2de59dd23f1fd592eeb149cfb70ce527 cancers_a2019v11p1301.pdf 02c5d62e5c6c8aba96583fb82de85dd78c02f36d cancers_a2019v11p1301.pdf 662fb282c8b249566990cca18e97b2e13fd4848dec14dea3096bf3a1172b87f5 cancers_a2019v11p1301.pdf Title: Immunotherapy with Monoclonal Antibodies in Lung Cancer of Mice: Oxidative Stress and Other Biological Events Subject: Background: Lung cancer (LC) is a major leading cause of death worldwide. Immunomodulators that target several immune mechanisms have proven to reduce tumor burden in experimental models through induction of the immune microenvironment. We hypothesized that other biological mechanisms may also favor tumor burden reduction in lung cancer-bearing mice treated with immunomodulators. Methods: Tumor weight, area, T cells and tumor growth (immunohistochemistry), oxidative stress, apoptosis, autophagy, and signaling (NF-B and sirtuin-1) markers were analyzed (immunoblotting) in subcutaneous tumor of BALB/c mice injected with LP07 adenocarcinoma cells treated with monoclonal antibodies (CD-137, CTLA-4, PD-1, and CD-19, N = 9/group) and non-treated control animals. Results: Compared to non-treated cancer mice, in tumors of monoclonal-treated animals, tumor area and weight and ki-67 were significantly reduced, while T cell counts, oxidative stress, apoptosis, autophagy, activated p65, and sirtuin-1 markers were increased. Conclusions: Immunomodulators elicited a reduction in tumor burden (reduced tumor size and weight) through decreased tumor proliferation and increased oxidative stress, apoptosis, autophagy, and signaling markers, which may have interfered with the immune profile of the tumor microenvironment. Future research should be devoted to the elucidation of the specific contribution of each biological mechanism to the reduced tumor burden. Keywords: experimental lung cancer; immunomodulators; oxidative stress; autophagy; tumor growth; sirtuin-1 Author: Jun Tang, Daniel Ramis-Cabrer, Xuejie Wang and Esther Barreiro Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.15 CreationDate: Wed Sep 4 12:23:29 2019 CEST ModDate: Wed Sep 4 12:23:29 2019 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 3487653 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- XOLCSQ+URWPalladioL-Ital Type 1 Custom yes yes no 123 0 KEZQJJ+URWPalladioL-Bold Type 1 Custom yes yes no 124 0 PEDJGM+URWPalladioL-Roma Type 1 Custom yes yes no 125 0 SVVJCD+Rpxr Type 1 Builtin yes yes no 126 0 KTITPW+VnURWPalladioL Type 1 Custom yes yes no 127 0 AYXMDM+EURM10 Type 1 Builtin yes yes no 128 0 LCJEVJ+TimesNewRomanPS-BoldItalicMT 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no 510 0 GBLQZB+Rpxi Type 1 Builtin yes yes no 544 0 PFMNHK+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 552 0 PFMNHM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 553 0 PFMNIN+PalatinoLinotype CID TrueType Identity-H yes yes yes 554 0 PFMNIO+PalatinoLinotype TrueType WinAnsi yes yes no 555 0 VSHNAE+Rpcxr Type 1 Builtin yes yes no 729 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2020-08-10 13:17:21 CEST RepresentationInformation: cancers_a2019v11p1301.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2020-01-10 12:18:21 CET Size: 3487653 Format: PDF Version: 1.5 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 0 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: ぉのぴひはつふっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸲ Item: Title: きづぴとはつびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮ㄩ‾㸊⡜㌷㙜㌷㝜〰ぁのどねちぬぜ〴ぜ〰ぅへばづひどねづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸲⸱⸱ Children: Item: Title: ぁのどねちぬぜ〴ぜ〰ぅへばづひどねづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸲⸱⸱ Children: Item: Title: ぅへばづひどねづのぴちぬぜ〴ぜ〰いづびどでのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸲⸱⸲ Item: Title: ぉのぜ〴ぜ〰ざどぶはぜ〴ぜ〰きづちびふひづねづのぴびぜ〴ぜ〰ぃはのつふっぴづつぜ〴ぜ〰はのぜ〴ぜ〰ぴとづぜ〴ぜ〰ぁのどねちぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸲⸱⸳ Item: Title: こちっひどてどっづぜ〴ぜ〰ちのつぜ〴ぜ〰こちねばぬづぜ〴ぜ〰ぃはぬぬづっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰きはぬづっふぬちひぜ〴ぜ〰あどはぬはでべぜ〴ぜ〰ぁのちぬべびづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸲⸲⸱ Item: Title: きはぬづっふぬちひぜ〴ぜ〰あどはぬはでべぜ〴ぜ〰ぁのちぬべびづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸲⸲⸱ Children: Item: Title: えどびぴはぬはでどっちぬぜ〴ぜ〰ぁのちぬべびづびぜ〴ぜ〰はてぜ〴ぜ〰ごふねはひぜ〴ぜ〰こちねばぬづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸲⸲⸲ Item: Title: ぉねねふのはぢぬはぴぴどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: げづびふぬぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮ㄩ‾㸊⡜㌷㙜㌷㝜〰きはのはっぬはのちぬぜ〴ぜ〰ぁのぴどぢはつどづびぜ〴ぜ〰ぉねばひはぶづつぜ〴ぜ〰ごふねはひぜ〴ぜ〰あふひつづのぜ〴ぜ〰ちのつぜ〴ぜ〰あはつべぜ〴ぜ〰しづどでとぴぜ〴ぜ〰どのぜ〴ぜ〰きどっづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰ぉねねふのづぜ〴ぜ〰きどっひはづのぶどひはのねづのぴぜ〴ぜ〰どのぜ〴ぜ〰げづびばはのびづぜ〴ぜ〰ぴはぜ〴ぜ〰ぴとづぜ〴ぜ〰ぉねねふのはねはつふぬちぴはひびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰ごふねはひぜ〴ぜ〰くへどつちぴどぶづぜ〴ぜ〰こぴひづびびぜ〴ぜ〰どのぜ〴ぜ〰げづびばはのびづぜ〴ぜ〰ぴはぜ〴ぜ〰ぴとづぜ〴ぜ〰ぉねねふのはねはつふぬちぴはひびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰ごふねはひぜ〴ぜ〰ぁばはばぴはびどびぜ〴ぜ〰ちのつぜ〴ぜ〰ぁふぴはばとちでべぜ〴ぜ〰きちひにづひびぜ〴ぜ〰どのぜ〴ぜ〰げづびばはのびづぜ〴ぜ〰ぴはぜ〴ぜ〰ぉねねふのはねはつふぬちぴはひびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㔩‾㸊⡜㌷㙜㌷㝜〰ぅててづっぴびぜ〴ぜ〰はてぜ〴ぜ〰ぴとづぜ〴ぜ〰ぉねねふのはねはつふぬちぴはひびぜ〴ぜ〰はのぜ〴ぜ〰こどでのちぬどのでぜ〴ぜ〰きちひにづひびぜ〴ぜ〰どのぜ〴ぜ〰ごふねはひびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Children: Item: Title: きはのはっぬはのちぬぜ〴ぜ〰ぁのぴどぢはつどづびぜ〴ぜ〰ぉねばひはぶづつぜ〴ぜ〰ごふねはひぜ〴ぜ〰あふひつづのぜ〴ぜ〰ちのつぜ〴ぜ〰あはつべぜ〴ぜ〰しづどでとぴぜ〴ぜ〰どのぜ〴ぜ〰きどっづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰ぉねねふのづぜ〴ぜ〰きどっひはづのぶどひはのねづのぴぜ〴ぜ〰どのぜ〴ぜ〰げづびばはのびづぜ〴ぜ〰ぴはぜ〴ぜ〰ぴとづぜ〴ぜ〰ぉねねふのはねはつふぬちぴはひびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰ごふねはひぜ〴ぜ〰くへどつちぴどぶづぜ〴ぜ〰こぴひづびびぜ〴ぜ〰どのぜ〴ぜ〰げづびばはのびづぜ〴ぜ〰ぴはぜ〴ぜ〰ぴとづぜ〴ぜ〰ぉねねふのはねはつふぬちぴはひびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰ごふねはひぜ〴ぜ〰ぁばはばぴはびどびぜ〴ぜ〰ちのつぜ〴ぜ〰ぁふぴはばとちでべぜ〴ぜ〰きちひにづひびぜ〴ぜ〰どのぜ〴ぜ〰げづびばはのびづぜ〴ぜ〰ぴはぜ〴ぜ〰ぉねねふのはねはつふぬちぴはひびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㔩‾㸊⡜㌷㙜㌷㝜〰ぅててづっぴびぜ〴ぜ〰はてぜ〴ぜ〰ぴとづぜ〴ぜ〰ぉねねふのはねはつふぬちぴはひびぜ〴ぜ〰はのぜ〴ぜ〰こどでのちぬどのでぜ〴ぜ〰きちひにづひびぜ〴ぜ〰どのぜ〴ぜ〰ごふねはひびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぉねねふのづぜ〴ぜ〰きどっひはづのぶどひはのねづのぴぜ〴ぜ〰どのぜ〴ぜ〰げづびばはのびづぜ〴ぜ〰ぴはぜ〴ぜ〰ぴとづぜ〴ぜ〰ぉねねふのはねはつふぬちぴはひびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰ごふねはひぜ〴ぜ〰くへどつちぴどぶづぜ〴ぜ〰こぴひづびびぜ〴ぜ〰どのぜ〴ぜ〰げづびばはのびづぜ〴ぜ〰ぴはぜ〴ぜ〰ぴとづぜ〴ぜ〰ぉねねふのはねはつふぬちぴはひびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰ごふねはひぜ〴ぜ〰ぁばはばぴはびどびぜ〴ぜ〰ちのつぜ〴ぜ〰ぁふぴはばとちでべぜ〴ぜ〰きちひにづひびぜ〴ぜ〰どのぜ〴ぜ〰げづびばはのびづぜ〴ぜ〰ぴはぜ〴ぜ〰ぉねねふのはねはつふぬちぴはひびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㔩‾㸊⡜㌷㙜㌷㝜〰ぅててづっぴびぜ〴ぜ〰はてぜ〴ぜ〰ぴとづぜ〴ぜ〰ぉねねふのはねはつふぬちぴはひびぜ〴ぜ〰はのぜ〴ぜ〰こどでのちぬどのでぜ〴ぜ〰きちひにづひびぜ〴ぜ〰どのぜ〴ぜ〰ごふねはひびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ごふねはひぜ〴ぜ〰くへどつちぴどぶづぜ〴ぜ〰こぴひづびびぜ〴ぜ〰どのぜ〴ぜ〰げづびばはのびづぜ〴ぜ〰ぴはぜ〴ぜ〰ぴとづぜ〴ぜ〰ぉねねふのはねはつふぬちぴはひびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰ごふねはひぜ〴ぜ〰ぁばはばぴはびどびぜ〴ぜ〰ちのつぜ〴ぜ〰ぁふぴはばとちでべぜ〴ぜ〰きちひにづひびぜ〴ぜ〰どのぜ〴ぜ〰げづびばはのびづぜ〴ぜ〰ぴはぜ〴ぜ〰ぉねねふのはねはつふぬちぴはひびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㔩‾㸊⡜㌷㙜㌷㝜〰ぅててづっぴびぜ〴ぜ〰はてぜ〴ぜ〰ぴとづぜ〴ぜ〰ぉねねふのはねはつふぬちぴはひびぜ〴ぜ〰はのぜ〴ぜ〰こどでのちぬどのでぜ〴ぜ〰きちひにづひびぜ〴ぜ〰どのぜ〴ぜ〰ごふねはひびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ごふねはひぜ〴ぜ〰ぁばはばぴはびどびぜ〴ぜ〰ちのつぜ〴ぜ〰ぁふぴはばとちでべぜ〴ぜ〰きちひにづひびぜ〴ぜ〰どのぜ〴ぜ〰げづびばはのびづぜ〴ぜ〰ぴはぜ〴ぜ〰ぉねねふのはねはつふぬちぴはひびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㔩‾㸊⡜㌷㙜㌷㝜〰ぅててづっぴびぜ〴ぜ〰はてぜ〴ぜ〰ぴとづぜ〴ぜ〰ぉねねふのはねはつふぬちぴはひびぜ〴ぜ〰はのぜ〴ぜ〰こどでのちぬどのでぜ〴ぜ〰きちひにづひびぜ〴ぜ〰どのぜ〴ぜ〰ごふねはひびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぅててづっぴびぜ〴ぜ〰はてぜ〴ぜ〰ぴとづぜ〴ぜ〰ぉねねふのはねはつふぬちぴはひびぜ〴ぜ〰はのぜ〴ぜ〰こどでのちぬどのでぜ〴ぜ〰きちひにづひびぜ〴ぜ〰どのぜ〴ぜ〰ごふねはひびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: いどびっふびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: ぃはのっぬふびどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: げづてづひづのっづび Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: AYXMDM+EURM10 FontSubset: true FirstChar: 20 LastChar: 22 FontDescriptor: FontName: AYXMDM+EURM10 Flags: Symbolic FontBBox: -32, -243, 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