ERCC1 and ERCC2 as predictive biomarkers to oxaliplatin-based chemotherapy in colorectal cancer patients from Egypt
The impact of Excision repair cross-complementation group 1 (ERCC1) and group 2 (ERCC2) expression levels on the efficacy of oxaliplatin-based chemotherapy is still controversial. The present study was conducted to determine the predictive value of these molecular biomarkers in stage III and IV colo...
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| Veröffentlicht in: | Experimental and molecular pathology 2017-02, Vol.102 (1), p.78-85 |
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| creator | Kassem, Amira B. Salem, Salem Eid Abdelrahim, Mohamed E. Said, Amira S.A. Salahuddin, Ahmad Hussein, Marwa Mahmoud Bahnassy, Abeer A. |
| description | The impact of Excision repair cross-complementation group 1 (ERCC1) and group 2 (ERCC2) expression levels on the efficacy of oxaliplatin-based chemotherapy is still controversial. The present study was conducted to determine the predictive value of these molecular biomarkers in stage III and IV colorectal cancer (CRC) patients receiving oxaliplatin (OX)-based chemotherapy as first-line treatment.
The study included 80 CRC patients who received first line oxaliplatin based chemotherapy The expression levels of ERCC1 and ERCC2-mRNA and proteins were determined in the primary tumors by quantitative real time reverse transcription polymerase chain reaction(RT-qPCR) and immunohistochemistry (IHC); respectively. The results of mRNA expression were correlated with patients' characteristics, response to treatment, overall- and event free survival (OS & EFS).
Sixty four out of the 80 patients were legible for assessment of ERCC1 and ERCC2 expression. The cut-off levels of ERCC1and ERCC2-RNA were 3.8×10−3& 4.6×10−3; respectively. Reduced ERCC1 and ERCC2 RNA expressions were detected in 50 (78.1%) and 48 (75%) cases, respectively whereas reduced proteins were detected in 48 cases (75%) for ERCC1 and ERCC2. After The median follow up period was 30.5months (range: 7–104months), Patients with low mRNAERCC1levels showed significantly longer OS (p=0.011) and EFS (p˂0.001). However, no significant relation was found between ERCC2 levels and OS or EFS. In multivariate analysis performance status (PS), stage of the disease and ERCC1-mRNA expression were independent prognostic factors for EFS whereas tumor histology and stage of the disease were independent factors for OS.
ERCC1 expression levels may help in selecting patients who benefit from oxaliplatin chemotherapy in stage III & IV CRC. Further large trials are needed to validate these data. |
| doi_str_mv | 10.1016/j.yexmp.2017.01.006 |
| format | Article |
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The study included 80 CRC patients who received first line oxaliplatin based chemotherapy The expression levels of ERCC1 and ERCC2-mRNA and proteins were determined in the primary tumors by quantitative real time reverse transcription polymerase chain reaction(RT-qPCR) and immunohistochemistry (IHC); respectively. The results of mRNA expression were correlated with patients' characteristics, response to treatment, overall- and event free survival (OS & EFS).
Sixty four out of the 80 patients were legible for assessment of ERCC1 and ERCC2 expression. The cut-off levels of ERCC1and ERCC2-RNA were 3.8×10−3& 4.6×10−3; respectively. Reduced ERCC1 and ERCC2 RNA expressions were detected in 50 (78.1%) and 48 (75%) cases, respectively whereas reduced proteins were detected in 48 cases (75%) for ERCC1 and ERCC2. After The median follow up period was 30.5months (range: 7–104months), Patients with low mRNAERCC1levels showed significantly longer OS (p=0.011) and EFS (p˂0.001). However, no significant relation was found between ERCC2 levels and OS or EFS. In multivariate analysis performance status (PS), stage of the disease and ERCC1-mRNA expression were independent prognostic factors for EFS whereas tumor histology and stage of the disease were independent factors for OS.
ERCC1 expression levels may help in selecting patients who benefit from oxaliplatin chemotherapy in stage III & IV CRC. Further large trials are needed to validate these data.</description><identifier>ISSN: 0014-4800</identifier><identifier>EISSN: 1096-0945</identifier><identifier>DOI: 10.1016/j.yexmp.2017.01.006</identifier><identifier>PMID: 28088319</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biomarkers, Tumor - biosynthesis ; Biomarkers, Tumor - genetics ; Colorectal Neoplasms - drug therapy ; Colorectal Neoplasms - pathology ; CRC ; DNA-Binding Proteins - biosynthesis ; DNA-Binding Proteins - genetics ; Egypt ; Endonucleases - biosynthesis ; Endonucleases - genetics ; ERCC1 ; ERCC2 ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic - drug effects ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Organoplatinum Compounds - administration & dosage ; Outcome Assessment (Health Care) - methods ; Outcome Assessment (Health Care) - statistics & numerical data ; Oxaliplatin ; Proportional Hazards Models ; Reverse Transcriptase Polymerase Chain Reaction ; Survival ; Xeroderma Pigmentosum Group D Protein - biosynthesis ; Xeroderma Pigmentosum Group D Protein - genetics ; Young Adult</subject><ispartof>Experimental and molecular pathology, 2017-02, Vol.102 (1), p.78-85</ispartof><rights>2017 Elsevier Inc.</rights><rights>Copyright © 2017 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c359t-8e2b0214aebff76e07ab6c1d181de2ca486cefed256cf5e2852c3ffc1292462b3</citedby><cites>FETCH-LOGICAL-c359t-8e2b0214aebff76e07ab6c1d181de2ca486cefed256cf5e2852c3ffc1292462b3</cites><orcidid>0000-0002-7382-4284</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0014480016303112$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28088319$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kassem, Amira B.</creatorcontrib><creatorcontrib>Salem, Salem Eid</creatorcontrib><creatorcontrib>Abdelrahim, Mohamed E.</creatorcontrib><creatorcontrib>Said, Amira S.A.</creatorcontrib><creatorcontrib>Salahuddin, Ahmad</creatorcontrib><creatorcontrib>Hussein, Marwa Mahmoud</creatorcontrib><creatorcontrib>Bahnassy, Abeer A.</creatorcontrib><title>ERCC1 and ERCC2 as predictive biomarkers to oxaliplatin-based chemotherapy in colorectal cancer patients from Egypt</title><title>Experimental and molecular pathology</title><addtitle>Exp Mol Pathol</addtitle><description>The impact of Excision repair cross-complementation group 1 (ERCC1) and group 2 (ERCC2) expression levels on the efficacy of oxaliplatin-based chemotherapy is still controversial. The present study was conducted to determine the predictive value of these molecular biomarkers in stage III and IV colorectal cancer (CRC) patients receiving oxaliplatin (OX)-based chemotherapy as first-line treatment.
The study included 80 CRC patients who received first line oxaliplatin based chemotherapy The expression levels of ERCC1 and ERCC2-mRNA and proteins were determined in the primary tumors by quantitative real time reverse transcription polymerase chain reaction(RT-qPCR) and immunohistochemistry (IHC); respectively. The results of mRNA expression were correlated with patients' characteristics, response to treatment, overall- and event free survival (OS & EFS).
Sixty four out of the 80 patients were legible for assessment of ERCC1 and ERCC2 expression. The cut-off levels of ERCC1and ERCC2-RNA were 3.8×10−3& 4.6×10−3; respectively. Reduced ERCC1 and ERCC2 RNA expressions were detected in 50 (78.1%) and 48 (75%) cases, respectively whereas reduced proteins were detected in 48 cases (75%) for ERCC1 and ERCC2. After The median follow up period was 30.5months (range: 7–104months), Patients with low mRNAERCC1levels showed significantly longer OS (p=0.011) and EFS (p˂0.001). However, no significant relation was found between ERCC2 levels and OS or EFS. In multivariate analysis performance status (PS), stage of the disease and ERCC1-mRNA expression were independent prognostic factors for EFS whereas tumor histology and stage of the disease were independent factors for OS.
ERCC1 expression levels may help in selecting patients who benefit from oxaliplatin chemotherapy in stage III & IV CRC. Further large trials are needed to validate these data.</description><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biomarkers, Tumor - biosynthesis</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Colorectal Neoplasms - drug therapy</subject><subject>Colorectal Neoplasms - pathology</subject><subject>CRC</subject><subject>DNA-Binding Proteins - biosynthesis</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Egypt</subject><subject>Endonucleases - biosynthesis</subject><subject>Endonucleases - genetics</subject><subject>ERCC1</subject><subject>ERCC2</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Kaplan-Meier Estimate</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multivariate Analysis</subject><subject>Neoplasm Staging</subject><subject>Organoplatinum Compounds - administration & dosage</subject><subject>Outcome Assessment (Health Care) - methods</subject><subject>Outcome Assessment (Health Care) - statistics & numerical data</subject><subject>Oxaliplatin</subject><subject>Proportional Hazards Models</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Survival</subject><subject>Xeroderma Pigmentosum Group D Protein - biosynthesis</subject><subject>Xeroderma Pigmentosum Group D Protein - genetics</subject><subject>Young Adult</subject><issn>0014-4800</issn><issn>1096-0945</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE2P0zAQhi0EYsvCL0BCPnJJmHES1zlwQFX5kFZCQnC2HGfMuiRxsN3V9t-vSxeOnGYOzzuv5mHsNUKNgPLdoT7R_bzWAnBbA9YA8gnbIPSygr7tnrINALZVqwCu2IuUDgDQA4rn7EooUKrBfsPS_ttuh9wsIz9vgpvE10ijt9nfER98mE38RTHxHHi4N5NfJ5P9Ug0m0cjtLc0h31I064n7hdswhUg2m4lbs1iKfC00LTlxF8PM9z9Pa37JnjkzJXr1OK_Zj4_777vP1c3XT192H24q23R9rhSJAQS2hgbntpJgawZpcUSFIwlrWiUtORpFJ63rSKhO2MY5i6IXrRRDc83eXu6uMfw-Usp69snSNJmFwjFpVBK7DnvZFrS5oDaGlCI5vUZfPj9pBH22rQ_6j219tq0BdbFdUm8eC47DTOO_zF-9BXh_Aai8eecp6mSLDVv8ni3pMfj_FjwANAKTYQ</recordid><startdate>201702</startdate><enddate>201702</enddate><creator>Kassem, Amira B.</creator><creator>Salem, Salem Eid</creator><creator>Abdelrahim, Mohamed E.</creator><creator>Said, Amira S.A.</creator><creator>Salahuddin, Ahmad</creator><creator>Hussein, Marwa Mahmoud</creator><creator>Bahnassy, Abeer A.</creator><general>Elsevier Inc</general><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><orcidid>https://orcid.org/0000-0002-7382-4284</orcidid></search><sort><creationdate>201702</creationdate><title>ERCC1 and ERCC2 as predictive biomarkers to oxaliplatin-based chemotherapy in colorectal cancer patients from Egypt</title><author>Kassem, Amira B. ; Salem, Salem Eid ; Abdelrahim, Mohamed E. ; Said, Amira S.A. ; Salahuddin, Ahmad ; Hussein, Marwa Mahmoud ; Bahnassy, Abeer A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c359t-8e2b0214aebff76e07ab6c1d181de2ca486cefed256cf5e2852c3ffc1292462b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Biomarkers, Tumor - biosynthesis</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Colorectal Neoplasms - drug therapy</topic><topic>Colorectal Neoplasms - pathology</topic><topic>CRC</topic><topic>DNA-Binding Proteins - biosynthesis</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Egypt</topic><topic>Endonucleases - biosynthesis</topic><topic>Endonucleases - genetics</topic><topic>ERCC1</topic><topic>ERCC2</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Kaplan-Meier Estimate</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Multivariate Analysis</topic><topic>Neoplasm Staging</topic><topic>Organoplatinum Compounds - administration & dosage</topic><topic>Outcome Assessment (Health Care) - methods</topic><topic>Outcome Assessment (Health Care) - statistics & numerical data</topic><topic>Oxaliplatin</topic><topic>Proportional Hazards Models</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Survival</topic><topic>Xeroderma Pigmentosum Group D Protein - biosynthesis</topic><topic>Xeroderma Pigmentosum Group D Protein - genetics</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kassem, Amira B.</creatorcontrib><creatorcontrib>Salem, Salem Eid</creatorcontrib><creatorcontrib>Abdelrahim, Mohamed E.</creatorcontrib><creatorcontrib>Said, Amira S.A.</creatorcontrib><creatorcontrib>Salahuddin, Ahmad</creatorcontrib><creatorcontrib>Hussein, Marwa Mahmoud</creatorcontrib><creatorcontrib>Bahnassy, Abeer A.</creatorcontrib><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>Experimental and molecular pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kassem, Amira B.</au><au>Salem, Salem Eid</au><au>Abdelrahim, Mohamed E.</au><au>Said, Amira S.A.</au><au>Salahuddin, Ahmad</au><au>Hussein, Marwa Mahmoud</au><au>Bahnassy, Abeer A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ERCC1 and ERCC2 as predictive biomarkers to oxaliplatin-based chemotherapy in colorectal cancer patients from Egypt</atitle><jtitle>Experimental and molecular pathology</jtitle><addtitle>Exp Mol Pathol</addtitle><date>2017-02</date><risdate>2017</risdate><volume>102</volume><issue>1</issue><spage>78</spage><epage>85</epage><pages>78-85</pages><issn>0014-4800</issn><eissn>1096-0945</eissn><abstract>The impact of Excision repair cross-complementation group 1 (ERCC1) and group 2 (ERCC2) expression levels on the efficacy of oxaliplatin-based chemotherapy is still controversial. The present study was conducted to determine the predictive value of these molecular biomarkers in stage III and IV colorectal cancer (CRC) patients receiving oxaliplatin (OX)-based chemotherapy as first-line treatment.
The study included 80 CRC patients who received first line oxaliplatin based chemotherapy The expression levels of ERCC1 and ERCC2-mRNA and proteins were determined in the primary tumors by quantitative real time reverse transcription polymerase chain reaction(RT-qPCR) and immunohistochemistry (IHC); respectively. The results of mRNA expression were correlated with patients' characteristics, response to treatment, overall- and event free survival (OS & EFS).
Sixty four out of the 80 patients were legible for assessment of ERCC1 and ERCC2 expression. The cut-off levels of ERCC1and ERCC2-RNA were 3.8×10−3& 4.6×10−3; respectively. Reduced ERCC1 and ERCC2 RNA expressions were detected in 50 (78.1%) and 48 (75%) cases, respectively whereas reduced proteins were detected in 48 cases (75%) for ERCC1 and ERCC2. After The median follow up period was 30.5months (range: 7–104months), Patients with low mRNAERCC1levels showed significantly longer OS (p=0.011) and EFS (p˂0.001). However, no significant relation was found between ERCC2 levels and OS or EFS. In multivariate analysis performance status (PS), stage of the disease and ERCC1-mRNA expression were independent prognostic factors for EFS whereas tumor histology and stage of the disease were independent factors for OS.
ERCC1 expression levels may help in selecting patients who benefit from oxaliplatin chemotherapy in stage III & IV CRC. Further large trials are needed to validate these data.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>28088319</pmid><doi>10.1016/j.yexmp.2017.01.006</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-7382-4284</orcidid></addata></record> |
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| subjects | Adult Aged Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biomarkers, Tumor - biosynthesis Biomarkers, Tumor - genetics Colorectal Neoplasms - drug therapy Colorectal Neoplasms - pathology CRC DNA-Binding Proteins - biosynthesis DNA-Binding Proteins - genetics Egypt Endonucleases - biosynthesis Endonucleases - genetics ERCC1 ERCC2 Female Follow-Up Studies Gene Expression Regulation, Neoplastic - drug effects Humans Immunohistochemistry Kaplan-Meier Estimate Male Middle Aged Multivariate Analysis Neoplasm Staging Organoplatinum Compounds - administration & dosage Outcome Assessment (Health Care) - methods Outcome Assessment (Health Care) - statistics & numerical data Oxaliplatin Proportional Hazards Models Reverse Transcriptase Polymerase Chain Reaction Survival Xeroderma Pigmentosum Group D Protein - biosynthesis Xeroderma Pigmentosum Group D Protein - genetics Young Adult |
| title | ERCC1 and ERCC2 as predictive biomarkers to oxaliplatin-based chemotherapy in colorectal cancer patients from Egypt |
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