[Possibilities of differential diagnosis by specificity determination of cold agglutinins].
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Autoantibodies↗
Biomedical subjects
W Ebert
Publications and source records attributed to W Ebert.
Cathepsin B in tumors, normal tissue and isolated cells from the human lung.
Human lung tumors of different histologic cell types and adjacent normal lung parenchyma, purified lung parenchyma, purified lung macrophages and three human lung-derived cell lines were investigated in an attempt to identify tumor specific premature and mature cathepsin B species. By polyacrylamide gel electrophoresis and immunoblotting techniques with specific antibodies we detected mature cathepsin B forms with molecular masses of 31 kDa and 32 kDa in tissues. Reductive conditions revealed in these populations single and double chain 31/32 kDa forms. The latter were recognized by their heavy part, the 26/27 kDa molecule forms. Qualitative differences in the pattern of cathepsin B species between tumor and corresponding normal material or between different histologies of lung tumors were not found. However, tumor material is considerably richer in cathepsin B activity than normal material. Isolated alveolar macrophage populations and established cell lines showed the same cathepsin B pattern as tissues. All these cells released cathepsin B proforms of 44 to 46 kDa into the culture medium, indicating that the release of pro-cathepsin B cannot be considered a tumor-specific mechanism. The secreted proforms were sensitive to in vitro activation by pepsin.
Cathepsin B↗
Prognostic value of increased lung tumor tissue cathepsin B.
In the study of 65 matched pairs of lung tumor tissue and normal lung parenchyma, cathepsin B (CB) activity was found to be increased about 4.6-fold, when regarding median levels. CB activity was found to be insignificantly higher in adenocarcinoma compared to the other histologic cell types. CB levels did not correlate with tumor stages (TNM) nor with cell differentiation, while increased CB activity was related to shorter survival rates of the patients. It is concluded that lung tumor CB is of some prognostic value for the outcome of the malignant disease.
Adult↗
Charge polymorphism in human lung cell pro-cathepsin B.
Secreted pro-cathepsin B of HS-24 human lung-tumour cells, human alveolar macrophages and Wi-38 human lung-fibroblast cells was pre-purified by ion exchange chromatography and investigated by 2D gel electrophoresis. Four (Wi-38), six (HS-24) and ten (alveolar macrophages) polypeptides differing in charge, but with the same molecular mass of 45 kDa, were found. The isoelectrical points of these polypeptides ranged from 5.43 to 6.57. Deglycosylation reduced the mass (7 kDa) but did not change the charge pattern. This investigation established cell type-specific patterns of secreted pro-cathepsin B-forms, but only parts of these may be cell type-specific forms depending on differentiated expression of mRNA and post-translational modification.
Carcinoma, Squamous Cell↗
Does the assessment of serum markers in patients with lung cancer aid in the clinical decision making process?
This survey describes potential clinical applications of the tumour markers CYFRA 21-1, SCC antigen, NSE, and CEA in patients with lung cancer. Due to the rather low prevalence of bronchogenic carcinoma in the general public and the limited diagnostic accuracy, currently available tumour markers are unsuitable for the screening of asymptomatic individuals. All studies performed so far in patients with histologically confirmed NSCLC, agree that the best performance characteristics, in terms of sensitivity and specificity, were obtained with the CYFRA 21-1 test (sensitivity: 40-66%, specificity: 95% versus patients with benign pulmonary disorders) while NSE was found to be the marker of first choice in patients with SCLC (sensitivity: 77-85%). For diagnostic purpose, the value of tumour markers must be compared with the efficiency of standard clinical methods including imaging techniques and cytopathological examinations (detection rates: sputum cytology: 40-70%, biopsy at bronchoscopy in central tumours: 95-98%, biopsy at bronchoscopy + bronchial washing + thin needle aspiration in peripheral tumours: 85%). These figures show that the diagnostic yield of cytopathological examinations by far exceeds that of tumour markers. In addition, these investigations supply with histology and give informations on the T-stage (bronchoscopy). Tumour markers, however, may be used for diagnosis in advanced stages in which patients are very often not eligible for extensive investigations due to their performance status. In the differential diagnosis between NSCLC and SCLC a combination of CYFRA 21-1 and NSE was claimed to be helpful. It was demonstrated that 97% of patients could be correctly classified. NSE was shown to be useful to distinguish SCLC from malignant lymphoma, both the Hodgkin's (rate of false-positive elevations: 6.5%) and the non-Hodgkin's (rate of false positive elevations: 22.4%) types. By applying a cut-off point of NSE assays of 21.9 ng/ml corresponding to a 95% specificity versus the lymphoma group, SCLC is still indicated by elevated NSE levels with a sensitivity of 57.7%. Although a positive correlation of marker concentrations with increasing anatomical tumour extent could be demonstrated, the markers cannot be used for staging purposes due to a considerable overlap of marker levels between the individual stages. CYFRA 21-1 was shown to be unable to differentiate between operable (TNM I-IIIa) and inoperable (TNM IIIb/IV) NSCLC patients. The latter were identified with a detection rate of only 17% by the CYFRA 21-1 test (specificity 95% versus operable patients, cut-off point 20 ng/ml). Pretreatment-measured tumour markers, in particular CYFRA 21-1, were shown to provide prognostic information for the overall survival. The negative prognostic effect of CYFRA-21-1 was independent of classical prognostic markers such as performance status and tumour extent. There are several potential applications of serially-assessed tumour markers for disease monitoring of patients under therapy. In SCLC, increasing NSE levels within the remission phase were demonstrated to be strongly suggestive of tumour recurrence. This finding should give rise to further diagnostic procedures. NSE, however, was not able to differentiate between partial and complete remission since, in both cases, NSE levels dropped to the normal range; thus, NSE cannot replace clinical response evaluations. In NSCLC, it was found that curative surgery resulted in a significant drop of preoperatively elevated CYFRA 21-1 or SCC antigen levels down to the normal range. Although rising SCC antigen levels in the postoperative surveillance of patients with squamous cell carcinoma indicated very early tumour relapse, these results are of minor clinical utility due to the absence of curative therapy. Serial measurement of CYFRA 21-1 during chemotherapy in patients with inoperable squamous cell carcinoma has shown that there is a concordance of 74% between the course of the m
Biomarkers, Tumor↗
Monitoring of therapy in inoperable lung cancer patients by measurement of CYFRA 21-1, TPA- TP CEA, and NSE.
In a series of 381 consecutive patients with lung tumors and benign pulmonary diseases, we examined whether tumor markers CYFRA 21-1 (EIA, Boehringer, Mannheim), TPA-M (IRMA AB Sangtec Medical, Bromma, Sweden), TPS (IRMA, Beki Diagnostics AB, Bromma, Sweden), CEA and NSE (EIA, Roche, Basel) have the potential to contribute to clinical decision-making processes with respect to diagnosis and assessment of response to therapy. The sensitivity values of the marker tests in NSCLC (CYFRA 21-1: 44.4% > 3.9 ng/ml, TPA-M: 39.4% > 200 U/ml, TPS: 13.2% > 230 U/ml, CEA: 37.5% > 8.6 ng/ml), in SCLC (NSE: 61.9% > 14.0 ng/ml) and in pleural mesothelioma (CYFRA 21-1 and TPS: 36.4%) were found to be clearly inferior to the yield of standard cytopathological examinations (85-98%) when using the 95% specificity versus the group with benign pulmonary disease as cut-off values. Therefore, currently available tumor markers are of minor value in the primary diagnosis of lung tumors. After curative surgery (Ro) of NSCLC only CYFRA 21-1 levels dropped to the normal range within one week. The other markers simulated residual tumor mass by displaying elevated marker levels after surgery. During the monitoring of response to chemo-/radiotherapy the changes in marker levels were compared to the clinical assessment according to standard criteria of the WHO. The criteria defined for marker response were a 65% decrease for a partial response and a 40% increase of the marker levels for progressive disease. Concordant results were obtained in 59.4% of the cases for CYFRA 21-1 (TPA-M: 63.3%, TPS: 65.5%, CEA: 54.8%, NSE: 68.9%). Most discordant results were obtained in tumor remission due to an insufficient decrease in the markers. Progressive disease was most effectively indicated by CYFRA 21-1 in NSCLC 60%) and by NSE in SCLC (70.0%). It is concluded that increasing marker levels may contribute to clinical decision making, at least in helping to decide which patients should no longer treated by ineffective and toxic drugs.
Adult↗