Contribution of CXCR4 and SMAD4 in predicting disease progression pattern and benefit from adjuvant chemotherapy in resected pancreatic adenocarcinoma
Prognosis of patients with pancreatic adenocarcinoma is poor. Many prognostic biomarkers have been tested, but most studies included heterogeneous patients. We aimed to investigate the prognostic and/or predictive values of four relevant biomarkers in a multicentric cohort of patients. A total of 47...
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| Veröffentlicht in: | Annals of oncology 2012-09, Vol.23 (9), p.2327-2335 |
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| creator | Bachet, J.B. Maréchal, R. Demetter, P. Bonnetain, F. Couvelard, A. Svrcek, M. Bardier-Dupas, A. Hammel, P. Sauvanet, A. Louvet, C. Paye, F. Rougier, P. Penna, C. Vaillant, J.C. André, T. Closset, J. Salmon, I. Emile, J.F. Van Laethem, J.L. |
| description | Prognosis of patients with pancreatic adenocarcinoma is poor. Many prognostic biomarkers have been tested, but most studies included heterogeneous patients. We aimed to investigate the prognostic and/or predictive values of four relevant biomarkers in a multicentric cohort of patients.
A total of 471 patients who had resected pancreatic adenocarcinoma were included. Using tissue microarray, we assessed the relationship of biomarker expressions with the overall survival: Smad4, type II TGF-β receptor, CXCR4, and LKB1.
High CXCR4 expression was found to be the only independent negative prognostic biomarker [hazard ratio (HR)=1.74; P |
| doi_str_mv | 10.1093/annonc/mdr617 |
| format | Article |
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A total of 471 patients who had resected pancreatic adenocarcinoma were included. Using tissue microarray, we assessed the relationship of biomarker expressions with the overall survival: Smad4, type II TGF-β receptor, CXCR4, and LKB1.
High CXCR4 expression was found to be the only independent negative prognostic biomarker [hazard ratio (HR)=1.74; P<0.0001]. In addition, it was significantly associated with a distant relapse pattern (HR=2.19; P<0.0001) and was the strongest prognostic factor compared with clinicopathological factors. In patients who did not received adjuvant treatment, there was a trend toward decrease in the overall survival for negative Smad4 expression. Loss of Smad4 expression was not correlated with recurrence pattern but was shown to be predictive for adjuvant chemotherapy (CT) benefit (HR=0.59; P=0.002).
CXCR4 is a strong independent prognostic biomarker associated with distant metastatic recurrence and appears as an attractive target to be evaluated in pancreatic adenocarcinoma. Negative SMAD4 expression should be considered as a potential predictor of adjuvant CT benefit.</description><identifier>ISSN: 0923-7534</identifier><identifier>EISSN: 1569-8041</identifier><identifier>DOI: 10.1093/annonc/mdr617</identifier><identifier>PMID: 22377565</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Adenocarcinoma - metabolism ; Adenocarcinoma - mortality ; Adenocarcinoma - secondary ; Adenocarcinoma - therapy ; adjuvant chemotherapy ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic agents ; Biological and medical sciences ; Biomarkers, Tumor - metabolism ; Chemotherapy, Adjuvant ; CXCR4 ; Disease Progression ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Humans ; Kaplan-Meier Estimate ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; LKB1 ; Lymphatic Metastasis ; Male ; Medical sciences ; Middle Aged ; Multivariate Analysis ; pancreatic adenocarcinoma ; Pancreatic Neoplasms - metabolism ; Pancreatic Neoplasms - mortality ; Pancreatic Neoplasms - pathology ; Pancreatic Neoplasms - therapy ; Pharmacology. Drug treatments ; Proportional Hazards Models ; Prospective Studies ; Receptors, CXCR4 - metabolism ; Smad4 ; Smad4 Protein - metabolism ; Treatment Outcome ; Tumors ; type II TGF-β receptor</subject><ispartof>Annals of oncology, 2012-09, Vol.23 (9), p.2327-2335</ispartof><rights>2012 European Society for Medical Oncology</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c371t-587b1ced1f9c53b8d6411515983b49f6ee42ef89a7ea2aaddd8fc3234451a0253</citedby><cites>FETCH-LOGICAL-c371t-587b1ced1f9c53b8d6411515983b49f6ee42ef89a7ea2aaddd8fc3234451a0253</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26294782$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22377565$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bachet, J.B.</creatorcontrib><creatorcontrib>Maréchal, R.</creatorcontrib><creatorcontrib>Demetter, P.</creatorcontrib><creatorcontrib>Bonnetain, F.</creatorcontrib><creatorcontrib>Couvelard, A.</creatorcontrib><creatorcontrib>Svrcek, M.</creatorcontrib><creatorcontrib>Bardier-Dupas, A.</creatorcontrib><creatorcontrib>Hammel, P.</creatorcontrib><creatorcontrib>Sauvanet, A.</creatorcontrib><creatorcontrib>Louvet, C.</creatorcontrib><creatorcontrib>Paye, F.</creatorcontrib><creatorcontrib>Rougier, P.</creatorcontrib><creatorcontrib>Penna, C.</creatorcontrib><creatorcontrib>Vaillant, J.C.</creatorcontrib><creatorcontrib>André, T.</creatorcontrib><creatorcontrib>Closset, J.</creatorcontrib><creatorcontrib>Salmon, I.</creatorcontrib><creatorcontrib>Emile, J.F.</creatorcontrib><creatorcontrib>Van Laethem, J.L.</creatorcontrib><title>Contribution of CXCR4 and SMAD4 in predicting disease progression pattern and benefit from adjuvant chemotherapy in resected pancreatic adenocarcinoma</title><title>Annals of oncology</title><addtitle>Ann Oncol</addtitle><description>Prognosis of patients with pancreatic adenocarcinoma is poor. Many prognostic biomarkers have been tested, but most studies included heterogeneous patients. We aimed to investigate the prognostic and/or predictive values of four relevant biomarkers in a multicentric cohort of patients.
A total of 471 patients who had resected pancreatic adenocarcinoma were included. Using tissue microarray, we assessed the relationship of biomarker expressions with the overall survival: Smad4, type II TGF-β receptor, CXCR4, and LKB1.
High CXCR4 expression was found to be the only independent negative prognostic biomarker [hazard ratio (HR)=1.74; P<0.0001]. In addition, it was significantly associated with a distant relapse pattern (HR=2.19; P<0.0001) and was the strongest prognostic factor compared with clinicopathological factors. In patients who did not received adjuvant treatment, there was a trend toward decrease in the overall survival for negative Smad4 expression. Loss of Smad4 expression was not correlated with recurrence pattern but was shown to be predictive for adjuvant chemotherapy (CT) benefit (HR=0.59; P=0.002).
CXCR4 is a strong independent prognostic biomarker associated with distant metastatic recurrence and appears as an attractive target to be evaluated in pancreatic adenocarcinoma. Negative SMAD4 expression should be considered as a potential predictor of adjuvant CT benefit.</description><subject>Adenocarcinoma - metabolism</subject><subject>Adenocarcinoma - mortality</subject><subject>Adenocarcinoma - secondary</subject><subject>Adenocarcinoma - therapy</subject><subject>adjuvant chemotherapy</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Chemotherapy, Adjuvant</subject><subject>CXCR4</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>LKB1</subject><subject>Lymphatic Metastasis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Multivariate Analysis</subject><subject>pancreatic adenocarcinoma</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Pancreatic Neoplasms - mortality</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Pancreatic Neoplasms - therapy</subject><subject>Pharmacology. Drug treatments</subject><subject>Proportional Hazards Models</subject><subject>Prospective Studies</subject><subject>Receptors, CXCR4 - metabolism</subject><subject>Smad4</subject><subject>Smad4 Protein - metabolism</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><subject>type II TGF-β receptor</subject><issn>0923-7534</issn><issn>1569-8041</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU9v1DAQxS0EotvCkSvyBYlLqB3bSXystlCQipD4I3GLJva4dbWxF9up1C_C58VLFjhxGmn0e08z7xHygrM3nGlxDiHEYM5nmzrePyIbrjrdDEzyx2TDdCuaXgl5Qk5zvmOMdbrVT8lJ24q-V53akJ_bGEry01J8DDQ6uv2-_SwpBEu_fLy4lNQHuk9ovSk-3FDrM0LGuoo3CXM-iPZQCqbwWzNhQOcLdSnOFOzdcg-hUHOLcyy3mGD_cDCsSjQFbZUGkxCKNxXGEA0k40Oc4Rl54mCX8flxnpFv795-3b5vrj9dfdheXDdG9Lw0augnbtByp40S02A7ybniSg9iktp1iLJFN2joEVoAa-3gjGiFlIoDa5U4I69X3_rQjwVzGWefDe52EDAueeRMKM6kYkNFmxU1Keac0I375GdIDxUaD1WMaxXjWkXlXx6tl2lG-5f-k30FXh0ByAZ2LtUwfP7Hda2W_dBWrl85rEHce0xjNh5DfdunGuNoo__PCb8A7EuqeQ</recordid><startdate>20120901</startdate><enddate>20120901</enddate><creator>Bachet, J.B.</creator><creator>Maréchal, R.</creator><creator>Demetter, P.</creator><creator>Bonnetain, F.</creator><creator>Couvelard, A.</creator><creator>Svrcek, M.</creator><creator>Bardier-Dupas, A.</creator><creator>Hammel, P.</creator><creator>Sauvanet, A.</creator><creator>Louvet, C.</creator><creator>Paye, F.</creator><creator>Rougier, P.</creator><creator>Penna, C.</creator><creator>Vaillant, J.C.</creator><creator>André, T.</creator><creator>Closset, J.</creator><creator>Salmon, I.</creator><creator>Emile, J.F.</creator><creator>Van Laethem, J.L.</creator><general>Elsevier Ltd</general><general>Oxford University Press</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20120901</creationdate><title>Contribution of CXCR4 and SMAD4 in predicting disease progression pattern and benefit from adjuvant chemotherapy in resected pancreatic adenocarcinoma</title><author>Bachet, J.B. ; Maréchal, R. ; Demetter, P. ; Bonnetain, F. ; Couvelard, A. ; Svrcek, M. ; Bardier-Dupas, A. ; Hammel, P. ; Sauvanet, A. ; Louvet, C. ; Paye, F. ; Rougier, P. ; Penna, C. ; Vaillant, J.C. ; André, T. ; Closset, J. ; Salmon, I. ; Emile, J.F. ; Van Laethem, J.L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c371t-587b1ced1f9c53b8d6411515983b49f6ee42ef89a7ea2aaddd8fc3234451a0253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adenocarcinoma - metabolism</topic><topic>Adenocarcinoma - mortality</topic><topic>Adenocarcinoma - secondary</topic><topic>Adenocarcinoma - therapy</topic><topic>adjuvant chemotherapy</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Chemotherapy, Adjuvant</topic><topic>CXCR4</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Humans</topic><topic>Kaplan-Meier Estimate</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>LKB1</topic><topic>Lymphatic Metastasis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Multivariate Analysis</topic><topic>pancreatic adenocarcinoma</topic><topic>Pancreatic Neoplasms - metabolism</topic><topic>Pancreatic Neoplasms - mortality</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Pancreatic Neoplasms - therapy</topic><topic>Pharmacology. Drug treatments</topic><topic>Proportional Hazards Models</topic><topic>Prospective Studies</topic><topic>Receptors, CXCR4 - metabolism</topic><topic>Smad4</topic><topic>Smad4 Protein - metabolism</topic><topic>Treatment Outcome</topic><topic>Tumors</topic><topic>type II TGF-β receptor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bachet, J.B.</creatorcontrib><creatorcontrib>Maréchal, R.</creatorcontrib><creatorcontrib>Demetter, P.</creatorcontrib><creatorcontrib>Bonnetain, F.</creatorcontrib><creatorcontrib>Couvelard, A.</creatorcontrib><creatorcontrib>Svrcek, M.</creatorcontrib><creatorcontrib>Bardier-Dupas, A.</creatorcontrib><creatorcontrib>Hammel, P.</creatorcontrib><creatorcontrib>Sauvanet, A.</creatorcontrib><creatorcontrib>Louvet, C.</creatorcontrib><creatorcontrib>Paye, F.</creatorcontrib><creatorcontrib>Rougier, P.</creatorcontrib><creatorcontrib>Penna, C.</creatorcontrib><creatorcontrib>Vaillant, J.C.</creatorcontrib><creatorcontrib>André, T.</creatorcontrib><creatorcontrib>Closset, J.</creatorcontrib><creatorcontrib>Salmon, I.</creatorcontrib><creatorcontrib>Emile, J.F.</creatorcontrib><creatorcontrib>Van Laethem, J.L.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Annals of oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bachet, J.B.</au><au>Maréchal, R.</au><au>Demetter, P.</au><au>Bonnetain, F.</au><au>Couvelard, A.</au><au>Svrcek, M.</au><au>Bardier-Dupas, A.</au><au>Hammel, P.</au><au>Sauvanet, A.</au><au>Louvet, C.</au><au>Paye, F.</au><au>Rougier, P.</au><au>Penna, C.</au><au>Vaillant, J.C.</au><au>André, T.</au><au>Closset, J.</au><au>Salmon, I.</au><au>Emile, J.F.</au><au>Van Laethem, J.L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Contribution of CXCR4 and SMAD4 in predicting disease progression pattern and benefit from adjuvant chemotherapy in resected pancreatic adenocarcinoma</atitle><jtitle>Annals of oncology</jtitle><addtitle>Ann Oncol</addtitle><date>2012-09-01</date><risdate>2012</risdate><volume>23</volume><issue>9</issue><spage>2327</spage><epage>2335</epage><pages>2327-2335</pages><issn>0923-7534</issn><eissn>1569-8041</eissn><abstract>Prognosis of patients with pancreatic adenocarcinoma is poor. Many prognostic biomarkers have been tested, but most studies included heterogeneous patients. We aimed to investigate the prognostic and/or predictive values of four relevant biomarkers in a multicentric cohort of patients.
A total of 471 patients who had resected pancreatic adenocarcinoma were included. Using tissue microarray, we assessed the relationship of biomarker expressions with the overall survival: Smad4, type II TGF-β receptor, CXCR4, and LKB1.
High CXCR4 expression was found to be the only independent negative prognostic biomarker [hazard ratio (HR)=1.74; P<0.0001]. In addition, it was significantly associated with a distant relapse pattern (HR=2.19; P<0.0001) and was the strongest prognostic factor compared with clinicopathological factors. In patients who did not received adjuvant treatment, there was a trend toward decrease in the overall survival for negative Smad4 expression. Loss of Smad4 expression was not correlated with recurrence pattern but was shown to be predictive for adjuvant chemotherapy (CT) benefit (HR=0.59; P=0.002).
CXCR4 is a strong independent prognostic biomarker associated with distant metastatic recurrence and appears as an attractive target to be evaluated in pancreatic adenocarcinoma. Negative SMAD4 expression should be considered as a potential predictor of adjuvant CT benefit.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>22377565</pmid><doi>10.1093/annonc/mdr617</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adenocarcinoma - metabolism Adenocarcinoma - mortality Adenocarcinoma - secondary Adenocarcinoma - therapy adjuvant chemotherapy Adult Aged Aged, 80 and over Antineoplastic agents Biological and medical sciences Biomarkers, Tumor - metabolism Chemotherapy, Adjuvant CXCR4 Disease Progression Female Gastroenterology. Liver. Pancreas. Abdomen Humans Kaplan-Meier Estimate Liver. Biliary tract. Portal circulation. Exocrine pancreas LKB1 Lymphatic Metastasis Male Medical sciences Middle Aged Multivariate Analysis pancreatic adenocarcinoma Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - mortality Pancreatic Neoplasms - pathology Pancreatic Neoplasms - therapy Pharmacology. Drug treatments Proportional Hazards Models Prospective Studies Receptors, CXCR4 - metabolism Smad4 Smad4 Protein - metabolism Treatment Outcome Tumors type II TGF-β receptor |
| title | Contribution of CXCR4 and SMAD4 in predicting disease progression pattern and benefit from adjuvant chemotherapy in resected pancreatic adenocarcinoma |
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