a9c208e6117b86568c4c78c0825be181 pmc_9452562.pdf ecf220915d94197852d1afd36691946971ed2413 pmc_9452562.pdf 092472993d94ddddba03144487dc0381cd792e5a2449bc13a2a33a3d4ee3644f pmc_9452562.pdf Title: High p16 expression and heterozygous RB1 loss are biomarkers for CDK4/6 inhibitor resistance in ER+ breast cancer Subject: Nature Communications, doi:10.1038/s41467-022-32828-6 Keywords: Author: Marta Palafox Creator: Springer Producer: iText® 5.3.5 ©2000-2012 1T3XT BVBA (SPRINGER SBM; licensed version) CreationDate: Wed Nov 2 06:11:19 2022 CET ModDate: Tue Nov 15 07:15:51 2022 CET Tagged: no UserProperties: no Suspects: no Form: AcroForm JavaScript: no Pages: 20 Encrypted: no Page size: 595.276 x 790.866 pts Page rot: 0 File size: 4272696 bytes Optimized: no PDF version: 1.4 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- BKCNIJ+AdvOTdd63dae3+20 Type 1C Custom yes yes yes 87 0 BKCNIG+AdvOTdd63dae3 Type 1C 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edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'bm_CR60' cannot be found Offset: 3615510 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'bm_CR21' cannot be found Offset: 3615510 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'bm_CR61' cannot be found Offset: 3615510 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'bm_CR25' cannot be found Offset: 3615510 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'bm_CR20' cannot be found Offset: 3615510 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced 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edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'bm_CR63' cannot be found Offset: 3615510 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'bm_CR64' cannot be found Offset: 3615510 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'bm_CR36' cannot be found Offset: 3615510 MIMEtype: application/pdf PDFMetadata: Objects: 1086 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseOutlines Language: EN Outlines: Item: Title: High p16 expression and heterozygous RB1 loss are biomarkers for CDK4/6 inhibitor resistance in ER+ breast cancer Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@eafc191 Children: Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612fc6eb Children: Item: Title: Ribociclib monotherapy has higher antitumor activity than other targeted agents in ER+ and HER2+ BC PDXs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1060b431 Item: Title: PDXs expressing high p16 are resistant to ribociclib Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612679d6 Item: Title: Biomarker validation in short-term patient-derived tumor cells (PDCs) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@11758f2a Item: Title: p16 and cyclin D1 overexpression attenuate the response to ribociclib in ER+ BC cell lines Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@e720b71 Item: Title: High p16 levels associated with lack of response to CDK4/6i in ER+ BC patients Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1b26f7b2 Item: Title: Acquisition of subclonal RB1 mutations as mechanism of acquired resistance to ribociclib in tumors with RB1 heterozygous loss Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@491cc5c9 Item: Title: The PI3K inhibitor alpelisib sensitizes non-basal-like BC PDX to ribociclib Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@74ad1f1f Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6a1aab78 Item: Title: Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@462d5aee Children: Item: Title: Study design Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@69b0fd6f Item: Title: Antibodies and reagents Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@757942a1 Item: Title: Cell lines Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4a87761d Item: Title: Generation of PDXs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@66d1af89 Item: Title: Molecular characterization of PDXs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@8646db9 Item: Title: In vivo experiments Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@37374a5e Item: Title: PDC ex’vivo cultures Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4671e53b Item: Title: Analysis of PDCs area Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@2db7a79b Item: Title: Analysis of S-nobreakphase entry cells by EdU incorporation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6950e31 Item: Title: Molecular modeling of the complex between p16 and P18IN003 Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@b7dd107 Item: Title: Immunohistochemistry (IHC) and image analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@42eca56e Item: Title: In vitro cell line assessment Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@52f759d7 Item: Title: Immunoblotting Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7cbd213e Item: Title: Lentiviral infection Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@192d3247 Item: Title: Real Time-qPCR ready custom panels Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3ecd23d9 Item: Title: Statistical analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@569cfc36 Item: Title: Reporting summary Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@43bd930a Item: Title: Data availability Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@33723e30 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@64f6106c Item: Title: Acknowledgements Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@553a3d88 Item: Title: Author contributions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a30d1e6 Item: Title: Competing interests Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5891e32e Item: Title: Additional information Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@cb0ed20 Info: Title: High p16 expression and heterozygous RB1 loss are biomarkers for CDK4/6 inhibitor resistance in ER+ breast cancer Author: Marta Palafox Subject: Nature Communications, doi:10.1038/s41467-022-32828-6 Keywords: Creator: Springer Producer: iText® 5.3.5 ©2000-2012 1T3XT BVBA (SPRINGER SBM; licensed version) CreationDate: Wed Nov 02 06:41:19 CET 2022 ModDate: Tue Nov 15 07:15:51 CET 2022 ID: 0x0601b350e2c6998db5f5b25f4ac73fb6, 0xf2d1ba0d7a184633603ab6957e443ac2 Filters: FilterPipeline: FlateDecode FilterPipeline: DCTDecode Images: Image: NisoImageMetadata: FormatName: image/png ImageWidth: 46 ImageHeight: 40 BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 1837 ImageHeight: 554 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Intent: Perceptual Image: NisoImageMetadata: FormatName: image/png ImageWidth: 138 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Flags: Nonsymbolic FontBBox: -93, -187, 854, 843 FontFile3: true Encoding: WinAnsiEncoding XMP: application/pdf doi:10.1038/s41467-022-32828-6 High p16 expression and heterozygous RB1 loss are biomarkers for CDK4/6 inhibitor resistance in ER+ breast cancer Marta Palafox Laia Monserrat Meritxell Bellet Guillermo Villacampa Abel Gonzalez-Perez Mafalda Oliveira Fara Brasó-Maristany Nusaibah Ibrahimi Srinivasaraghavan Kannan Leonardo Mina Maria Teresa Herrera-Abreu Andreu Òdena Mònica Sánchez-Guixé Marta Capelán Analía Azaro Alejandra Bruna Olga Rodríguez Marta Guzmán Judit Grueso Cristina Viaplana Javier Hernández Faye Su Kui Lin Robert B. Clarke Carlos Caldas Joaquín Arribas Stefan Michiels Alicia García-Sanz Nicholas C. Turner Aleix Prat Paolo Nuciforo Rodrigo Dienstmann Chandra S. Verma Nuria Lopez-Bigas Maurizio Scaltriti Monica Arnedos Cristina Saura Violeta Serra Springer US Nature Communications, doi:10.1038/s41467-022-32828-6 Springer 2022-11-15T07:15:51+01:00 2022-11-02T10:41:19+05:30 2022-11-15T07:15:51+01:00 True iText® 5.3.5 ©2000-2012 1T3XT BVBA (SPRINGER SBM; licensed version) uuid:a550c113-4dd8-43d1-97db-5acd573c0bbd uuid:3935ddd5-7f12-4ad4-b6c0-a0cfd2ce0248 default 1 converted uuid:3a09b50f-e8a1-4d40-b3ea-654f0aa157f8 converted to PDF/A-2b pdfToolbox 2022-11-02T10:42:05+05:30 2 B http://ns.adobe.com/pdf/1.3/ pdf Adobe PDF Schema internal A name object indicating whether the document has been modified to include trapping information Trapped Text http://ns.adobe.com/pdfx/1.3/ pdfx Adobe Document Info PDF eXtension Schema internal ID of PDF/X standard GTS_PDFXVersion Text internal Conformance level of PDF/X standard GTS_PDFXConformance Text internal Company creating the PDF Company Text internal Date when document was last modified SourceModified Text http://ns.adobe.com/xap/1.0/mm/ xmpMM XMP Media Management Schema internal UUID based identifier for specific incarnation of a document InstanceID URI internal The common identifier for all versions and renditions of a document. 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