Loading…
Implication of Akt, ERK1/2 and alternative p38MAPK signalling pathways in human colon cancer cell apoptosis induced by green tea EGCG
We investigated apoptosis induced by the green tea component the epigallocatechin-3-gallate (EGCG) and the pathways underlying its activity in a colon cancer cell line. A complete understanding of the mechanism(s) and molecules targeted by green tea polyphenols could be useful in developing novel th...
Saved in:
| Published in: | Food and chemical toxicology 2015-10, Vol.84, p.125-132 |
|---|---|
| Main Authors: | , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c386t-f0ab62c17030722e27701fb524f399b16ab42ceb5ab358fc89b36ff5169a37f53 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c386t-f0ab62c17030722e27701fb524f399b16ab42ceb5ab358fc89b36ff5169a37f53 |
| container_end_page | 132 |
| container_issue | |
| container_start_page | 125 |
| container_title | Food and chemical toxicology |
| container_volume | 84 |
| creator | Cerezo-Guisado, María Isabel Zur, Rafal Lorenzo, María Jesús Risco, Ana Martín-Serrano, Miguel A. Alvarez-Barrientos, Alberto Cuenda, Ana Centeno, Francisco |
| description | We investigated apoptosis induced by the green tea component the epigallocatechin-3-gallate (EGCG) and the pathways underlying its activity in a colon cancer cell line. A complete understanding of the mechanism(s) and molecules targeted by green tea polyphenols could be useful in developing novel therapeutic approaches for cancer treatment. EGCG, which is the major polyphenol in green tea, has cytotoxic effects and induced cell death in HT-29 cell death. In this study, we evaluated the effect EGCG on mitogen-activated protein kinase (MAPK) and Akt pathways. EGCG treatment increased phospho-ERK1/2, -JNK1/2 and -p38α, -p38γ and -p38δ, as well as phospho-Akt levels. Using a combination of kinase inhibitors, we found that EGCG-induced cell death is partially blocked by inhibiting Akt, ERK1/2 or alternative p38MAPK activity. Our data suggest that these kinase pathways are involved in the anti-cancer effects of EGCG and indicate potential use of this compound as chemotherapeutic agent for colon cancer treatment.
•Evidence supports a preventive role for epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, in cancer.•EGCG-induced cell death on the HT-29 human colon adenocarcinoma cell line.•Akt, ERK1/2 and p38δ pathways are implicated in EGCG-induced cell death. |
| doi_str_mv | 10.1016/j.fct.2015.08.017 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1762371566</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0278691515300399</els_id><sourcerecordid>1718915268</sourcerecordid><originalsourceid>FETCH-LOGICAL-c386t-f0ab62c17030722e27701fb524f399b16ab42ceb5ab358fc89b36ff5169a37f53</originalsourceid><addsrcrecordid>eNqNkc1u1DAURi1ERYfCA7BBXrJoUv80tiNWo9EwVG1VhGBtOc711EPiBDspmgfgvfFo2i4rVndxz_109R2EPlBSUkLFxa50dioZoVVJVEmofIUWVEleCF7R12hBmFSFqGl1it6mtCOESCrFG3TKBCecSb5Af6_6sfPWTH4IeHB4-Ws6x-vv1_SCYRNabLoJYsjrB8AjV7fLb9c4-W0wXefDFo9muv9j9gn7gO_n3gRshy4nWRMsRGyh67AZh3Eakj9A7Wyhxc0ebyNAwBMYvN6sNu_QiTNdgveP8wz9_LL-sfpa3NxtrlbLm8JyJabCEdMIZqkknEjGgElJqGsqdul4XTdUmOaSWWgq0_BKOavqhgvnKipqw6Wr-Bn6dMwd4_B7hjTp3qfDkybAMCed22Fc0kqI_0Cpys0yoTJKj6iNQ0oRnB6j703ca0r0QZTe6SxKH0RponQWlW8-PsbPTQ_t88WTmQx8PgKQ-3jwEHWyHnKrrY-Qw9rBvxD_Dxi0oic</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1718915268</pqid></control><display><type>article</type><title>Implication of Akt, ERK1/2 and alternative p38MAPK signalling pathways in human colon cancer cell apoptosis induced by green tea EGCG</title><source>ScienceDirect Journals</source><creator>Cerezo-Guisado, María Isabel ; Zur, Rafal ; Lorenzo, María Jesús ; Risco, Ana ; Martín-Serrano, Miguel A. ; Alvarez-Barrientos, Alberto ; Cuenda, Ana ; Centeno, Francisco</creator><creatorcontrib>Cerezo-Guisado, María Isabel ; Zur, Rafal ; Lorenzo, María Jesús ; Risco, Ana ; Martín-Serrano, Miguel A. ; Alvarez-Barrientos, Alberto ; Cuenda, Ana ; Centeno, Francisco</creatorcontrib><description>We investigated apoptosis induced by the green tea component the epigallocatechin-3-gallate (EGCG) and the pathways underlying its activity in a colon cancer cell line. A complete understanding of the mechanism(s) and molecules targeted by green tea polyphenols could be useful in developing novel therapeutic approaches for cancer treatment. EGCG, which is the major polyphenol in green tea, has cytotoxic effects and induced cell death in HT-29 cell death. In this study, we evaluated the effect EGCG on mitogen-activated protein kinase (MAPK) and Akt pathways. EGCG treatment increased phospho-ERK1/2, -JNK1/2 and -p38α, -p38γ and -p38δ, as well as phospho-Akt levels. Using a combination of kinase inhibitors, we found that EGCG-induced cell death is partially blocked by inhibiting Akt, ERK1/2 or alternative p38MAPK activity. Our data suggest that these kinase pathways are involved in the anti-cancer effects of EGCG and indicate potential use of this compound as chemotherapeutic agent for colon cancer treatment.
•Evidence supports a preventive role for epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, in cancer.•EGCG-induced cell death on the HT-29 human colon adenocarcinoma cell line.•Akt, ERK1/2 and p38δ pathways are implicated in EGCG-induced cell death.</description><identifier>ISSN: 0278-6915</identifier><identifier>EISSN: 1873-6351</identifier><identifier>DOI: 10.1016/j.fct.2015.08.017</identifier><identifier>PMID: 26303273</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Akt ; Anticarcinogenic Agents - metabolism ; Antioxidants - metabolism ; Apoptosis ; Apoptosis - drug effects ; Catechin - analogs & derivatives ; Catechin - metabolism ; Cell Line, Tumor ; Colon cancer ; Colonic Neoplasms - chemically induced ; Colonic Neoplasms - enzymology ; Colonic Neoplasms - metabolism ; Colonic Neoplasms - prevention & control ; EGCG ; ERK ; Food Handling ; HEK293 Cells ; Humans ; Isoenzymes - antagonists & inhibitors ; Isoenzymes - chemistry ; Isoenzymes - genetics ; Isoenzymes - metabolism ; MAP Kinase Signaling System - drug effects ; Osmolar Concentration ; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors ; p38 Mitogen-Activated Protein Kinases - chemistry ; p38 Mitogen-Activated Protein Kinases - genetics ; p38 Mitogen-Activated Protein Kinases - metabolism ; p38γ/p38δ ; Phosphorylation - drug effects ; Protein Kinase Inhibitors - pharmacology ; Protein Processing, Post-Translational - drug effects ; Proto-Oncogene Proteins c-akt - agonists ; Proto-Oncogene Proteins c-akt - antagonists & inhibitors ; Proto-Oncogene Proteins c-akt - metabolism ; RNA Interference ; RNA, Small Interfering ; Tea - chemistry</subject><ispartof>Food and chemical toxicology, 2015-10, Vol.84, p.125-132</ispartof><rights>2015 Elsevier Ltd</rights><rights>Copyright © 2015 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-f0ab62c17030722e27701fb524f399b16ab42ceb5ab358fc89b36ff5169a37f53</citedby><cites>FETCH-LOGICAL-c386t-f0ab62c17030722e27701fb524f399b16ab42ceb5ab358fc89b36ff5169a37f53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26303273$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cerezo-Guisado, María Isabel</creatorcontrib><creatorcontrib>Zur, Rafal</creatorcontrib><creatorcontrib>Lorenzo, María Jesús</creatorcontrib><creatorcontrib>Risco, Ana</creatorcontrib><creatorcontrib>Martín-Serrano, Miguel A.</creatorcontrib><creatorcontrib>Alvarez-Barrientos, Alberto</creatorcontrib><creatorcontrib>Cuenda, Ana</creatorcontrib><creatorcontrib>Centeno, Francisco</creatorcontrib><title>Implication of Akt, ERK1/2 and alternative p38MAPK signalling pathways in human colon cancer cell apoptosis induced by green tea EGCG</title><title>Food and chemical toxicology</title><addtitle>Food Chem Toxicol</addtitle><description>We investigated apoptosis induced by the green tea component the epigallocatechin-3-gallate (EGCG) and the pathways underlying its activity in a colon cancer cell line. A complete understanding of the mechanism(s) and molecules targeted by green tea polyphenols could be useful in developing novel therapeutic approaches for cancer treatment. EGCG, which is the major polyphenol in green tea, has cytotoxic effects and induced cell death in HT-29 cell death. In this study, we evaluated the effect EGCG on mitogen-activated protein kinase (MAPK) and Akt pathways. EGCG treatment increased phospho-ERK1/2, -JNK1/2 and -p38α, -p38γ and -p38δ, as well as phospho-Akt levels. Using a combination of kinase inhibitors, we found that EGCG-induced cell death is partially blocked by inhibiting Akt, ERK1/2 or alternative p38MAPK activity. Our data suggest that these kinase pathways are involved in the anti-cancer effects of EGCG and indicate potential use of this compound as chemotherapeutic agent for colon cancer treatment.
•Evidence supports a preventive role for epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, in cancer.•EGCG-induced cell death on the HT-29 human colon adenocarcinoma cell line.•Akt, ERK1/2 and p38δ pathways are implicated in EGCG-induced cell death.</description><subject>Akt</subject><subject>Anticarcinogenic Agents - metabolism</subject><subject>Antioxidants - metabolism</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Catechin - analogs & derivatives</subject><subject>Catechin - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Colon cancer</subject><subject>Colonic Neoplasms - chemically induced</subject><subject>Colonic Neoplasms - enzymology</subject><subject>Colonic Neoplasms - metabolism</subject><subject>Colonic Neoplasms - prevention & control</subject><subject>EGCG</subject><subject>ERK</subject><subject>Food Handling</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Isoenzymes - antagonists & inhibitors</subject><subject>Isoenzymes - chemistry</subject><subject>Isoenzymes - genetics</subject><subject>Isoenzymes - metabolism</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Osmolar Concentration</subject><subject>p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors</subject><subject>p38 Mitogen-Activated Protein Kinases - chemistry</subject><subject>p38 Mitogen-Activated Protein Kinases - genetics</subject><subject>p38 Mitogen-Activated Protein Kinases - metabolism</subject><subject>p38γ/p38δ</subject><subject>Phosphorylation - drug effects</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Protein Processing, Post-Translational - drug effects</subject><subject>Proto-Oncogene Proteins c-akt - agonists</subject><subject>Proto-Oncogene Proteins c-akt - antagonists & inhibitors</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>RNA Interference</subject><subject>RNA, Small Interfering</subject><subject>Tea - chemistry</subject><issn>0278-6915</issn><issn>1873-6351</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNqNkc1u1DAURi1ERYfCA7BBXrJoUv80tiNWo9EwVG1VhGBtOc711EPiBDspmgfgvfFo2i4rVndxz_109R2EPlBSUkLFxa50dioZoVVJVEmofIUWVEleCF7R12hBmFSFqGl1it6mtCOESCrFG3TKBCecSb5Af6_6sfPWTH4IeHB4-Ws6x-vv1_SCYRNabLoJYsjrB8AjV7fLb9c4-W0wXefDFo9muv9j9gn7gO_n3gRshy4nWRMsRGyh67AZh3Eakj9A7Wyhxc0ebyNAwBMYvN6sNu_QiTNdgveP8wz9_LL-sfpa3NxtrlbLm8JyJabCEdMIZqkknEjGgElJqGsqdul4XTdUmOaSWWgq0_BKOavqhgvnKipqw6Wr-Bn6dMwd4_B7hjTp3qfDkybAMCed22Fc0kqI_0Cpys0yoTJKj6iNQ0oRnB6j703ca0r0QZTe6SxKH0RponQWlW8-PsbPTQ_t88WTmQx8PgKQ-3jwEHWyHnKrrY-Qw9rBvxD_Dxi0oic</recordid><startdate>201510</startdate><enddate>201510</enddate><creator>Cerezo-Guisado, María Isabel</creator><creator>Zur, Rafal</creator><creator>Lorenzo, María Jesús</creator><creator>Risco, Ana</creator><creator>Martín-Serrano, Miguel A.</creator><creator>Alvarez-Barrientos, Alberto</creator><creator>Cuenda, Ana</creator><creator>Centeno, Francisco</creator><general>Elsevier Ltd</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><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>201510</creationdate><title>Implication of Akt, ERK1/2 and alternative p38MAPK signalling pathways in human colon cancer cell apoptosis induced by green tea EGCG</title><author>Cerezo-Guisado, María Isabel ; Zur, Rafal ; Lorenzo, María Jesús ; Risco, Ana ; Martín-Serrano, Miguel A. ; Alvarez-Barrientos, Alberto ; Cuenda, Ana ; Centeno, Francisco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-f0ab62c17030722e27701fb524f399b16ab42ceb5ab358fc89b36ff5169a37f53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Akt</topic><topic>Anticarcinogenic Agents - metabolism</topic><topic>Antioxidants - metabolism</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Catechin - analogs & derivatives</topic><topic>Catechin - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Colon cancer</topic><topic>Colonic Neoplasms - chemically induced</topic><topic>Colonic Neoplasms - enzymology</topic><topic>Colonic Neoplasms - metabolism</topic><topic>Colonic Neoplasms - prevention & control</topic><topic>EGCG</topic><topic>ERK</topic><topic>Food Handling</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Isoenzymes - antagonists & inhibitors</topic><topic>Isoenzymes - chemistry</topic><topic>Isoenzymes - genetics</topic><topic>Isoenzymes - metabolism</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Osmolar Concentration</topic><topic>p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors</topic><topic>p38 Mitogen-Activated Protein Kinases - chemistry</topic><topic>p38 Mitogen-Activated Protein Kinases - genetics</topic><topic>p38 Mitogen-Activated Protein Kinases - metabolism</topic><topic>p38γ/p38δ</topic><topic>Phosphorylation - drug effects</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Protein Processing, Post-Translational - drug effects</topic><topic>Proto-Oncogene Proteins c-akt - agonists</topic><topic>Proto-Oncogene Proteins c-akt - antagonists & inhibitors</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>RNA Interference</topic><topic>RNA, Small Interfering</topic><topic>Tea - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cerezo-Guisado, María Isabel</creatorcontrib><creatorcontrib>Zur, Rafal</creatorcontrib><creatorcontrib>Lorenzo, María Jesús</creatorcontrib><creatorcontrib>Risco, Ana</creatorcontrib><creatorcontrib>Martín-Serrano, Miguel A.</creatorcontrib><creatorcontrib>Alvarez-Barrientos, Alberto</creatorcontrib><creatorcontrib>Cuenda, Ana</creatorcontrib><creatorcontrib>Centeno, Francisco</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><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Food and chemical toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cerezo-Guisado, María Isabel</au><au>Zur, Rafal</au><au>Lorenzo, María Jesús</au><au>Risco, Ana</au><au>Martín-Serrano, Miguel A.</au><au>Alvarez-Barrientos, Alberto</au><au>Cuenda, Ana</au><au>Centeno, Francisco</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Implication of Akt, ERK1/2 and alternative p38MAPK signalling pathways in human colon cancer cell apoptosis induced by green tea EGCG</atitle><jtitle>Food and chemical toxicology</jtitle><addtitle>Food Chem Toxicol</addtitle><date>2015-10</date><risdate>2015</risdate><volume>84</volume><spage>125</spage><epage>132</epage><pages>125-132</pages><issn>0278-6915</issn><eissn>1873-6351</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>We investigated apoptosis induced by the green tea component the epigallocatechin-3-gallate (EGCG) and the pathways underlying its activity in a colon cancer cell line. A complete understanding of the mechanism(s) and molecules targeted by green tea polyphenols could be useful in developing novel therapeutic approaches for cancer treatment. EGCG, which is the major polyphenol in green tea, has cytotoxic effects and induced cell death in HT-29 cell death. In this study, we evaluated the effect EGCG on mitogen-activated protein kinase (MAPK) and Akt pathways. EGCG treatment increased phospho-ERK1/2, -JNK1/2 and -p38α, -p38γ and -p38δ, as well as phospho-Akt levels. Using a combination of kinase inhibitors, we found that EGCG-induced cell death is partially blocked by inhibiting Akt, ERK1/2 or alternative p38MAPK activity. Our data suggest that these kinase pathways are involved in the anti-cancer effects of EGCG and indicate potential use of this compound as chemotherapeutic agent for colon cancer treatment.
•Evidence supports a preventive role for epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, in cancer.•EGCG-induced cell death on the HT-29 human colon adenocarcinoma cell line.•Akt, ERK1/2 and p38δ pathways are implicated in EGCG-induced cell death.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>26303273</pmid><doi>10.1016/j.fct.2015.08.017</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0278-6915 |
| ispartof | Food and chemical toxicology, 2015-10, Vol.84, p.125-132 |
| issn | 0278-6915 1873-6351 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1762371566 |
| source | ScienceDirect Journals |
| subjects | Akt Anticarcinogenic Agents - metabolism Antioxidants - metabolism Apoptosis Apoptosis - drug effects Catechin - analogs & derivatives Catechin - metabolism Cell Line, Tumor Colon cancer Colonic Neoplasms - chemically induced Colonic Neoplasms - enzymology Colonic Neoplasms - metabolism Colonic Neoplasms - prevention & control EGCG ERK Food Handling HEK293 Cells Humans Isoenzymes - antagonists & inhibitors Isoenzymes - chemistry Isoenzymes - genetics Isoenzymes - metabolism MAP Kinase Signaling System - drug effects Osmolar Concentration p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors p38 Mitogen-Activated Protein Kinases - chemistry p38 Mitogen-Activated Protein Kinases - genetics p38 Mitogen-Activated Protein Kinases - metabolism p38γ/p38δ Phosphorylation - drug effects Protein Kinase Inhibitors - pharmacology Protein Processing, Post-Translational - drug effects Proto-Oncogene Proteins c-akt - agonists Proto-Oncogene Proteins c-akt - antagonists & inhibitors Proto-Oncogene Proteins c-akt - metabolism RNA Interference RNA, Small Interfering Tea - chemistry |
| title | Implication of Akt, ERK1/2 and alternative p38MAPK signalling pathways in human colon cancer cell apoptosis induced by green tea EGCG |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-22T15%3A30%3A01IST&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=Implication%20of%20Akt,%20ERK1/2%20and%20alternative%20p38MAPK%20signalling%20pathways%20in%20human%20colon%20cancer%20cell%20apoptosis%20induced%20by%20green%20tea%20EGCG&rft.jtitle=Food%20and%20chemical%20toxicology&rft.au=Cerezo-Guisado,%20Mar%C3%ADa%20Isabel&rft.date=2015-10&rft.volume=84&rft.spage=125&rft.epage=132&rft.pages=125-132&rft.issn=0278-6915&rft.eissn=1873-6351&rft_id=info:doi/10.1016/j.fct.2015.08.017&rft_dat=%3Cproquest_cross%3E1718915268%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c386t-f0ab62c17030722e27701fb524f399b16ab42ceb5ab358fc89b36ff5169a37f53%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1718915268&rft_id=info:pmid/26303273&rfr_iscdi=true |