These results were better than those obtained with chest radiography and conventional roentgen tomography. “Co-BLM scintigmphy is routinely used in the staging of patients with lung cancer, obviating the need for mediastinoscopy.
This was significantly greater than binding to eight lung membranes:median, 6.1 fmol/mg of protein (range, 1 .O to 14.5) (P < 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 lo-l0 M/liter. However, the tumors had a signiftcantly higher concentration of these receptor sites: median, 30.4 fmol/mg of protein versus a median of 6.2 fmollmg of protein on normal lung membranes (P < 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 < 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 ligandcomplexed drugs. Elevation of sialyl stage-specific moose embryonic antigen levels in pleural effusion in patients with adenocarcinoma of the lung. IguchiH,HaraN,MiyazakiK,OhtsuY,SonodaF,OhtaM.Deparhent ofBiochemisrry, Nadomd Kyushu Cancer Center, Minomi-ku, Fukwka 815. Cancer 1989;63:1327-30. Sialyl stage-specific mouse embryonic antigen (SSEA-1) levels were measured in pleural effusions obtained from patients with lung cancer and benign pulmonary disease, using a solid-phase immunoradiometric sandwich assay. The mean (- SEM) levels (unit/ml) of pleural fluid sialyl SSEA-1 were 3620 - 1419 in adenocarcinoma (n = 25). 123 30 in nonadenocarcinoma (n = 13) and 95 * 19 in benign pulmonary disease (n = 13). respectively. The positive rate was 64% in adenocarcinoma, 7.7% in nonadenocarcinoma, and 0% in benign pulmonary disease, respectively, when a cutoff level was defined as the mean +3 SD value (300 unit/ml) based on pleural fluid sialyl SSEA- 1 levels in benign pulmonary disease. There wasa significantpositive correlation between pleural fluid levels of sialyl SSEA-1 and those of carcinoembryonic antigen in adenocarcinoma patients (r = 0.8246, Pi 0.01). Pleural fluid sialyl SSEA-I levels correlated with cytologic findings in adenocarcinema patients. These observations suggest that sialyl SSEA-1 in pleural effusion is a useful marker to discriminate malignant from nonmalignant and adenocarcinoma from nonadenccarcinoma of the lung. ??
Neuron-specific enohw and tbymidine kinase as an aid to the diagnosis and treatment monitoring of small cell lung caacer. Fischbach W, Schwarz-Wallrauch C, Jany B. Medizinische Poliklinik, Universily of Wwzburg. D-8700 Wwzburg. Cancer 1989;63: 1143-9. The serum levels of newon specific enolase. (s-NSE) and thymidine kinase (s-n<) were studied in detail in patients with small cell lung cancer (SCLC) to evaluate as to whether their combined use may aid to diagnosis and follow-up of this particular tumor. Only s-NSE could differentiate between SCLC and non-small cell lung cancer (NSCLC) or benign pulmonary diseases (BPD) to some extent, pathologic serum concentrations occurring in 81%, 17%. and 0%. respectively. The comparable figures for s-TK were 62%. 24%. and 28%. respectively. Serum NSE decreased and increased parallelling tumor regression and progression, respectively, except when brain metastases were present. Alterations of s-TK, in contrast, did not usually mirror the coarse of disease.Duringinitialchemotherapy(CT)atransitoryincreaseofserum levels was observed for both NSE and TK. Monitoring, based on daily blood samples, showed comparable peaks only for s-TK during the following CTcycles, whereas s-NSE was within the normal range even when tumor mass was still present. Those subsequent s-TKpeaks under CTmaybedueto tumorcell IysisasaresultofCTindicatingtheefficacy of treatment by this way. Rapidly prolifemting tissues such as bone marrow or bowel mucosa, however, have also to be considered as possible sources of s-TK.
Characterization of epidermal growth factor receptor ia primary human non-small cell lung cancer. Veale D, Kerr N, Gibson GJ, Harris AL. Deparmwnr of Respirarory Medicine, Freeman Hospital, Newcasrle upon Tyne NE7 7DN. Cancer Res 1989;49:1313-7. 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 ConcentrationsofEGFreceptors wereassessedbyligandbindingstudies using ‘=I-radiolabeled EGF. In two point saturation experiments using 0.3 nM ‘=I-EGF incubated with membranes from 35 primary lung tumors,amedian of 18 fmol/mg ofprotein (range, 1 .l to530) was found.
Lambert-Eaton myasthenic syndrome: Immanoglobulin G iahibition of Ca” flux ia tumor cells correlates with disease severity. Lang B, Vincent A, Murray NMF, Newsom-Davis J. Deparrmenz of Neurological Science, Royal Free Hospital School of Medicine, Hampslead, L.ondon. Ann Neural 1989;25:265-71. We compared the effects of Lambert-Eaton myasthenic syndrome (LEMS) immunoglobulin G (IgG) obtained from patients with and without small-cell lung carcinoma (XIX) on voltage-gated (K+stimulated) ‘sCa2+ flux in cell lines derived from a human SCLC (MARIO) and from a ratphecchromccytoma (X12) and related these to electromyographic indexes of clinical severity. Control IgG was obtained from patients with other neurological disorders or healthy individuals. Inhibition of Ca2* flux by LEMS IgG was time and dose dependent. The flux was significantly reduced in MAR10 cells grown in either SCLC-LEMS IgG (0.38 nmol/l06 cells; p < 0.001) or nonSCLC-LEMS IgG (0.35 nmol/106 cells; p < 0.001). compared with that in MARIO cells grown in control IgG (0.7 nmol/lt? cells). Similar significant reductions were also observed in PC12 cells. The reduction in amplitude of the resting compound muscle action potential in the LEMS patients correlated positively (r = 0.70; p = 0.007) with the inhibition of Ca*+ flux in MARIO cells by their IgG. These results strongly support the view that IgG autoantibodies that can inhibit CaZ+ flux in SCLCcellsareresponsibleforthedisorderoftransmitterrelease at motor nerves in SCLC-associated LEMS.