bluuebunny/crossref_metadata_2025 huggingface dataset:
Figure S2 from Adenocarcinoma of the Uterine Cervix Shows Impaired Recruitment of cDC1 and CD8+ T Cells and Elevated β-Catenin Activation Compared with Squamous Cell Carcinoma
Authors: Rotman Jossie , Heeren A. Marijne , Gassama Awa A. , Lougheed Sinead M. , Pocorni Noëlle , Stam Anita G.M. , Bleeker Maaike C.G. , Zijlmans Henry J.M.A.A , Mom Constantijne H. , Kenter Gemma G. , Jordanova Ekaterina S. , de Gruijl Tanja D.
Published: April 2023

Immune checkpoint levels on conventional CD4+ Th cells in AC PT vs SCC PT
Supplementary Data from Integrative Molecular Characterization of Resistance to Neoadjuvant Chemoradiation in Rectal Cancer
Authors: Kamran Sophia C. , Lennerz Jochen K. , Margolis Claire A. , Liu David , Reardon Brendan , Wankowicz Stephanie A. , Van Seventer Emily E. , Tracy Adam , Wo Jennifer Y. , Carter Scott L. , Willers Henning , Corcoran Ryan B. , Hong Theodore S. , Van Allen Eliezer M.
Published: April 2023

Supplemental Figure Captions
Supplemental Table 1 from Integrative Molecular Characterization of Resistance to Neoadjuvant Chemoradiation in Rectal Cancer
Authors: Kamran Sophia C. , Lennerz Jochen K. , Margolis Claire A. , Liu David , Reardon Brendan , Wankowicz Stephanie A. , Van Seventer Emily E. , Tracy Adam , Wo Jennifer Y. , Carter Scott L. , Willers Henning , Corcoran Ryan B. , Hong Theodore S. , Van Allen Eliezer M.
Published: April 2023

IHC Antibody Details
Table S3 from The Proteome of Prostate Cancer Bone Metastasis Reveals Heterogeneity with Prognostic Implications
Authors: Iglesias-Gato Diego , Thysell Elin , Tyanova Stefka , Crnalic Sead , Santos Alberto , Lima Thiago S. , Geiger Tamar , Cox Jürgen , Widmark Anders , Bergh Anders , Mann Matthias , Flores-Morales Amilcar , Wikström Pernilla
Published: April 2023

Table S3
Supplementary Data from Randomized Phase 0/I Trial of the Mitochondrial Inhibitor ME-344 or Placebo Added to Bevacizumab in Early HER2-Negative Breast Cancer
Authors: Quintela-Fandino Miguel , Morales Serafín , Cortés-Salgado Alfonso , Manso Luis , Apala Juan V. , Muñoz Manuel , Gasol Cudos Ariadna , Salla Fortuny Joel , Gion María , Lopez-Alonso Antonio , Cortés Javier , Guerra Juan , Malón Diego , Caleiras Eduardo , Mulero Francisca , Mouron Silvana
Published: April 2023

Supplementary material
Suppl FigS4 from The Proteome of Prostate Cancer Bone Metastasis Reveals Heterogeneity with Prognostic Implications
Authors: Iglesias-Gato Diego , Thysell Elin , Tyanova Stefka , Crnalic Sead , Santos Alberto , Lima Thiago S. , Geiger Tamar , Cox Jürgen , Widmark Anders , Bergh Anders , Mann Matthias , Flores-Morales Amilcar , Wikström Pernilla
Published: April 2023

Suppl FigS4
Suppl FigS2 from The Proteome of Prostate Cancer Bone Metastasis Reveals Heterogeneity with Prognostic Implications
Authors: Iglesias-Gato Diego , Thysell Elin , Tyanova Stefka , Crnalic Sead , Santos Alberto , Lima Thiago S. , Geiger Tamar , Cox Jürgen , Widmark Anders , Bergh Anders , Mann Matthias , Flores-Morales Amilcar , Wikström Pernilla
Published: April 2023

Suppl FigS2
Table S6 from PARP Inhibition Suppresses GR–MYCN–CDK5–RB1–E2F1 Signaling and Neuroendocrine Differentiation in Castration-Resistant Prostate Cancer
Authors: Liu Bo , Li Likun , Yang Guang , Geng Chuandong , Luo Yong , Wu Wenhui , Manyam Ganiraju C. , Korentzelos Dimitrios , Park Sanghee , Tang Zhe , Wu Cheng , Dong Zhenyang , Sigouros Michael , Sboner Andrea , Beltran Himisha , Chen Yu , Corn Paul G. , Tetzlaff Michael T. , Troncoso Patricia , Broom Bradley , Thompson Timothy C.
Published: April 2023

Supplemental Table S6
Supplementary Figures from PARP Inhibition Suppresses GR–MYCN–CDK5–RB1–E2F1 Signaling and Neuroendocrine Differentiation in Castration-Resistant Prostate Cancer
Authors: Liu Bo , Li Likun , Yang Guang , Geng Chuandong , Luo Yong , Wu Wenhui , Manyam Ganiraju C. , Korentzelos Dimitrios , Park Sanghee , Tang Zhe , Wu Cheng , Dong Zhenyang , Sigouros Michael , Sboner Andrea , Beltran Himisha , Chen Yu , Corn Paul G. , Tetzlaff Michael T. , Troncoso Patricia , Broom Bradley , Thompson Timothy C.
Published: April 2023

Supplementary Figures
Figure S1 from Talazoparib Is a Potent Radiosensitizer in Small Cell Lung Cancer Cell Lines and Xenografts
Authors: Laird James H. , Lok Benjamin H. , Ma Jennifer , Bell Andrew , de Stanchina Elisa , Poirier John T. , Rudin Charles M.
Published: April 2023

Mouse Weights after treatment with talazoparib + IR
Supplementary data from TERT Promoter Mutation Detection in Cell-Free Tumor-Derived DNA in Patients with IDH Wild-Type Glioblastomas: A Pilot Prospective Study
Authors: Juratli Tareq A. , Stasik Sebastian , Zolal Amir , Schuster Caroline , Richter Sven , Daubner Dirk , Juratli Mazen A. , Thowe Rachel , Hennig Silke , Makina Meriem , Meinhardt Matthias , Lautenschlaeger Tim , Schackert Gabriele , Krex Dietmar , Thiede Christian
Published: April 2023

Supplementary Figure S1: Dilution experiment of TERTp mutant DNA. Supplementary Figure S2. Reprehensive MR-images of a patient with a TERTp-mutant glioblastoma. Supplementary Figure S3: Postoperative CSF-tDNA data in five patients who underwent a lumbar drainage placement to treat a postoperative CSF.
Supplementary Table 1 from TERT Promoter Mutation Detection in Cell-Free Tumor-Derived DNA in Patients with IDH Wild-Type Glioblastomas: A Pilot Prospective Study
Authors: Juratli Tareq A. , Stasik Sebastian , Zolal Amir , Schuster Caroline , Richter Sven , Daubner Dirk , Juratli Mazen A. , Thowe Rachel , Hennig Silke , Makina Meriem , Meinhardt Matthias , Lautenschlaeger Tim , Schackert Gabriele , Krex Dietmar , Thiede Christian
Published: April 2023

Characteristics and tumor features in four cases with IDH-mutant/TERTp-mutant gliomas (oligodendrogliomas).
Table S1 from Periostin and Epithelial–Mesenchymal Transition Score as Novel Prognostic Markers for Leiomyosarcoma, Myxofibrosarcoma, and Undifferentiated Pleomorphic Sarcoma
Authors: Piano Maria Assunta , Brunello Antonella , Cappellesso Rocco , Del Bianco Paola , Mattiolo Adriana , Fritegotto Chiara , Montini Barbara , Zamuner Carolina , Del Fiore Paolo , Rastrelli Marco , Sommariva Antonio , De Salvo Gian Luca , Montesco Maria Cristina , Rossi Carlo Riccardo , Zagonel Vittorina , Calabrò Maria Luisa
Published: April 2023

Univariate Cox regression models for association between molecular markers and OS.
Figures S1 and S2 from Extended Adjuvant Therapy with Neratinib Plus Fulvestrant Blocks ER/HER2 Crosstalk and Maintains Complete Responses of ER+/HER2+ Breast Cancers: Implications to the ExteNET Trial
Authors: Sudhan Dhivya R. , Schwarz Luis J. , Guerrero-Zotano Angel , Formisano Luigi , Nixon Mellissa J. , Croessmann Sarah , González Ericsson Paula I. , Sanders Melinda , Balko Justin M. , Avogadri-Connors Francesca , Cutler Richard E. , Lalani Alshad S. , Bryce Richard , Auerbach Alan , Arteaga Carlos L.
Published: April 2023

Supplementary figure files
Supplementary Data from Phase I Trial of Debio 1143, an Antagonist of Inhibitor of Apoptosis Proteins, Combined with Cisplatin Chemoradiotherapy in Patients with Locally Advanced Squamous Cell Carcinoma of the Head and Neck
Authors: Le Tourneau Christophe , Tao Yungan , Gomez-Roca Carlos , Cristina Valerie , Borcoman Edith , Deutsch Eric , Bahleda Rastislav , Calugaru Valentin , Modesto Anouchka , Rouits Elisabeth , Gollmer Kathrin , Vuagniaux Gregoire , Crompton Philippa , Zanna Claudio , Szyldergemajn Sergio , Delord Jean-Pierre , Bourhis Jean
Published: April 2023

Supplementary Methods (DLT & efficay) and Tables S1 (Grade 3-4 AEs in {greater than or equal to}2 patients), S2 (late onset toxicity), S3 (PK parameters)
Figure S2 from AXL Mediates Cetuximab and Radiation Resistance Through Tyrosine 821 and the c-ABL Kinase Pathway in Head and Neck Cancer
Authors: McDaniel Nellie K. , Iida Mari , Nickel Kwangok P. , Longhurst Colin A. , Fischbach Samantha R. , Rodems Tamara S. , Kranjac Carlene A. , Bo Amber Y. , Luo Qianyun , Gallagher Meghan M. , Welke Noah B. , Mitchell Kaitlyn R. , Schulz Alison E. , Eckers Jaimee C. , Hu Rong , Salgia Ravi , Hong Seungpyo , Bruce Justine Y. , Kimple Randall J. , Wheeler Deric L.
Published: April 2023

Apoptotic bodies in treatment studies
Supplement 4 from Efficacy and Tolerability of High- versus Low-dose Lenalidomide Maintenance Therapy of Multiple Myeloma after Autologous Blood Stem Cell Transplantation
Authors: Fenk Roland , Giagounidis Aristoteles , Goldschmidt Hartmut , Heinsch Michael , Rummel Mathias , Kroger Nicolaus , Boquoi Amelie , Lopez David , Gerrlich Celina , Baier Julia , Liesenjohann Svenja , Hauck Katarzyna , Savickaite Ingrida , Mai Elias K. , Aul Carlo , Strapatsas Judith , Dienst Ariane , Kondakci Mustafa , Haas Rainer , Kobbe Guido
Published: April 2023

Subgroup analysis by randomization strata II
Trial Protocol from Prospective Evaluation of Bone Metabolic Markers as Surrogate Markers of Response to Radium-223 Therapy in Metastatic Castration-resistant Prostate Cancer
Authors: Agarwal Neeraj , Nussenzveig Roberto , Hahn Andrew W. , Hoffman John M. , Morton Kathryn , Gupta Sumati , Batten Julia , Thorley Jared , Hawks Josiah , Santos Victor Sacristan , Nachaegari Gayatri , Wang Xuechen , Boucher Kenneth , Haaland Benjamin , Maughan Benjamin L.
Published: April 2023

Trial Protocol
Authorship change form from Immunotherapy of Ipilimumab and Nivolumab in Patients with Advanced Neuroendocrine Tumors: A Subgroup Analysis of the CA209-538 Clinical Trial for Rare Cancers
Authors: Klein Oliver , Kee Damien , Markman Ben , Michael Michael , Underhill Craig , Carlino Matteo S. , Jackett Louise , Lum Caroline , Scott Clare , Nagrial Adnan , Behren Andreas , So Jane Y. , Palmer Jodie , Cebon Jonathan
Published: April 2023

Authorship change form
Figure S2 from Routine-Dose and High-Dose Icotinib in Patients with Advanced Non–Small Cell Lung Cancer Harboring EGFR Exon 21-L858R Mutation: the Randomized, Phase II, INCREASE Trial
Authors: Li Xi , Zhang Li , Jiang Da , Wang Yan , Zang Aimin , Ding Cuimin , Zhao Min , Su Wuyun , Zhang Yan , Zhong Diansheng , Wu Jin , Zhang Cuiying , An Guangyu , Hu Xingsheng , Cheng Gang , Wang Huaqing , Li Yongqun , He Xiaohui , Liu Junli , Liang Li , Ding Lieming , Mao Li , Zhang Shucai
Published: April 2023

Differential binding of icotinib for L858R vs exon19del mutant EGFR. The green represents icotinib; the gray represents pocket residues; the blue represents αC-helix; the red represents delE746-A750; the yellow dotted line indicates hydrogen bond; the Dark green dotted line represents the cation-pi interaction; the GK means gatekeeper.
Supplemental Figure 1 from A Prospective, Phase 1 Trial of Nivolumab, Ipilimumab, and Radiotherapy in Patients with Advanced Melanoma
Authors: Postow Michael A. , Knox Susan J. , Goldman Debra A. , Elhanati Yuval , Mavinkurve Vikram , Wong Phillip , Halpenny Darragh , Reddy Sunil K. , Vado Kenya , McCabe Danielle , Ramirez Kristen Aufiero , Macri Mary , Schwarzenberger Paul , Ricciardi Toni , Ryan Aileen , Venhaus Ralph , Momtaz Parisa , Shoushtari Alexander N. , Callahan Margaret K. , Chapman Paul B. , Wolchok Jedd D. , Subrahmanyam Priyanka B. , Maecker Holden T. , Panageas Katherine S. , Barker Christopher A.
Published: April 2023

Timeline of Treatment
Supplementary Figure S5 from Genome Instability Profiles Predict Disease Outcome in a Cohort of 4,003 Patients with Breast Cancer
Authors: Lischka Annette , Doberstein Natalie , Freitag-Wolf Sandra , Koçak Ayla , Gemoll Timo , Heselmeyer-Haddad Kerstin , Ried Thomas , Auer Gert , Habermann Jens K.
Published: April 2023

Multivariable Cox regressions including the standard proliferation variable.
Figure S2 from Copy Number Loss of 17q22 Is Associated with Enzalutamide Resistance and Poor Prognosis in Metastatic Castration-Resistant Prostate Cancer
Authors: Guan Xiangnan , Sun Duanchen , Lu Eric , Urrutia Joshua A. , Reiter Robert Evan , Rettig Matthew , Evans Christopher P. , Lara Primo , Gleave Martin , Beer Tomasz M. , Thomas George V. , Huang Jiaoti , Aggarwal Rahul R. , Quigley David A. , Foye Adam , Chen William S. , Youngren Jack , Weinstein Alana S. , Stuart Joshua M. , Feng Felix Y. , Small Eric J. , Xia Zheng , Alumkal Joshi J.
Published: April 2023

Figure S2 shows a heatmap illustrating copy number alteration of the 124 protein-coding genes in individual samples.
Supplementary Table ST9 from Radiological Evaluation of Newly Diagnosed Non-Brainstem Pediatric High-Grade Glioma in the HERBY Phase II Trial
Authors: Rodriguez Gutierrez Daniel , Jones Chris , Varlet Pascale , Mackay Alan , Warren Daniel , Warmuth-Metz Monika , Aliaga Esther Sánchez , Calmon Raphael , Hargrave Darren R. , Cañete Adela , Massimino Maura , Azizi Amedeo A. , Le Deley Marie-Cécile , Saran Frank , Rousseau Raphael F. , Zahlmann Gudrun , Garcia Josep , Vassal Gilles , Grill Jacques , Morgan Paul S. , Jaspan Tim
Published: April 2023

Outcome related to tumor grade
Supplementary Table ST2 from Radiological Evaluation of Newly Diagnosed Non-Brainstem Pediatric High-Grade Glioma in the HERBY Phase II Trial
Authors: Rodriguez Gutierrez Daniel , Jones Chris , Varlet Pascale , Mackay Alan , Warren Daniel , Warmuth-Metz Monika , Aliaga Esther Sánchez , Calmon Raphael , Hargrave Darren R. , Cañete Adela , Massimino Maura , Azizi Amedeo A. , Le Deley Marie-Cécile , Saran Frank , Rousseau Raphael F. , Zahlmann Gudrun , Garcia Josep , Vassal Gilles , Grill Jacques , Morgan Paul S. , Jaspan Tim
Published: April 2023

Demographics of major mutational groups
Supplemental Figure 3 from Multiplexed Evaluation of Microdosed Antineoplastic Agents In Situ in the Tumor Microenvironment of Patients with Soft Tissue Sarcoma
Authors: Gundle Kenneth R. , Deutsch Gary B. , Goodman Howard J. , Pollack Seth M. , Thompson Matthew J. , Davis Jessica L. , Lee Mee-Young , Ramirez Daniel C. , Kerwin William , Bertout Jessica A. , Grenley Marc O. , Sottero Kimberly H.W. , Beirne Emily , Frazier Jason , Dey Joyoti , Ellison Micah , Klinghoffer Richard A. , Maki Robert G.
Published: April 2023

Distinct drug induced phenotypes and apoptotic responses specific to drug mechanism of action are seen at sites of CIVO microinjection.
Table S4 from A Four-Chemokine Signature Is Associated with a T-cell–Inflamed Phenotype in Primary and Metastatic Pancreatic Cancer
Authors: Romero Joan M. , Grünwald Barbara , Jang Gun-Ho , Bavi Prashant P. , Jhaveri Aaditeya , Masoomian Mehdi , Fischer Sandra E. , Zhang Amy , Denroche Robert E. , Lungu Ilinca M. , De Luca Angela , Bartlett John M.S. , Xu Jing , Li Niandong , Dhaliwal Sharon , Liang Sheng-Ben , Chadwick Dianne , Vyas Foram , Bronsert Peter , Khokha Rama , McGaha Tracy L. , Notta Faiyaz , Ohashi Pamela S. , Done Susan J. , O'Kane Grainne M. , Wilson Julie M. , Knox Jennifer J. , Connor Ashton , Wang Yifan , Zogopoulos George , Gallinger Steven
Published: April 2023

Supplementary Table 4: Summary statistics for cellularity between 4-chemokinehi and 4-chemokinelo groups in liver metastases
Table S1 from A Four-Chemokine Signature Is Associated with a T-cell–Inflamed Phenotype in Primary and Metastatic Pancreatic Cancer
Authors: Romero Joan M. , Grünwald Barbara , Jang Gun-Ho , Bavi Prashant P. , Jhaveri Aaditeya , Masoomian Mehdi , Fischer Sandra E. , Zhang Amy , Denroche Robert E. , Lungu Ilinca M. , De Luca Angela , Bartlett John M.S. , Xu Jing , Li Niandong , Dhaliwal Sharon , Liang Sheng-Ben , Chadwick Dianne , Vyas Foram , Bronsert Peter , Khokha Rama , McGaha Tracy L. , Notta Faiyaz , Ohashi Pamela S. , Done Susan J. , O'Kane Grainne M. , Wilson Julie M. , Knox Jennifer J. , Connor Ashton , Wang Yifan , Zogopoulos George , Gallinger Steven
Published: April 2023

Supplementary Table 1: Top 99 genes associating with CD8+ TIL counts in primary resected cases
Figure S5 from A Four-Chemokine Signature Is Associated with a T-cell–Inflamed Phenotype in Primary and Metastatic Pancreatic Cancer
Authors: Romero Joan M. , Grünwald Barbara , Jang Gun-Ho , Bavi Prashant P. , Jhaveri Aaditeya , Masoomian Mehdi , Fischer Sandra E. , Zhang Amy , Denroche Robert E. , Lungu Ilinca M. , De Luca Angela , Bartlett John M.S. , Xu Jing , Li Niandong , Dhaliwal Sharon , Liang Sheng-Ben , Chadwick Dianne , Vyas Foram , Bronsert Peter , Khokha Rama , McGaha Tracy L. , Notta Faiyaz , Ohashi Pamela S. , Done Susan J. , O'Kane Grainne M. , Wilson Julie M. , Knox Jennifer J. , Connor Ashton , Wang Yifan , Zogopoulos George , Gallinger Steven
Published: April 2023

Supplementary Figure 5: The 4-chemokine signature identified an antitumor phenotype in liver metastases, independent of mutational burden
Figure S4 from A Four-Chemokine Signature Is Associated with a T-cell–Inflamed Phenotype in Primary and Metastatic Pancreatic Cancer
Authors: Romero Joan M. , Grünwald Barbara , Jang Gun-Ho , Bavi Prashant P. , Jhaveri Aaditeya , Masoomian Mehdi , Fischer Sandra E. , Zhang Amy , Denroche Robert E. , Lungu Ilinca M. , De Luca Angela , Bartlett John M.S. , Xu Jing , Li Niandong , Dhaliwal Sharon , Liang Sheng-Ben , Chadwick Dianne , Vyas Foram , Bronsert Peter , Khokha Rama , McGaha Tracy L. , Notta Faiyaz , Ohashi Pamela S. , Done Susan J. , O'Kane Grainne M. , Wilson Julie M. , Knox Jennifer J. , Connor Ashton , Wang Yifan , Zogopoulos George , Gallinger Steven
Published: April 2023

Supplementary Figure 4: Immune phenotypes were not impacted by cellularity in primary tumors
Supplementary Figure 6 from Safety and Efficacy of Vorinostat Plus Sirolimus or Everolimus in Patients with Relapsed Refractory Hodgkin Lymphoma
Authors: Janku Filip , Park Haeseong , Call S. Greg , Madwani Kiran , Oki Yasuhiro , Subbiah Vivek , Hong David S. , Naing Aung , Velez-Bravo Vivianne M. , Barnes Tamara G. , Hagemeister Fredrick B. , Falchook Gerald S. , Karp Daniel D. , Wheler Jennifer J. , Piha-Paul Sarina A. , Garrido-Laguna Ignacio , Shpall Elizabeth J. , Fayad Luis E. , Neelapu Sattva S. , Meric-Bernstam Funda , Kurzrock Razelle , Fanale Michelle A.
Published: April 2023

In patients treated with vorinostat and everolimus, there was a longer median progression-free survival in patients with normal albumin compared to patients with low albumin (5.8 months, 4.4 - 7.2 vs. 1.6 months, 95% CI 1.3-1.9; P < 0.001).
Figure S3 from Surfactant Expression Defines an Inflamed Subtype of Lung Adenocarcinoma Brain Metastases that Correlates with Prolonged Survival
Authors: Pocha Kolja , Mock Andreas , Rapp Carmen , Dettling Steffen , Warta Rolf , Geisenberger Christoph , Jungk Christine , Martins Leila R. , Grabe Niels , Reuss David , Debus Juergen , von Deimling Andreas , Abdollahi Amir , Unterberg Andreas , Herold-Mende Christel C.
Published: April 2023

Correlation plots of T cell subtypes.
Figure S2 from Surfactant Expression Defines an Inflamed Subtype of Lung Adenocarcinoma Brain Metastases that Correlates with Prolonged Survival
Authors: Pocha Kolja , Mock Andreas , Rapp Carmen , Dettling Steffen , Warta Rolf , Geisenberger Christoph , Jungk Christine , Martins Leila R. , Grabe Niels , Reuss David , Debus Juergen , von Deimling Andreas , Abdollahi Amir , Unterberg Andreas , Herold-Mende Christel C.
Published: April 2023

Example of HE and immunofluorescent stainings.
Supplementary Figure 9 from Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus–Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial
Authors: Uppaluri Ravindra , Campbell Katie M. , Egloff Ann Marie , Zolkind Paul , Skidmore Zachary L. , Nussenbaum Brian , Paniello Randal C. , Rich Jason T. , Jackson Ryan , Pipkorn Patrik , Michel Loren S. , Ley Jessica , Oppelt Peter , Dunn Gavin P. , Barnell Erica K. , Spies Nicholas C. , Lin Tianxiang , Li Tiantian , Mulder David T. , Hanna Youstina , Cirlan Iulia , Pugh Trevor J. , Mudianto Tenny , Riley Rachel , Zhou Liye , Jo Vickie Y. , Stachler Matthew D. , Hanna Glenn J. , Kass Jason , Haddad Robert , Schoenfeld Jonathan D. , Gjini Evisa , Lako Ana , Thorstad Wade , Gay Hiram A. , Daly Mackenzie , Rodig Scott J. , Hagemann Ian S. , Kallogjeri Dorina , Piccirillo Jay F. , Chernock Rebecca D. , Griffith Malachi , Griffith Obi L. , Adkins Douglas R.
Published: April 2023

Supplementary Figure
Supplementary Figure 3 from Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus–Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial
Authors: Uppaluri Ravindra , Campbell Katie M. , Egloff Ann Marie , Zolkind Paul , Skidmore Zachary L. , Nussenbaum Brian , Paniello Randal C. , Rich Jason T. , Jackson Ryan , Pipkorn Patrik , Michel Loren S. , Ley Jessica , Oppelt Peter , Dunn Gavin P. , Barnell Erica K. , Spies Nicholas C. , Lin Tianxiang , Li Tiantian , Mulder David T. , Hanna Youstina , Cirlan Iulia , Pugh Trevor J. , Mudianto Tenny , Riley Rachel , Zhou Liye , Jo Vickie Y. , Stachler Matthew D. , Hanna Glenn J. , Kass Jason , Haddad Robert , Schoenfeld Jonathan D. , Gjini Evisa , Lako Ana , Thorstad Wade , Gay Hiram A. , Daly Mackenzie , Rodig Scott J. , Hagemann Ian S. , Kallogjeri Dorina , Piccirillo Jay F. , Chernock Rebecca D. , Griffith Malachi , Griffith Obi L. , Adkins Douglas R.
Published: April 2023

Supplementary Figure
Supplemental Figure 4 from Safety and Clinical Activity of a New Anti-PD-L1 Antibody as Monotherapy or Combined with Targeted Therapy in Advanced Solid Tumors: The PACT Phase Ia/Ib Trial
Authors: Patnaik Amita , Yap Timothy A. , Chung Hyun Cheol , de Miguel Maria J. , Bang Yung-Jue , Lin Chia-Chi , Su Wu-Chou , Italiano Antoine , Chow Kay Hoong , Szpurka Anna M. , Yu Danni , Zhao Yumin , Carlsen Michelle , Schmidt Shelly , Vangerow Burkhard , Gandhi Leena , Xu Xiaojian , Bendell Johanna
Published: April 2023

Soluble PD-L1 concentrations in sera in LY3300054 monotherapy cohorts
Figure S2 from Phase I Trial of N-803, an IL15 Receptor Agonist, with Rituximab in Patients with Indolent Non-Hodgkin Lymphoma
Authors: Foltz Jennifer A. , Hess Brian T. , Bachanova Veronika , Bartlett Nancy L. , Berrien-Elliott Melissa M. , McClain Ethan , Becker-Hapak Michelle , Foster Mark , Schappe Timothy , Kahl Brad , Mehta-Shah Neha , Cashen Amanda F. , Marin Nancy D. , McDaniels Kristen , Moreno Chaz , Mosior Matthew , Gao Feng , Griffith Obi L. , Griffith Malachi , Wagner Julia A. , Epperla Narendranath , Rock Amy D. , Lee John , Petti Allegra A. , Soon-Shiong Patrick , Fehniger Todd A.
Published: April 2023

Effect of N-803 and Rituximab on CD4+ T cells
Figure S1 from Phase I Trial of N-803, an IL15 Receptor Agonist, with Rituximab in Patients with Indolent Non-Hodgkin Lymphoma
Authors: Foltz Jennifer A. , Hess Brian T. , Bachanova Veronika , Bartlett Nancy L. , Berrien-Elliott Melissa M. , McClain Ethan , Becker-Hapak Michelle , Foster Mark , Schappe Timothy , Kahl Brad , Mehta-Shah Neha , Cashen Amanda F. , Marin Nancy D. , McDaniels Kristen , Moreno Chaz , Mosior Matthew , Gao Feng , Griffith Obi L. , Griffith Malachi , Wagner Julia A. , Epperla Narendranath , Rock Amy D. , Lee John , Petti Allegra A. , Soon-Shiong Patrick , Fehniger Todd A.
Published: April 2023

Serum Immunogenicity and Cytokine Measurements
Table S2 from Clonal Architecture of EGFR Mutation Predicts the Efficacy of EGFR-Tyrosine Kinase Inhibitors in Advanced NSCLC: A Prospective Multicenter Study (NCT03059641)
Authors: Ai Xinghao , Cui Jiuwei , Zhang Jiexia , Chen Rongrong , Lin Wen , Xie Congying , Liu Anwen , Zhang Junping , Yang Weihua , Hu Xiaohua , Zhao Qiong , Rao Chuangzhou , Zang Yuan-Sheng , Ning Ruiling , Li Pansong , Chang Lianpeng , Yi Xin , Lu Shun
Published: April 2023

Quality Control data of the tissue and ctDNA analyzed in the study
Supplementary Figure S5 from The PSMA-targeting Half-life Extended BiTE Therapy AMG 160 has Potent Antitumor Activity in Preclinical Models of Metastatic Castration-resistant Prostate Cancer
Authors: Deegen Petra , Thomas Oliver , Nolan-Stevaux Olivier , Li Shyun , Wahl Joachim , Bogner Pamela , Aeffner Famke , Friedrich Matthias , Liao Michael Z. , Matthes Katja , Rau Doris , Rattel Benno , Raum Tobias , Kufer Peter , Coxon Angela , Bailis Julie M.
Published: April 2023

Figure S5. AMG 160 engages NHP PSMA and CD3 in vitro.
Supplementary Data from A Somatostatin Receptor Subtype-3 (SST3) Peptide Agonist Shows Antitumor Effects in Experimental Models of Nonfunctioning Pituitary Tumors
Authors: Vázquez-Borrego Mari C. , Gupta Vandana , Ibáñez-Costa Alejandro , Gahete Manuel D. , Venegas-Moreno Eva , Toledano-Delgado Álvaro , Cano David A. , Blanco-Acevedo Cristóbal , Ortega-Salas Rosa , Japón Miguel A. , Barrera-Martín Ana , Vasiljevic Alexandre , Hill Jason , Zhang Shengwen , Halem Heather , Solivera Juan , Raverot Gérald , Gálvez María A. , Soto-Moreno Alfonso , Paez-Pereda Marcelo , Culler Michael D. , Castaño Justo P. , Luque Raúl M.
Published: April 2023

This supplementary file contains supplementary methods (library screening and statistical analysis) and table S1 (Pharmacological characterization of SST3-selective compounds), table S2 (Relation of functional experiments performed in responsive (RP) and unresponsive (URP) NFPTs), table S3 (Percentage of responsive and unresponsive NFPTs regarding SST3-specific agonists in terms of cell viability), table S4 (Results from Chi-square test of clinical parameters between responsive and unresponsive NFPTs), and table S5 (Clinical data and SST3 mRNA expression levels of individual NFPTs).
Figure S3 from CAR T cells Targeting Human Immunoglobulin Light Chains Eradicate Mature B-cell Malignancies While Sparing a Subset of Normal B Cells
Authors: Ranganathan Raghuveer , Shou Peishun , Ahn Sarah , Sun Chuang , West John , Savoldo Barbara , Dotti Gianpietro
Published: April 2023

CD19-T cells show equivalent antitumor activity in a lymphoma tumor model in vivo at a lower dose of CAR-T cells
Figure S1 from CAR T cells Targeting Human Immunoglobulin Light Chains Eradicate Mature B-cell Malignancies While Sparing a Subset of Normal B Cells
Authors: Ranganathan Raghuveer , Shou Peishun , Ahn Sarah , Sun Chuang , West John , Savoldo Barbara , Dotti Gianpietro
Published: April 2023

Modifications of the hinge and transmembrane domain
Suppl Figure 6 from VLA4-Targeted Nanoparticles Hijack Cell Adhesion–Mediated Drug Resistance to Target Refractory Myeloma Cells and Prolong Survival
Authors: Fontana Francesca , Scott Michael J. , Allen John S. , Yang Xiaoxia , Cui Grace , Pan Dipanjan , Yanaba Noriko , Fiala Mark A. , O'Neal Julie , Schmieder-Atteberry Anne H. , Ritchey Julie , Rettig Michael , Simons Kathleen , Fletcher Steven , Vij Ravi , DiPersio John F. , Lanza Gregory M.
Published: April 2023

Supplemental Figure 6 Color
Supplement from Alpha-smooth Muscle Actin Expression in the Stroma Predicts Resistance to Trastuzumab in Patients with Early-stage HER2-positive Breast Cancer
Authors: Vathiotis Ioannis A. , Moutafi Myrto K. , Divakar Prajan , Aung Thazin Nwe , Qing Tao , Fernandez Aileen , Yaghoobi Vesal , El-Abed Sarra , Wang Yingbo , Guillaume Sebastien , Nuciforo Paolo , Huober Jens , Di Cosimo Serena , Kim Sung-Bae , Harbeck Nadia , Gomez Henry , Shafi Saba , Syrigos Konstantinos N. , Fountzilas George , Sotiriou Christos , Pusztai Lajos , Warren Sarah , Rimm David L.
Published: April 2023

Supplementary Table and Supplementary Figure Legends
Figure S5 from The Landscape of Alterations in DNA Damage Response Pathways in Colorectal Cancer
Authors: Arai Hiroyuki , Elliott Andrew , Xiu Joanne , Wang Jingyuan , Battaglin Francesca , Kawanishi Natsuko , Soni Shivani , Zhang Wu , Millstein Joshua , Sohal Davendra , Goldberg Richard M. , Hall Michael J. , Scott Aaron J. , Khushman Moh'd , Hwang Jimmy J. , Lou Emil , Weinberg Benjamin A. , Marshall John L. , Lockhart Albert C. , Stafford Phillip , Zhang Jian , Moretto Roberto , Cremolini Chiara , Korn W. Michael , Lenz Heinz-Josef
Published: April 2023

The frequency of DDR pathways alteration by CMS
Supplementary Figure S20 from Evolution of Castration-Resistant Prostate Cancer in ctDNA during Sequential Androgen Receptor Pathway Inhibition
Authors: Annala Matti , Taavitsainen Sinja , Khalaf Daniel J. , Vandekerkhove Gillian , Beja Kevin , Sipola Joonatan , Warner Evan W. , Herberts Cameron , Wong Amanda , Fu Simon , Finch Daygen L. , Oja Conrad D. , Vergidis Joanna , Zulfiqar Muhammad , Eigl Bernhard J. , Kollmansberger Christian K. , Nykter Matti , Gleave Martin E. , Chi Kim N. , Wyatt Alexander W.
Published: April 2023

Supplementary Figure S20 shows genomic changes in selected prostate cancer driver genes after treatment with abiraterone/enzalutamide
Supplementary Figure S16 from Evolution of Castration-Resistant Prostate Cancer in ctDNA during Sequential Androgen Receptor Pathway Inhibition
Authors: Annala Matti , Taavitsainen Sinja , Khalaf Daniel J. , Vandekerkhove Gillian , Beja Kevin , Sipola Joonatan , Warner Evan W. , Herberts Cameron , Wong Amanda , Fu Simon , Finch Daygen L. , Oja Conrad D. , Vergidis Joanna , Zulfiqar Muhammad , Eigl Bernhard J. , Kollmansberger Christian K. , Nykter Matti , Gleave Martin E. , Chi Kim N. , Wyatt Alexander W.
Published: April 2023

Supplementary Figure S16 shows patients without evidence for somatic mutation profile change after treatment progression based on 72-gene targeted sequencing
Supplementary Figure S1 from Evolution of Castration-Resistant Prostate Cancer in ctDNA during Sequential Androgen Receptor Pathway Inhibition
Authors: Annala Matti , Taavitsainen Sinja , Khalaf Daniel J. , Vandekerkhove Gillian , Beja Kevin , Sipola Joonatan , Warner Evan W. , Herberts Cameron , Wong Amanda , Fu Simon , Finch Daygen L. , Oja Conrad D. , Vergidis Joanna , Zulfiqar Muhammad , Eigl Bernhard J. , Kollmansberger Christian K. , Nykter Matti , Gleave Martin E. , Chi Kim N. , Wyatt Alexander W.
Published: April 2023

Supplementary Figure S1 shows independent estimation of circulating tumor DNA fraction using whole exome sequencing.
Figure S5 from Circulating Protein Biomarkers for Use in Pancreatic Ductal Adenocarcinoma Identification
Authors: Lindgaard Sidsel C. , Sztupinszki Zsófia , Maag Emil , Chen Inna M. , Johansen Astrid Z. , Jensen Benny V. , Bojesen Stig E. , Nielsen Dorte L. , Hansen Carsten P. , Hasselby Jane P. , Nielsen Kaspar R. , Szallasi Zoltan , Johansen Julia S.
Published: April 2023

Supplementary figure S5 shows an illustration of the proteins in the Olink immuno-oncology panel and the percentage of samples with NPX values missing or values below limit of detection (LOD)
Supplementary Figure from Differences in Prostate Cancer Genomes by Self-reported Race: Contributions of Genetic Ancestry, Modifiable Cancer Risk Factors, and Clinical Factors
Authors: Stopsack Konrad H. , Nandakumar Subhiksha , Arora Kanika , Nguyen Bastien , Vasselman Samantha E. , Nweji Barbara , McBride Sean M. , Morris Michael J. , Rathkopf Dana E. , Slovin Susan F. , Danila Daniel C. , Autio Karen A. , Scher Howard I. , Mucci Lorelei A. , Solit David B. , Gönen Mithat , Chen Yu , Berger Michael F. , Schultz Nikolaus , Abida Wassim , Kantoff Philip W.
Published: April 2023

Supplementary Figure from Differences in Prostate Cancer Genomes by Self-reported Race: Contributions of Genetic Ancestry, Modifiable Cancer Risk Factors, and Clinical Factors
Supplementary Figure from Determinants of Response to Talazoparib in Patients with HER2-Negative, Germline BRCA1/2-Mutated Breast Cancer
Authors: Blum Joanne L. , Laird A. Douglas , Litton Jennifer K. , Rugo Hope S. , Ettl Johannes , Hurvitz Sara A. , Martin Miguel , Roché Henri H. , Lee Kyung-Hun , Goodwin Annabel , Chen Ying , Lanzalone Silvana , Chelliserry Jijumon , Czibere Akos , Hopkins Julia F. , Albacker Lee A. , Mina Lida A.
Published: April 2023

Supplementary Figure from Determinants of Response to Talazoparib in Patients with HER2-Negative, Germline BRCA1/2-Mutated Breast Cancer
Supplementary Data from Diminished Immune Surveillance during Histologic Progression of Intraductal Papillary Mucinous Neoplasms Offers a Therapeutic Opportunity for Cancer Interception
Authors: Hernandez Sharia , Parra Edwin Roger , Uraoka Naohiro , Tang Ximing , Shen Yu , Qiao Wei , Jiang Mei , Zhang Shanyu , Mino Barbara , Lu Wei , Pandurengan Renganayaki , Haymaker Cara , Affolter Kajsa , Scaife Courtney L. , Yip-Schneider Michele , Schmidt C. Max , Firpo Matthew A. , Mulvihill Sean J. , Koay Eugene J. , Wang Huamin , Wistuba Ignacio I. , Maitra Anirban , Solis Luisa M. , Sen Subrata
Published: April 2023

Supplementary Data from Diminished Immune Surveillance during Histologic Progression of Intraductal Papillary Mucinous Neoplasms Offers a Therapeutic Opportunity for Cancer Interception
Supplementary Methods S1 from Zinc Finger MYND-Type Containing 8 (ZMYND8) Is Epigenetically Regulated in Mutant Isocitrate Dehydrogenase 1 (IDH1) Glioma to Promote Radioresistance
Authors: Carney Stephen V. , Banerjee Kaushik , Mujeeb Anzar , Zhu Brandon , Haase Santiago , Varela Maria L. , Kadiyala Padma , Tronrud Claire E. , Zhu Ziwen , Mukherji Devarshi , Gorla Preethi , Sun Yilun , Tagett Rebecca , Núñez Felipe J. , Luo Maowu , Luo Weibo , Ljungman Mats , Liu Yayuan , Xia Ziyun , Schwendeman Anna , Qin Tingting , Sartor Maureen A. , Costello Joseph F. , Cahill Daniel P. , Lowenstein Pedro R. , Castro Maria G.
Published: April 2023

Supplementary Methods
Supplementary Table S3 from Loss of CDKN2A Cooperates with WWTR1(TAZ)–CAMTA1 Gene Fusion to Promote Tumor Progression in Epithelioid Hemangioendothelioma
Authors: Seavey Caleb N. , Hallett Andrea , Li Shuo , Che Kepeng , Pobbati Ajaybabu V. , Ma Shuang , Burtscher Ashley , Kanai Ryan , Lamar John M. , Rubin Brian P.
Published: April 2023

Supplemental Table 3. Single cell RNA sequencing of GEMM EHE tumors
Differentially expressed genes between normal endothelial cells and Cdkn2a WT and KO tumors by single cell RNA sequencing. Functional annotations with the gene ontology sets are displayed for the Cdkn2a KO vs WT comparison, graphically displayed in Figure 3D. Transcripts used for the EHE tumor gene set are similarly displayed.
Data from A Five-Gene Molecular Grade Index and HOXB13:IL17BR Are Complementary Prognostic Factors in Early Stage Breast Cancer
Authors: Ma Xiao-Jun , Salunga Ranelle , Dahiya Sonika , Wang Wilson , Carney Erin , Durbecq Virginie , Harris Adrian , Goss Paul , Sotiriou Christos , Erlander Mark , Sgroi Dennis
Published: April 2023

Abstract
Purpose: Histologic tumor grade is a well-established prognostic factor for breast cancer, and tumor grade–associated genes are the common denominator of many prognostic gene signatures. The objectives of this study are as follows: (a) to develop a simple gene expression index for tumor grade (molecular grade index or MGI), and (b) to determine whether MGI and our previously described HOXB13:IL17BR index together provide improved prognostic information.

Experimental Design: From our previously published list of genes whose expression correlates with both tumor grade and tumor stage progression, we selected five cell cycle–related genes to build MGI and evaluated MGI in two publicly available microarray data sets totaling 410 patients. Using two additional cohorts (n = 323), we developed a real-time reverse transcription PCR assay for MGI, validated its prognostic utility, and examined its interaction with HOXB13:IL17BR.

Results: MGI performed consistently as a strong prognostic factor and was comparable with a more complex 97-gene genomic grade index in multiple data sets. In patients treated with endocrine therapy, MGI and HOXB13:IL17BR modified each other's prognostic performance. High MGI was associated with significantly worse outcome only in combination with high HOXB13:IL17BR, and likewise, high HOXB13:IL17BR was significantly associated with poor outcome only in combination with high MGI.

Conclusions: We developed and validated a five-gene reverse transcription PCR assay for MGI suitable for analyzing routine formalin-fixed paraffin-embedded clinical samples. The combination of MGI and HOXB13:IL17BR outperforms either alone and identifies a subgroup (∼30%) of early stage estrogen receptor–positive breast cancer patients with very poor outcome despite endocrine therapy.
Data from Ubiquitin Proteasome System Stress Underlies Synergistic Killing of Ovarian Cancer Cells by Bortezomib and a Novel HDAC6 Inhibitor
Authors: Bazzaro Martina , Lin Zhenhua , Santillan Antonio , Lee Michael K. , Wang Mei-Cheng , Chan Kwun C. , Bristow Robert E. , Mazitschek Ralph , Bradner James , Roden Richard B.S.
Published: April 2023

Abstract
Purpose: Elevated metabolic activity of ovarian cancer cells causes increased ubiquitin-proteasome-system (UPS) stress, resulting in their greater sensitivity to the toxic effects of proteasomal inhibition. The proteasomes and a potentially compensatory histone deacetylase 6 (HDAC6)-dependent lysosomal pathway mediate eukaryotic protein turnover. We hypothesized that up-regulation of the HDAC6-dependent lysosomal pathway occurs in response to UPS stress and proteasomal inhibition, and thus, ovarian cancer cell death can be triggered most effectively by coinhibition of both the proteasome- and HDAC6-dependent protein degradation pathways.

Experimental Design: To address this hypothesis, we examined HDAC6 expression patterns in normal and cancerous ovarian tissues and used a novel HDAC6-specific inhibitor, NK84, to address HDAC6 function in ovarian cancer.

Results: Abnormally high levels of HDAC6 are expressed by ovarian cancer cells in situ and in culture relative to benign epithelium and immortalized ovarian surface epithelium, respectively. Specific HDAC6 inhibition acts in synergy with the proteasome inhibitor Bortezomib (PS-341) to cause selective apoptotic cell death of ovarian cancer cells at doses that do not cause significant toxicity when used individually. Levels of UPS stress regulate the sensitivity of ovarian cancer cells to proteasome/HDAC6 inhibition. Pharmacologic inhibition of HDAC6 also reduces ovarian cancer cell spreading and migration consistent with its known function in regulating microtubule polymerization via deacetylation of α-tubulin.

Conclusion: Our results suggest the elevation of both the proteasomal and alternate HDAC6-dependent proteolytic pathways in ovarian cancer and the potential of combined inhibition of proteasome and HDAC6 as a therapy for ovarian cancer.
Data from Identification of a Novel Tumor-Associated Antigen, Cadherin 3/P-Cadherin, as a Possible Target for Immunotherapy of Pancreatic, Gastric, and Colorectal Cancers
Authors: Imai Katsunori , Hirata Shinya , Irie Atsushi , Senju Satoru , Ikuta Yoshiaki , Yokomine Kazunori , Harao Michiko , Inoue Mitsuhiro , Tsunoda Takuya , Nakatsuru Shuichi , Nakagawa Hidewaki , Nakamura Yusuke , Baba Hideo , Nishimura Yasuharu
Published: April 2023

Abstract
Purpose: To establish cancer immunotherapy, it is important to identify the tumor-associated antigens (TAA) that are strongly expressed in the tumor cells but not in the normal cells. In this study, to establish an effective anticancer immunotherapy, we tried to identify the useful TAA of pancreatic cancer.

Experimental Design: Based on a previous genome-wide cDNA microarray analysis of pancreatic cancer, we focused on cadherin 3 (CDH3)/P-cadherin as a novel candidate TAA for anticancer immunotherapy. To identify the HLA-A2 (A*0201)–restricted CTL epitopes of CDH3, we used HLA-A2.1 (HHD) transgenic mice (Tgm). Furthermore, we examined the cytotoxicity against the tumor cells in vitro and in vivo of CTLs specific to CDH3 induced from HLA-A2–positive healthy donors and cancer patients.

Results:CDH3 was overexpressed in the majority of pancreatic cancer and various other malignancies, including gastric and colorectal cancers, but not in their noncancerous counterparts or in many normal adult tissues. In the experiment using HLA-A2.1 Tgm, we found that the CDH3-4655-663 (FILPVLGAV) and CDH3-7757-765 (FIIENLKAA) peptides could induce HLA-A2–restricted CTLs in Tgm. In addition, peptides-reactive CTLs were successfully induced from peripheral blood mononuclear cells by in vitro stimulation with these two peptides in HLA-A2–positive healthy donors and cancer patients, and these CTLs exhibited cytotoxicity specific to cancer cells expressing both CDH3 and HLA-A2. Furthermore, the adoptive transfer of the CDH3-specific CTLs could inhibit the tumor growth of human cancer cells engrafted into nonobese diabetic/severe combined immunodeficiency mice.

Conclusions: These results suggest that CDH3 is a novel TAA useful for immunotherapy against a broad spectrum of cancers, including pancreatic cancer.
Data from Apicularen A Induces Cell Death through Fas Ligand Up-Regulation and Microtubule Disruption by Tubulin Down-Regulation in HM7 Human Colon Cancer Cells
Authors: Kim Jong-Seok , Lee Young-Chul , Nam Ho-Tak , Li Ge , Yun Eun-Jin , Song Kyoung-Sub , Seo Kang-Sik , Park Ji-Hoon , Ahn Jong-Woong , Zee OkPyo , Park Jong-Il , Yoon Wan-Hee , Lim Kyu , Hwang Byung-Doo
Published: April 2023

Abstract
Purpose: Apicularen A has been shown to cause growth inhibition and apoptosis in several cancer cell lines. However, the mechanisms of apicularen A–induced cell death and in vivo effects remain unclear. In this study, we investigated the molecular mechanisms of apicularen A–induced cell death in HM7 human colon cancer cells in vitro and anticancer activity in vivo.

Experimental Design: We tested cytotoxicity with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, apoptosis with DNA fragmentation assay, mitochondrial membrane potential, and cell cycle with fluorescence-activated cell sorting. Caspase activation was done by fluorometry. Alterations of microtubule structure, tubulin protein, and mRNA level were assessed by immunofluorescence, Western blot, and reverse transcription-PCR. In vivo studies were assessed using nude mice tumor cell growth in xenograft model and liver colonization assay.

Results: Apicularen A treatment of HM7 cells inhibited cell growth and this inhibition was partially rescued by z-VAD-fmk. Apicularen A caused accumulation of sub-G1-G0, DNA fragmentation, Fas ligand induction, and activation of caspase-8 and caspase-3, but mitochondrial membrane potential was not changed. Furthermore, β-tubulin protein and mRNA were decreased by apicularen A, but in vitro polymerization of tubulin was not affected. Concurrently, apicularen A–treated cell showed disruption of microtubule architecture. In in vivo studies, apicularen A reduced tumor volume by ∼72% at the end of a 15-day treatment. Moreover, apicularen A reduced liver colonization as much as 95.6% (50 μg/kg/d).

Conclusion: Apicularen A induces cell death of HM7 cells through up-regulating Fas ligand and disruption of microtubule architecture with down-regulation of tubulin level. These findings indicate that apicularen A is a promising new microtubule-targeting compound.
Data from Photodynamic Therapy: A Light in the Darkness?
Authors: Lin Alexander , Hahn Stephen M.
Published: April 2023

Abstract
Photodynamic therapy (PDT) is used to treat localized premalignant or early malignant disease. This study reports the enhanced, systemic antitumor immune response from PDT, suggesting that it may have a potential role as a therapy to address both local and disseminated disease.
Data from ABCC2, ABCC3, and ABCB1, but not CYP3A, Protect against Trabectedin-Mediated Hepatotoxicity
Authors: van Waterschoot Robert A.B. , Eman Rhandy M. , Wagenaar Els , van der Kruijssen Cornelia M.M. , Rosing Hilde , Beijnen Jos H. , Schinkel Alfred H.
Published: April 2023

Abstract
Purpose: Trabectedin (Yondelis, ET-743) is a novel anticancer drug with potent activity against various tumors. However, dose-limiting hepatotoxicity was observed during clinical trials. Because recent reports have suggested that cytochrome P450 3A (CYP3A), as well as the drug transporters ABCB1, ABCC2, and ABCC3 might protect against trabectedin-mediated hepatotoxicity, we investigated the individual and combined roles of these detoxifying systems.

Experimental Design: Madin-Darby canine kidney cells expressing ABCC2 and ABCC3 were used to study in vitro trabectedin transport. We investigated the hepatotoxicity of trabectedin, and the plasma and liver levels of this drug and its metabolites in mice deficient for CYP3A, Abcb1a/1b, Abcc2, and/or Abcc3 after i.v. trabectedin administration.

Results: Trabectedin was transported by ABCC2 but only modestly by ABCC3. Contrary to our expectation, absence of CYP3A resulted in only a marginal increase in hepatotoxicity. Some hepatotoxicity was observed in Abcc2−/− mice, but very little in Abcb1a/1b−/− and Abcc3−/− mice. Strikingly, severe hepatotoxicity was found in Abcb1a/1b/Abcc2−/− and Abcc2/Abcc3−/− mice. However, hepatotoxicity was drastically decreased in Cyp3a/Abcb1a/1b/Abcc2−/− compared with Abcb1a/1b/Abcc2−/− mice. This suggests that the formation of CYP3A-specific metabolites is an important prerequisite for trabectedin-mediated hepatotoxicity. Further studies revealed that there is increased accumulation of metabolites of trabectedin, but not of trabectedin itself, in the livers of mice that lack Abcc2 but are CYP3A proficient.

Conclusions: Our data show that ABCB1, ABCC2, and ABCC3 have a profound and partially redundant function in protection from trabectedin-mediated hepatotoxicity, presumably by clearing the liver from hepatotoxic trabectedin metabolites that are primarily formed by CYP3A. (Clin Cancer Res 2009;15(24):7616–23)
Data from EGFRvIII Deletion Mutations in Pediatric High-Grade Glioma and Response to Targeted Therapy in Pediatric Glioma Cell Lines
Authors: Bax Dorine A. , Gaspar Nathalie , Little Suzanne E. , Marshall Lynley , Perryman Lara , Regairaz Marie , Viana-Pereira Marta , Vuononvirta Raisa , Sharp Swee Y. , Reis-Filho Jorge S. , Stávale João N. , Al-Sarraj Safa , Reis Rui M. , Vassal Gilles , Pearson Andrew D.J. , Hargrave Darren , Ellison David W. , Workman Paul , Jones Chris
Published: April 2023

Abstract
Purpose: The epidermal growth factor receptor (EGFR) is amplified and overexpressed in adult glioblastoma, with response to targeted inhibition dependent on the underlying biology of the disease. EGFR has thus far been considered to play a less important role in pediatric glioma, although extensive data are lacking. We have sought to clarify the role of EGFR in pediatric high-grade glioma (HGG).

Experimental Design: We retrospectively studied a total of 90 archival pediatric HGG specimens for EGFR protein overexpression, gene amplification, and mutation and assessed the in vitro sensitivity of pediatric glioma cell line models to the small-molecule EGFR inhibitor erlotinib.

Results: Amplification was detected in 11% of cases, with corresponding overexpression of the receptor. No kinase or extracellular domain mutations were observed; however, 6 of 35 (17%) cases harbored the EGFRvIII deletion, including two anaplastic oligodendrogliomas and a gliosarcoma overexpressing EGFRvIII in the absence of gene amplification and coexpressing platelet-derived growth factor receptor α. Pediatric glioblastoma cells transduced with wild-type or deletion mutant EGFRvIII were not rendered more sensitive to erlotinib despite expressing wild-type PTEN. Phosphorylated receptor tyrosine kinase profiling showed a specific activation of platelet-derived growth factor receptor α/β in EGFRvIII-transduced pediatric glioblastoma cells, and targeted coinhibition with erlotinib and imatinib leads to enhanced efficacy in this model.

Conclusions: These data identify an elevated frequency of EGFR gene amplification and EGFRvIII mutation in pediatric HGG than previously recognized and show the likely necessity of targeting multiple genetic alterations in the tumors of these children. (Clin Cancer Res 2009;15(18):5753–61)