Alterations in Polyamine Metabolism in Patients With Lymphangioleiomyomatosis and Tuberous Sclerosis Complex 2-Deficient Cells.
Identifieur interne : 000045 ( PubMed/Corpus ); précédent : 000044; suivant : 000046Alterations in Polyamine Metabolism in Patients With Lymphangioleiomyomatosis and Tuberous Sclerosis Complex 2-Deficient Cells.
Auteurs : Yan Tang ; Souheil El-Chemaly ; Angelo Taveira-Dasilva ; Hilary J. Goldberg ; Shefali Bagwe ; Ivan O. Rosas ; Joel Moss ; Carmen Priolo ; Elizabeth P. HenskeSource :
- Chest [ 1931-3543 ] ; 2019.
Abstract
Lymphangioleiomyomatosis (LAM), a destructive lung disease that affects primarily women, is caused by loss-of-function mutations in TSC1 or TSC2, leading to hyperactivation of mechanistic/mammalian target of rapamycin complex 1 (mTORC1). Rapamycin (sirolimus) treatment suppresses mTORC1 but also induces autophagy, which promotes the survival of TSC2-deficient cells. Based on the hypothesis that simultaneous inhibition of mTORC1 and autophagy would limit the availability of critical nutrients and inhibit LAM cells, we conducted a phase 1 clinical trial of sirolimus and hydroxychloroquine for LAM. Here, we report the analyses of plasma metabolomic profiles from the clinical trial.
DOI: 10.1016/j.chest.2019.05.038
PubMed: 31299246
Links to Exploration step
pubmed:31299246Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Alterations in Polyamine Metabolism in Patients With Lymphangioleiomyomatosis and Tuberous Sclerosis Complex 2-Deficient Cells.</title><author><name sortKey="Tang, Yan" sort="Tang, Yan" uniqKey="Tang Y" first="Yan" last="Tang">Yan Tang</name><affiliation><nlm:affiliation>Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.</nlm:affiliation></affiliation></author><author><name sortKey="El Chemaly, Souheil" sort="El Chemaly, Souheil" uniqKey="El Chemaly S" first="Souheil" last="El-Chemaly">Souheil El-Chemaly</name><affiliation><nlm:affiliation>Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.</nlm:affiliation></affiliation></author><author><name sortKey="Taveira Dasilva, Angelo" sort="Taveira Dasilva, Angelo" uniqKey="Taveira Dasilva A" first="Angelo" last="Taveira-Dasilva">Angelo Taveira-Dasilva</name><affiliation><nlm:affiliation>Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.</nlm:affiliation></affiliation></author><author><name sortKey="Goldberg, Hilary J" sort="Goldberg, Hilary J" uniqKey="Goldberg H" first="Hilary J" last="Goldberg">Hilary J. Goldberg</name><affiliation><nlm:affiliation>Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.</nlm:affiliation></affiliation></author><author><name sortKey="Bagwe, Shefali" sort="Bagwe, Shefali" uniqKey="Bagwe S" first="Shefali" last="Bagwe">Shefali Bagwe</name><affiliation><nlm:affiliation>Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.</nlm:affiliation></affiliation></author><author><name sortKey="Rosas, Ivan O" sort="Rosas, Ivan O" uniqKey="Rosas I" first="Ivan O" last="Rosas">Ivan O. Rosas</name><affiliation><nlm:affiliation>Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.</nlm:affiliation></affiliation></author><author><name sortKey="Moss, Joel" sort="Moss, Joel" uniqKey="Moss J" first="Joel" last="Moss">Joel Moss</name><affiliation><nlm:affiliation>Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.</nlm:affiliation></affiliation></author><author><name sortKey="Priolo, Carmen" sort="Priolo, Carmen" uniqKey="Priolo C" first="Carmen" last="Priolo">Carmen Priolo</name><affiliation><nlm:affiliation>Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. Electronic address: Carmen_priolo@dfci.harvard.edu.</nlm:affiliation></affiliation></author><author><name sortKey="Henske, Elizabeth P" sort="Henske, Elizabeth P" uniqKey="Henske E" first="Elizabeth P" last="Henske">Elizabeth P. Henske</name><affiliation><nlm:affiliation>Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2019">2019</date><idno type="RBID">pubmed:31299246</idno><idno type="pmid">31299246</idno><idno type="doi">10.1016/j.chest.2019.05.038</idno><idno type="wicri:Area/PubMed/Corpus">000045</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000045</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Alterations in Polyamine Metabolism in Patients With Lymphangioleiomyomatosis and Tuberous Sclerosis Complex 2-Deficient Cells.</title><author><name sortKey="Tang, Yan" sort="Tang, Yan" uniqKey="Tang Y" first="Yan" last="Tang">Yan Tang</name><affiliation><nlm:affiliation>Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.</nlm:affiliation></affiliation></author><author><name sortKey="El Chemaly, Souheil" sort="El Chemaly, Souheil" uniqKey="El Chemaly S" first="Souheil" last="El-Chemaly">Souheil El-Chemaly</name><affiliation><nlm:affiliation>Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.</nlm:affiliation></affiliation></author><author><name sortKey="Taveira Dasilva, Angelo" sort="Taveira Dasilva, Angelo" uniqKey="Taveira Dasilva A" first="Angelo" last="Taveira-Dasilva">Angelo Taveira-Dasilva</name><affiliation><nlm:affiliation>Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.</nlm:affiliation></affiliation></author><author><name sortKey="Goldberg, Hilary J" sort="Goldberg, Hilary J" uniqKey="Goldberg H" first="Hilary J" last="Goldberg">Hilary J. Goldberg</name><affiliation><nlm:affiliation>Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.</nlm:affiliation></affiliation></author><author><name sortKey="Bagwe, Shefali" sort="Bagwe, Shefali" uniqKey="Bagwe S" first="Shefali" last="Bagwe">Shefali Bagwe</name><affiliation><nlm:affiliation>Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.</nlm:affiliation></affiliation></author><author><name sortKey="Rosas, Ivan O" sort="Rosas, Ivan O" uniqKey="Rosas I" first="Ivan O" last="Rosas">Ivan O. Rosas</name><affiliation><nlm:affiliation>Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.</nlm:affiliation></affiliation></author><author><name sortKey="Moss, Joel" sort="Moss, Joel" uniqKey="Moss J" first="Joel" last="Moss">Joel Moss</name><affiliation><nlm:affiliation>Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.</nlm:affiliation></affiliation></author><author><name sortKey="Priolo, Carmen" sort="Priolo, Carmen" uniqKey="Priolo C" first="Carmen" last="Priolo">Carmen Priolo</name><affiliation><nlm:affiliation>Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. Electronic address: Carmen_priolo@dfci.harvard.edu.</nlm:affiliation></affiliation></author><author><name sortKey="Henske, Elizabeth P" sort="Henske, Elizabeth P" uniqKey="Henske E" first="Elizabeth P" last="Henske">Elizabeth P. Henske</name><affiliation><nlm:affiliation>Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Chest</title><idno type="eISSN">1931-3543</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Lymphangioleiomyomatosis (LAM), a destructive lung disease that affects primarily women, is caused by loss-of-function mutations in TSC1 or TSC2, leading to hyperactivation of mechanistic/mammalian target of rapamycin complex 1 (mTORC1). Rapamycin (sirolimus) treatment suppresses mTORC1 but also induces autophagy, which promotes the survival of TSC2-deficient cells. Based on the hypothesis that simultaneous inhibition of mTORC1 and autophagy would limit the availability of critical nutrients and inhibit LAM cells, we conducted a phase 1 clinical trial of sirolimus and hydroxychloroquine for LAM. Here, we report the analyses of plasma metabolomic profiles from the clinical trial.</div></front></TEI><pubmed><MedlineCitation Status="In-Data-Review" Owner="NLM"><PMID Version="1">31299246</PMID><DateRevised><Year>2019</Year><Month>12</Month><Day>22</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1931-3543</ISSN><JournalIssue CitedMedium="Internet"><Volume>156</Volume><Issue>6</Issue><PubDate><Year>2019</Year><Month>Dec</Month></PubDate></JournalIssue><Title>Chest</Title><ISOAbbreviation>Chest</ISOAbbreviation></Journal><ArticleTitle>Alterations in Polyamine Metabolism in Patients With Lymphangioleiomyomatosis and Tuberous Sclerosis Complex 2-Deficient Cells.</ArticleTitle><Pagination><MedlinePgn>1137-1148</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0012-3692(19)31310-8</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.chest.2019.05.038</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Lymphangioleiomyomatosis (LAM), a destructive lung disease that affects primarily women, is caused by loss-of-function mutations in TSC1 or TSC2, leading to hyperactivation of mechanistic/mammalian target of rapamycin complex 1 (mTORC1). Rapamycin (sirolimus) treatment suppresses mTORC1 but also induces autophagy, which promotes the survival of TSC2-deficient cells. Based on the hypothesis that simultaneous inhibition of mTORC1 and autophagy would limit the availability of critical nutrients and inhibit LAM cells, we conducted a phase 1 clinical trial of sirolimus and hydroxychloroquine for LAM. Here, we report the analyses of plasma metabolomic profiles from the clinical trial.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">We analyzed the plasma metabolome in samples obtained before, during, and after 6 months of treatment with sirolimus and hydroxychloroquine, using univariate statistical models and machine learning approaches. Metabolites and metabolic pathways were validated in TSC2-deficient cells derived from patients with LAM. Single-cell RNA-Seq was employed to assess metabolic enzymes in an early-passage culture from an LAM lung.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">Metabolomic profiling revealed changes in polyamine metabolism during treatment, with 5'-methylthioadenosine and arginine among the most highly upregulated metabolites. Similar findings were observed in TSC2-deficient cells derived from patients with LAM. Single-cell transcriptomic profiling of primary LAM cultured cells revealed that mTORC1 inhibition upregulated key enzymes in the polyamine metabolism pathway, including adenosylmethionine decarboxylase 1.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Our data demonstrate that polyamine metabolic pathways are targeted by the combination of rapamycin and hydroxychloroquine, leading to upregulation of 5'-methylthioadenosine and arginine in the plasma of patients with LAM and in TSC2-deficient cells derived from a patient with LAM upon treatment with this drug combination.</AbstractText><AbstractText Label="TRIAL REGISTRY" NlmCategory="BACKGROUND">ClinicalTrials.gov; No.: NCT01687179; URL: www.clinicaltrials.gov. Partners Human Research Committee, protocol No. 2012P000669.</AbstractText><CopyrightInformation>Copyright © 2019 American College of Chest Physicians. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Tang</LastName><ForeName>Yan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>El-Chemaly</LastName><ForeName>Souheil</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Taveira-Dasilva</LastName><ForeName>Angelo</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Goldberg</LastName><ForeName>Hilary J</ForeName><Initials>HJ</Initials><AffiliationInfo><Affiliation>Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bagwe</LastName><ForeName>Shefali</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rosas</LastName><ForeName>Ivan O</ForeName><Initials>IO</Initials><AffiliationInfo><Affiliation>Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Moss</LastName><ForeName>Joel</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Priolo</LastName><ForeName>Carmen</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. Electronic address: Carmen_priolo@dfci.harvard.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Henske</LastName><ForeName>Elizabeth P</ForeName><Initials>EP</Initials><AffiliationInfo><Affiliation>Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><DataBankList CompleteYN="Y"><DataBank><DataBankName>ClinicalTrials.gov</DataBankName><AccessionNumberList><AccessionNumber>NCT01687179</AccessionNumber></AccessionNumberList></DataBank></DataBankList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>07</Month><Day>09</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Chest</MedlineTA><NlmUniqueID>0231335</NlmUniqueID><ISSNLinking>0012-3692</ISSNLinking></MedlineJournalInfo><CitationSubset>AIM</CitationSubset><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">5′-methylthioadenosine</Keyword><Keyword MajorTopicYN="N">angiomyolipoma</Keyword><Keyword MajorTopicYN="N">arginine</Keyword><Keyword MajorTopicYN="N">autophagy</Keyword><Keyword MajorTopicYN="N">hydroxychloroquine</Keyword><Keyword MajorTopicYN="N">lymphangioleiomyomatosis</Keyword><Keyword MajorTopicYN="N">mechanistic/mammalian target of rapamycin complex 1</Keyword><Keyword MajorTopicYN="N">metabolomics</Keyword><Keyword MajorTopicYN="N">polyamines</Keyword><Keyword MajorTopicYN="N">rapamycin</Keyword><Keyword MajorTopicYN="N">single-cell transcriptomics</Keyword><Keyword MajorTopicYN="N">sirolimus</Keyword><Keyword MajorTopicYN="N">tuberous sclerosis</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>02</Month><Day>03</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2019</Year><Month>04</Month><Day>29</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>05</Month><Day>06</Day></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2020</Year><Month>12</Month><Day>01</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>7</Month><Day>13</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>7</Month><Day>13</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>7</Month><Day>13</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31299246</ArticleId><ArticleId IdType="pii">S0012-3692(19)31310-8</ArticleId><ArticleId IdType="doi">10.1016/j.chest.2019.05.038</ArticleId><ArticleId IdType="pmc">PMC6904859</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Annu Rev Genet. 2009;43:67-93</Citation><ArticleIdList><ArticleId IdType="pubmed">19653858</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Nat Immunol. 2019 Feb;20(2):163-172</Citation><ArticleIdList><ArticleId IdType="pubmed">30643263</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Chest. 2017 Jun;151(6):1302-1310</Citation><ArticleIdList><ArticleId IdType="pubmed">28192114</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Nature. 2017 Jul 6;547(7661):109-113</Citation><ArticleIdList><ArticleId IdType="pubmed">28658205</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Chest. 2018 Nov;154(5):1070-1082</Citation><ArticleIdList><ArticleId IdType="pubmed">30144422</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Proc Natl Acad Sci U S A. 2000 May 23;97(11):6085-90</Citation><ArticleIdList><ArticleId IdType="pubmed">10823953</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Bioinformatics. 2010 May 15;26(10):1308-15</Citation><ArticleIdList><ArticleId IdType="pubmed">20363728</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Am J Respir Crit Care Med. 2013 Mar 15;187(6):663-5</Citation><ArticleIdList><ArticleId IdType="pubmed">23504366</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>N Engl J Med. 2011 Apr 28;364(17):1595-606</Citation><ArticleIdList><ArticleId IdType="pubmed">21410393</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Am J Pathol. 2017 Aug;187(8):1750-1762</Citation><ArticleIdList><ArticleId IdType="pubmed">28623674</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Nucleic Acids Res. 2015 Apr 20;43(7):e47</Citation><ArticleIdList><ArticleId IdType="pubmed">25605792</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Mol Cancer Res. 2014 Jan;12(1):48-57</Citation><ArticleIdList><ArticleId IdType="pubmed">24296756</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Science. 2016 Mar 11;351(6278):1208-13</Citation><ArticleIdList><ArticleId IdType="pubmed">26912361</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Cell. 2017 Mar 9;168(6):960-976</Citation><ArticleIdList><ArticleId IdType="pubmed">28283069</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Nat Biotechnol. 2018 Jun;36(5):411-420</Citation><ArticleIdList><ArticleId IdType="pubmed">29608179</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Proc Natl Acad Sci U S A. 2011 Jul 26;108(30):12455-60</Citation><ArticleIdList><ArticleId IdType="pubmed">21746920</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Nucleic Acids Res. 2018 Jul 2;46(W1):W486-W494</Citation><ArticleIdList><ArticleId IdType="pubmed">29762782</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Eur Respir J. 2018 Nov 1;52(5):</Citation><ArticleIdList><ArticleId IdType="pubmed">30093573</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Exp Med. 2014 Jan 13;211(1):15-28</Citation><ArticleIdList><ArticleId IdType="pubmed">24395886</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Biochem Pharmacol. 1982 Feb 1;31(3):277-88</Citation><ArticleIdList><ArticleId IdType="pubmed">6803807</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Nat Rev Dis Primers. 2016 May 26;2:16035</Citation><ArticleIdList><ArticleId IdType="pubmed">27226234</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Clin Invest. 2012 Nov;122(11):3807-16</Citation><ArticleIdList><ArticleId IdType="pubmed">23114603</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Nat Rev Cancer. 2012 Apr 26;12(6):401-10</Citation><ArticleIdList><ArticleId IdType="pubmed">22534666</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Nat Rev Mol Cell Biol. 2014 Mar;15(3):155-62</Citation><ArticleIdList><ArticleId IdType="pubmed">24556838</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Curr Opin Cell Biol. 2017 Apr;45:72-82</Citation><ArticleIdList><ArticleId IdType="pubmed">28411448</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Am J Respir Cell Mol Biol. 2015 Jul;53(1):33-41</Citation><ArticleIdList><ArticleId IdType="pubmed">25780943</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Trends Mol Med. 2013 Aug;19(8):447-53</Citation><ArticleIdList><ArticleId IdType="pubmed">23769623</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Expert Rev Respir Med. 2018 Feb;12(2):95-102</Citation><ArticleIdList><ArticleId IdType="pubmed">29171770</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Cancer Cell. 2017 Nov 13;32(5):624-638.e5</Citation><ArticleIdList><ArticleId IdType="pubmed">29056426</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Biochem Biophys Res Commun. 2014 Jan 3;443(1):285-9</Citation><ArticleIdList><ArticleId IdType="pubmed">24309102</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/PubMed/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000045 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PubMed/Corpus/biblio.hfd -nk 000045 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= ChloroquineV1
|flux= PubMed
|étape= Corpus
|type= RBID
|clé= pubmed:31299246
|texte= Alterations in Polyamine Metabolism in Patients With Lymphangioleiomyomatosis and Tuberous Sclerosis Complex 2-Deficient Cells.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Corpus/RBID.i -Sk "pubmed:31299246" \
| HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a ChloroquineV1
| This area was generated with Dilib version V0.6.33. |  |