Cathepsin B, Plasminogenactivator-inhibitor (PAI-1) and Plasminogenactivator-receptor (uPAR) are Prognostic Factors for Patients with Non-small Cell Lung Cancer
To evaluate the possible role of cysteine proteases and serine proteases, as well as their respective inhibitors and receptors, as new prognostic factors in NSCLC, we examined, for the first time, 10 biological parameters related to three proteolytic systems within a homogeneous collective of 147 ca...
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| creator | WERLE, B KOTZSCH, M MAGDOLEN, V SCHMITT, M HARBECK, N LAH, T. T KOS, J GABRIJELCIC-GEIGER, D SPIESS, E SCHIRREN, J EBERT, W FIEHN, W LUTHER, T |
| description | To evaluate the possible role of cysteine proteases and serine proteases, as well as their respective inhibitors and receptors,
as new prognostic factors in NSCLC, we examined, for the first time, 10 biological parameters related to three proteolytic
systems within a homogeneous collective of 147 cases of NSCLC. Activities (cath B AT , cath B A7.5 ) and protein levels of cath B C , cath L C , uPA, PAI-1, uPAR [measured by three different assays uPAR (ADI), uPAR (HD13), uPAR (IIIF10)] and TF were measured in homogenates
of lung tumour tissue and corresponding non-malignant lung parenchyma. Total cath B activity (cath B AT ) and enzymatic activity of the fraction of cath B, which is stable and active at pH 7.5 (cath B A7.5 ), were determined by a fluorogenic assay using synthetic substrate Z-Arg-Arg-AMC. The concentrations of cath B C , cath L C , uPA, PAI-1, uPAR and TF were determined by ELISAs. uPAR was determined using three different ELISA formats. The median levels
of cath B AT (5.1-fold), cath B A7.5 (2.5-fold), cath B C , (8.5-fold), cath L C (6.6-fold), uPA (6.5-fold), PAI-1 (4.2-fold), uPAR (ADI) (2.2-fold), uPAR (HD13) (4.0-fold) and uPAR (IIIF10)(2.6-fold) were
higher in tumour tissue compared to the lung parenchyma. Cath B AT , cath B A7.5 and cath B C in primary tumours correlated with lymph node metastases. Regarding histologies, the concentration of PAI-1 seems to be associated
with the histological cell types of NSCLC. We found the highest values of PAI-1 in large cell carcinoma > SCC, AC > carcinoid
and lowest values in metastases of primary tumours of other organs. Only PAI-1 was significantly increased in poorly-differentiated
cells (G3) compared to well- and moderately- differentiated cells (G1/G2). PAI-1 significantly correlated with cath B AT and cath B A7.5 with uPAR (ADI), uPAR (HD13), uPAR (IIIF10) with uPA, and only weakly with TF, but not with cath B C and cath L C . Significant correlations with overall survival in the total population of NSCLC patients were observed in univariate analysis
for cath B AT , cath B C , PAI-1, uPAR (ADI), uPAR (HD13), and uPAR (IIIF10). Cath L C was not significantly associated with poor prognosis. Regarding the histological tumour type, only in patients with squamous
cell carcinomas did cath B A7.5 and PAI-1 remain significant prognostic factors. In multivariate survival analysis only two proteolytic factors, PAI-1 and
uPAR (III10F), stayed significant. In conclusion, among 10 biological parameters |
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as new prognostic factors in NSCLC, we examined, for the first time, 10 biological parameters related to three proteolytic
systems within a homogeneous collective of 147 cases of NSCLC. Activities (cath B AT , cath B A7.5 ) and protein levels of cath B C , cath L C , uPA, PAI-1, uPAR [measured by three different assays uPAR (ADI), uPAR (HD13), uPAR (IIIF10)] and TF were measured in homogenates
of lung tumour tissue and corresponding non-malignant lung parenchyma. Total cath B activity (cath B AT ) and enzymatic activity of the fraction of cath B, which is stable and active at pH 7.5 (cath B A7.5 ), were determined by a fluorogenic assay using synthetic substrate Z-Arg-Arg-AMC. The concentrations of cath B C , cath L C , uPA, PAI-1, uPAR and TF were determined by ELISAs. uPAR was determined using three different ELISA formats. The median levels
of cath B AT (5.1-fold), cath B A7.5 (2.5-fold), cath B C , (8.5-fold), cath L C (6.6-fold), uPA (6.5-fold), PAI-1 (4.2-fold), uPAR (ADI) (2.2-fold), uPAR (HD13) (4.0-fold) and uPAR (IIIF10)(2.6-fold) were
higher in tumour tissue compared to the lung parenchyma. Cath B AT , cath B A7.5 and cath B C in primary tumours correlated with lymph node metastases. Regarding histologies, the concentration of PAI-1 seems to be associated
with the histological cell types of NSCLC. We found the highest values of PAI-1 in large cell carcinoma > SCC, AC > carcinoid
and lowest values in metastases of primary tumours of other organs. Only PAI-1 was significantly increased in poorly-differentiated
cells (G3) compared to well- and moderately- differentiated cells (G1/G2). PAI-1 significantly correlated with cath B AT and cath B A7.5 with uPAR (ADI), uPAR (HD13), uPAR (IIIF10) with uPA, and only weakly with TF, but not with cath B C and cath L C . Significant correlations with overall survival in the total population of NSCLC patients were observed in univariate analysis
for cath B AT , cath B C , PAI-1, uPAR (ADI), uPAR (HD13), and uPAR (IIIF10). Cath L C was not significantly associated with poor prognosis. Regarding the histological tumour type, only in patients with squamous
cell carcinomas did cath B A7.5 and PAI-1 remain significant prognostic factors. In multivariate survival analysis only two proteolytic factors, PAI-1 and
uPAR (III10F), stayed significant. In conclusion, among 10 biological parameters evaluated within the same cohort of patients,
only PAI-1, uPAR (ADI), uPAR (HD13), uPAR (IIIF10), cath B AT and cath B C are prognostic factors for overall survival of NSCLC patients. Moreover, PAI-1 and uPAR (IIIF10) add independent prognostic
information with regard to established clinical and histomorphological factors in NSCLC.</description><identifier>ISSN: 0250-7005</identifier><identifier>EISSN: 1791-7530</identifier><identifier>PMID: 15736466</identifier><language>eng</language><publisher>Attiki: International Institute of Anticancer Research</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Analysis of Variance ; Biological and medical sciences ; Biomarkers, Tumor - metabolism ; Carcinoma, Non-Small-Cell Lung - enzymology ; Carcinoma, Non-Small-Cell Lung - pathology ; Cathepsin B - metabolism ; Female ; Humans ; Lung Neoplasms - enzymology ; Lung Neoplasms - pathology ; Male ; Medical sciences ; Middle Aged ; Neoplasm Staging ; Plasminogen Activator Inhibitor 1 - metabolism ; Pneumology ; Receptors, Cell Surface - metabolism ; Receptors, Urokinase Plasminogen Activator ; Survival Rate ; Tumors ; Tumors of the respiratory system and mediastinum</subject><ispartof>Anticancer research, 2004-11, Vol.24 (6), p.4147-4161</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16551944$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15736466$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>WERLE, B</creatorcontrib><creatorcontrib>KOTZSCH, M</creatorcontrib><creatorcontrib>MAGDOLEN, V</creatorcontrib><creatorcontrib>SCHMITT, M</creatorcontrib><creatorcontrib>HARBECK, N</creatorcontrib><creatorcontrib>LAH, T. T</creatorcontrib><creatorcontrib>KOS, J</creatorcontrib><creatorcontrib>GABRIJELCIC-GEIGER, D</creatorcontrib><creatorcontrib>SPIESS, E</creatorcontrib><creatorcontrib>SCHIRREN, J</creatorcontrib><creatorcontrib>EBERT, W</creatorcontrib><creatorcontrib>FIEHN, W</creatorcontrib><creatorcontrib>LUTHER, T</creatorcontrib><title>Cathepsin B, Plasminogenactivator-inhibitor (PAI-1) and Plasminogenactivator-receptor (uPAR) are Prognostic Factors for Patients with Non-small Cell Lung Cancer</title><title>Anticancer research</title><addtitle>Anticancer Res</addtitle><description>To evaluate the possible role of cysteine proteases and serine proteases, as well as their respective inhibitors and receptors,
as new prognostic factors in NSCLC, we examined, for the first time, 10 biological parameters related to three proteolytic
systems within a homogeneous collective of 147 cases of NSCLC. Activities (cath B AT , cath B A7.5 ) and protein levels of cath B C , cath L C , uPA, PAI-1, uPAR [measured by three different assays uPAR (ADI), uPAR (HD13), uPAR (IIIF10)] and TF were measured in homogenates
of lung tumour tissue and corresponding non-malignant lung parenchyma. Total cath B activity (cath B AT ) and enzymatic activity of the fraction of cath B, which is stable and active at pH 7.5 (cath B A7.5 ), were determined by a fluorogenic assay using synthetic substrate Z-Arg-Arg-AMC. The concentrations of cath B C , cath L C , uPA, PAI-1, uPAR and TF were determined by ELISAs. uPAR was determined using three different ELISA formats. The median levels
of cath B AT (5.1-fold), cath B A7.5 (2.5-fold), cath B C , (8.5-fold), cath L C (6.6-fold), uPA (6.5-fold), PAI-1 (4.2-fold), uPAR (ADI) (2.2-fold), uPAR (HD13) (4.0-fold) and uPAR (IIIF10)(2.6-fold) were
higher in tumour tissue compared to the lung parenchyma. Cath B AT , cath B A7.5 and cath B C in primary tumours correlated with lymph node metastases. Regarding histologies, the concentration of PAI-1 seems to be associated
with the histological cell types of NSCLC. We found the highest values of PAI-1 in large cell carcinoma > SCC, AC > carcinoid
and lowest values in metastases of primary tumours of other organs. Only PAI-1 was significantly increased in poorly-differentiated
cells (G3) compared to well- and moderately- differentiated cells (G1/G2). PAI-1 significantly correlated with cath B AT and cath B A7.5 with uPAR (ADI), uPAR (HD13), uPAR (IIIF10) with uPA, and only weakly with TF, but not with cath B C and cath L C . Significant correlations with overall survival in the total population of NSCLC patients were observed in univariate analysis
for cath B AT , cath B C , PAI-1, uPAR (ADI), uPAR (HD13), and uPAR (IIIF10). Cath L C was not significantly associated with poor prognosis. Regarding the histological tumour type, only in patients with squamous
cell carcinomas did cath B A7.5 and PAI-1 remain significant prognostic factors. In multivariate survival analysis only two proteolytic factors, PAI-1 and
uPAR (III10F), stayed significant. In conclusion, among 10 biological parameters evaluated within the same cohort of patients,
only PAI-1, uPAR (ADI), uPAR (HD13), uPAR (IIIF10), cath B AT and cath B C are prognostic factors for overall survival of NSCLC patients. Moreover, PAI-1 and uPAR (IIIF10) add independent prognostic
information with regard to established clinical and histomorphological factors in NSCLC.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analysis of Variance</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Carcinoma, Non-Small-Cell Lung - enzymology</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Cathepsin B - metabolism</subject><subject>Female</subject><subject>Humans</subject><subject>Lung Neoplasms - enzymology</subject><subject>Lung Neoplasms - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>Plasminogen Activator Inhibitor 1 - metabolism</subject><subject>Pneumology</subject><subject>Receptors, Cell Surface - metabolism</subject><subject>Receptors, Urokinase Plasminogen Activator</subject><subject>Survival Rate</subject><subject>Tumors</subject><subject>Tumors of the respiratory system and mediastinum</subject><issn>0250-7005</issn><issn>1791-7530</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0EtLxDAQAOAiiq6PvyC5KAoW0jyb41p8waJF9Fym3XQbadM1SRX_jT_VoCtevMwMw8cwM1vJLJMqSyWneDuZYcJxKjHme8m-9y8YC6FyupvsZVxSwYSYJZ8FhE6vvbHo8gKVPfjB2HGlLTTBvEEYXWpsZ2oTK3RWzu_S7ByBXf5PnW70-ltO5fwxQqdR6caVHX0wDbqOcnQetVGUEIy2waN3Ezp0P9rUD9D3qNAxLCa7QgXYRrvDZKeF3uujTT5Inq-vnorbdPFwc1fMF2lHhAopEVLnhNe51Eph0rI6p5THbi1aokieY6IUZLRlmshaMeDtsqm5bJYcY5wDPUhOf-au3fg6aR-qwfgmLgNWj5OvhCScqJxFeLyBUz3oZbV2ZgD3Uf3-NIKTDQDfQN-6eIfxf05wninG_lxnVt27cbr6_kAcSytwhFWiYhmT9AskOo4f</recordid><startdate>20041101</startdate><enddate>20041101</enddate><creator>WERLE, B</creator><creator>KOTZSCH, M</creator><creator>MAGDOLEN, V</creator><creator>SCHMITT, M</creator><creator>HARBECK, N</creator><creator>LAH, T. T</creator><creator>KOS, J</creator><creator>GABRIJELCIC-GEIGER, D</creator><creator>SPIESS, E</creator><creator>SCHIRREN, J</creator><creator>EBERT, W</creator><creator>FIEHN, W</creator><creator>LUTHER, T</creator><general>International Institute of Anticancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20041101</creationdate><title>Cathepsin B, Plasminogenactivator-inhibitor (PAI-1) and Plasminogenactivator-receptor (uPAR) are Prognostic Factors for Patients with Non-small Cell Lung Cancer</title><author>WERLE, B ; KOTZSCH, M ; MAGDOLEN, V ; SCHMITT, M ; HARBECK, N ; LAH, T. T ; KOS, J ; GABRIJELCIC-GEIGER, D ; SPIESS, E ; SCHIRREN, J ; EBERT, W ; FIEHN, W ; LUTHER, T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h269t-267e825b87e9902f4b8335267b6f292880299a13f4e27b94a5fdcb57cd50008a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Analysis of Variance</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Carcinoma, Non-Small-Cell Lung - enzymology</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Cathepsin B - metabolism</topic><topic>Female</topic><topic>Humans</topic><topic>Lung Neoplasms - enzymology</topic><topic>Lung Neoplasms - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neoplasm Staging</topic><topic>Plasminogen Activator Inhibitor 1 - metabolism</topic><topic>Pneumology</topic><topic>Receptors, Cell Surface - metabolism</topic><topic>Receptors, Urokinase Plasminogen Activator</topic><topic>Survival Rate</topic><topic>Tumors</topic><topic>Tumors of the respiratory system and mediastinum</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>WERLE, B</creatorcontrib><creatorcontrib>KOTZSCH, M</creatorcontrib><creatorcontrib>MAGDOLEN, V</creatorcontrib><creatorcontrib>SCHMITT, M</creatorcontrib><creatorcontrib>HARBECK, N</creatorcontrib><creatorcontrib>LAH, T. T</creatorcontrib><creatorcontrib>KOS, J</creatorcontrib><creatorcontrib>GABRIJELCIC-GEIGER, D</creatorcontrib><creatorcontrib>SPIESS, E</creatorcontrib><creatorcontrib>SCHIRREN, J</creatorcontrib><creatorcontrib>EBERT, W</creatorcontrib><creatorcontrib>FIEHN, W</creatorcontrib><creatorcontrib>LUTHER, T</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Anticancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>WERLE, B</au><au>KOTZSCH, M</au><au>MAGDOLEN, V</au><au>SCHMITT, M</au><au>HARBECK, N</au><au>LAH, T. T</au><au>KOS, J</au><au>GABRIJELCIC-GEIGER, D</au><au>SPIESS, E</au><au>SCHIRREN, J</au><au>EBERT, W</au><au>FIEHN, W</au><au>LUTHER, T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cathepsin B, Plasminogenactivator-inhibitor (PAI-1) and Plasminogenactivator-receptor (uPAR) are Prognostic Factors for Patients with Non-small Cell Lung Cancer</atitle><jtitle>Anticancer research</jtitle><addtitle>Anticancer Res</addtitle><date>2004-11-01</date><risdate>2004</risdate><volume>24</volume><issue>6</issue><spage>4147</spage><epage>4161</epage><pages>4147-4161</pages><issn>0250-7005</issn><eissn>1791-7530</eissn><abstract>To evaluate the possible role of cysteine proteases and serine proteases, as well as their respective inhibitors and receptors,
as new prognostic factors in NSCLC, we examined, for the first time, 10 biological parameters related to three proteolytic
systems within a homogeneous collective of 147 cases of NSCLC. Activities (cath B AT , cath B A7.5 ) and protein levels of cath B C , cath L C , uPA, PAI-1, uPAR [measured by three different assays uPAR (ADI), uPAR (HD13), uPAR (IIIF10)] and TF were measured in homogenates
of lung tumour tissue and corresponding non-malignant lung parenchyma. Total cath B activity (cath B AT ) and enzymatic activity of the fraction of cath B, which is stable and active at pH 7.5 (cath B A7.5 ), were determined by a fluorogenic assay using synthetic substrate Z-Arg-Arg-AMC. The concentrations of cath B C , cath L C , uPA, PAI-1, uPAR and TF were determined by ELISAs. uPAR was determined using three different ELISA formats. The median levels
of cath B AT (5.1-fold), cath B A7.5 (2.5-fold), cath B C , (8.5-fold), cath L C (6.6-fold), uPA (6.5-fold), PAI-1 (4.2-fold), uPAR (ADI) (2.2-fold), uPAR (HD13) (4.0-fold) and uPAR (IIIF10)(2.6-fold) were
higher in tumour tissue compared to the lung parenchyma. Cath B AT , cath B A7.5 and cath B C in primary tumours correlated with lymph node metastases. Regarding histologies, the concentration of PAI-1 seems to be associated
with the histological cell types of NSCLC. We found the highest values of PAI-1 in large cell carcinoma > SCC, AC > carcinoid
and lowest values in metastases of primary tumours of other organs. Only PAI-1 was significantly increased in poorly-differentiated
cells (G3) compared to well- and moderately- differentiated cells (G1/G2). PAI-1 significantly correlated with cath B AT and cath B A7.5 with uPAR (ADI), uPAR (HD13), uPAR (IIIF10) with uPA, and only weakly with TF, but not with cath B C and cath L C . Significant correlations with overall survival in the total population of NSCLC patients were observed in univariate analysis
for cath B AT , cath B C , PAI-1, uPAR (ADI), uPAR (HD13), and uPAR (IIIF10). Cath L C was not significantly associated with poor prognosis. Regarding the histological tumour type, only in patients with squamous
cell carcinomas did cath B A7.5 and PAI-1 remain significant prognostic factors. In multivariate survival analysis only two proteolytic factors, PAI-1 and
uPAR (III10F), stayed significant. In conclusion, among 10 biological parameters evaluated within the same cohort of patients,
only PAI-1, uPAR (ADI), uPAR (HD13), uPAR (IIIF10), cath B AT and cath B C are prognostic factors for overall survival of NSCLC patients. Moreover, PAI-1 and uPAR (IIIF10) add independent prognostic
information with regard to established clinical and histomorphological factors in NSCLC.</abstract><cop>Attiki</cop><pub>International Institute of Anticancer Research</pub><pmid>15736466</pmid><tpages>15</tpages></addata></record> |
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| subjects | Adolescent Adult Aged Aged, 80 and over Analysis of Variance Biological and medical sciences Biomarkers, Tumor - metabolism Carcinoma, Non-Small-Cell Lung - enzymology Carcinoma, Non-Small-Cell Lung - pathology Cathepsin B - metabolism Female Humans Lung Neoplasms - enzymology Lung Neoplasms - pathology Male Medical sciences Middle Aged Neoplasm Staging Plasminogen Activator Inhibitor 1 - metabolism Pneumology Receptors, Cell Surface - metabolism Receptors, Urokinase Plasminogen Activator Survival Rate Tumors Tumors of the respiratory system and mediastinum |
| title | Cathepsin B, Plasminogenactivator-inhibitor (PAI-1) and Plasminogenactivator-receptor (uPAR) are Prognostic Factors for Patients with Non-small Cell Lung Cancer |
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