Msi-1 is a Predictor of Survival and a Novel Therapeutic Target in Colon Cancer

Background Musashi1 (Msi-1), a neural RNA-binding protein, plays an important role in regulating cell differentiation in precursor cells. Recently, aberrant expression of Msi-1 has been detected in several malignancies. However, its role in the progression of colon cancer is largely unknown. Materia...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Annals of surgical oncology 2011-07, Vol.18 (7), p.2074-2083
Hauptverfasser: Li, Dawei, Peng, Xiao, Yan, Dongwang, Tang, Huamei, Huang, Fei, Yang, Yinxue, Peng, Zhihai
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 2083
container_issue 7
container_start_page 2074
container_title Annals of surgical oncology
container_volume 18
creator Li, Dawei
Peng, Xiao
Yan, Dongwang
Tang, Huamei
Huang, Fei
Yang, Yinxue
Peng, Zhihai
description Background Musashi1 (Msi-1), a neural RNA-binding protein, plays an important role in regulating cell differentiation in precursor cells. Recently, aberrant expression of Msi-1 has been detected in several malignancies. However, its role in the progression of colon cancer is largely unknown. Materials and Methods We used Western blotting to examine Msi-1 protein expression in 8 cases of primary colon cancer lesions and paired normal colonic mucosa. Msi-1 expression and clinicopathological significance were determined by immunohistochemical staining in a tissue microarray (TMA) containing 203 cases of primary colon cancer paired with noncancerous tissue and 66 lymph node metastasis (LNM) tissues. RNAi was used to analyze the biological function of Msi-1 in vitro. Results LNM tissue exhibited a striking increase in Msi-1 expression when compared with primary colon cancer and adjacent normal mucosa (87.9% vs. 64.5% vs. 16.7%, P  
doi_str_mv 10.1245/s10434-011-1567-9
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_872127243</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2374770531</sourcerecordid><originalsourceid>FETCH-LOGICAL-c436t-9bd48470f89c7b54872e84d99f531fe77d138b3d19eac410089ce8ffdaafc1113</originalsourceid><addsrcrecordid>eNp1kEtLxDAQx4Movj-AFwlePFUzTdI0R1l8gS9wPYdsOtFKt1mTdsFvb2R9gOAlEzK_-Wf4EXIA7ARKIU8TMMFFwQAKkJUq9BrZBplfRFXDer6zqi50WcktspPSK2OgOJObZKsEIUou2Ta5v01tAbRN1NKHiE3rhhBp8PRxjMt2aTtq-yb37sISOzp9wWgXOA6to1Mbn3GgbU8noQv5tL3DuEc2vO0S7n_VXfJ0cT6dXBU395fXk7ObwgleDYWeNaIWivlaOzWTolYl1qLR2ksOHpVqgNcz3oBG6wQwljmsvW-s9Q4A-C45XuUuYngbMQ1m3iaHXWd7DGMyORBKVQqeyaM_5GsYY5-XyxAoJTWXGYIV5GJIKaI3i9jObXw3wMyna7NybbJr8-na6Dxz-BU8zubY_Ex8y81AuQJSbvXPGH9__j_1A6O4h1M</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>871775935</pqid></control><display><type>article</type><title>Msi-1 is a Predictor of Survival and a Novel Therapeutic Target in Colon Cancer</title><source>MEDLINE</source><source>SpringerLink Journals</source><creator>Li, Dawei ; Peng, Xiao ; Yan, Dongwang ; Tang, Huamei ; Huang, Fei ; Yang, Yinxue ; Peng, Zhihai</creator><creatorcontrib>Li, Dawei ; Peng, Xiao ; Yan, Dongwang ; Tang, Huamei ; Huang, Fei ; Yang, Yinxue ; Peng, Zhihai</creatorcontrib><description>Background Musashi1 (Msi-1), a neural RNA-binding protein, plays an important role in regulating cell differentiation in precursor cells. Recently, aberrant expression of Msi-1 has been detected in several malignancies. However, its role in the progression of colon cancer is largely unknown. Materials and Methods We used Western blotting to examine Msi-1 protein expression in 8 cases of primary colon cancer lesions and paired normal colonic mucosa. Msi-1 expression and clinicopathological significance were determined by immunohistochemical staining in a tissue microarray (TMA) containing 203 cases of primary colon cancer paired with noncancerous tissue and 66 lymph node metastasis (LNM) tissues. RNAi was used to analyze the biological function of Msi-1 in vitro. Results LNM tissue exhibited a striking increase in Msi-1 expression when compared with primary colon cancer and adjacent normal mucosa (87.9% vs. 64.5% vs. 16.7%, P  &lt; .001). Overexpression of Msi-1 was associated with higher clinical stage, T stage, lymph node metastasis, presence of distant metastasis, and Ki-67 positivity. Msi-1 served as an independent prognostic marker whose expression levels correlated with poorer metastasis-free survival (MFS) (HR 5.4; P  &lt; .001) and poorer overall survival (OS) (HR 3.8; P  &lt; .001). Msi-1 silencing significantly inhibited proliferation ability and attenuated the migration and invasion activity of colon cancer cells. Conclusions Our study provides the basis to explore the use of Msi-1 as a novel prognostic biomarker in colon cancer patients. Aberrant overexpression of Msi-1 during metastasis of colon cancer also suggests that it is a potential therapeutic target.</description><identifier>ISSN: 1068-9265</identifier><identifier>EISSN: 1534-4681</identifier><identifier>DOI: 10.1245/s10434-011-1567-9</identifier><identifier>PMID: 21442350</identifier><language>eng</language><publisher>New York: Springer-Verlag</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Blotting, Western ; Cell Adhesion ; Cell Differentiation ; Cell Movement ; Cell Proliferation ; Colon - metabolism ; Colon - pathology ; Colonic Neoplasms - metabolism ; Colonic Neoplasms - mortality ; Colonic Neoplasms - pathology ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Male ; Medicine ; Medicine &amp; Public Health ; Middle Aged ; Nerve Tissue Proteins - antagonists &amp; inhibitors ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; Oncology ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; RNA, Small Interfering - genetics ; RNA-Binding Proteins - antagonists &amp; inhibitors ; RNA-Binding Proteins - genetics ; RNA-Binding Proteins - metabolism ; Surgery ; Surgical Oncology ; Survival Rate ; Tissue Array Analysis ; Translational Research and Biomarkers ; Tumor Cells, Cultured ; Young Adult</subject><ispartof>Annals of surgical oncology, 2011-07, Vol.18 (7), p.2074-2083</ispartof><rights>Society of Surgical Oncology 2011</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c436t-9bd48470f89c7b54872e84d99f531fe77d138b3d19eac410089ce8ffdaafc1113</citedby><cites>FETCH-LOGICAL-c436t-9bd48470f89c7b54872e84d99f531fe77d138b3d19eac410089ce8ffdaafc1113</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1245/s10434-011-1567-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1245/s10434-011-1567-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21442350$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Dawei</creatorcontrib><creatorcontrib>Peng, Xiao</creatorcontrib><creatorcontrib>Yan, Dongwang</creatorcontrib><creatorcontrib>Tang, Huamei</creatorcontrib><creatorcontrib>Huang, Fei</creatorcontrib><creatorcontrib>Yang, Yinxue</creatorcontrib><creatorcontrib>Peng, Zhihai</creatorcontrib><title>Msi-1 is a Predictor of Survival and a Novel Therapeutic Target in Colon Cancer</title><title>Annals of surgical oncology</title><addtitle>Ann Surg Oncol</addtitle><addtitle>Ann Surg Oncol</addtitle><description>Background Musashi1 (Msi-1), a neural RNA-binding protein, plays an important role in regulating cell differentiation in precursor cells. Recently, aberrant expression of Msi-1 has been detected in several malignancies. However, its role in the progression of colon cancer is largely unknown. Materials and Methods We used Western blotting to examine Msi-1 protein expression in 8 cases of primary colon cancer lesions and paired normal colonic mucosa. Msi-1 expression and clinicopathological significance were determined by immunohistochemical staining in a tissue microarray (TMA) containing 203 cases of primary colon cancer paired with noncancerous tissue and 66 lymph node metastasis (LNM) tissues. RNAi was used to analyze the biological function of Msi-1 in vitro. Results LNM tissue exhibited a striking increase in Msi-1 expression when compared with primary colon cancer and adjacent normal mucosa (87.9% vs. 64.5% vs. 16.7%, P  &lt; .001). Overexpression of Msi-1 was associated with higher clinical stage, T stage, lymph node metastasis, presence of distant metastasis, and Ki-67 positivity. Msi-1 served as an independent prognostic marker whose expression levels correlated with poorer metastasis-free survival (MFS) (HR 5.4; P  &lt; .001) and poorer overall survival (OS) (HR 3.8; P  &lt; .001). Msi-1 silencing significantly inhibited proliferation ability and attenuated the migration and invasion activity of colon cancer cells. Conclusions Our study provides the basis to explore the use of Msi-1 as a novel prognostic biomarker in colon cancer patients. Aberrant overexpression of Msi-1 during metastasis of colon cancer also suggests that it is a potential therapeutic target.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Blotting, Western</subject><subject>Cell Adhesion</subject><subject>Cell Differentiation</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Colon - metabolism</subject><subject>Colon - pathology</subject><subject>Colonic Neoplasms - metabolism</subject><subject>Colonic Neoplasms - mortality</subject><subject>Colonic Neoplasms - pathology</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Humans</subject><subject>Immunoenzyme Techniques</subject><subject>Lymphatic Metastasis</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Middle Aged</subject><subject>Nerve Tissue Proteins - antagonists &amp; inhibitors</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Oncology</subject><subject>Prognosis</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Small Interfering - genetics</subject><subject>RNA-Binding Proteins - antagonists &amp; inhibitors</subject><subject>RNA-Binding Proteins - genetics</subject><subject>RNA-Binding Proteins - metabolism</subject><subject>Surgery</subject><subject>Surgical Oncology</subject><subject>Survival Rate</subject><subject>Tissue Array Analysis</subject><subject>Translational Research and Biomarkers</subject><subject>Tumor Cells, Cultured</subject><subject>Young Adult</subject><issn>1068-9265</issn><issn>1534-4681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kEtLxDAQx4Movj-AFwlePFUzTdI0R1l8gS9wPYdsOtFKt1mTdsFvb2R9gOAlEzK_-Wf4EXIA7ARKIU8TMMFFwQAKkJUq9BrZBplfRFXDer6zqi50WcktspPSK2OgOJObZKsEIUou2Ta5v01tAbRN1NKHiE3rhhBp8PRxjMt2aTtq-yb37sISOzp9wWgXOA6to1Mbn3GgbU8noQv5tL3DuEc2vO0S7n_VXfJ0cT6dXBU395fXk7ObwgleDYWeNaIWivlaOzWTolYl1qLR2ksOHpVqgNcz3oBG6wQwljmsvW-s9Q4A-C45XuUuYngbMQ1m3iaHXWd7DGMyORBKVQqeyaM_5GsYY5-XyxAoJTWXGYIV5GJIKaI3i9jObXw3wMyna7NybbJr8-na6Dxz-BU8zubY_Ex8y81AuQJSbvXPGH9__j_1A6O4h1M</recordid><startdate>20110701</startdate><enddate>20110701</enddate><creator>Li, Dawei</creator><creator>Peng, Xiao</creator><creator>Yan, Dongwang</creator><creator>Tang, Huamei</creator><creator>Huang, Fei</creator><creator>Yang, Yinxue</creator><creator>Peng, Zhihai</creator><general>Springer-Verlag</general><general>Springer Nature B.V</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>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20110701</creationdate><title>Msi-1 is a Predictor of Survival and a Novel Therapeutic Target in Colon Cancer</title><author>Li, Dawei ; Peng, Xiao ; Yan, Dongwang ; Tang, Huamei ; Huang, Fei ; Yang, Yinxue ; Peng, Zhihai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c436t-9bd48470f89c7b54872e84d99f531fe77d138b3d19eac410089ce8ffdaafc1113</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Blotting, Western</topic><topic>Cell Adhesion</topic><topic>Cell Differentiation</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Colon - metabolism</topic><topic>Colon - pathology</topic><topic>Colonic Neoplasms - metabolism</topic><topic>Colonic Neoplasms - mortality</topic><topic>Colonic Neoplasms - pathology</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Humans</topic><topic>Immunoenzyme Techniques</topic><topic>Lymphatic Metastasis</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine &amp; Public Health</topic><topic>Middle Aged</topic><topic>Nerve Tissue Proteins - antagonists &amp; inhibitors</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Oncology</topic><topic>Prognosis</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Small Interfering - genetics</topic><topic>RNA-Binding Proteins - antagonists &amp; inhibitors</topic><topic>RNA-Binding Proteins - genetics</topic><topic>RNA-Binding Proteins - metabolism</topic><topic>Surgery</topic><topic>Surgical Oncology</topic><topic>Survival Rate</topic><topic>Tissue Array Analysis</topic><topic>Translational Research and Biomarkers</topic><topic>Tumor Cells, Cultured</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Dawei</creatorcontrib><creatorcontrib>Peng, Xiao</creatorcontrib><creatorcontrib>Yan, Dongwang</creatorcontrib><creatorcontrib>Tang, Huamei</creatorcontrib><creatorcontrib>Huang, Fei</creatorcontrib><creatorcontrib>Yang, Yinxue</creatorcontrib><creatorcontrib>Peng, Zhihai</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health &amp; Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health &amp; Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Annals of surgical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Dawei</au><au>Peng, Xiao</au><au>Yan, Dongwang</au><au>Tang, Huamei</au><au>Huang, Fei</au><au>Yang, Yinxue</au><au>Peng, Zhihai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Msi-1 is a Predictor of Survival and a Novel Therapeutic Target in Colon Cancer</atitle><jtitle>Annals of surgical oncology</jtitle><stitle>Ann Surg Oncol</stitle><addtitle>Ann Surg Oncol</addtitle><date>2011-07-01</date><risdate>2011</risdate><volume>18</volume><issue>7</issue><spage>2074</spage><epage>2083</epage><pages>2074-2083</pages><issn>1068-9265</issn><eissn>1534-4681</eissn><abstract>Background Musashi1 (Msi-1), a neural RNA-binding protein, plays an important role in regulating cell differentiation in precursor cells. Recently, aberrant expression of Msi-1 has been detected in several malignancies. However, its role in the progression of colon cancer is largely unknown. Materials and Methods We used Western blotting to examine Msi-1 protein expression in 8 cases of primary colon cancer lesions and paired normal colonic mucosa. Msi-1 expression and clinicopathological significance were determined by immunohistochemical staining in a tissue microarray (TMA) containing 203 cases of primary colon cancer paired with noncancerous tissue and 66 lymph node metastasis (LNM) tissues. RNAi was used to analyze the biological function of Msi-1 in vitro. Results LNM tissue exhibited a striking increase in Msi-1 expression when compared with primary colon cancer and adjacent normal mucosa (87.9% vs. 64.5% vs. 16.7%, P  &lt; .001). Overexpression of Msi-1 was associated with higher clinical stage, T stage, lymph node metastasis, presence of distant metastasis, and Ki-67 positivity. Msi-1 served as an independent prognostic marker whose expression levels correlated with poorer metastasis-free survival (MFS) (HR 5.4; P  &lt; .001) and poorer overall survival (OS) (HR 3.8; P  &lt; .001). Msi-1 silencing significantly inhibited proliferation ability and attenuated the migration and invasion activity of colon cancer cells. Conclusions Our study provides the basis to explore the use of Msi-1 as a novel prognostic biomarker in colon cancer patients. Aberrant overexpression of Msi-1 during metastasis of colon cancer also suggests that it is a potential therapeutic target.</abstract><cop>New York</cop><pub>Springer-Verlag</pub><pmid>21442350</pmid><doi>10.1245/s10434-011-1567-9</doi><tpages>10</tpages></addata></record>
fulltext fulltext
identifier ISSN: 1068-9265
ispartof Annals of surgical oncology, 2011-07, Vol.18 (7), p.2074-2083
issn 1068-9265
1534-4681
language eng
recordid cdi_proquest_miscellaneous_872127243
source MEDLINE; SpringerLink Journals
subjects Adult
Aged
Aged, 80 and over
Blotting, Western
Cell Adhesion
Cell Differentiation
Cell Movement
Cell Proliferation
Colon - metabolism
Colon - pathology
Colonic Neoplasms - metabolism
Colonic Neoplasms - mortality
Colonic Neoplasms - pathology
Female
Follow-Up Studies
Humans
Immunoenzyme Techniques
Lymphatic Metastasis
Male
Medicine
Medicine & Public Health
Middle Aged
Nerve Tissue Proteins - antagonists & inhibitors
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Oncology
Prognosis
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
RNA, Small Interfering - genetics
RNA-Binding Proteins - antagonists & inhibitors
RNA-Binding Proteins - genetics
RNA-Binding Proteins - metabolism
Surgery
Surgical Oncology
Survival Rate
Tissue Array Analysis
Translational Research and Biomarkers
Tumor Cells, Cultured
Young Adult
title Msi-1 is a Predictor of Survival and a Novel Therapeutic Target in Colon Cancer
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-21T21%3A33%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Msi-1%20is%20a%20Predictor%20of%20Survival%20and%20a%20Novel%20Therapeutic%20Target%20in%20Colon%20Cancer&rft.jtitle=Annals%20of%20surgical%20oncology&rft.au=Li,%20Dawei&rft.date=2011-07-01&rft.volume=18&rft.issue=7&rft.spage=2074&rft.epage=2083&rft.pages=2074-2083&rft.issn=1068-9265&rft.eissn=1534-4681&rft_id=info:doi/10.1245/s10434-011-1567-9&rft_dat=%3Cproquest_cross%3E2374770531%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=871775935&rft_id=info:pmid/21442350&rfr_iscdi=true