NAPRT Silencing in FH-Deficient Renal Cell Carcinoma Confers Therapeutic Vulnerabilities via NAD+ Depletion
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by loss of function mutations in fumarate hydratase (FH) and results in an aggressive subtype of renal cell carcinoma with limited treatment options. Loss of FH leads to accumulation of fumarate, an oncometabolite that disrupts mul...
Saved in:
| Published in | Molecular cancer research Vol. 22; no. 10; pp. 973 - 988 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Association for Cancer Research
02.10.2024
|
| Subjects | |
| Online Access | Get full text |
| ISSN | 1541-7786 1557-3125 1557-3125 |
| DOI | 10.1158/1541-7786.MCR-23-1003 |
Cover
Loading…
| Abstract | Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by loss of function mutations in fumarate hydratase (FH) and results in an aggressive subtype of renal cell carcinoma with limited treatment options. Loss of FH leads to accumulation of fumarate, an oncometabolite that disrupts multiple cellular processes and drives tumor progression. High levels of fumarate inhibit alpha ketoglutarate-dependent dioxygenases, including the ten–eleven translocation (TET) enzymes, and can lead to global DNA hypermethylation. Here, we report patterns of hypermethylation in FH-mutant cell lines and tumor samples are associated with the silencing of nicotinate phosphoribosyl transferase (NAPRT), a rate-limiting enzyme in the Preiss–Handler pathway of NAD+ biosynthesis, in a subset of HLRCC cases. NAPRT is hypermethylated at a CpG island in the promoter in cell line models and patient samples, resulting in loss of NAPRT expression. We find that FH-deficient RCC models with loss of NAPRT expression, as well as other oncometabolite-producing cancer models that silence NAPRT, are extremely sensitive to nicotinamide phosphoribosyl transferase inhibitors (NAMPTi). NAPRT silencing was also associated with synergistic tumor cell killing with PARP inhibitors and NAMPTis, which was associated with effects on PAR-mediated DNA repair. Overall, our findings indicate that NAPRT silencing can be targeted in oncometabolite-producing cancers and elucidates how oncometabolite-associated hypermethylation can impact diverse cellular processes and lead to therapeutically relevant vulnerabilities in cancer cells.
Implications: NAPRT is a novel biomarker for targeting NAD+ metabolism in FH-deficient HLRCCs with NAMPTis alone and targeting DNA repair processes with the combination of NAMPTis and PARP inhibitors. |
|---|---|
| AbstractList | Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by loss of function mutations in fumarate hydratase (
FH
) and results in an aggressive subtype of renal cell carcinoma with limited treatment options. Loss of FH leads to accumulation of fumarate, an oncometabolite that disrupts multiple cellular processes and drives tumor progression. High levels of fumarate inhibit alpha ketoglutarate-dependent dioxygenases, including the ten–eleven translocation (TET) enzymes, and can lead to global DNA hypermethylation. Here, we report patterns of hypermethylation in FH-mutant cell lines and tumor samples are associated with the silencing of nicotinate phosphoribosyl transferase (NAPRT), a rate-limiting enzyme in the Preiss–Handler pathway of NAD
+
biosynthesis, in a subset of HLRCC cases.
NAPRT
is hypermethylated at a CpG island in the promoter in cell line models and patient samples, resulting in loss of NAPRT expression. We find that FH-deficient RCC models with loss of NAPRT expression, as well as other oncometabolite-producing cancer models that silence NAPRT, are extremely sensitive to nicotinamide phosphoribosyl transferase inhibitors (NAMPTi). NAPRT silencing was also associated with synergistic tumor cell killing with PARP inhibitors and NAMPTis, which was associated with effects on PAR-mediated DNA repair. Overall, our findings indicate that NAPRT silencing can be targeted in oncometabolite-producing cancers and elucidates how oncometabolite-associated hypermethylation can impact diverse cellular processes and lead to therapeutically relevant vulnerabilities in cancer cells.
Implications:
NAPRT is a novel biomarker for targeting NAD
+
metabolism in FH-deficient HLRCCs with NAMPTis alone and targeting DNA repair processes with the combination of NAMPTis and PARP inhibitors. Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by loss of function mutations in fumarate hydratase (FH) and results in an aggressive subtype of renal cell carcinoma with limited treatment options. Loss of FH leads to accumulation of fumarate, an oncometabolite that disrupts multiple cellular processes and drives tumor progression. High levels of fumarate inhibit alpha ketoglutarate-dependent dioxygenases, including the ten-eleven translocation (TET) enzymes, and can lead to global DNA hypermethylation. Here, we report patterns of hypermethylation in FH-mutant cell lines and tumor samples are associated with the silencing of nicotinate phosphoribosyl transferase (NAPRT), a rate-limiting enzyme in the Preiss-Handler pathway of NAD+ biosynthesis, in a subset of HLRCC cases. NAPRT is hypermethylated at a CpG island in the promoter in cell line models and patient samples, resulting in loss of NAPRT expression. We find that FH-deficient RCC models with loss of NAPRT expression, as well as other oncometabolite-producing cancer models that silence NAPRT, are extremely sensitive to nicotinamide phosphoribosyl transferase inhibitors (NAMPTi). NAPRT silencing was also associated with synergistic tumor cell killing with PARP inhibitors and NAMPTis, which was associated with effects on PAR-mediated DNA repair. Overall, our findings indicate that NAPRT silencing can be targeted in oncometabolite-producing cancers and elucidates how oncometabolite-associated hypermethylation can impact diverse cellular processes and lead to therapeutically relevant vulnerabilities in cancer cells. Implications: NAPRT is a novel biomarker for targeting NAD+ metabolism in FH-deficient HLRCCs with NAMPTis alone and targeting DNA repair processes with the combination of NAMPTis and PARP inhibitors.Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by loss of function mutations in fumarate hydratase (FH) and results in an aggressive subtype of renal cell carcinoma with limited treatment options. Loss of FH leads to accumulation of fumarate, an oncometabolite that disrupts multiple cellular processes and drives tumor progression. High levels of fumarate inhibit alpha ketoglutarate-dependent dioxygenases, including the ten-eleven translocation (TET) enzymes, and can lead to global DNA hypermethylation. Here, we report patterns of hypermethylation in FH-mutant cell lines and tumor samples are associated with the silencing of nicotinate phosphoribosyl transferase (NAPRT), a rate-limiting enzyme in the Preiss-Handler pathway of NAD+ biosynthesis, in a subset of HLRCC cases. NAPRT is hypermethylated at a CpG island in the promoter in cell line models and patient samples, resulting in loss of NAPRT expression. We find that FH-deficient RCC models with loss of NAPRT expression, as well as other oncometabolite-producing cancer models that silence NAPRT, are extremely sensitive to nicotinamide phosphoribosyl transferase inhibitors (NAMPTi). NAPRT silencing was also associated with synergistic tumor cell killing with PARP inhibitors and NAMPTis, which was associated with effects on PAR-mediated DNA repair. Overall, our findings indicate that NAPRT silencing can be targeted in oncometabolite-producing cancers and elucidates how oncometabolite-associated hypermethylation can impact diverse cellular processes and lead to therapeutically relevant vulnerabilities in cancer cells. Implications: NAPRT is a novel biomarker for targeting NAD+ metabolism in FH-deficient HLRCCs with NAMPTis alone and targeting DNA repair processes with the combination of NAMPTis and PARP inhibitors. Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by loss of function mutations in fumarate hydratase (FH) and results in an aggressive subtype of renal cell carcinoma with limited treatment options. Loss of FH leads to accumulation of fumarate, an oncometabolite that disrupts multiple cellular processes and drives tumor progression. High levels of fumarate inhibit alpha ketoglutarate-dependent dioxygenases, including the ten–eleven translocation (TET) enzymes, and can lead to global DNA hypermethylation. Here, we report patterns of hypermethylation in FH-mutant cell lines and tumor samples are associated with the silencing of nicotinate phosphoribosyl transferase (NAPRT), a rate-limiting enzyme in the Preiss–Handler pathway of NAD+ biosynthesis, in a subset of HLRCC cases. NAPRT is hypermethylated at a CpG island in the promoter in cell line models and patient samples, resulting in loss of NAPRT expression. We find that FH-deficient RCC models with loss of NAPRT expression, as well as other oncometabolite-producing cancer models that silence NAPRT, are extremely sensitive to nicotinamide phosphoribosyl transferase inhibitors (NAMPTi). NAPRT silencing was also associated with synergistic tumor cell killing with PARP inhibitors and NAMPTis, which was associated with effects on PAR-mediated DNA repair. Overall, our findings indicate that NAPRT silencing can be targeted in oncometabolite-producing cancers and elucidates how oncometabolite-associated hypermethylation can impact diverse cellular processes and lead to therapeutically relevant vulnerabilities in cancer cells. Implications: NAPRT is a novel biomarker for targeting NAD+ metabolism in FH-deficient HLRCCs with NAMPTis alone and targeting DNA repair processes with the combination of NAMPTis and PARP inhibitors. Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by loss of function mutations in fumarate hydratase (FH) and results in an aggressive subtype of renal cell carcinoma with limited treatment options. Loss of FH leads to accumulation of fumarate, an oncometabolite that disrupts multiple cellular processes and drives tumor progression. High levels of fumarate inhibit alpha ketoglutarate-dependent dioxygenases, including the ten-eleven translocation (TET) enzymes, and can lead to global DNA hypermethylation. Here, we report patterns of hypermethylation in FH-mutant cell lines and tumor samples are associated with the silencing of nicotinate phosphoribosyl transferase (NAPRT), a rate-limiting enzyme in the Preiss-Handler pathway of NAD+ biosynthesis, in a subset of HLRCC cases. NAPRT is hypermethylated at a CpG island in the promoter in cell line models and patient samples, resulting in loss of NAPRT expression. We find that FH-deficient RCC models with loss of NAPRT expression, as well as other oncometabolite-producing cancer models that silence NAPRT, are extremely sensitive to nicotinamide phosphoribosyl transferase inhibitors (NAMPTi). NAPRT silencing was also associated with synergistic tumor cell killing with PARP inhibitors and NAMPTis, which was associated with effects on PAR-mediated DNA repair. Overall, our findings indicate that NAPRT silencing can be targeted in oncometabolite-producing cancers and elucidates how oncometabolite-associated hypermethylation can impact diverse cellular processes and lead to therapeutically relevant vulnerabilities in cancer cells. Implications: NAPRT is a novel biomarker for targeting NAD+ metabolism in FH-deficient HLRCCs with NAMPTis alone and targeting DNA repair processes with the combination of NAMPTis and PARP inhibitors. |
| Author | Edmonds, Joseph Lucas, Karlie N. Shuch, Brian Noronha, Katelyn J. Raponi, Mitch Zeng, Hao Spurrier, Josh Sundaram, Ranjini K. Friedman, Sam Sachs, Chana Vasquez, Juan C. Liu, Samantha Paradkar, Sateja Murray, Matthew A. Sajed, Dipti P. Liang, Jiayu Bindra, Ranjit S. |
| AuthorAffiliation | 1 Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 2 Department of Therapeutic Radiology, Yale University, New Haven, Connecticut 8 Department of Pediatric Hematology and Oncology, Yale University, New Haven, Connecticut 4 Department of Pathology, University of California Los Angeles, Los Angeles, California 3 Department of Experimental Pathology, Yale University, New Haven, Connecticut 7 Institute of Urologic Oncology, Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California 6 Department of Urology, West China Hospital, Sichuan University, Chengdu, P.R. China 5 Alphina Therapeutics, New Haven, Connecticut |
| AuthorAffiliation_xml | – name: 3 Department of Experimental Pathology, Yale University, New Haven, Connecticut – name: 8 Department of Pediatric Hematology and Oncology, Yale University, New Haven, Connecticut – name: 2 Department of Therapeutic Radiology, Yale University, New Haven, Connecticut – name: 4 Department of Pathology, University of California Los Angeles, Los Angeles, California – name: 5 Alphina Therapeutics, New Haven, Connecticut – name: 6 Department of Urology, West China Hospital, Sichuan University, Chengdu, P.R. China – name: 1 Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut – name: 7 Institute of Urologic Oncology, Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California |
| Author_xml | – sequence: 1 givenname: Katelyn J. orcidid: 0000-0003-1994-2754 surname: Noronha fullname: Noronha, Katelyn J. – sequence: 2 givenname: Karlie N. orcidid: 0009-0001-0520-186X surname: Lucas fullname: Lucas, Karlie N. – sequence: 3 givenname: Sateja orcidid: 0000-0002-0630-9792 surname: Paradkar fullname: Paradkar, Sateja – sequence: 4 givenname: Joseph orcidid: 0000-0001-6785-9256 surname: Edmonds fullname: Edmonds, Joseph – sequence: 5 givenname: Sam orcidid: 0000-0003-1686-2791 surname: Friedman fullname: Friedman, Sam – sequence: 6 givenname: Matthew A. orcidid: 0000-0002-6424-3883 surname: Murray fullname: Murray, Matthew A. – sequence: 7 givenname: Samantha orcidid: 0009-0006-3960-7784 surname: Liu fullname: Liu, Samantha – sequence: 8 givenname: Dipti P. orcidid: 0000-0001-5357-1788 surname: Sajed fullname: Sajed, Dipti P. – sequence: 9 givenname: Chana orcidid: 0009-0006-8489-0283 surname: Sachs fullname: Sachs, Chana – sequence: 10 givenname: Josh orcidid: 0000-0002-6267-7231 surname: Spurrier fullname: Spurrier, Josh – sequence: 11 givenname: Mitch orcidid: 0009-0004-1838-7765 surname: Raponi fullname: Raponi, Mitch – sequence: 12 givenname: Jiayu orcidid: 0000-0002-5126-4511 surname: Liang fullname: Liang, Jiayu – sequence: 13 givenname: Hao orcidid: 0000-0003-0818-8151 surname: Zeng fullname: Zeng, Hao – sequence: 14 givenname: Ranjini K. orcidid: 0000-0002-5725-0284 surname: Sundaram fullname: Sundaram, Ranjini K. – sequence: 15 givenname: Brian orcidid: 0000-0003-2065-3570 surname: Shuch fullname: Shuch, Brian – sequence: 16 givenname: Juan C. orcidid: 0000-0002-9031-7639 surname: Vasquez fullname: Vasquez, Juan C. – sequence: 17 givenname: Ranjit S. orcidid: 0000-0002-3255-0467 surname: Bindra fullname: Bindra, Ranjit S. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/38949523$$D View this record in MEDLINE/PubMed |
| BookMark | eNpVkV1PFDEUhhuCkQ_9CZhekpDBfk5nrshmFsQE0awrt02nnEJ1tl3aGRL_vZ2wEr1pe9In78k5zxHaDzEAQieUnFMqm49UClop1dTnX7pVxXhFCeF76JBKqSpOmdyf3zvmAB3l_JMQRqiq36ID3rSilYwfol-3i2-rNf7uBwjWhwfsA766rpbgvPUQRryCYAbcwVAOkwoSNwZ3MThIGa8fIZktTKO3-G4aQql6P_jRQ8bP3uDbxfIML2E7wOhjeIfeODNkeL-7j9GPq8t1d13dfP30uVvcVJbXZKxa1jrHmJStA-MYdUpy5QQwbpvGSOUMAbC9sVQRp1phKCPC1L1TQtG-6fkxunjJ3U79Bu5tGSOZQW-T35j0W0fj9f8_wT_qh_isKRVC1qItCae7hBSfJsij3vhsyw5MgDhlzYkSlDc1aQr64d9mr13-rrgA8gWwKeacwL0ilOhZpZ416VmTLio143pWyf8AYueSFQ |
| Cites_doi | 10.1158/0008-5472.CAN-16-3079 10.1038/s41598-019-45346-1 10.1038/nature19353 10.1038/s41467-019-11732-6 10.1038/nature10866 10.1093/bioinformatics/btw230 10.1016/j.ccr.2010.12.014 10.1158/1078-0432.CCR-13-1186 10.1002/prp2.149 10.1016/j.ccell.2015.11.006 10.1158/0008-5472.CAN-12-2753 10.1093/narcan/zcab018 10.1016/j.cmet.2018.03.018 10.1200/JCO.2020.38.15_suppl.5004 10.1158/1535-7163.MCT-24-0012 10.1158/1078-0432.CCR-17-1121 10.1186/s13073-023-01182-7 10.1074/jbc.M610357200 10.1093/toxsci/kfu268 10.1158/1535-7163.MCT-16-0674 10.1158/1078-0432.CCR-12-1773 10.1073/pnas.1405005111 10.1016/j.ejca.2021.04.009 10.1371/journal.pone.0278108 10.1172/JCI165028 10.1002/emmm.201201250 10.1158/2159-8290.CD-20-0226 10.1016/j.cmet.2022.11.004 10.3389/fphar.2020.00656 10.1038/s41416-020-0874-y 10.1038/s41588-018-0170-4 10.1016/j.cancergen.2012.05.001 10.1056/NEJMoa1505917 10.1667/RR14746.1 10.1093/nar/gkaa718 10.1101/gad.191056.112 10.1016/j.ccr.2010.11.015 10.1016/j.ccr.2013.04.018 10.1016/j.cancergencyto.2009.08.018 10.1093/nar/gkt090 10.1038/s41586-020-2363-0 10.1016/j.celrep.2021.108840 10.1053/j.gastro.2018.05.024 10.1593/neo.131304 10.1158/1078-0432.CCR-20-3788 10.21105/joss.03021 10.1038/s41588-017-0001-z 10.1038/s41592-019-0686-2 10.1126/scitranslmed.aal2463 10.18632/oncotarget.28273 10.1111/j.2517-6161.1995.tb02031.x 10.1186/1471-2407-10-4 10.1158/1541-7786.MCR-17-0293 |
| ContentType | Journal Article |
| Copyright | 2024 The Authors; Published by the American Association for Cancer Research. 2024 The Authors; Published by the American Association for Cancer Research 2024 American Association for Cancer Research |
| Copyright_xml | – notice: 2024 The Authors; Published by the American Association for Cancer Research. – notice: 2024 The Authors; Published by the American Association for Cancer Research 2024 American Association for Cancer Research |
| DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM 7X8 5PM |
| DOI | 10.1158/1541-7786.MCR-23-1003 |
| DatabaseName | CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic PubMed Central (Full Participant titles) |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic CrossRef MEDLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine Biology |
| DocumentTitleAlternate | Therapeutic Vulnerabilities in NAPRT Silenced FH-RCC |
| EISSN | 1557-3125 |
| EndPage | 988 |
| ExternalDocumentID | PMC11445649 38949523 10_1158_1541_7786_MCR_23_1003 |
| Genre | Research Support, U.S. Gov't, P.H.S Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: Robert Wood Johnson Foundation (RWJF) – fundername: U.S. Department of Defense (DOD) grantid: W81XWH-22-1-0549 – fundername: NCI NIH HHS grantid: R01 CA215453 – fundername: NCI NIH HHS grantid: F31 CA260794 – fundername: National Cancer Institute (NCI) grantid: R01CA21543-05 – fundername: National Cancer Institute (NCI) grantid: 1-K08 CA258796-01 – fundername: National Cancer Institute (NCI) grantid: F31CA260794 – fundername: NCI NIH HHS grantid: K08 CA258796 – fundername: National Cancer Institute (NCI) grantid: F31CA261129 – fundername: Doris Duke Charitable Foundation (DDCF) grantid: 2015216 – fundername: ; grantid: F31CA261129 – fundername: ; – fundername: ; grantid: W81XWH-22-1-0549 – fundername: ; grantid: F31CA260794 – fundername: ; grantid: IRG-21-132-60-IRG – fundername: ; grantid: 2015216 – fundername: ; grantid: 1-K08 CA258796-01 – fundername: ; grantid: R01CA21543-05 |
| GroupedDBID | --- 123 18M 2FS 2WC 34G 39C 53G 5RE AAJMC AAYXX ACGFO ACPRK ADBBV AENEX AFHIN AFRAH AFUMD ALMA_UNASSIGNED_HOLDINGS BAWUL BR6 BTFSW CITATION CS3 DU5 E3Z EBS EJD F5P IH2 KQ8 L7B OK1 QTD RCR RHI TR2 WOQ YKV CGR CUY CVF ECM EIF NPM 7X8 5PM 5VS DIK GX1 HH5 W8F |
| ID | FETCH-LOGICAL-c360t-929ff22559feaf21f7537f4e23c88a57fa0eecbac170f794a1204a6bf7471b8b3 |
| ISSN | 1541-7786 1557-3125 |
| IngestDate | Thu Aug 21 18:34:58 EDT 2025 Fri Jul 11 16:54:51 EDT 2025 Sat Mar 15 01:21:17 EDT 2025 Tue Jul 01 04:31:32 EDT 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 10 |
| Language | English |
| License | 2024 The Authors; Published by the American Association for Cancer Research. This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license. |
| LinkModel | OpenURL |
| MergedId | FETCHMERGED-LOGICAL-c360t-929ff22559feaf21f7537f4e23c88a57fa0eecbac170f794a1204a6bf7471b8b3 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 J.C. Vasquez and R.S. Bindra jointly directed the work. Mol Cancer Res 2024;22:973–88 |
| ORCID | 0009-0006-3960-7784 0000-0002-6267-7231 0000-0002-6424-3883 0000-0002-5725-0284 0000-0002-5126-4511 0000-0002-0630-9792 0000-0003-0818-8151 0000-0001-5357-1788 0000-0003-2065-3570 0000-0002-9031-7639 0000-0003-1686-2791 0000-0003-1994-2754 0009-0001-0520-186X 0000-0001-6785-9256 0009-0006-8489-0283 0000-0002-3255-0467 0009-0004-1838-7765 |
| OpenAccessLink | https://pubmed.ncbi.nlm.nih.gov/PMC11445649 |
| PMID | 38949523 |
| PQID | 3074138608 |
| PQPubID | 23479 |
| PageCount | 16 |
| ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_11445649 proquest_miscellaneous_3074138608 pubmed_primary_38949523 crossref_primary_10_1158_1541_7786_MCR_23_1003 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 2024-10-02 |
| PublicationDateYYYYMMDD | 2024-10-02 |
| PublicationDate_xml | – month: 10 year: 2024 text: 2024-10-02 day: 02 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Molecular cancer research |
| PublicationTitleAlternate | Mol Cancer Res |
| PublicationYear | 2024 |
| Publisher | American Association for Cancer Research |
| Publisher_xml | – name: American Association for Cancer Research |
| References | Zhao (2024100207065408700_bib52) 2017; 16 Wu (2024100207065408700_bib27) 2021; 2 Sulkowski (2024100207065408700_bib40) 2020; 582 Ueno (2024100207065408700_bib50) 2022; 13 Zheng (2024100207065408700_bib1) 2023; 133 Swift (2024100207065408700_bib45) 2021; 34 Ricketts (2024100207065408700_bib12) 2022; 17 Zabka (2024100207065408700_bib51) 2015; 144 Liu (2024100207065408700_bib54) 2018; 27 Heske (2024100207065408700_bib55) 2017; 23 Xiao (2024100207065408700_bib7) 2012; 26 Carril-Ajuria (2024100207065408700_bib3) 2021; 151 Piacente (2024100207065408700_bib43) 2017; 77 Di Veroli (2024100207065408700_bib21) 2016; 32 Cancer Genome Atlas Research Network; Linehan WM, Spellman PT, Ricketts CJ, Creighton CJ, Fei SS, Davis C, et al (2024100207065408700_bib47) 2016; 374 Lee (2024100207065408700_bib48) 2018; 155 Benjamini (2024100207065408700_bib29) 1995; 57 Murai (2024100207065408700_bib42) 2012; 72 Sule (2024100207065408700_bib19) 2021; 3 Shames (2024100207065408700_bib32) 2013; 19 Zhou (2024100207065408700_bib24) 2018; 46 Sun (2024100207065408700_bib13) 2021; 27 Yu (2024100207065408700_bib28) 2024 Hara (2024100207065408700_bib34) 2007; 282 Yang (2024100207065408700_bib4) 2012; 18 Sulkowski (2024100207065408700_bib15) 2018; 50 Yang (2024100207065408700_bib16) 2010; 196 Muthurajan (2024100207065408700_bib39) 2014; 111 Letouzé (2024100207065408700_bib14) 2013; 23 Galli (2024100207065408700_bib53) 2020; 11 Foucquier (2024100207065408700_bib41) 2015; 3 Sulkowski (2024100207065408700_bib20) 2017; 9 Chellappa (2024100207065408700_bib35) 2022; 34 Tateishi (2024100207065408700_bib30) 2015; 28 Nagashima (2024100207065408700_bib57) 2020; 10 Srinivasan (2024100207065408700_bib2) 2020; 38 Shao (2024100207065408700_bib38) 2020; 48 Liang (2024100207065408700_bib46) 2023; 15 Oeck (2024100207065408700_bib22) 2017; 188 Turcan (2024100207065408700_bib9) 2018; 50 Peterse (2024100207065408700_bib31) 2017; 15 Figueroa (2024100207065408700_bib11) 2010; 18 Hornigold (2024100207065408700_bib36) 2020; 123 Unruh (2024100207065408700_bib10) 2019; 9 Perrier-Trudova (2024100207065408700_bib17) 2015; 35 Yang (2024100207065408700_bib18) 2012; 205 Virtanen (2024100207065408700_bib26) 2020; 17 Banáth (2024100207065408700_bib44) 2010; 10 Triche (2024100207065408700_bib23) 2013; 41 Xiao (2024100207065408700_bib37) 2013; 15 Turcan (2024100207065408700_bib8) 2012; 483 Bajrami (2024100207065408700_bib56) 2012; 4 Waskom (2024100207065408700_bib25) 2021; 6 Murray (2024100207065408700_bib49) 2024 12 [ ] Fons (2024100207065408700_bib33) 2019; 10 Xu (2024100207065408700_bib6) 2011; 19 Sciacovelli (2024100207065408700_bib5) 2016; 537 |
| References_xml | – volume: 77 start-page: 3857 year: 2017 ident: 2024100207065408700_bib43 article-title: Nicotinic acid phosphoribosyltransferase regulates cancer cell metabolism, susceptibility to NAMPT inhibitors, and DNA repair publication-title: Cancer Res doi: 10.1158/0008-5472.CAN-16-3079 – volume: 9 start-page: 8946 year: 2019 ident: 2024100207065408700_bib10 article-title: Methylation and transcription patterns are distinct in IDH mutant gliomas compared to other IDH mutant cancers publication-title: Sci Rep doi: 10.1038/s41598-019-45346-1 – volume: 537 start-page: 544 year: 2016 ident: 2024100207065408700_bib5 article-title: Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition publication-title: Nature doi: 10.1038/nature19353 – volume: 10 start-page: 3790 year: 2019 ident: 2024100207065408700_bib33 article-title: PPM1D mutations silence NAPRT gene expression and confer NAMPT inhibitor sensitivity in glioma publication-title: Nat Commun doi: 10.1038/s41467-019-11732-6 – volume: 483 start-page: 479 year: 2012 ident: 2024100207065408700_bib8 article-title: IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype publication-title: Nature doi: 10.1038/nature10866 – volume: 32 start-page: 2866 year: 2016 ident: 2024100207065408700_bib21 article-title: Combenefit: an interactive platform for the analysis and visualization of drug combinations publication-title: Bioinformatics doi: 10.1093/bioinformatics/btw230 – volume: 19 start-page: 17 year: 2011 ident: 2024100207065408700_bib6 article-title: Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases publication-title: Cancer Cell doi: 10.1016/j.ccr.2010.12.014 – volume: 19 start-page: 6912 year: 2013 ident: 2024100207065408700_bib32 article-title: Loss of NAPRT1 expression by tumor-specific promoter methylation provides a novel predictive biomarker for NAMPT inhibitors publication-title: Clin Cancer Res doi: 10.1158/1078-0432.CCR-13-1186 – volume: 3 start-page: e00149 year: 2015 ident: 2024100207065408700_bib41 article-title: Analysis of drug combinations: current methodological landscape publication-title: Pharmacol Res Perspect doi: 10.1002/prp2.149 – volume: 28 start-page: 773 year: 2015 ident: 2024100207065408700_bib30 article-title: Extreme vulnerability of IDH1 mutant cancers to NAD+ depletion publication-title: Cancer Cell doi: 10.1016/j.ccell.2015.11.006 – volume: 72 start-page: 5588 year: 2012 ident: 2024100207065408700_bib42 article-title: Trapping of PARP1 and PARP2 by clinical PARP inhibitors publication-title: Cancer Res doi: 10.1158/0008-5472.CAN-12-2753 – volume: 3 start-page: zcab018 year: 2021 ident: 2024100207065408700_bib19 article-title: Targeting IDH1/2 mutant cancers with combinations of ATR and PARP inhibitors publication-title: NAR Cancer doi: 10.1093/narcan/zcab018 – volume: 27 start-page: 1067 year: 2018 ident: 2024100207065408700_bib54 article-title: Quantitative analysis of NAD synthesis-breakdown fluxes publication-title: Cell Metab doi: 10.1016/j.cmet.2018.03.018 – volume: 2 start-page: 100141 year: 2021 ident: 2024100207065408700_bib27 article-title: clusterProfiler 4.0: a universal enrichment tool for interpreting omics data publication-title: Innovation (Camb) – volume: 38 start-page: 5004 issue: 15_Suppl year: 2020 ident: 2024100207065408700_bib2 article-title: Results from a phase II study of bevacizumab and erlotinib in subjects with advanced hereditary leiomyomatosis and renal cell cancer (HLRCC) or sporadic papillary renal cell cancer publication-title: J Clin Oncol doi: 10.1200/JCO.2020.38.15_suppl.5004 – year: 2024 12 [ ] ident: 2024100207065408700_bib49 article-title: Exploiting metabolic defects in glioma with nanoparticle encapsulated NAMPT inhibitors publication-title: Mol Cancer Ther doi: 10.1158/1535-7163.MCT-24-0012 – volume: 23 start-page: 7301 year: 2017 ident: 2024100207065408700_bib55 article-title: Matrix screen identifies synergistic combination of PARP inhibitors and nicotinamide phosphoribosyltransferase (NAMPT) inhibitors in Ewing sarcoma publication-title: Clin Cancer Res doi: 10.1158/1078-0432.CCR-17-1121 – volume: 15 start-page: 31 year: 2023 ident: 2024100207065408700_bib46 article-title: Genomic and transcriptomic features between primary and paired metastatic fumarate hydratase–deficient renal cell carcinoma publication-title: Genome Med doi: 10.1186/s13073-023-01182-7 – volume: 282 start-page: 24574 year: 2007 ident: 2024100207065408700_bib34 article-title: Elevation of cellular NAD levels by nicotinic acid and involvement of nicotinic acid phosphoribosyltransferase in human cells publication-title: J Biol Chem doi: 10.1074/jbc.M610357200 – volume: 144 start-page: 163 year: 2015 ident: 2024100207065408700_bib51 article-title: Retinal toxicity, in vivo and in vitro, associated with inhibition of nicotinamide phosphoribosyltransferase publication-title: Toxicol Sci doi: 10.1093/toxsci/kfu268 – volume: 16 start-page: 2677 year: 2017 ident: 2024100207065408700_bib52 article-title: Discovery of a highly selective NAMPT inhibitor that demonstrates robust efficacy and improved retinal toxicity with nicotinic acid coadministration publication-title: Mol Cancer Ther doi: 10.1158/1535-7163.MCT-16-0674 – volume: 18 start-page: 5562 year: 2012 ident: 2024100207065408700_bib4 article-title: IDH1 and IDH2 mutations in tumorigenesis: mechanistic insights and clinical perspectives publication-title: Clin Cancer Res doi: 10.1158/1078-0432.CCR-12-1773 – volume: 111 start-page: 12752 year: 2014 ident: 2024100207065408700_bib39 article-title: Automodification switches PARP-1 function from chromatin architectural protein to histone chaperone publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.1405005111 – volume: 151 start-page: 106 year: 2021 ident: 2024100207065408700_bib3 article-title: Response to systemic therapy in fumarate hydratase-deficient renal cell carcinoma publication-title: Eur J Cancer doi: 10.1016/j.ejca.2021.04.009 – volume: 17 start-page: e0278108 year: 2022 ident: 2024100207065408700_bib12 article-title: Kidney tumors associated with germline mutations of FH and SDHB show a CpG island methylator phenotype (CIMP) publication-title: PLoS One doi: 10.1371/journal.pone.0278108 – volume: 46 start-page: e123 year: 2018 ident: 2024100207065408700_bib24 article-title: SeSAMe: reducing artifactual detection of DNA methylation by infinium BeadChips in genomic deletions publication-title: Nucleic Acids Res – volume: 133 start-page: e165028 year: 2023 ident: 2024100207065408700_bib1 article-title: Circulating succinate-modifying metabolites accurately classify and reflect the status of fumarate hydratase–deficient renal cell carcinoma publication-title: J Clin Invest doi: 10.1172/JCI165028 – volume: 4 start-page: 1087 year: 2012 ident: 2024100207065408700_bib56 article-title: Synthetic lethality of PARP and NAMPT inhibition in triple-negative breast cancer cells publication-title: EMBO Mol Med doi: 10.1002/emmm.201201250 – volume: 10 start-page: 1672 year: 2020 ident: 2024100207065408700_bib57 article-title: Poly(ADP-ribose) glycohydrolase inhibition sequesters NAD+ to potentiate the metabolic lethality of alkylating chemotherapy in IDH-mutant tumor cells publication-title: Cancer Discov doi: 10.1158/2159-8290.CD-20-0226 – volume-title: enrichplot: Visualization of functional enrichment result year: 2024 ident: 2024100207065408700_bib28 – volume: 34 start-page: 1947 year: 2022 ident: 2024100207065408700_bib35 article-title: NAD precursors cycle between host tissues and the gut microbiome publication-title: Cell Metab doi: 10.1016/j.cmet.2022.11.004 – volume: 11 start-page: 656 year: 2020 ident: 2024100207065408700_bib53 article-title: Recent advances in NAMPT inhibitors: a novel immunotherapic strategy publication-title: Front Pharmacol doi: 10.3389/fphar.2020.00656 – volume: 123 start-page: 137 year: 2020 ident: 2024100207065408700_bib36 article-title: Dysregulation at multiple points of the kynurenine pathway is a ubiquitous feature of renal cancer: implications for tumour immune evasion publication-title: Br J Cancer doi: 10.1038/s41416-020-0874-y – volume: 50 start-page: 1086 year: 2018 ident: 2024100207065408700_bib15 article-title: Krebs-cycle-deficient hereditary cancer syndromes are defined by defects in homologous-recombination DNA repair publication-title: Nat Genet doi: 10.1038/s41588-018-0170-4 – volume: 205 start-page: 377 year: 2012 ident: 2024100207065408700_bib18 article-title: A novel fumarate hydratase-deficient HLRCC kidney cancer cell line, UOK268: a model of the Warburg effect in cancer publication-title: Cancer Genet doi: 10.1016/j.cancergen.2012.05.001 – volume: 374 start-page: 135 year: 2016 ident: 2024100207065408700_bib47 article-title: Comprehensive molecular characterization of papillary renal-cell carcinoma publication-title: N Engl J Med doi: 10.1056/NEJMoa1505917 – volume: 188 start-page: 114 year: 2017 ident: 2024100207065408700_bib22 article-title: The focinator v2-0 - graphical interface, four channels, colocalization analysis and cell phase identification publication-title: Radiat Res doi: 10.1667/RR14746.1 – volume: 48 start-page: 9694 year: 2020 ident: 2024100207065408700_bib38 article-title: Clinical PARP inhibitors do not abrogate PARP1 exchange at DNA damage sites in vivo publication-title: Nucleic Acids Res doi: 10.1093/nar/gkaa718 – volume: 26 start-page: 1326 year: 2012 ident: 2024100207065408700_bib7 article-title: Inhibition of α-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors publication-title: Genes Dev doi: 10.1101/gad.191056.112 – volume: 18 start-page: 553 year: 2010 ident: 2024100207065408700_bib11 article-title: Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation publication-title: Cancer Cell doi: 10.1016/j.ccr.2010.11.015 – volume: 23 start-page: 739 year: 2013 ident: 2024100207065408700_bib14 article-title: SDH mutations establish a hypermethylator phenotype in paraganglioma publication-title: Cancer Cell doi: 10.1016/j.ccr.2013.04.018 – volume: 35 start-page: 6639 year: 2015 ident: 2024100207065408700_bib17 article-title: Fumarate hydratase-deficient cell line NCCFH1 as a new in vitro model of hereditary papillary renal cell carcinoma type 2 publication-title: Anticancer Res – volume: 196 start-page: 45 year: 2010 ident: 2024100207065408700_bib16 article-title: UOK 262 cell line, fumarate hydratase deficient (FH-/FH-) hereditary leiomyomatosis renal cell carcinoma: in vitro and in vivo model of an aberrant energy metabolic pathway in human cancer publication-title: Cancer Genet Cytogenet doi: 10.1016/j.cancergencyto.2009.08.018 – volume: 41 start-page: e90 year: 2013 ident: 2024100207065408700_bib23 article-title: Low-level processing of illumina infinium DNA methylation BeadArrays publication-title: Nucleic Acids Res doi: 10.1093/nar/gkt090 – volume: 582 start-page: 586 year: 2020 ident: 2024100207065408700_bib40 article-title: Oncometabolites suppress DNA repair by disrupting local chromatin signalling publication-title: Nature doi: 10.1038/s41586-020-2363-0 – volume: 34 start-page: 108840 year: 2021 ident: 2024100207065408700_bib45 article-title: DSB repair pathway choice is regulated by recruitment of 53BP1 through cell cycle-dependent regulation of Sp1 publication-title: Cell Rep doi: 10.1016/j.celrep.2021.108840 – volume: 155 start-page: 799 year: 2018 ident: 2024100207065408700_bib48 article-title: Selective cytotoxicity of the NAMPT inhibitor FK866 toward gastric cancer cells with markers of the epithelial-mesenchymal transition, due to loss of NAPRT publication-title: Gastroenterology doi: 10.1053/j.gastro.2018.05.024 – volume: 15 start-page: 1151 year: 2013 ident: 2024100207065408700_bib37 article-title: Dependence of tumor cell lines and patient-derived tumors on the NAD salvage pathway renders them sensitive to NAMPT inhibition with GNE-618 publication-title: Neoplasia doi: 10.1593/neo.131304 – volume: 27 start-page: 1734 year: 2021 ident: 2024100207065408700_bib13 article-title: Integrated molecular characterization of fumarate hydratase–deficient renal cell carcinoma publication-title: Clin Cancer Res doi: 10.1158/1078-0432.CCR-20-3788 – volume: 6 start-page: 3021 year: 2021 ident: 2024100207065408700_bib25 article-title: Seaborn: statistical data visualization publication-title: J Open Source Softw doi: 10.21105/joss.03021 – volume: 50 start-page: 62 year: 2018 ident: 2024100207065408700_bib9 article-title: Mutant-IDH1-dependent chromatin state reprogramming, reversibility, and persistence publication-title: Nat Genet doi: 10.1038/s41588-017-0001-z – volume: 17 start-page: 261 year: 2020 ident: 2024100207065408700_bib26 article-title: SciPy 1.0: fundamental algorithms for scientific computing in Python publication-title: Nat Methods doi: 10.1038/s41592-019-0686-2 – volume: 9 start-page: eaal2463 year: 2017 ident: 2024100207065408700_bib20 article-title: 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity publication-title: Sci Transl Med doi: 10.1126/scitranslmed.aal2463 – volume: 13 start-page: 1054 year: 2022 ident: 2024100207065408700_bib50 article-title: Targeting Krebs-cycle-deficient renal cell carcinoma with Poly ADP-ribose polymerase inhibitors and low-dose alkylating chemotherapy publication-title: Oncotarget doi: 10.18632/oncotarget.28273 – volume: 57 start-page: 289 year: 1995 ident: 2024100207065408700_bib29 article-title: Controlling the false discovery rate: a practical and powerful approach to multiple testing publication-title: J R Stat Soc Series B Stat Methodol doi: 10.1111/j.2517-6161.1995.tb02031.x – volume: 10 start-page: 4 year: 2010 ident: 2024100207065408700_bib44 article-title: Residual gammaH2AX foci as an indication of lethal DNA lesions publication-title: BMC Cancer doi: 10.1186/1471-2407-10-4 – volume: 15 start-page: 1714 year: 2017 ident: 2024100207065408700_bib31 article-title: NAD synthesis pathway interference is a viable therapeutic strategy for chondrosarcoma publication-title: Mol Cancer Res doi: 10.1158/1541-7786.MCR-17-0293 |
| SSID | ssj0020176 |
| Score | 2.4430423 |
| Snippet | Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by loss of function mutations in fumarate hydratase (FH) and results in an aggressive... Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by loss of function mutations in fumarate hydratase ( FH ) and results in an aggressive... |
| SourceID | pubmedcentral proquest pubmed crossref |
| SourceType | Open Access Repository Aggregation Database Index Database |
| StartPage | 973 |
| SubjectTerms | Animals Cancer Interception Carcinoma, Renal Cell - drug therapy Carcinoma, Renal Cell - genetics Carcinoma, Renal Cell - metabolism Carcinoma, Renal Cell - pathology Cell Line, Tumor Dna Damage And Repair DNA Methylation Epigenetics Fumarate Hydratase - deficiency Fumarate Hydratase - genetics Fumarate Hydratase - metabolism Gene Expression Regulation, Neoplastic Gene Silencing Genitourinary Cancers Humans Kidney Neoplasms - drug therapy Kidney Neoplasms - genetics Kidney Neoplasms - metabolism Kidney Neoplasms - pathology Leiomyomatosis Metabolism Mice NAD - metabolism Neoplastic Syndromes, Hereditary Pentosyltransferases - genetics Rare Cancers Skin Neoplasms Uterine Neoplasms |
| Title | NAPRT Silencing in FH-Deficient Renal Cell Carcinoma Confers Therapeutic Vulnerabilities via NAD+ Depletion |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/38949523 https://www.proquest.com/docview/3074138608 https://pubmed.ncbi.nlm.nih.gov/PMC11445649 |
| Volume | 22 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3db9MwELfKEGgvCAaM8iUjwVOUkjjO12PpNlVDrUbXob1FTmJrZVs6dSnS-Lv4A7lLHDftJsR4iap8OJHvV9-d7-53hHzM49xnoYrtOJXC5qGT2ZHMAtvlKVcCCc8URnRH42B4wg9P_dNO53cra2lZpr3s1511Jf8jVTgHcsUq2XtI1gwKJ-A3yBeOIGE4_pOMx_2jydQ6nmHhkK5NORjaexJZITDGP5Foaw5we26APYOK-aXQNX7XmGvRVF5Z35cXyD5dJcqC62z9nAlr3N_7xL7AgnSF_Nxaek3vp6apLiaNZXJhac6g1d4yEiOc6XKzUl7cFNZhzyT_YKM1XYkGJrA1NleOxELk53XO9zE898Mojf0cZjVvBy1a2xWMV4lvrL3CctdG0rpaAelzPm6W1hXQzbLMWBt-TmuRjevmJ1pfx3VbwNuqwMfyBvO63mgwsRnm4TneSvc18f4NlWgSFSsXyY8SHCbBYRIYJmEeUj17D8hDBs4J9s34-s3ErsCiqloamjfrujEY5vOdX7NuEd1yczazdVvmz_QpeaL9FtqvQfiMdGSxQx7VnUxvdsjjkc7ReE7OK1RSg0o6K2gblbRCJUVUUoNKqlFJW6ikG6ikgEoKqLSoweQLcnKwPx0Mbd3Sw868wCltMMaVYujGKikUcxV4y6HiknlZFAk_VMKRMktF5oaOAlUhXOZwEaQK907SKPVekq1iXshXhOZBlIUpEx7LFQezPVIylyqORRBL15O8S3rNtCZXNXNL8ldxdsmHZvITWGMxcCYKOV9eJx7a3V4UOFGX7NbCMEOCwc9jn8HT0ZqYzA3I375-pZidVTzursuRzCl-fd8vfUO2V3-tt2SrXCzlO7CNy_R9BcU_QWm0xA |
| linkProvider | Colorado Alliance of Research Libraries |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=NAPRT+Silencing+in+FH-Deficient+Renal+Cell+Carcinoma+Confers+Therapeutic+Vulnerabilities+via+NAD%2B+Depletion&rft.jtitle=Molecular+cancer+research&rft.au=Noronha%2C+Katelyn+J.&rft.au=Lucas%2C+Karlie+N.&rft.au=Paradkar%2C+Sateja&rft.au=Edmonds%2C+Joseph&rft.date=2024-10-02&rft.issn=1541-7786&rft.eissn=1557-3125&rft.volume=22&rft.issue=10&rft.spage=973&rft.epage=988&rft_id=info:doi/10.1158%2F1541-7786.MCR-23-1003&rft.externalDBID=n%2Fa&rft.externalDocID=10_1158_1541_7786_MCR_23_1003 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1541-7786&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1541-7786&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1541-7786&client=summon |