bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Exploring the Immunogenicity of Noncanonical HLA-I Tumor Ligands Identified through Proteogenomics
Authors: Lozano-Rabella Maria , Garcia-Garijo Andrea , Palomero Jara , Yuste-Estevanez Anna , Erhard Florian , Farriol-Duran Roc , Martín-Liberal Juan , Ochoa-de-Olza Maria , Matos Ignacio , Gartner Jared J. , Ghosh Michael , Canals Francesc , Vidal August , Piulats Josep Maria , Matías-Guiu Xavier , Brana Irene , Muñoz-Couselo Eva , Garralda Elena , Schlosser Andreas , Gros Alena
Published: April 2023

AbstractPurpose:
Tumor antigens are central to antitumor immunity. Recent evidence suggests that peptides from noncanonical (nonC) aberrantly translated proteins can be presented on HLA-I by tumor cells. Here, we investigated the immunogenicity of nonC tumor HLA-I ligands (nonC-TL) to better understand their contribution to cancer immunosurveillance and their therapeutic applicability.
Experimental Design:
Peptides presented on HLA-I were identified in 9 patient-derived tumor cell lines from melanoma, gynecologic, and head and neck cancer through proteogenomics. A total of 507 candidate tumor antigens, including nonC-TL, neoantigens, cancer-germline, or melanocyte differentiation antigens, were tested for T-cell recognition of preexisting responses in patients with cancer. Donor peripheral blood lymphocytes (PBL) were in vitro sensitized against 170 selected nonC-TL to isolate antigen-specific T-cell receptors (TCR) and evaluate their therapeutic potential.
Results:
We found no recognition of the 507 nonC-TL tested by autologous ex vivo expanded tumor-reactive T-cell cultures while the same cultures demonstrated reactivity to mutated, cancer-germline, or melanocyte differentiation antigens. However, in vitro sensitization of donor PBL against 170 selected nonC-TL, led to the identification of TCRs specific to three nonC-TL, two of which mapped to the 5′ UTR regions of HOXC13 and ZKSCAN1, and one mapping to a noncoding spliced variant of C5orf22C. T cells targeting these nonC-TL recognized cancer cell lines naturally presenting their corresponding antigens. Expression of the three immunogenic nonC-TL was shared across tumor types and barely or not detected in normal cells.
Conclusions:
Our findings predict a limited contribution of nonC-TL to cancer immunosurveillance but demonstrate they may be attractive novel targets for widely applicable immunotherapies.

See related commentary by Fox et al., p. 2173
Supplementary Fig. S3 from Heparin-binding epidermal growth factor–like growth factor promotes transcoelomic metastasis in ovarian cancer through epithelial-mesenchymal transition
Authors: Yagi Hiroshi , Yotsumoto Fusanori , Miyamoto Shingo
Published: April 2023

Supplementary Fig. S3 from Heparin-binding epidermal growth factor–like growth factor promotes transcoelomic metastasis in ovarian cancer through epithelial-mesenchymal transition
Supplementary Fig. S2 from Role of glutathione S-transferase P1-1 in the cellular detoxification of cisplatin
Authors: Peklak-Scott Christina , Smitherman Pamela K. , Townsend Alan J. , Morrow Charles S.
Published: April 2023

Supplementary Fig. S2 from Role of glutathione S-transferase P1-1 in the cellular detoxification of cisplatin
Supplementary Figure Legends from Lysophosphatidylcholine Pretreatment Reduces VLA-4 and P-Selectin–Mediated B16.F10 Melanoma Cell Adhesion In vitro and Inhibits Metastasis-Like Lung Invasion In vivo
Authors: Jantscheff Peter , Schlesinger Martin , Fritzsche Juliane , Taylor Lenka A. , Graeser Ralph , Kirfel Gregor , Fürst Dieter O. , Massing Ulrich , Bendas Gerd
Published: April 2023

Supplementary Figure Legends from Lysophosphatidylcholine Pretreatment Reduces VLA-4 and P-Selectin–Mediated B16.F10 Melanoma Cell Adhesion In vitro and Inhibits Metastasis-Like Lung Invasion In vivo
Supplementary Fig. S1 from Key role for Bak activation and Bak-Bax interaction in the apoptotic response to vinblastine
Authors: Upreti Meenakshi , Chu Rong , Galitovskaya Elena , Smart Sherri K. , Chambers Timothy C.
Published: April 2023

Supplementary Fig. S1 from Key role for Bak activation and Bak-Bax interaction in the apoptotic response to vinblastine
Supplementary Fig. from Polymeric nanogels containing the triphosphate form of cytotoxic nucleoside analogues show antitumor activity against breast and colorectal cancer cell lines
Authors: Galmarini Carlos M. , Warren Galya , Kohli Ekta , Zeman Arin , Mitin Anton , Vinogradov Serguei V.
Published: April 2023

Supplementary Fig. from Polymeric nanogels containing the triphosphate form of cytotoxic nucleoside analogues show antitumor activity against breast and colorectal cancer cell lines
Supplementary Fig. S1 from Inhibition of fatty acid synthase by luteolin post-transcriptionally down-regulates c-Met expression independent of proteosomal/lysosomal degradation
Authors: Coleman David T. , Bigelow Rebecca , Cardelli James A.
Published: April 2023

Supplementary Fig. S1 from Inhibition of fatty acid synthase by luteolin post-transcriptionally down-regulates c-Met expression independent of proteosomal/lysosomal degradation
Supplementary Table S5 from Antitumor activity and molecular effects of the novel heat shock protein 90 inhibitor, IPI-504, in pancreatic cancer
Authors: Song Dongweon , Chaerkady Raghothama , Tan Aik Choon , García-García Elena , Nalli Anuradha , Suárez-Gauthier Ana , López-Ríos Fernando , Zhang Xian Feng , Solomon Anna , Tong Jeffrey , Read Margaret , Fritz Christian , Jimeno Antonio , Pandey Akhilesh , Hidalgo Manuel
Published: April 2023

Supplementary Table S5 from Antitumor activity and molecular effects of the novel heat shock protein 90 inhibitor, IPI-504, in pancreatic cancer
Supplementary Fig. S1 from Hypoxia-induced resistance to anticancer drugs is associated with decreased senescence and requires hypoxia-inducible factor-1 activity
Authors: Sullivan Richard , Paré Geneviève C. , Frederiksen Lisa J. , Semenza Gregg L. , Graham Charles H.
Published: April 2023

Supplementary Fig. S1 from Hypoxia-induced resistance to anticancer drugs is associated with decreased senescence and requires hypoxia-inducible factor-1 activity
Supplementary Table S1 from NS-398, ibuprofen, and cyclooxygenase-2 RNA interference produce significantly different gene expression profiles in prostate cancer cells
Authors: John-Aryankalayil Molykutty , Palayoor Sanjeewani T. , Cerna David , Falduto Michael T. , Magnuson Scott R. , Coleman C. Norman
Published: April 2023

Supplementary Table S1 from NS-398, ibuprofen, and cyclooxygenase-2 RNA interference produce significantly different gene expression profiles in prostate cancer cells
Supplementary Fig. S4 from Mitogen-activated protein kinase kinase signaling promotes growth and vascularization of fibrosarcoma
Authors: Ding Yan , Boguslawski Elissa A. , Berghuis Bree D. , Young John J. , Zhang Zhongfa , Hardy Kim , Furge Kyle , Kort Eric , Frankel Arthur E. , Hay Rick V. , Resau James H. , Duesbery Nicholas S.
Published: April 2023

Supplementary Fig. S4 from Mitogen-activated protein kinase kinase signaling promotes growth and vascularization of fibrosarcoma
Supplementary Table S2 from Quantitative live imaging of cancer and normal cells treated with Kinesin-5 inhibitors indicates significant differences in phenotypic responses and cell fate
Authors: Orth James D. , Tang Yangzhong , Shi Jade , Loy Clement T. , Amendt Christiane , Wilm Claudia , Zenke Frank T. , Mitchison Timothy J.
Published: April 2023

Supplementary Table S2 from Quantitative live imaging of cancer and normal cells treated with Kinesin-5 inhibitors indicates significant differences in phenotypic responses and cell fate
Supplementary Fig. S7 from Quantitative live imaging of cancer and normal cells treated with Kinesin-5 inhibitors indicates significant differences in phenotypic responses and cell fate
Authors: Orth James D. , Tang Yangzhong , Shi Jade , Loy Clement T. , Amendt Christiane , Wilm Claudia , Zenke Frank T. , Mitchison Timothy J.
Published: April 2023

Supplementary Fig. S7 from Quantitative live imaging of cancer and normal cells treated with Kinesin-5 inhibitors indicates significant differences in phenotypic responses and cell fate
Supplementary Fig. S3 from Quantitative live imaging of cancer and normal cells treated with Kinesin-5 inhibitors indicates significant differences in phenotypic responses and cell fate
Authors: Orth James D. , Tang Yangzhong , Shi Jade , Loy Clement T. , Amendt Christiane , Wilm Claudia , Zenke Frank T. , Mitchison Timothy J.
Published: April 2023

Supplementary Fig. S3 from Quantitative live imaging of cancer and normal cells treated with Kinesin-5 inhibitors indicates significant differences in phenotypic responses and cell fate
Supplementary Fig. S2 from Bortezomib is ineffective in an orthotopic mouse model of pancreatic adenocarcinoma
Authors: Märten Angela , Zeiss Nina , Serba Susanne , Mehrle Stefan , von Lilienfeld-Toal Marie , Schmidt Jan
Published: April 2023

Supplementary Fig. S2 from Bortezomib is ineffective in an orthotopic mouse model of pancreatic adenocarcinoma
Supplementary Table 1, Supplementary Figures 1-3 from TRA-8 anti-DR5 monoclonal antibody and gemcitabine induce apoptosis and inhibit radiologically validated orthotopic pancreatic tumor growth
Authors: DeRosier Leo Christopher , Vickers Selwyn M. , Zinn Kurt R. , Huang Zhi , Wang Wenquan , Grizzle William E. , Sellers Jeffrey , Stockard Cecil R. , Zhou Tong , Oliver Patsy G. , Arnoletti Pablo , LoBuglio Albert F. , Buchsbaum Donald J.
Published: April 2023

Supplementary Table 1, Supplementary Figures 1-3 from TRA-8 anti-DR5 monoclonal antibody and gemcitabine induce apoptosis and inhibit radiologically validated orthotopic pancreatic tumor growth
Supplementary Fig. S2 from Comparison of biochemical and biological effects of ML858 (salinosporamide A) and bortezomib
Authors: Williamson Mark J. , Blank Jonathan L. , Bruzzese Frank J. , Cao Yueying , Daniels J. Scott , Dick Lawrence R. , Labutti Jason , Mazzola Anne M. , Patil Ashok D. , Reimer Corinne L. , Solomon Marjorie S. , Stirling Matthew , Tian Yuan , Tsu Christopher A. , Weatherhead Gabriel S. , Zhang Julie X. , Rolfe Mark
Published: April 2023

Supplementary Fig. S2 from Comparison of biochemical and biological effects of ML858 (salinosporamide A) and bortezomib
Supplementary Fig. S1 from Comparison of biochemical and biological effects of ML858 (salinosporamide A) and bortezomib
Authors: Williamson Mark J. , Blank Jonathan L. , Bruzzese Frank J. , Cao Yueying , Daniels J. Scott , Dick Lawrence R. , Labutti Jason , Mazzola Anne M. , Patil Ashok D. , Reimer Corinne L. , Solomon Marjorie S. , Stirling Matthew , Tian Yuan , Tsu Christopher A. , Weatherhead Gabriel S. , Zhang Julie X. , Rolfe Mark
Published: April 2023

Supplementary Fig. S1 from Comparison of biochemical and biological effects of ML858 (salinosporamide A) and bortezomib
Supplementary Fig. S2 from Cyclin D3 is down-regulated by rapamycin in HER-2-overexpressing breast cancer cells
Authors: García-Morales Pilar , Hernando Eva , Carrasco-García Estefanía , Menéndez-Gutierrez María Piedad , Saceda Miguel , Martínez-Lacaci Isabel
Published: April 2023

Supplementary Fig. S2 from Cyclin D3 is down-regulated by rapamycin in HER-2-overexpressing breast cancer cells
Supplementary Figures 1-6 from Enhanced targeting with heterobivalent ligands
Authors: Xu Liping , Vagner Josef , Josan Jatinder , Lynch Ronald M. , Morse David L. , Baggett Brenda , Han Haiyong , Mash Eugene A. , Hruby Victor J. , Gillies Robert J.
Published: April 2023

Supplementary Figures 1-6 from Enhanced targeting with heterobivalent ligands
Supplementary Figures 1-6 from Reovirus Virotherapy Overrides Tumor Antigen Presentation Evasion and Promotes Protective Antitumor Immunity
Authors: Gujar Shashi A. , Marcato Paola , Pan Da , Lee Patrick W.K.
Published: April 2023

Supplementary Figures 1-6 from Reovirus Virotherapy Overrides Tumor Antigen Presentation Evasion and Promotes Protective Antitumor Immunity
Supplementary Figure 2 from Combination of Two Insulin-Like Growth Factor-I Receptor Inhibitory Antibodies Targeting Distinct Epitopes Leads to an Enhanced Antitumor Response
Authors: Dong Jianying , Demarest Stephen J. , Sereno Arlene , Tamraz Susan , Langley Emma , Doern Adam , Snipas Tracey , Perron Keli , Joseph Ingrid , Glaser Scott M. , Ho Steffan N. , Reff Mitchell E. , Hariharan Kandasamy
Published: April 2023

Supplementary Figure 2 from Combination of Two Insulin-Like Growth Factor-I Receptor Inhibitory Antibodies Targeting Distinct Epitopes Leads to an Enhanced Antitumor Response
Supplementary Table, Materials and References from Activity of dasatinib against L576P KIT mutant melanoma: Molecular, cellular, and clinical correlates
Authors: Woodman Scott E. , Trent Jonathan C. , Stemke-Hale Katherine , Lazar Alexander J. , Pricl Sabrina , Pavan Giovanni M. , Fermeglia Maurizio , Gopal Y.N. Vashisht , Yang Dan , Podoloff Donald A. , Ivan Doina , Kim Kevin B. , Papadopoulos Nicholas , Hwu Patrick , Mills Gordon B. , Davies Michael A.
Published: April 2023

Supplementary Table, Materials and References from Activity of dasatinib against L576P KIT mutant melanoma: Molecular, cellular, and clinical correlates
Supplementary Figure 2 from A Novel E1B-55kD-Deleted Oncolytic Adenovirus Carrying Mutant KRAS-Regulated hdm2 Transgene Exerts Specific Antitumor Efficacy on Colorectal Cancer Cells
Authors: Liu Chin-Cheng , Liu Jin-Hwang , Wu Suh-Chin , Yen Chueh-Chuan , Chen Wei-Shone , Tsai Ying-Chieh
Published: April 2023

Supplementary Figure 2 from A Novel E1B-55kD-Deleted Oncolytic Adenovirus Carrying Mutant KRAS-Regulated hdm2 Transgene Exerts Specific Antitumor Efficacy on Colorectal Cancer Cells
Supplementary Table S2 from Engineered anti-CD70 antibody-drug conjugate with increased therapeutic index
Authors: McDonagh Charlotte F. , Kim Kristine M. , Turcott Eileen , Brown Lindsay L. , Westendorf Lori , Feist Tiffany , Sussman Django , Stone Ivan , Anderson Martha , Miyamoto Jamie , Lyon Robert , Alley Stephen C. , Gerber Hans-Peter , Carter Paul J.
Published: April 2023

Supplementary Table S2 from Engineered anti-CD70 antibody-drug conjugate with increased therapeutic index
Supplementary Data from Zinc Protoporphyrin IX Stimulates Tumor Immunity by Disrupting the Immunosuppressive Enzyme Indoleamine 2,3-Dioxygenase
Authors: Metz Richard , DuHadaway James B. , Rust Sonja , Munn David H. , Muller Alexander J. , Mautino Mario , Prendergast George C.
Published: April 2023

Supplementary Data from Zinc Protoporphyrin IX Stimulates Tumor Immunity by Disrupting the Immunosuppressive Enzyme Indoleamine 2,3-Dioxygenase
Supplementary Data from Effects of Src kinase inhibition induced by dasatinib in non–small cell lung cancer cell lines treated with cisplatin
Authors: Ceppi Paolo , Papotti Mauro , Monica Valentina , Iacono Marco Lo , Saviozzi Silvia , Pautasso Marisa , Novello Silvia , Mussino Stefano , Bracco Enrico , Volante Marco , Scagliotti Giorgio V.
Published: April 2023

Supplementary Data from Effects of Src kinase inhibition induced by dasatinib in non–small cell lung cancer cell lines treated with cisplatin
Supplementary Figures 1 and 2 from Silencing Kinase-Interacting Stathmin Gene Enhances Erlotinib Sensitivity by Inhibiting Ser10 p27 Phosphorylation in Epidermal Growth Factor Receptor–Expressing Breast Cancer
Authors: Zhang Dongwei , Tari Ana M. , Akar Ugur , Arun Banu K. , LaFortune Tiffany A. , Nieves-Alicea Rene , Hortobagyi Gabriel N. , Ueno Naoto T.
Published: April 2023

Supplementary Figures 1 and 2 from Silencing Kinase-Interacting Stathmin Gene Enhances Erlotinib Sensitivity by Inhibiting Ser10 p27 Phosphorylation in Epidermal Growth Factor Receptor–Expressing Breast Cancer
Supplementary Figure 4 from Multigene Expression–Based Predictors for Sensitivity to Vorinostat and Velcade in Non–Small Cell Lung Cancer
Authors: Nagji Alykhan S. , Cho Sang-Hoon , Liu Yuan , Lee Jae K. , Jones David R.
Published: April 2023

Supplementary Figure 4 from Multigene Expression–Based Predictors for Sensitivity to Vorinostat and Velcade in Non–Small Cell Lung Cancer
Supplementary Figures 7-8 from Aflibercept Exerts Antivascular Effects and Enhances Levels of Anthracycline Chemotherapy In vivo in Human Acute Myeloid Leukemia Models
Authors: Lal Deepika , Park Jennifer A. , Demock Kellie , Marinaro Joseph , Perez Amanda M. , Lin Mei-Hui , Tian Lili , Mashtare Terry J. , Murphy Michael , Prey Joshua , Wetzler Meir , Fetterly Gerald J. , Wang Eunice S.
Published: April 2023

Supplementary Figures 7-8 from Aflibercept Exerts Antivascular Effects and Enhances Levels of Anthracycline Chemotherapy In vivo in Human Acute Myeloid Leukemia Models
Supplementary Tables 1-2 from Double EGFR mutants containing rare EGFR mutant types show reduced in vitro response to gefitinib compared with common activating missense mutations
Authors: Tam Issan Yee-San , Leung Elaine Lai-Han , Tin Vicky Pui-Chi , Chua Daniel Tsin-Tien , Sihoe Alan Dart-Loon , Cheng Lik-Cheung , Chung Lap-Ping , Wong Maria Pik
Published: April 2023

Supplementary Tables 1-2 from Double EGFR mutants containing rare EGFR mutant types show reduced in vitro response to gefitinib compared with common activating missense mutations
Supplementary Tables S1-S2 from An oncogenic isoform of HER2 associated with locally disseminated breast cancer and trastuzumab resistance
Authors: Mitra Doyel , Brumlik Michael J. , Okamgba Stella U. , Zhu Yun , Duplessis Tamika T. , Parvani Jenny G. , Lesko Samuel M. , Brogi Edi , Jones Frank E.
Published: April 2023

Supplementary Table 1. Clinical characteristics of 85 primary breast tumors used for statistical analysis; Supplementary Table 2. HER2 and HER2ï�„16 coexpression compared clinicopathological parameters.
Supplementary Data from Expression of a suicidal gene under control of the human secreted protein acidic and rich in cysteine (SPARC) promoter in tumor or stromal cells led to the inhibition of tumor cell growth
Authors: Lopez María V. , Blanco Patricia , Viale Diego L. , Cafferata Eduardo G. , Carbone Cecilia , Gould David , Chernajovsky Yuti , Podhajcer Osvaldo L.
Published: April 2023

Supplementary Data from Expression of a suicidal gene under control of the human secreted protein acidic and rich in cysteine (SPARC) promoter in tumor or stromal cells led to the inhibition of tumor cell growth
Supplementary Figure 3 from A Fully Human Insulin-Like Growth Factor-I Receptor Antibody SCH 717454 (Robatumumab) Has Antitumor Activity as a Single Agent and in Combination with Cytotoxics in Pediatric Tumor Xenografts
Authors: Wang Yaolin , Lipari Philip , Wang Xiaoying , Hailey Judith , Liang Lianzhu , Ramos Robert , Liu Ming , Pachter Jonathan A. , Bishop W. Robert , Wang Yan
Published: April 2023

Supplementary Figure 3 from A Fully Human Insulin-Like Growth Factor-I Receptor Antibody SCH 717454 (Robatumumab) Has Antitumor Activity as a Single Agent and in Combination with Cytotoxics in Pediatric Tumor Xenografts
Supplementary Figure 2 from A Fully Human Insulin-Like Growth Factor-I Receptor Antibody SCH 717454 (Robatumumab) Has Antitumor Activity as a Single Agent and in Combination with Cytotoxics in Pediatric Tumor Xenografts
Authors: Wang Yaolin , Lipari Philip , Wang Xiaoying , Hailey Judith , Liang Lianzhu , Ramos Robert , Liu Ming , Pachter Jonathan A. , Bishop W. Robert , Wang Yan
Published: April 2023

Supplementary Figure 2 from A Fully Human Insulin-Like Growth Factor-I Receptor Antibody SCH 717454 (Robatumumab) Has Antitumor Activity as a Single Agent and in Combination with Cytotoxics in Pediatric Tumor Xenografts
Supplementary Fig. S1 from Recombinant, refolded tetrameric p53 and gonadotropin-releasing hormone-p53 slow proliferation and induce apoptosis in p53-deficient cancer cells
Authors: LaFevre-Bernt Michelle , Wu Shili , Lin Xinli
Published: April 2023

Supplementary Fig. S1 from Recombinant, refolded tetrameric p53 and gonadotropin-releasing hormone-p53 slow proliferation and induce apoptosis in p53-deficient cancer cells
Supplementary Data from ARQ 197, a Novel and Selective Inhibitor of the Human c-Met Receptor Tyrosine Kinase with Antitumor Activity
Authors: Munshi Neru , Jeay Sébastien , Li Youzhi , Chen Chang-Rung , France Dennis S. , Ashwell Mark A. , Hill Jason , Moussa Magdi M. , Leggett David S. , Li Chiang J.
Published: April 2023

Supplementary Data from ARQ 197, a Novel and Selective Inhibitor of the Human c-Met Receptor Tyrosine Kinase with Antitumor Activity
Supplementary Methods from KD5170, a novel mercaptoketone-based histone deacetylase inhibitor that exhibits broad spectrum antitumor activity in vitro and in vivo
Authors: Hassig Christian A. , Symons Kent T. , Guo Xin , Nguyen Phan-Manh , Annable Tami , Wash Paul L. , Payne Joseph E. , Jenkins David A. , Bonnefous Céline , Trotter Carol , Wang Yan , Anzola John V. , Milkova Elena L. , Hoffman Timothy Z. , Dozier Sara J. , Wiley Brandon M. , Saven Alan , Malecha James W. , Davis Robert L. , Muhammad Jerry , Shiau Andrew K. , Noble Stewart A. , Rao Tadimeti S. , Smith Nicholas D. , Hager Jeffrey H.
Published: April 2023

Supplementary Methods from KD5170, a novel mercaptoketone-based histone deacetylase inhibitor that exhibits broad spectrum antitumor activity in vitro and in vivo
Supplementary Figure 1 from Antimitotic effect of the retinoid 4-oxo-fenretinide through inhibition of tubulin polymerization: a novel mechanism of retinoid growth–inhibitory activity
Authors: Appierto Valentina , Tiberio Paola , Cavadini Elena , Casalini Patrizia , Cappelletti Graziella , Formelli Franca
Published: April 2023

Supplementary Figure 1 from Antimitotic effect of the retinoid 4-oxo-fenretinide through inhibition of tubulin polymerization: a novel mechanism of retinoid growth–inhibitory activity
Supplementary Movie S3 from Induction of apoptosis by monastrol, an inhibitor of the mitotic kinesin Eg5, is independent of the spindle checkpoint
Authors: Chin Gregory M. , Herbst Ronald
Published: April 2023

BubR1 siRNA Monastrol
Supplementary Movie S2 from Induction of apoptosis by monastrol, an inhibitor of the mitotic kinesin Eg5, is independent of the spindle checkpoint
Authors: Chin Gregory M. , Herbst Ronald
Published: April 2023

BubR1 siRNA
Supplementary Fig. S3 from Antitumor activity of a membrane lytic peptide cyclized with a linker sensitive to membrane type 1-matrix metalloproteinase
Authors: Zhong Jieying , Chau Ying
Published: April 2023

Supplementary Fig. S3 from Antitumor activity of a membrane lytic peptide cyclized with a linker sensitive to membrane type 1-matrix metalloproteinase
Supplementary Figure 1 from Human Mutations That Confer Paclitaxel Resistance
Authors: Yin Shanghua , Bhattacharya Rajat , Cabral Fernando
Published: April 2023

Supplementary Figure 1 from Human Mutations That Confer Paclitaxel Resistance
Supplementary Figure Legends from Overexpression of GRIM-19 in Cancer Cells Suppresses STAT3-Mediated Signal Transduction and Cancer Growth
Authors: Okamoto Takashi , Inozume Takashi , Mitsui Hiroshi , Kanzaki Mirei , Harada Kazutoshi , Shibagaki Naotaka , Shimada Shinji
Published: April 2023

Supplementary Figure Legends from Overexpression of GRIM-19 in Cancer Cells Suppresses STAT3-Mediated Signal Transduction and Cancer Growth
Supplementary Data from Analyses of melanoma-targeted oncolytic adenoviruses with tyrosinase enhancer/promoter-driven E1A, E4, or both in submerged cells and organotypic cultures
Authors: Banerjee N. Sanjib , Rivera Angel A. , Wang Minghui , Chow Louise T. , Broker Thomas R. , Curiel David T. , Nettelbeck Dirk M.
Published: April 2023

Supplementary Data from Analyses of melanoma-targeted oncolytic adenoviruses with tyrosinase enhancer/promoter-driven E1A, E4, or both in submerged cells and organotypic cultures
Supplementary Figure 2 from An antagonist of the chemokine receptor CXCR4 induces mitotic catastrophe in ovarian cancer cells
Authors: Kwong Joseph , Kulbe Hagen , Wong Donald , Chakravarty Probir , Balkwill Fran
Published: April 2023

Supplementary Figure 2 from An antagonist of the chemokine receptor CXCR4 induces mitotic catastrophe in ovarian cancer cells
Supplementary Table 1 from Aurora A is a negative prognostic factor and a new therapeutic target in human neuroblastoma
Authors: Shang Xiaoying , Burlingame Susan M. , Okcu M. Fatih , Ge Ningling , Russell Heidi V. , Egler Rachel A. , David Rodney D. , Vasudevan Sanjeev A. , Yang Jianhua , Nuchtern Jed G.
Published: April 2023

Supplementary Table 1 from Aurora A is a negative prognostic factor and a new therapeutic target in human neuroblastoma
Supplementary Figure 1 from Aurora A is a negative prognostic factor and a new therapeutic target in human neuroblastoma
Authors: Shang Xiaoying , Burlingame Susan M. , Okcu M. Fatih , Ge Ningling , Russell Heidi V. , Egler Rachel A. , David Rodney D. , Vasudevan Sanjeev A. , Yang Jianhua , Nuchtern Jed G.
Published: April 2023

Supplementary Figure 1 from Aurora A is a negative prognostic factor and a new therapeutic target in human neuroblastoma
Supplementary Data from Resolving conflicting data on expression of the Tn antigen and implications for clinical trials with cancer vaccines
Authors: Li Qian , Anver Miriam R. , Butcher Donna O. , Gildersleeve Jeffrey C.
Published: April 2023

Supplementary Data from Resolving conflicting data on expression of the Tn antigen and implications for clinical trials with cancer vaccines
Supplementary Data from Systemic Administration of Polymeric Nanoparticle-Encapsulated Curcumin (NanoCurc) Blocks Tumor Growth and Metastases in Preclinical Models of Pancreatic Cancer
Authors: Bisht Savita , Mizuma Masamichi , Feldmann Georg , Ottenhof Niki A. , Hong Seung-Mo , Pramanik Dipankar , Chenna Venugopal , Karikari Collins , Sharma Rajni , Goggins Michael G. , Rudek Michelle A. , Ravi Rajani , Maitra Amarnath , Maitra Anirban
Published: April 2023

Supplementary Data from Systemic Administration of Polymeric Nanoparticle-Encapsulated Curcumin (NanoCurc) Blocks Tumor Growth and Metastases in Preclinical Models of Pancreatic Cancer
Supplementary Table S1 from DNA fingerprinting of the NCI-60 cell line panel
Authors: Lorenzi Philip L. , Reinhold William C. , Varma Sudhir , Hutchinson Amy A. , Pommier Yves , Chanock Stephen J. , Weinstein John N.
Published: April 2023

Supplementary Table S1 from DNA fingerprinting of the NCI-60 cell line panel
Supplementary Fig. S1 from Dasatinib-induced autophagy is enhanced in combination with temozolomide in glioma
Authors: Milano Vanessa , Piao Yuji , LaFortune Tiffany , de Groot John
Published: April 2023

Supplementary Fig. S1 from Dasatinib-induced autophagy is enhanced in combination with temozolomide in glioma
Supplementary Fig. S1 from Caspase-2 functions upstream of mitochondria in endoplasmic reticulum stress-induced apoptosis by bortezomib in human myeloma cells
Authors: Gu Hongtao , Chen Xiequn , Gao Guangxun , Dong Hongjuan
Published: April 2023

Supplementary Fig. S1 from Caspase-2 functions upstream of mitochondria in endoplasmic reticulum stress-induced apoptosis by bortezomib in human myeloma cells
Supplementary Data from Identification of c-Src as a Potential Therapeutic Target for Gastric Cancer and of MET Activation as a Cause of Resistance to c-Src Inhibition
Authors: Okamoto Wataru , Okamoto Isamu , Yoshida Takeshi , Okamoto Kunio , Takezawa Ken , Hatashita Erina , Yamada Yuki , Kuwata Kiyoko , Arao Tokuzo , Yanagihara Kazuyoshi , Fukuoka Masahiro , Nishio Kazuto , Nakagawa Kazuhiko
Published: April 2023

Supplementary Data from Identification of c-Src as a Potential Therapeutic Target for Gastric Cancer and of MET Activation as a Cause of Resistance to c-Src Inhibition
Supplementary Figure 4 from Context-Dependent Role of Angiopoietin-1 Inhibition in the Suppression of Angiogenesis and Tumor Growth: Implications for AMG 386, an Angiopoietin-1/2–Neutralizing Peptibody
Authors: Coxon Angela , Bready James , Min Hosung , Kaufman Stephen , Leal Juan , Yu Dongyin , Lee Tani Ann , Sun Ji-Rong , Estrada Juan , Bolon Brad , McCabe James , Wang Ling , Rex Karen , Caenepeel Sean , Hughes Paul , Cordover David , Kim Haejin , Han Seog Joon , Michaels Mark L. , Hsu Eric , Shimamoto Grant , Cattley Russell , Hurh Eunju , Nguyen Linh , Wang Shao Xiong , Ndifor Anthony , Hayward Isaac J. , Falcón Beverly L. , McDonald Donald M. , Li Luke , Boone Tom , Kendall Richard , Radinsky Robert , Oliner Jonathan D.
Published: April 2023

Supplementary Figure 4 from Context-Dependent Role of Angiopoietin-1 Inhibition in the Suppression of Angiogenesis and Tumor Growth: Implications for AMG 386, an Angiopoietin-1/2–Neutralizing Peptibody
Supplementary Data from Pharmacologic Inactivation of Kinase Suppressor of Ras1 Sensitizes Epidermal Growth Factor Receptor and Oncogenic Ras-Dependent Tumors to Ionizing Radiation Treatment
Authors: Xiao Hongyan , Zhang Qingbei , Shen Jikun , Bindokas Vytas , Xing H. Rosie
Published: April 2023

Includes Supplementary Figures 1 through 5 with corresponding figure legends
Supplementary Figure 3B from Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941
Authors: Raynaud Florence I. , Eccles Suzanne A. , Patel Sonal , Alix Sonia , Box Gary , Chuckowree Irina , Folkes Adrian , Gowan Sharon , De Haven Brandon Alexis , Di Stefano Francesca , Hayes Angela , Henley Alan T. , Lensun Letitia , Pergl-Wilson Giles , Robson Anthony , Saghir Nahid , Zhyvoloup Alexander , McDonald Edward , Sheldrake Peter , Shuttleworth Stephen , Valenti Melanie , Wan Nan Chi , Clarke Paul A. , Workman Paul
Published: April 2023

Supplementary Figure 3B from Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941
Supplementary Figure 2 from Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941
Authors: Raynaud Florence I. , Eccles Suzanne A. , Patel Sonal , Alix Sonia , Box Gary , Chuckowree Irina , Folkes Adrian , Gowan Sharon , De Haven Brandon Alexis , Di Stefano Francesca , Hayes Angela , Henley Alan T. , Lensun Letitia , Pergl-Wilson Giles , Robson Anthony , Saghir Nahid , Zhyvoloup Alexander , McDonald Edward , Sheldrake Peter , Shuttleworth Stephen , Valenti Melanie , Wan Nan Chi , Clarke Paul A. , Workman Paul
Published: April 2023

Supplementary Figure 2 from Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941
Supplementary Figure 1 from Small-molecule inhibition of Wee1 kinase by MK-1775 selectively sensitizes p53-deficient tumor cells to DNA-damaging agents
Authors: Hirai Hiroshi , Iwasawa Yoshikazu , Okada Megumu , Arai Tsuyoshi , Nishibata Toshihide , Kobayashi Makiko , Kimura Toshifumi , Kaneko Naoki , Ohtani Junko , Yamanaka Kazunori , Itadani Hiraku , Takahashi-Suzuki Ikuko , Fukasawa Kazuhiro , Oki Hiroko , Nambu Tadahiro , Jiang Jian , Sakai Takumi , Arakawa Hiroharu , Sakamoto Toshihiro , Sagara Takeshi , Yoshizumi Takashi , Mizuarai Shinji , Kotani Hidehito
Published: April 2023

Supplementary Figure 1 from Small-molecule inhibition of Wee1 kinase by MK-1775 selectively sensitizes p53-deficient tumor cells to DNA-damaging agents
Supplementary Fig. S2 from ClC-3 expression enhances etoposide resistance by increasing acidification of the late endocytic compartment
Authors: Weylandt Karsten H. , Nebrig Maxim , Jansen-Rosseck Nils , Amey Joanna S. , Carmena David , Wiedenmann Bertram , Higgins Christopher F. , Sardini Alessandro
Published: April 2023

Supplementary Fig. S2 from ClC-3 expression enhances etoposide resistance by increasing acidification of the late endocytic compartment
Supplementary Fig. S4 from Genetic variants associated with carboplatin-induced cytotoxicity in cell lines derived from Africans
Authors: Huang R. Stephanie , Duan Shiwei , Kistner Emily O. , Hartford Christine M. , Dolan M. Eileen
Published: April 2023

Supplementary Fig. S4 from Genetic variants associated with carboplatin-induced cytotoxicity in cell lines derived from Africans
Supplementary Figure 4 from Knockdown of Inwardly Rectifying Potassium Channel Kir2.2 Suppresses Tumorigenesis by Inducing Reactive Oxygen Species–Mediated Cellular Senescence
Authors: Lee Inkyoung , Park Chaehwa , Kang Won Ki
Published: April 2023

Supplementary Figure 4 from Knockdown of Inwardly Rectifying Potassium Channel Kir2.2 Suppresses Tumorigenesis by Inducing Reactive Oxygen Species–Mediated Cellular Senescence
Supplementary Fig. S2 from Proteasome inhibitor PS-341 (VELCADE) induces stabilization of the TRAIL receptor DR5 mRNA through the 3′-untranslated region
Authors: Kandasamy Karthikeyan , Kraft Andrew S.
Published: April 2023

Supplementary Fig. S2 from Proteasome inhibitor PS-341 (VELCADE) induces stabilization of the TRAIL receptor DR5 mRNA through the 3′-untranslated region
Data from Heparin-binding epidermal growth factor–like growth factor promotes transcoelomic metastasis in ovarian cancer through epithelial-mesenchymal transition
Authors: Yagi Hiroshi , Yotsumoto Fusanori , Miyamoto Shingo
Published: April 2023

Abstract
Heparin-binding epidermal growth factor–like growth factor (HB-EGF) is involved in several biological processes including cell adhesion, invasion, and angiogenesis. HB-EGF also plays a pivotal role in the progression of ovarian cancer. To investigate the significance of HB-EGF in peritoneal dissemination, we examined the roles of HB-EGF in cell adhesion, invasion, and angiogenesis in ovarian cancer. Through the suppression of focal adhesion kinase and EGF receptor activation, cell adhesive properties mediated by integrin β1 were diminished by the inhibition of HB-EGF expression. The reduction of HB-EGF expression attenuated the chemotactic invasive ability and the expression of matrix metalloprotease (MMP)-2 and vascular endothelial growth factor (VEGF), leading to the inhibition of cell invasion and angiogenesis. Suppression of the Snail family, which regulates the epithelial-mesenchymal transition, blocked the cell adhesion properties on extracellular matrices, the chemotactic invasive ability, and the expression of MMP9 and VEGF through the reduction of HB-EGF expression. The volume of tumor burden in the peritoneal cavity was dependent on the expression of HB-EGF. According to these results, HB-EGF contributes to cell adhesion, invasion, and angiogenesis, which are integral to transcoelomic metastasis in ovarian cancer. CRM197, an inhibitor of HB-EGF, resulted in a significant decrease of tumor burden in peritoneal dissemination, accompanied with a reduction in both cellular spreading, when assayed on an extracellular matrix, and invasive ability, when assayed in a chemotaxis chamber, as well as decreased expression of MMP9 and VEGF. Thus, HB-EGF is a mutual validating target in the peritoneal dissemination of ovarian cancer, and CRM197 may be useful as a anticancer agent for advanced ovarian cancer. [Mol Cancer Ther 2008;7(9):3441–51]
Data from A genomic approach to identify molecular pathways associated with chemotherapy resistance
Authors: Riedel Richard F. , Porrello Alessandro , Pontzer Emily , Chenette Emily J. , Hsu David S. , Balakumaran Bala , Potti Anil , Nevins Joseph , Febbo Phillip G.
Published: April 2023

Abstract
Resistance to chemotherapy in cancer is common. As gene expression profiling has been shown to anticipate chemotherapeutic resistance, we sought to identify cellular pathways associated with resistance to facilitate effective combination therapy. Gene set enrichment analysis was used to associate pathways with resistance in two data sets: the NCI-60 cancer cell lines deemed sensitive and resistant to specific chemotherapeutic agents (Adriamycin, cyclophosphamide, docetaxel, etoposide, 5-fluorouracil, paclitaxel, and topotecan) and a series of 40 lung cancer cell lines for which sensitivity to cisplatin and docetaxel was determined. Candidate pathways were further screened in silico using the Connectivity Map. The lead candidate pathway was functionally validated in vitro. Gene set enrichment analysis associated the matrix metalloproteinase, p53, methionine metabolism, and free pathways with cytotoxic resistance in the NCI-60 cell lines across multiple agents, but no gene set was common to all drugs. Analysis of the lung cancer cell lines identified the bcl-2 pathway to be associated with cisplatin resistance and the AKT pathway enriched in cisplatin- and docetaxel-resistant cell lines. Results from Connectivity Map supported an association between phosphatidylinositol 3-kinase/AKT and docetaxel resistance but did not support the association with cisplatin. Targeted inhibition of the phosphatidylinositol 3-kinase/AKT pathway with LY294002, in combination with docetaxel, resulted in a synergistic effect in previously docetaxel-resistant cell lines but not with cisplatin. These results support the use of a genomic approach to identify drug-specific targets associated with the development of chemotherapy resistance and underscore the importance of disease context in identifying these pathways. [Mol Cancer Ther 2008;7(10):3141–9]
Data from Nitro-chloromethylbenzindolines: hypoxia-activated prodrugs of potent adenine N3 DNA minor groove alkylators
Authors: Wilson William R. , Stribbling Stephen M. , Pruijn Frederik B. , Syddall Sophie P. , Patterson Adam V. , Liyanage H.D. Sarath , Smith Eileen , Botting K. Jane , Tercel Moana
Published: April 2023

Abstract
Hypoxia represents an important therapeutic target in tumors because of the resistance of hypoxic cells to radiotherapy and chemotherapy and because it is more severe in many tumors than in normal tissues. Here, we describe a class of prodrugs, nitro-chloromethylindolines, which undergo hypoxia-selective activation by endogenous nitroreductases in tumor cells to form the corresponding amino compounds. The latter are chemically related to the cyclopropylindoline antitumor antibiotics and they share the same properties of sequence-selective DNA minor groove alkylation and high cytotoxic potency. Of three alkylating subunits investigated, the chloromethylbenzindoline (CBI) structure provided the most favorable prodrug properties: aerobic cytotoxic potency of the amines was approximately 90- to 3,000-fold higher than the corresponding nitro compounds, and the nitro compounds showed air/anoxia potency differentials of up to 300-fold. Selective alkylation of adenine N3 in calf thymus DNA by an amino-CBI was shown by characterization of the thermal depurination product; the same adduct was shown in hypoxic RIF-1 cells exposed to the corresponding nitro-CBI prodrug under hypoxic (but not oxic) conditions. The amino metabolite generated from a nitro-CBI by cells expressing Escherichia coli nfsB nitroreductase in multicellular layer cultures was shown to elicit bystander killing of surrounding cells. Nitro-CBI prodrugs were >500-fold less toxic to mice than amino-CBIs by i.p. administration and provided selective killing of hypoxic cells in RIF-1 tumors (although only at maximally tolerated doses). Nitro-CBIs are novel lead hypoxia-activated prodrugs that represent the first examples of hypoxia-selective generation of potent DNA minor groove alkylating agents. [Mol Cancer Ther 2009;8(10):2903–13]
Data from The natural product honokiol preferentially inhibits cellular FLICE-inhibitory protein and augments death receptor–induced apoptosis
Authors: Raja Shruti M. , Chen Shuzhen , Yue Ping , Acker Timothy M. , Lefkove Benjamin , Arbiser Jack L. , Khuri Fadlo R. , Sun Shi-Yong
Published: April 2023

Abstract
Targeting death receptor–mediated apoptosis has emerged as an effective strategy for cancer therapy. However, certain types of cancer cells are intrinsically resistant to death receptor–mediated apoptosis. In an effort to identify agents that can sensitize cancer cells to death receptor–induced apoptosis, we have identified honokiol, a natural product with anticancer activity, as shown in various preclinical studies, as an effective sensitizer of death receptor–mediated apoptosis. Honokiol alone moderately inhibited the growth of human lung cancer cells; however, when combined with tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), greater effects on decreasing cell survival and inducing apoptosis than TRAIL alone were observed, indicating that honokiol cooperates with TRAIL to enhance apoptosis. This was also true to Fas-induced apoptosis when combined with Fas ligand or an agonistic anti-Fas antibody. Among several apoptosis-associated proteins tested, cellular FLICE-inhibitory protein (c-FLIP) was the only one that was rapidly down-regulated by honokiol in all of the tested cell lines. The down-regulation of c-FLIP by honokiol could be prevented by the proteasome inhibitor MG132. Moreover, honokiol increased c-FLIP ubiquitination. These results indicate that honokiol down-regulates c-FLIP by facilitating its degradation through a ubiquitin/proteasome-mediated mechanism. Enforced expression of ectopic c-FLIP abolished the ability of honokiol to enhance TRAIL-induced apoptosis. Several honokiol derivatives, which exhibited more potent effects on down-regulation of c-FLIP than honokiol, showed better efficacy than honokiol in inhibiting the growth and enhancing TRAIL-induced apoptosis as well. Collectively, we conclude that c-FLIP down-regulation is a key event for honokiol to modulate the death receptor–induced apoptosis. [Mol Cancer Ther 2008;7(7):2212–23]
Data from EBP1, an ErbB3-binding protein, is decreased in prostate cancer and implicated in hormone resistance
Authors: Zhang Yuexing , Linn Douglas , Liu Zhenqiu , Melamed Jonathan , Tavora Fabio , Young Charles Y. , Burger Angelika M. , Hamburger Anne W.
Published: April 2023

Abstract
Aberrant activation of the androgen receptor (AR) by the ErbB2/ErbB3 heterodimer contributes to the development of hormone resistance in prostate cancer. EBP1, an ErbB3-binding protein, acts as an AR corepressor. As EBP1 is decreased in preclinical models of hormone-refractory prostate cancer, we studied the expression of EBP1 in human prostate cancer. We found that the expression of the EBP1 gene was significantly decreased in prostate cancer tissues compared with benign prostate at both mRNA and protein levels. Restoration of EBP1 expression in the hormone-refractory LNCaP C81 cell line led to an amelioration of the androgen-independent phenotype based on established biological criteria and a reduction in the expression of a cohort of AR target genes. The ability of the ErbB3 ligand heregulin (HRG) to stimulate growth and AKT phosphorylation of hormone-refractory prostate cancer cells was abolished. Abrogation of EBP1 expression by short hairpin RNA in hormone-dependent LNCaP cells, which undergo apoptosis in response to HRG, resulted in HRG-stimulated cell growth. Restoration of EBP1 expression decreased the tumorigenicity of C81 xenografts in female mice, whereas elimination of EBP1 expression enhanced the ability of LNCaP cells to grow in female mice. Our data support a role for EBP1 in the development of hormone-refractory prostate cancer via inhibition of both AR- and HRG-stimulated growth and present a novel strategy for treating androgen-refractory prostate cancer. [Mol Cancer Ther 2008;7(10):3176–86]
Data from Loss of prostaglandin D2 synthase: a key molecular event in the transition of a low-grade astrocytoma to an anaplastic astrocytoma
Authors: Payne Cathy A. , Maleki Sanaz , Messina Marinella , O'Sullivan Maree G. , Stone Glenn , Hall Nathan R. , Parkinson Jonathon F. , Wheeler Helen R. , Cook Raymond J. , Biggs Michael T. , Little Nicholas S. , Teo Charles , Robinson Bruce G. , McDonald Kerrie L.
Published: April 2023

Abstract
Reduction in the mRNA and protein expression of lipocalin-like prostaglandin D2 (PGD2) synthase (PGDS), the main arachidonic acid metabolite produced in neurons and glial cells of the central nervous system, is a significant biological event involved in the malignant progression of astrocytomas and is predictive of poor survival. In vitro, the addition of the main PGDS metabolite, PGD2, to A172 glioblastoma cells devoid of PGDS resulted in antiproliferative activity and cell death. In vitro PGD2 substitution also enhanced the efficacy of cyclo-oxygenase-2 inhibitors. This finding has exciting implications for early interventional efforts for the grade 2 and 3 astrocytomas. [Mol Cancer Ther 2008;7(10):3420–8]
Data from NS-398, ibuprofen, and cyclooxygenase-2 RNA interference produce significantly different gene expression profiles in prostate cancer cells
Authors: John-Aryankalayil Molykutty , Palayoor Sanjeewani T. , Cerna David , Falduto Michael T. , Magnuson Scott R. , Coleman C. Norman
Published: April 2023

Abstract
Cyclooxygenase-2 (COX-2) plays a significant role in tumor development and progression. Nonsteroidal anti-inflammatory drugs (NSAID) exhibit potent anticancer effects in vitro and in vivo by COX-2-dependent and COX-2-independent mechanisms. In this study, we used microarray analysis to identify the change of expression profile regulated by a COX-2-specific NSAID NS-398 (0.01 and 0.1 mmol/L), a nonspecific NSAID ibuprofen (0.1 and 1.5 mmol/L) and RNA interference (RNAi)-mediated COX-2 inhibition in PC3 prostate cancer cells. A total of 3,362 differentially expressed genes with 2-fold change and P < 0.05 were identified. Low concentrations of NSAIDs and COX-2 RNAi altered very few genes (1-3%) compared with the higher concentration of NS-398 (17%) and ibuprofen (80%). Ingenuity Pathway Analysis was used for distributing the differentially expressed genes into biological networks and for evaluation of functional significance. The top 3 networks for both NSAIDs included functional categories of DNA replication, recombination and repair, and gastrointestinal disease. Immunoresponse function was specific to NS-398, and cell cycle and cellular movement were among the top functions for ibuprofen. Ingenuity Pathway Analysis also identified renal and urologic disease as a function specific for ibuprofen. This comprehensive study identified several COX-2-independent targets of NSAIDs, which may help explain the antitumor and radiosensitizing effects of NSAIDs. However, none of these categories were reflected in the identified networks in PC3 cells treated with clinically relevant low concentrations of NS-398 and ibuprofen or with COX-2 RNAi, suggesting the benefit to fingerprinting preclinical drug concentrations to improve their relevance to the clinical setting. [Mol Cancer Ther 2009;8(1):261–73]
Data from A novel mode of action of YC-1 in HIF inhibition: stimulation of FIH-dependent p300 dissociation from HIF-1α
Authors: Li Shan Hua , Shin Dong Hoon , Chun Yang-Sook , Lee Myung Kyu , Kim Myung-Suk , Park Jong-Wan
Published: April 2023

Abstract
Hypoxia-inducible factor (HIF)-1 plays a key role in tumor promotion by inducing ∼60 genes required for tumor adaptation to hypoxia; thus, it is viewed as a target for cancer therapy. For this reason, YC-1, which down-regulates HIF-1α and HIF-2α at the post-translational level, is being developed as a novel anticancer drug. We here found that YC-1 acts in a novel manner to inhibit HIF-1. In the Gal4 reporter system, which is not degraded by YC-1, YC-1 was found to significantly inactivate the COOH-terminal transactivation domain (CAD) of HIF-1α, whereas it failed to inactivate CAD(N803A) mutant. In coimmunoprecipitation assays, YC-1 stimulated factor inhibiting HIF (FIH) binding to CAD even in hypoxia, whereas it failed to increase the cellular levels of hydroxylated Asn803 of CAD. It was also found that YC-1 prevented p300 recruitment by CAD in mammalian two-hybrid and coimmunoprecipitation assays. The involvement of FIH in YC-1-induced CAD inactivation was confirmed in EPO-enhancer and Gal4 reporter systems using FIH small interfering RNA and dimethyloxalylglycine FIH inhibitor. Indeed, FIH inhibition rescued HIF target gene expressions repressed by YC-1. In cancer cell lines other than Hep3B, YC-1 inhibits HIF-1α via the FIH-dependent CAD inactivation as well as via the protein down-regulation. Given these results, we suggest that the functional inactivation of HIF-α contributes to the YC-1-induced deregulation of hypoxia-induced genes. [Mol Cancer Ther 2008;7(12):3729–38]