Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present work we studied the levels of activities of dipeptidyl-peptidase I (or cathepsin C, DPP-I) and dipeptidyl-peptidase II (DPP-II) and examined their isoelectric focusing profiles in matched pairs of human squamous cell lung carcinoma (SQCLC) and the lung from surgically treated patients (n = 33). The mean specific activities of DPP-I and DPP-II were higher in SQCLC (Stages I and II) than in the lung, but only the activity of DPP-II in Stage I SQCLC was significantly higher compared to the lung. The activities of both enzymes were higher in the tumor than in the lung in 10 of 20 Stage I SQCLC patients, but only in 3 of 13 Stage II SQCLC patients. The specific activities of DPP-I and DPP-II in the lungs showed a good correlation while the correlation of both enzyme activities in SQCLCs was poor. We observed only a small and mutually comparable activation of DPP-I in extracts from SQCLCs and from the lungs by dithiothreitol. The isoelectric focusing profile of several DPP-II forms in SQCLCs and the lungs was similar and the single major DPP-II isoform revealed in the tumors and lungs showed a pIapp of 5.3-5.2. The isoelectric focusing profile of DPP-I showed multiple enzyme forms in SQCLCs (pIapp 6.3-4.5) as well as in the lungs (pIapp 6.4-4.8). In SQCLCs, as well as in the lungs, the activities of the DPP-I forms with pIapp values < or = 5.6 were shifted by neuraminidase treatment to the site of the major DPP-I isoform with pIapp of about 6.0 and the zymograms then showed an another DPP-I with pIapp of 5.7, which was less discernible in the lung. In some patients, the DPP-I forms with pIapp values < or = 5.6 from SQCLC retained a greater percentage of activity distribution than did the DPP-I pIapp-counterparts from the lung.
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PMID:Lysosomal dipeptidyl-peptidases I and II in human squamous cell lung carcinoma and lung parenchyma. 884 4

We investigated activities of the cysteine protease cathepsin B (CB; EC 3.4.22.1), the levels of reduced glutathione (GSH) and cysteine and the activity of gamma-glutamyltransferase (gamma-GT; EC 2.3.2.2) in squamous-cell lung carcinoma (SQCLC) and the lung parenchyma specimens from surgically treated patients. The basal CB activity, assayed in tissue extracts in the absence of exogenous activators, was significantly higher in SQCLC compared to the lung. The residual CB activity, remaining in tissue extracts after preincubation at 37 degrees C, was not any longer significantly different in SQCLC and the lungs. The inhibited CB activity, calculated as the difference between the basal and residual CB activities, was significantly higher in SQCLC compared to the lung. In the case of the cysteine protease cathepsin C (CC; EC 3.4.14.1), neither the basal nor the residual nor the inhibited CC activities in SQCLC and the lung were significantly different. Compared to CC, the powerfulness of endogenous cysteine protease inhibitors to inhibit CB was much higher in both SQCLC and the lung. The cysteine protease inhibitors from SQCLC and the lung which effectively inhibited CB could be related to the inhibitors with an apparent M(r) ranging from 10,000 to 30,000. Isoelectric focusing studies indicated significant differences in the progress of inhibition of the activity of CB isoforms in SQCLC and lung parenchyma extracts. The levels of both GSH and Cys were significantly higher in SQCLC compared to the lung and the level of GSH was significantly higher in Stage III tumors compared to Stage I tumors. The activity of gamma-GT was not significantly different in SQCLC and the lung but it was significantly higher in Stage I tumors compared to Stage III tumors and showed a significant negative correlation with GSH level in SQCLC. Dithiothreitol did not increase the basal activity of CB from SQCLC and the lung which indicates that reversibly oxidized forms of CB do not accumulate in the tumors and the lungs. The basal activity of CB from SQCLC and the lung was competitively inhibited by Cys. Moreover, increasing Cys concentrations had a modulatory effect on the basal activity of CB from SQCLC and the lung which was featured by Cys-induced inhibition of CB activity and by subsequent Cys-effected recovery of CB activity from its previous inhibition by Cys.
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PMID:Cathepsin B, thiols and cysteine protease inhibitors in squamous-cell lung cancer. 947 76

In this study we investigated the levels of two lysosomal cysteine protease proteins cathepsin B (CB) and cathepsin L (CL) and the levels of three cysteine protease inhibitor proteins stefin A (SFA), stefin B (SFB) and cystatin C (CNC) in squamous-cell lung carcinoma (SQCLC) and matched lung parenchyma specimens and examined the inhibition of CB and cathepsin C (CC) activities by endogenous inhibitors in extracts from SQCLC, lung adenocarcinoma (LAC) and lung parenchyma specimens. We found that Stage I SQCLCs contained significantly increased levels of CB protein, CB activity and SFA protein as compared to matched lungs. Neither the levels of CL protein nor the levels of SFB protein nor the levels of CNC protein in Stage I SQCLCs and the lungs were significantly different, but the levels of CB and CL proteins as well as the levels of SFA and SFB proteins showed significant positive correlation in SQCLCs. In SQCLCs as well as in the lungs the level of SFB protein was significantly higher than the level of SFA protein or the level of CNC protein. In the lungs the levels of SFA protein and CNC protein revealed a weak negative correlation trend. In extracts from SQCLCs the level of SFA protein showed a weak negative correlation with the residual CB activity (i.e. the activity remaining after extract preincubation) whereas in extracts from the lungs the level of CNC protein displayed a weak negative correlation trend with the residual CB activity and with the residual CC activity. We observed that SQCLCs and LACs contained not only a significantly increased activity of CB but also a significantly higher inhibitory potential against the activity of endogenous CB as compared to matched lungs. Leupeptin, a small inhibitor of CB, was capable to protect CB in lung carcinoma and lung parenchyma extracts from preincubation-induced inhibition, revealing an active-site directed and competitive nature of CB inhibition by endogenous cystatins. Ultrafiltration passaged protein preparations of nominal Mr < or = 30,000 obtained from extracts of SQCLCs inhibited significantly higher quantities of activity of purified bovine spleen CC than did such protein preparations from matched lungs. Reaction courses of purified bovine spleen CC that had been preincubated with such protein preparations resembled those of endogenous CC from SQCLC and lung extracts showing a slow steady-state approach. These observations and the relaxation kinetics of CC from SQCLC and lung extracts suggest that CC in the extracts may be complexed with some cystatins. In conclusion, our results indicate that quantitatively different combinations of cystatins are the major constituents of the inhibitory potential against CB and CC in SQCLCs and the lungs.
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PMID:Cysteine proteases and cysteine protease inhibitors in non-small cell lung cancer. 992 22