bluuebunny/crossref_metadata_2025 huggingface dataset:
Figure S1, S2, S3, S4, S5, S6, S7, S8, and S9 from ARID5B Influences Antimetabolite Drug Sensitivity and Prognosis of Acute Lymphoblastic Leukemia
Authors: Xu Heng , Zhao Xujie , Bhojwani Deepa , E Shuyu , Goodings Charnise , Zhang Hui , Seibel Nita L. , Yang Wentao , Li Chunliang , Carroll William L. , Evans William E. , Yang Jun J.
Published: April 2023

Figure S1 shows the knock-down effect of ARID5B with different shRNAs in Nalm6 cells; Figure S2 shows the correlation between MTX and 6-MP sensitivity with different levels of ARID5B knock-down in Nalm6 cells; Figure S3 shows that down-regulation of ARID5B mediated MTX and 6-MP drug resistance can be reversed by re-expression of ARID5B; Figure S4 shows that the levels of MTX and 6-MP active metabolites were reduced significantly after ARID5B knockdown; Figure S5 shows similar MTX and 6-MP drug resistance after CRISPR-mediated ARID5B downregulation; Figure S6 shows that decreased cell growth was detected by BrdU-uptake assay; Figure S7 shows treatment with increased concentrations of MTX and 6-MP led to gradually decreased p21 level; Figure S8 shows that a potential ARID5B binding site 25kb distal to CDKN1A locus was identified by ATAC-seq signal and Histone modification marks; Figure S9 shows an enrichment of components of the p53 signaling pathway was differentially expressed upon ARID5B knockdown.
Supplementary Figure S2 from Reciprocal and Autonomous Glucocorticoid and Androgen Receptor Activation in Salivary Duct Carcinoma
Authors: Mitani Yoshitsugu , Lin Sue-Hwa , Pytynia Kristen B. , Ferrarotto Renata , El-Naggar Adel K.
Published: April 2023

Ligand independent AR activation and AR downstream target genes expression in SDC cell lines.
Figure S9 from Disease Monitoring Using Post-induction Circulating Tumor DNA Analysis Following First-Line Therapy in Patients with Metastatic Colorectal Cancer
Authors: Max Ma Xiaoju , Bendell Johanna C. , Hurwitz Herbert I. , Ju Christine , Lee John J. , Lovejoy Alex , Mancao Christoph , Nicholas Alan , Price Richard , Sommer Nicolas , Tikoo Nalin , Yao Lijing , Yaung Stephanie J. , Palma John F.
Published: April 2023

Supplementary Figure
Supplementary Data from Cell-free Circulating Tumor DNA Variant Allele Frequency Associates with Survival in Metastatic Cancer
Authors: Pairawan Seyed , Hess Kenneth R. , Janku Filip , Sanchez Nora S. , Mills Shaw Kenna R. , Eng Cathy , Damodaran Senthilkumar , Javle Milind , Kaseb Ahmed O. , Hong David S. , Subbiah Vivek , Fu Siqing , Fogelman David R. , Raymond Victoria M. , Lanman Richard B. , Meric-Bernstam Funda
Published: April 2023

Supplemental Table 4
Supplementary Data Methods from Methylation-dependent Tissue Factor Suppression Contributes to the Reduced Malignancy of IDH1-mutant Gliomas
Authors: Unruh Dusten , Mirkov Snezana , Wray Brian , Drumm Michael , Lamano Jonathan , Li Yuping D. , Haider Qazi F. , Javier Rodrigo , McCortney Kathleen , Saratsis Amanda , Scholtens Denise M. , Sarkaria Jann N. , James C. David , Horbinski Craig
Published: April 2023

description of the methods in the supplementary data
Table S3 from Significance of BRCA2 and RB1 Co-loss in Aggressive Prostate Cancer Progression
Authors: Chakraborty Goutam , Armenia Joshua , Mazzu Ying Z. , Nandakumar Subhiksha , Stopsack Konrad H. , Atiq Mohammad O. , Komura Kazumasa , Jehane Lina , Hirani Rahim , Chadalavada Kalyani , Yoshikawa Yuki , Khan Nabeela A. , Chen Yu , Abida Wassim , Mucci Lorelei A. , Lee Gwo-Shu Mary , Nanjangud Gouri J. , Kantoff Philip W.
Published: April 2023

Supplementary Table S3
Tables S11-S12 from Genomic Evolutionary Patterns of Leiomyosarcoma and Liposarcoma
Authors: Amin-Mansour Ali , George Suzanne , Sioletic Stefano , Carter Scott L. , Rosenberg Mara , Taylor-Weiner Amaro , Stewart Chip , Chevalier Aaron , Seepo Sara , Tracy Adam , Getz Gad , Hornick Jason L. , Nucci Marisa R. , Quade Bradley , Demetri George D. , Raut Chandrajit P. , Garraway Levi A. , Van Allen Eliezer M. , Wagner Andrew J.
Published: April 2023

Supplementary Tables 11-12
Table S3 from Characterization of Alternative Splicing Events in HPV-Negative Head and Neck Squamous Cell Carcinoma Identifies an Oncogenic DOCK5 Variant
Authors: Liu Chao , Guo Theresa , Xu Guorong , Sakai Akihiro , Ren Shuling , Fukusumi Takahito , Ando Mizuo , Sadat Sayed , Saito Yuki , Khan Zubair , Fisch Kathleen M. , Califano Joseph
Published: April 2023

Distribution of 580 validated junctions in each tumor sample
Supplementary Figure 6 from Chemerin Reactivates PTEN and Suppresses PD-L1 in Tumor Cells via Modulation of a Novel CMKLR1-mediated Signaling Cascade
Authors: Rennier Keith , Shin Woo Jae , Krug Ethan , Virdi Gurpal , Pachynski Russell K.
Published: April 2023

Supplementary Figure 6. A. Optimizing effector to target ratio using activated human T cells. Varying effector to target (E:T) ratios showing T cell mediated cytotoxicity in PBS vs 6nM chemerin treated DU145. (*p < 0.05, using triplicate samples for each experiment and repeated for n = 3 independent experiments). B. Inhibition of chemerin-augmented T cell alloreactivity by MHCI blockade. Non-HLA matched donor T cells were used as effector cells with DU145 tumor target cells at 3:1 E:T ratio. Anti-MHCI (anti-human HLA-ABC cat#311402, clone W6/32, Biolegend) or isotype control (Mouse IgG2a, ÃŽÂº) monoclonal antibodies were used to pretreat tumor cells. % lysis of tumor cells was determined as described in Methods. Figure is representative of n=2 replicate experiments each with n=3 replicates per condition with mean and SD shown ; *p < 0.05, NS=not significant. C. Chemerin treatment does not significantly alter tumor MHCI expression in the presence or absence of IFNg. DU145 tumor cells were treated with PBS or 6nM chemerin for 48h; for samples indicated, 50 ng/mL of IFNg was added at the 24-hour time point. Cells were then stained for MHCI expression (anti-human HLA-ABC PE conjugated, 311406, Biolegend) and analyzed by FACS with MFI relative to Control PBS shown. D. Human T cells do not express detectable CMKLR1. Human T cells were negatively isolated from donor PBMCs and activated, as described in methods. Isotype control or an anti-human CMKLR1 PE (cat#FAB362P, R&D Systems) conjugated antibodies were used to stain cells and analyze by flow cytometry. E. Chemerin treatment does not alter PTEN expression in activated T cells. Isolated human T cells were activated, as described in the Methods, in the absence or presence of recombinant human chemerin 6nM. Isolated RNA was analyzed for PTEN expression. Graph is representative of 3 independent experiments with similar results. F. Chemerin does not significantly alter T cell cytolytic function. Isolated human T cells were used as described in cytotoxicity assays with DU145 tumor targets. Tumor cells were treated with PBS (gray) or chemerin (black). NaÃƒÂ¯ve and activated T cells were used as indicated. T cells were pretreated with 6nM chemerin for 48h, then washed, prior to co-culture with tumor cells, as indicated. 6nM chemerin was added to the media at the start of the co-culture and kept in for the duration of the experiment (overnight), as indicated. Graphs are representative of at least two replicate experiments with similar results.
Supplementary Results from The MD Anderson Prostate Cancer Patient-derived Xenograft Series (MDA PCa PDX) Captures the Molecular Landscape of Prostate Cancer and Facilitates Marker-driven Therapy Development
Authors: Palanisamy Nallasivam , Yang Jun , Shepherd Peter D.A. , Li-Ning-Tapia Elsa M. , Labanca Estefania , Manyam Ganiraju C. , Ravoori Murali K. , Kundra Vikas , Araujo John C. , Efstathiou Eleni , Pisters Louis L. , Wan Xinhai , Wang Xuemei , Vazquez Elba S. , Aparicio Ana M. , Carskadon Shannon L. , Tomlins Scott A. , Kunju Lakshmi P. , Chinnaiyan Arul M. , Broom Bradley M. , Logothetis Christopher J. , Troncoso Patricia , Navone Nora M.
Published: April 2023

Supplementary Results
Supplemental Figure 4 from Multiparametric MR-PET Imaging Predicts Pharmacokinetics and Clinical Response to GDC-0084 in Patients with Recurrent High-Grade Glioma
Authors: Ellingson Benjamin M. , Yao Jingwen , Raymond Catalina , Nathanson David A. , Chakhoyan Ararat , Simpson Jeremy , Garner James S. , Olivero Alan G. , Mueller Lars U. , Rodon Jordi , Gerstner Elizabeth , Cloughesy Timothy F. , Wen Patrick Y.
Published: April 2023

Correlation between Cmax and AUC.
Supplementary Figure S3 from Telomerase Reverse Transcriptase Promoter Mutations Identify a Genomically Defined and Highly Aggressive Human Pleural Mesothelioma Subgroup
Authors: Pirker Christine , Bilecz Agnes , Grusch Michael , Mohr Thomas , Heidenreich Barbara , Laszlo Viktoria , Stockhammer Paul , Lötsch-Gojo Daniela , Gojo Johannes , Gabler Lisa , Spiegl-Kreinecker Sabine , Dome Balazs , Steindl Ariane , Klikovits Thomas , Hoda Mir Alireza , Jakopovic Marko , Samarzija Miroslav , Mohorcic Katja , Kern Izidor , Kiesel Barbara , Brcic Luka , Oberndorfer Felicitas , Müllauer Leonhard , Klepetko Walter , Schmidt Wolfgang M. , Kumar Rajiv , Hegedus Balazs , Berger Walter
Published: April 2023

Supplementary Figure S3: The impact of TERT promoter mutation status on telomere parameters.
Supplementary information from A20 and RBX1 Regulate Brentuximab Vedotin Sensitivity in Hodgkin Lymphoma Models
Authors: Wei Wei , Lin Yuquan , Song Zhihui , Xiao Wenming , Chen Liqi , Yin Jiejing , Zhou Yan , Barta Stefan K. , Petrus Michael , Waldmann Thomas A. , Yang Yibin
Published: April 2023

Supplementary Information. Including Supplemental Experimental Procedures, and Supplementary Figure 1-6.
Table S4 from Rhabdoid Tumors Are Sensitive to the Protein-Translation Inhibitor Homoharringtonine
Authors: Howard Thomas P. , Oberlick Elaine M. , Rees Matthew G. , Arnoff Taylor E. , Pham Minh-Tam , Brenan Lisa , DoCarmo Mariana , Hong Andrew L. , Kugener Guillaume , Chou Hsien-Chao , Drosos Yiannis , Mathias Kaeli M. , Ramos Pilar , Seashore-Ludlow Brinton , Giacomelli Andrew O. , Wang Xiaofeng , Freeman Burgess B. , Blankenship Kaley , Hoffmann Lauren , Tiv Hong L. , Gokhale Prafulla C. , Johannessen Cory M. , Stewart Elizabeth A. , Schreiber Stuart L. , Hahn William C. , Roberts Charles W.M.
Published: April 2023

Raw data for follow-up xenograft studies. Note different tabs for each xenograft type.
Supplementary Data from IL15 Stimulation with TIGIT Blockade Reverses CD155-mediated NK-Cell Dysfunction in Melanoma
Authors: Chauvin Joe-Marc , Ka Mignane , Pagliano Ornella , Menna Carmine , Ding Quanquan , DeBlasio Richelle , Sanders Cindy , Hou Jiajie , Li Xian-Yang , Ferrone Soldano , Davar Diwakar , Kirkwood John M. , Johnston Robert J. , Korman Alan J. , Smyth Mark J. , Zarour Hassane M.
Published: April 2023

Supplemental Figure 4. IL-15 counteracts CD155-induced NK cell dysfunction.
Supplementary Table 2 from The Outcome of Ex Vivo TIL Expansion Is Highly Influenced by Spatial Heterogeneity of the Tumor T-Cell Repertoire and Differences in Intrinsic In Vitro Growth Capacity between T-Cell Clones
Authors: Poschke Isabel C. , Hassel Jessica C. , Rodriguez-Ehrenfried Aaron , Lindner Katharina A.M. , Heras-Murillo Ignacio , Appel Lena M. , Lehmann Johanna , Lövgren Tanja , Wickström Stina L. , Lauenstein Claudia , Roth Jasmin , König Anna-Katharina , Haanen John B.A.G. , van den Berg Joost , Kiessling Rolf , Bergmann Frank , Flossdorf Michael , Strobel Oliver , Offringa Rienk
Published: April 2023

Supplementary Table 2
Supplementary Table S3 from Evidencing a Pancreatic Ductal Adenocarcinoma Subpopulation Sensitive to the Proteasome Inhibitor Carfilzomib
Authors: Fraunhoffer Nicolas A. , Abuelafia Analía Meilerman , Bigonnet Martin , Gayet Odile , Roques Julie , Telle Emmanuel , Santofimia-Castaño Patricia , Borrello María Teresa , Chuluyan Eduardo , Dusetti Nelson , Iovanna Juan
Published: April 2023

Supplementary Table S3
Supplementary methods and Table S1 from Gut Microbiome Components Predict Response to Neoadjuvant Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer: A Prospective, Longitudinal Study
Authors: Yi Yuxi , Shen Lijun , Shi Wei , Xia Fan , Zhang Hui , Wang Yan , Zhang Jing , Wang Yaqi , Sun Xiaoyang , Zhang Zhiyuan , Zou Wei , Yang Wang , Zhang Lingyi , Zhu Ji , Goel Ajay , Ma Yanlei , Zhang Zhen
Published: April 2023

Details on inclusion and exclusion criteria, and supplementary table showing the frequency of patients with discriminatory taxa in fecal samples.
Figure S3 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

Associations among EGFR clonality, p53 mutations, and EGFR clearance
Figure S2 from Overcoming MET-Dependent Resistance to Selective RET Inhibition in Patients with RET Fusion–Positive Lung Cancer by Combining Selpercatinib with Crizotinib
Authors: Rosen Ezra Y. , Johnson Melissa L. , Clifford Sarah E. , Somwar Romel , Kherani Jennifer F. , Son Jieun , Bertram Arrien A. , Davare Monika A. , Gladstone Eric , Ivanova Elena V. , Henry Dahlia N. , Kelley Elaine M. , Lin Mika , Milan Marina S.D. , Nair Binoj C. , Olek Elizabeth A. , Scanlon Jenna E. , Vojnic Morana , Ebata Kevin , Hechtman Jaclyn F. , Li Bob T. , Sholl Lynette M. , Taylor Barry S. , Ladanyi Marc , Jänne Pasi A. , Rothenberg S. Michael , Drilon Alexander , Oxnard Geoffrey R.
Published: April 2023

Supplemental Figure 2
Table S1 from The Genomic Landscape of SMARCA4 Alterations and Associations with Outcomes in Patients with Lung Cancer
Authors: Schoenfeld Adam J. , Bandlamudi Chai , Lavery Jessica A. , Montecalvo Joseph , Namakydoust Azadeh , Rizvi Hira , Egger Jacklynn , Concepcion Carla P. , Paul Sonal , Arcila Maria E. , Daneshbod Yahya , Chang Jason , Sauter Jennifer L. , Beras Amanda , Ladanyi Marc , Jacks Tyler , Rudin Charles M. , Taylor Barry S. , Donoghue Mark T.A. , Heller Glenn , Hellmann Matthew D. , Rekhtman Natasha , Riely Gregory J.
Published: April 2023

Frequency of altered individual genes within SMARCA4 Class 1 vs SMARCA4 Class 2 subgroups.
eFigure1 from Tumor Mutational Burden and PTEN Alterations as Molecular Correlates of Response to PD-1/L1 Blockade in Metastatic Triple-Negative Breast Cancer
Authors: Barroso-Sousa Romualdo , Keenan Tanya E. , Pernas Sonia , Exman Pedro , Jain Esha , Garrido-Castro Ana C. , Hughes Melissa , Bychkovsky Brittany , Umeton Renato , Files Janet L. , Lindeman Neal I. , MacConaill Laura E. , Hodi F. Stephen , Krop Ian E. , Dillon Deborah , Winer Eric P. , Wagle Nikhil , Lin Nancy U. , Mittendorf Elizabeth A. , Van Allen Eliezer M. , Tolaney Sara M.
Published: April 2023

Most commonly mutated genes in anti-PD-1/L1-treated mTNBC. Each column represents a tumor unique to a patient. Shown are the most commonly mutated genes in this cohort (TP53, BRCA1, ATM, PIK3CA, PTEN, CREBBP, NF1, PRKDC, NOTCH1, MLH2, KMT2D, GLI2).
Supplementary Figure 2C from Efficacy and Safety of Duvelisib Following Disease Progression on Ofatumumab in Patients with Relapsed/Refractory CLL or SLL in the DUO Crossover Extension Study
Authors: Davids Matthew S. , Kuss Bryone J. , Hillmen Peter , Montillo Marco , Moreno Carol , Essell James , Lamanna Nicole , Nagy Zsolt , Tam Constantine S. , Stilgenbauer Stephan , Ghia Paolo , Delgado Julio , Lustgarten Stephanie , Weaver David T. , Youssoufian Hagop , Jäger Ulrich
Published: April 2023

Figure S2C displays probability of progression-free survival over time in subgroups of patients with and without bulky disease
Supplementary Data from Intratumor CMS Heterogeneity Impacts Patient Prognosis in Localized Colon Cancer
Authors: Marisa Laetitia , Blum Yuna , Taieb Julien , Ayadi Mira , Pilati Camilla , Le Malicot Karine , Lepage Côme , Salazar Ramon , Aust Daniela , Duval Alex , Blons Hélène , Taly Valérie , Gentien David , Rapinat Audrey , Selves Janick , Mouillet-Richard Sophie , Boige Valérie , Emile Jean-François , de Reyniès Aurélien , Laurent-Puig Pierre
Published: April 2023

Table S1
Graphical Abstract from Recurrent Human Papillomavirus–Related Head and Neck Cancer Undergoes Metabolic Reprogramming and Is Driven by Oxidative Phosphorylation
Authors: Vyas Avani , Harbison R. Alex , Faden Daniel L. , Kubik Mark , Palmer Drake , Zhang Qing , Osmanbeyoglu Hatice U. , Kiselyov Kirill , Méndez Eduardo , Duvvuri Umamaheswar
Published: April 2023

Graphical Abstract
Supplementary Figure S4 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 S4 shows our classification scheme for androgen receptor genomic structural rearrangements (AR-GSRs)
Supplementary Data from Molecular Features of Cancer-associated Fibroblast Subtypes and their Implication on Cancer Pathogenesis, Prognosis, and Immunotherapy Resistance
Authors: Galbo Phillip M. , Zang Xingxing , Zheng Deyou
Published: April 2023

Supplementary text, supplemental figures and legends, supplemental table description
Supplementary Table S7 from Genome-wide Copy-number Alterations in Circulating Tumor DNA as a Novel Biomarker for Patients with High-grade Serous Ovarian Cancer
Authors: Paracchini Lara , Beltrame Luca , Grassi Tommaso , Inglesi Alessia , Fruscio Robert , Landoni Fabio , Ippolito Davide , Delle Marchette Martina , Paderno Mariachiara , Adorni Marco , Jaconi Marta , Romualdi Chiara , D'Incalci Maurizio , Siravegna Giulia , Marchini Sergio
Published: April 2023

List of genes encoded on cytoband 11q13.3, within the significant focal region identified by GISTIC
Supplementary Data from Validation of Anticorrelated TGFβ Signaling and Alternative End-Joining DNA Repair Signatures that Predict Response to Genotoxic Cancer Therapy
Authors: Guix Ines , Liu Qi , Pujana Miquel Angel , Ha Patrick , Piulats Josep , Linares Isabel , Guedea Ferran , Mao Jian-Hua , Lazar Ann , Chapman Jocelyn , Yom Sue S. , Ashworth Alan , Barcellos-Hoff Mary Helen
Published: April 2023

Supplementary Data from Validation of Anticorrelated TGFβ Signaling and Alternative End-Joining DNA Repair Signatures that Predict Response to Genotoxic Cancer Therapy
Supplementary Data from The Added Value of Baseline Circulating Tumor DNA Profiling in Patients with Molecularly Hyperselected, Left-sided Metastatic Colorectal Cancer
Authors: Manca Paolo , Corallo Salvatore , Busico Adele , Lonardi Sara , Corti Francesca , Antoniotti Carlotta , Procaccio Letizia , Clavarezza Matteo , Smiroldo Valeria , Tomasello Gianluca , Murialdo Roberto , Sartore-Bianchi Andrea , Racca Patrizia , Pagani Filippo , Randon Giovanni , Martinetti Antonia , Sottotetti Elisa , Palermo Federica , Perrone Federica , Tamborini Elena , Prisciandaro Michele , Raimondi Alessandra , Di Bartolomeo Maria , Morano Federica , Pietrantonio Filippo
Published: April 2023

Suppl Table 1
Supplementary Data from Targeting Refractory Mantle Cell Lymphoma for Imaging and Therapy Using C-X-C Chemokine Receptor Type 4 Radioligands
Authors: Kwon Daniel , Takata Katsuyoshi , Zhang Zhengxing , Chong Lauren , Fraser Bryan , Zeisler Jutta , Miyata-Takata Tomoko , Merkens Helen , Rousseau Julie , Aoki Tomohiro , Kuo Hsiou-Ting , Tan Ruiyan , Zhang Chengcheng , Lau Joseph , Villa Diego , Uribe Carlos F. , Lin Kuo-Shyan , Steidl Christian , Benard Francois
Published: April 2023

Supplementary Data from Targeting Refractory Mantle Cell Lymphoma for Imaging and Therapy Using C-X-C Chemokine Receptor Type 4 Radioligands
Supplementary Data from Prostate-Specific Membrane Antigen Expression and Response to DNA Damaging Agents in Prostate Cancer
Authors: Sheehan Beshara , Neeb Antje , Buroni Lorenzo , Paschalis Alec , Riisnaes Ruth , Gurel Bora , Gil Veronica , Miranda Susana , Crespo Mateus , Guo Christina , Jiménez Vacas Juan , Figueiredo Ines , Ferreira Ana , Welti Jon , Yuan Wei , Carreira Suzanne , Sharp Adam , de Bono Johann
Published: April 2023

Supplementary Data from Prostate-Specific Membrane Antigen Expression and Response to DNA Damaging Agents in Prostate Cancer
Supplementary Data from Combined Perioperative Lapatinib and Trastuzumab in Early HER2-Positive Breast Cancer Identifies Early Responders: Randomized UK EPHOS-B Trial Long-Term Results
Authors: Bundred Nigel , Porta Nuria , Brunt Adrian Murray , Cramer Angela , Hanby Andrew , Shaaban Abeer M. , Rakha Emad A. , Armstrong Anne , Cutress Ramsey I. , Dodwell David , Emson Marie A. , Evans Abigail , Hartup Sue M. , Horgan Kieran , Miller Sarah E. , McIntosh Stuart A. , Morden James P. , Naik Jay , Narayanan Sankaran , Ooi Jane , Skene Anthony I. , Cameron David A. , Bliss Judith M.
Published: April 2023

Supplementary Data from Combined Perioperative Lapatinib and Trastuzumab in Early HER2-Positive Breast Cancer Identifies Early Responders: Randomized UK EPHOS-B Trial Long-Term Results
Supplementary figures and tables FTS1 from Intraperitoneal Monocytes plus IFNs as a Novel Cellular Immunotherapy for Ovarian Cancer: Mechanistic Characterization and Results from a Phase I Clinical Trial
Authors: Green Daniel S. , Ning Franklin , Duemler Anna , Myers Timothy G. , Trewhitt Kathryn , Ekwede Irene , McCoy Ann , Houston Nicole , Lee Jung-min , Lipkowitz Stanley , Zimmer Alexandra , Pavelova Miroslava , Villanueva Erin N. , Smith Leslie , Blakely Andrew , Casablanca Yovanni , Highfill Steven L. , Stroncek David F. , Collins-Johnson Naoza , Panch Sandhya , Procter JoLynn , Pham Chauha , Korrapati Soumya , Holland Steven M. , Rosen Lindsey B. , Nunes Ana T. , Zoon Kathryn C. , Cole Christopher B. , Annunziata Christina M.
Published: April 2023

Supplementary figures and tables
Figure S7 from Vaccination with Designed Neopeptides Induces Intratumoral, Cross-reactive CD4+ T-cell Responses in Glioblastoma
Authors: Wang Jian , Weiss Tobias , Neidert Marian C. , Toussaint Nora C. , Naghavian Reza , Sellés Moreno Carla , Foege Magdalena , Tomas Ojer Paula , Medici Gioele , Jelcic Ivan , Schulz Daniel , Rushing Elisabeth , Dettwiler Susanne , Schrörs Barbara , Shin Joo Heon , McKay Ron , Wu Catherine J. , Lutterotti Andreas , Sospedra Mireia , Moch Holger , Greiner Erich F. , Bodenmiller Bernd , Regli Luca , Weller Michael , Roth Patrick , Martin Roland
Published: April 2023

Designed mutations increase the stimulatory strength of D-neopeptides above N-peptides. (A) TILs were stimulated with 5 μM class I-peptides, including N-peptides and D-neopeptides, for 5 days. 5 replicate wells were tested for proliferation, and proliferation was measured by 3H-thymidine incorporation assay. In each group, the N-peptides and their corresponding D-neopeptides are included, and the designed mutated positions are highlighted in the red box. The blue dotted line indicates the mean value of the no peptide control. The red dotted line indicates the mean value plus three standard deviations of the no peptide control. Values above the red dotted line were considered positive. (#) indicates the peptide that was used in the 1st to 4th vaccinations. (B) TILs were stimulated with 5 μM class II-peptides, including N-peptides and D-neopeptides, for 5 days. 5 replicate wells were tested for proliferation, and proliferation was measured by 3H-thymidine incorporation assay.
Supplementary Figure S4 from A Sequential Targeting Strategy Interrupts AKT-Driven Subclone-Mediated Progression in Glioblastoma
Authors: Kebir Sied , Ullrich Vivien , Berger Pia , Dobersalske Celia , Langer Sarah , Rauschenbach Laurèl , Trageser Daniel , Till Andreas , Lorbeer Franziska K. , Wieland Anja , Wilhelm-Buchstab Timo , Ahmad Ashar , Fröhlich Holger , Cima Igor , Prasad Shruthi , Matschke Johann , Jendrossek Verena , Remke Marc , Grüner Barbara M. , Roesch Alexander , Siveke Jens T. , Herold-Mende Christel , Blau Tobias , Keyvani Kathy , van Landeghem Frank K.H. , Pietsch Torsten , Felsberg Jörg , Reifenberger Guido , Weller Michael , Sure Ulrich , Brüstle Oliver , Simon Matthias , Glas Martin , Scheffler Björn
Published: April 2023

Extended Data relating to Main Figure 4/Targeting of AKT-driven subclonal progression of ALDH1A1+ cells. A, Collected source data for main Figs. 4B,C,F-H. Left, diagrams: in vitro cell confluence dynamics of paired treatment naive vs. TMZ-related experimental (TMZ→eR; BN46) or clinical (RT/TMZ; BN118, BN123, BN132) relapse patient cells. Monitoring of cell confluence by software-based cell recognition. Assay specified in Fig. 4A. Right, graphs: Readout results from the indicated cases in line, representing source data for Figs. 4B (Cell Confluence), 4C (Cell Viability), and 4H (Apoptosis). Respective assays specified in the main Figure Legends. Data as mean ± SD. p values calculated by pairwise Wilcoxon rank-sum test followed by multiple testing correction using Benjamini-Hochberg method. B, IF of ALDH1A1 and Ki67 in the BN46-donor cell tumor PDX model. Shown is an example from a TMZ+MK2206-treated mouse (OS = 148 days; low levels of cellular co-expression). Scale bar: 20 µm. C, Comparison of overall survival under the investigated treatment conditions (refer to Fig. 4J). Hazard ratio 95% confidence interval estimates and significance levels derived from Cox regression are shown.
Supplementary fig 1 from Sustained Minimal Residual Disease Negativity in Multiple Myeloma is Associated with Stool Butyrate and Healthier Plant-Based Diets
Authors: Shah Urvi A. , Maclachlan Kylee H. , Derkach Andriy , Salcedo Meghan , Barnett Kelly , Caple Julia , Blaslov Jenna , Tran Linh , Ciardiello Amanda , Burge Miranda , Shekarkhand Tala , Adintori Peter , Cross Justin , Pianko Matthew J. , Hosszu Kinga , McAvoy Devin , Mailankody Sham , Korde Neha , Hultcrantz Malin , Hassoun Hani , Tan Carlyn R. , Lu Sydney X. , Patel Dhwani , Diamond Benjamin , Shah Gunjan , Scordo Michael , Lahoud Oscar , Chung David J. , Landau Heather , Usmani Saad Z. , Giralt Sergio , Taur Ying , Landgren C. Ola , Block Gladys , Block Torin , Peled Jonathan U. , van den Brink Marcel R.M. , Lesokhin Alexander M.
Published: April 2023

Supplementary Figure S1. Volcano plot showing the difference in the relative abundance of butyrate producers between sustained MRD negative and MRD positive/non-sustained MRD negative.
Supplementary Figure S1 from Palbociclib Rechallenge for Hormone Receptor–Positive/HER-Negative Advanced Breast Cancer: Findings from the Phase II BioPER Trial
Authors: Albanell Joan , Pérez-García José Manuel , Gil-Gil Miguel , Curigliano Giuseppe , Ruíz-Borrego Manuel , Comerma Laura , Gibert Joan , Bellet Meritxell , Bermejo Begoña , Calvo Lourdes , de la Haba Juan , Espinosa Enrique , Minisini Alessandro Marco , Quiroga Vanesa , Santaballa Bertran Ana , Mina Leonardo , Bellosillo Beatriz , Rojo Federico , Menéndez Silvia , Sampayo-Cordero Miguel , Popa Crina , Malfettone Andrea , Cortés Javier , Llombart-Cussac Antonio
Published: April 2023

Kaplan-Meier analyses of investigator-assessed progression-free survival and overall survival in the efficacy population.
Supplementary Tables TS1 from Neoadjuvant Chemotherapy Is Associated with Altered Immune Cell Infiltration and an Anti-Tumorigenic Microenvironment in Resected Pancreatic Cancer
Authors: Dias Costa Andressa , Väyrynen Sara A. , Chawla Akhil , Zhang Jinming , Väyrynen Juha P. , Lau Mai Chan , Williams Hannah L. , Yuan Chen , Morales-Oyarvide Vicente , Elganainy Dalia , Singh Harshabad , Cleary James M. , Perez Kimberly , Ng Kimmie , Freed-Pastor William , Mancias Joseph D. , Dougan Stephanie K. , Wang Jiping , Rubinson Douglas A. , Dunne Richard F. , Kozak Margaret M. , Brais Lauren , Reilly Emma , Clancy Thomas , Linehan David C. , Chang Daniel T. , Hezel Aram F. , Koong Albert C. , Aguirre Andrew J. , Wolpin Brian M. , Nowak Jonathan A.
Published: April 2023

Supplementary Tables
Supplementary Table S4 from Safety, Outcomes, and T-Cell Characteristics in Patients with Relapsed or Refractory MDS or CMML Treated with Atezolizumab in Combination with Guadecitabine
Authors: O'Connell Casey L. , Baer Maria R. , Ørskov Andreas Due , Saini Sunil Kumar , Duong Vu H. , Kropf Patricia , Hansen Jakob Werner , Tsao-Wei Denice , Jang Hyo Sik , Emadi Ashkan , Holmberg-Thyden Staffan , Cowland Jack , Brinker Brett T. , Horwood Kristin , Burgos Ryan , Hostetter Galen , Youngblood Benjamin A. , Hadrup Sine Reker , Issa Jean-Pierre , Jones Peter , Baylin Stephen B. , Siddiqi Imran , Grønbaek Kirsten
Published: April 2023

Representativeness of Study Participants
Supplementary Tables S1-S10 from ACTA2 Expression Predicts Survival and Is Associated with Response to Immune Checkpoint Inhibitors in Gastric Cancer
Authors: Park Sunho , Karalis John D. , Hong Changjin , Clemenceau Jean R. , Porembka Matthew R. , Kim In-Ho , Lee Sung Hak , Wang Sam C. , Cheong Jae-Ho , Hwang Tae Hyun
Published: April 2023

Supplementary Table 1. Univariable associations of the multivariable Cox proportional hazards model in the Yonsei cohort.Supplementary Table 2. Clinical characteristics of patients in the pooled validation cohort.Supplementary Table 3. Univariable associations of the multivariable Cox proportional hazards model of the pooled validation cohort.Supplementary Table 4. Univariable Cox proportional hazards regression of the association of individual genes of the 32-gene signature and their association with overall survival in the Yonsei cohort.Supplementary Table 5. Univariable Cox proportional hazards regression of the association of individual genes of the 32-gene signature and their association with overall survival in the pooled cohort.Supplementary Table 6. Multivariable analysis of the pooled cohort including microsatellite stability status.Supplementary Table 7. Multivariable analysis of the association of ACTA2 expression with recurrence-free survival in the pooled cohort.Supplementary Table 8. Clinical characteristics of patients treated with immune checkpoint inhibitors.Supplementary Table 9. ACTA2 expression in cells analyzed by single nuclear RNA sequencing cohort.Supplementary Table 10. Characteristics of patients analzyed by digital spatial transcriptomics.
Figure S6 from Targeting MET and FGFR in Relapsed or Refractory Acute Myeloid Leukemia: Preclinical and Clinical Findings, and Signal Transduction Correlates
Authors: Chen Evan C. , Gandler Helen , Tošić Isidora , Fell Geoffrey G. , Fiore Ashlee , Pozdnyakova Olga , DeAngelo Daniel J. , Galinsky Ilene , Luskin Marlise R. , Wadleigh Martha , Winer Eric S. , Leonard Rebecca , O'Day Kelsey , de Jonge Adrienne , Neuberg Donna , Look A. Thomas , Stone Richard M. , Frank David A. , Garcia Jacqueline S.
Published: April 2023

Effects on STAT phosphorylation following ex vivo exposure of pre-treatment patient myeloblasts to merestinib and LY2874455. Changes in pSTAT3 and pSTAT5 after drug treatment were measured by phospho-flow cytometry and normalized to vehicle-treated controls after 1-hr incubation with drug ex vivo.
Figure S5 from Targeting MET and FGFR in Relapsed or Refractory Acute Myeloid Leukemia: Preclinical and Clinical Findings, and Signal Transduction Correlates
Authors: Chen Evan C. , Gandler Helen , Tošić Isidora , Fell Geoffrey G. , Fiore Ashlee , Pozdnyakova Olga , DeAngelo Daniel J. , Galinsky Ilene , Luskin Marlise R. , Wadleigh Martha , Winer Eric S. , Leonard Rebecca , O'Day Kelsey , de Jonge Adrienne , Neuberg Donna , Look A. Thomas , Stone Richard M. , Frank David A. , Garcia Jacqueline S.
Published: April 2023

Pharmacokinetic analysis of merestinib and LY2874455. A, Merestinib plasma levels were measured at the time points shown and compared between patients receiving single-agent merestinib in Cohort 1 (n=7, black line) and patients receiving merestinib + LY2874455 in Cohort 2 (n=8, red line). Geometric mean is displayed. Error bars denote standard error. * signifies p < 0.05. B, Plasma levels of merestinib (first column) and its metabolites LSN2800870 and LSN2887652 (second and third columns, respectively) in patients receiving merestinib monotherapy (first row) and merestinib + LY2874455 (second row). C, Plasma levels of LY2874455 in patients receiving merestinib + LY2874455. Abbreviations: Cohort 1 = patients receiving single-agent merestinib; Cohort 2 = patients receiving merestinib + LY2874455.
Supplementary Figure S3 from Genetic Heterogeneity and Tissue-specific Patterns of Tumors with Multiple PIK3CA Mutations
Authors: Sivakumar Smruthy , Jin Dexter X. , Rathod Ruchita , Ross Jeffrey , Cantley Lewis C. , Scaltriti Maurizio , Chen Jessica W. , Hutchinson Katherine E. , Wilson Timothy R. , Sokol Ethan S. , Vasan Neil
Published: April 2023

Patterns of mutual exclusivity as well as co-occurrence between multi-PIK3CA mutations and alterations in other cancer associated genes.
Supplementary Figure 9 from Molecular Clusters and Tumor-Immune Drivers of IgM Monoclonal Gammopathies
Authors: Mondello Patrizia , Paludo Jonas , Novak Joseph P. , Wenzl Kerstin , Yang Zhi-Zhang , Jalali Shahrzad , Krull Jordan E. , Braggio Esteban , Dasari Surendra , Manske Michelle K. , Abeykoon Jithma A. , Sarangi Vivekananda , Kapoor Prashant , Paulus Aneel , Reeder Craig B. , Ailawadhi Sikander , Chanan-Khan Asher A. , Kyle Robert A. , Gertz Morie A. , Novak Anne J. , Ansell Stephen M.
Published: April 2023

Supplementary Figure 9 SPADE maps of CD4+ CTLA-4+ T cells from concatenated files (C1, n=7; C2, n=4). The dots in red and blue indicate high and low expression, respectively. The dot size is representative of cell events, with the big size containing more cell events.
Supplementary Table S4 from Prediction of Response to Lenvatinib Monotherapy for Unresectable Hepatocellular Carcinoma by Machine Learning Radiomics: A Multicenter Cohort Study
Authors: Bo Zhiyuan , Chen Bo , Zhao Zhengxiao , He Qikuan , Mao Yicheng , Yang Yunjun , Yao Fei , Yang Yi , Chen Ziyan , Yang Jinhuan , Yu Haitao , Ma Jun , Wu Lijun , Chen Kaiyu , Wang Luhui , Wang Mingxun , Shi Zhehao , Yao Xinfei , Dong Yulong , Shi Xintong , Shan Yunfeng , Yu Zhengping , Wang Yi , Chen Gang
Published: April 2023

The radiomics features extracted from CECT images.
Supplementary Figure S1 from Influence of Genomic Landscape on Cancer Immunotherapy for Newly Diagnosed Ovarian Cancer: Biomarker Analyses from the IMagyn050 Randomized Clinical Trial
Authors: Landen Charles N. , Molinero Luciana , Hamidi Habib , Sehouli Jalid , Miller Austin , Moore Kathleen N. , Taskiran Cagatay , Bookman Michael , Lindemann Kristina , Anderson Charles , Berger Regina , Myers Tashanna , Beiner Mario , Reid Thomas , Van Nieuwenhuysen Els , Green Andrew , Okamoto Aikou , Aghajanian Carol , Thaker Premal H. , Blank Stephanie V. , Khor Victor K. , Chang Ching-Wei , Lin Yvonne G. , Pignata Sandro
Published: April 2023

CCNE1 amplifications are mutually exclusive with BRCA1 and BRCA2 mutations.
Supplementary Figure S3 from Survival Outcomes, Digital TILs, and On-treatment PET/CT During Neoadjuvant Therapy for HER2-positive Breast Cancer: Results from the Randomized PREDIX HER2 Trial
Authors: Matikas Alexios , Johansson Hemming , Grybäck Per , Bjöhle Judith , Acs Balazs , Boyaci Ceren , Lekberg Tobias , Fredholm Hanna , Elinder Ellinor , Margolin Sara , Isaksson-Friman Erika , Bosch Ana , Lindman Henrik , Adra Jamila , Andersson Anne , Agartz Susanne , Hellström Mats , Zerdes Ioannis , Hartman Johan , Bergh Jonas , Hatschek Thomas , Foukakis Theodoros
Published: April 2023

Supplementary Figure S3: Probability for pathologic complete response in the four groups of the combined classification according to SUVmax at cycle 2 (median value 2.6 as cut-off) and baseline DTIL (median value 8.7% as cut-off)
Supplementary Movie S3 from Anticoagulants Enhance Molecular and Cellular Immunotherapy of Cancer by Improving Tumor Microcirculation Structure and Function and Redistributing Tumor Infiltrates
Authors: Wei Fang , Su Yuling , Quan Yibo , Li Xiaojia , Zou Qi , Zhang Liuxi , Li Shu , Jiang Mengmeng , Lin Guohuan , Liang Ping , He Jie , Xie Keping
Published: April 2023

Supplementary Movie S3. IVIM in vivo imaging was used to observe that heparin promoted the infiltration of transferred CD8+ T cells into Panc02 orthotopic tumors. The video corresponded to the experiment shown in Figure 6B. Representative images at 24h of CD8+ T adoptive transfer group were shown in Figure 6B (Blue, angiography Evans Blue; Green, CFSE-CD8+ T cells).
Data from HLA Class I–Associated Immunodominance Affects CTL Responsiveness to an ESO Recombinant Protein Tumor Antigen Vaccine
Authors: Bioley Gilles , Guillaume Philippe , Luescher Immanuel , Yeh Alice , Dupont Bo , Bhardwaj Nina , Mears Gregory , Old Lloyd J. , Valmori Danila , Ayyoub Maha
Published: April 2023

Abstract
Purpose: Vaccination with full-length human tumor antigens aims at inducing or increasing antitumor immune responses, including CD8 CTL in cancer patients across the HLA barrier. We have recently reported that vaccination with a recombinant tumor-specific NY-ESO-1 (ESO) protein, administered with Montanide and CpG resulted in the induction of specific integrated antibody and CD4 T cell responses in all vaccinated patients examined, and significant CTL responses in half of them. Vaccine-induced CTL mostly recognized a single immunodominant region (ESO 81-110). The purpose of the present study was to identify genetic factor(s) distinguishing CTL responders from nonresponders.

Experimental Design: We determined the HLA class I alleles expressed by CTL responders and nonresponders using high-resolution molecular typing. Using short overlapping peptides spanning the ESO immunodominant CTL region and HLA class I/ESO peptide tetramers, we determined the epitopes recognized by the majority of vaccine-induced CTL.

Results: CTL induced by vaccination with ESO protein mostly recognized distinct but closely overlapping epitopes restricted by a few frequently expressed HLA-B35 and HLA-Cw3 alleles. All CTL responders expressed at least one of the identified alleles, whereas none of the nonresponders expressed them.

Conclusions: Expression of HLA-B35 and HLA-Cw3 is associated with the induction of immunodominant CTL responses following vaccination with recombinant ESO protein. Because recombinant tumor-specific proteins are presently among the most promising candidate anticancer vaccines, our findings indicate that the monitoring of cancer vaccine trials should systematically include the assessment of HLA association with responsiveness.
Data from Cleaved Forms of the Urokinase Plasminogen Activator Receptor in Plasma Have Diagnostic Potential and Predict Postoperative Survival in Patients with Ovarian Cancer
Authors: Henić Emir , Borgfeldt Christer , Christensen Ib Jarle , Casslén Bertil , Høyer-Hansen Gunilla
Published: April 2023

Abstract
Purpose: To evaluate the plasma level of different forms of soluble urokinase plasminogen activator receptor (suPAR) as discriminators between malignant, borderline, and benign ovarian tumors and as prognostic markers in patients with ovarian cancer.

Experimental Design: The different suPAR forms were measured in preoperative plasma samples obtained from 335 patients with adnexal lesions using three different time-resolved fluoresence assays (TR-FIA): TR-FIA 1 measuring intact suPAR, suPAR(I-III), TR-FIA 2 measuring the total amount of suPAR(I-III) and the cleaved form, suPAR(II-III), and TR-FIA 3 measuring the liberated uPAR(I). Tumors were classified as benign (n = 211), borderline (possibly malignant; n = 30), and well (n = 19), moderately (n = 15), and poorly (n = 60) differentiated malignant.

Results: All uPAR forms as well as CA125 were statistically significant in univariate analysis discriminating between benign, borderline, and invasive tumors. Restricting the analysis of invasive tumors to early stage (I and II) showed similar results. A combination of CA125 and suPAR(I-III) + suPAR(II-III) discriminated between malignant (all stages) and benign tumors [AUC, 0.94; 95% confidence interval (95% CI), 0.90-0.98] as well as borderline and benign tumors (AUC, 0.78; 95% CI, 0.67-0.89). All suPAR forms were markers for poor prognosis in univariate analyses, and high preoperative plasma level of uPAR(I) is an independent predictor of poor prognosis (hazard ratio, 1.84; 95% CI, 1.15-2.95; P = 0.011) in multivariate analyses including age and CA125.

Conclusions: High concentration of plasma uPAR(I) is an independent preoperative marker of poor prognosis in patients with ovarian cancer. The combination of plasma suPAR(I-III) + suPAR(II-III) and CA125 discriminates between malignant and benign tumors with an AUC of 0.94.
Data from Inhibition of Mammalian Target of Rapamycin by Rapamycin Causes the Regression of Carcinogen-Induced Skin Tumor Lesions
Authors: Amornphimoltham Panomwat , Leelahavanichkul Kantima , Molinolo Alfredo , Patel Vyomesh , Gutkind J. Silvio
Published: April 2023

Abstract
Purpose: The activation of Akt/mammalian target of rapamycin (mTOR) pathway represents a frequent event in squamous cell carcinoma (SCC) progression, thus raising the possibility of using specific mTOR inhibitors for the treatment of SCC patients. In this regard, blockade of mTOR with rapamycin prevents the growth of human head and neck SCC cells when xenotransplanted into immunodeficient mice. However, therapeutic responses in xenograft tumors are not always predictive of clinical anticancer activity.

Experimental Design: As genetically defined and chemically induced animal cancer models often reflect better the complexity of the clinical setting, we used here a two-step chemical carcinogenesis model to explore the effectiveness of rapamycin for the treatment of skin SCC.

Results: Rapamycin exerted a remarkable anticancer activity in this chemically induced cancer model, decreasing the tumor burden of mice harboring early and advanced tumor lesions, and even recurrent skin SCCs. Immunohistochemical studies on tumor biopsies and clustering analysis revealed that rapamycin causes the rapid decrease in the phosphorylation status of mTOR targets followed by the apoptotic death of cancer cells and the reduction in the growth and metabolic activity of the surviving ones, concomitant with a decrease in the population of cancer cells expressing mutant p53. This approach enabled investigating the relationship among molecular changes caused by mTOR inhibition, thus helping identify relevant biomarkers for monitoring the effectiveness of mTOR inhibition in the clinical setting.

Conclusions: Together, these findings provide a strong rationale for the early evaluation of mTOR inhibitors as a molecular targeted approach to treat SCC.
Data from Identification of GRP75 as an Independent Favorable Prognostic Marker of Neuroblastoma by a Proteomics Analysis
Authors: Hsu Wen-Ming , Lee Hsinyu , Juan Hsueh-Fen , Shih Yu-Yin , Wang Bo-Jeng , Pan Chien-Yuan , Jeng Yung-Ming , Chang Hsiu-Hao , Lu Meng-Yao , Lin Kai-Hsin , Lai Hong-Shiee , Chen Wei-Jao , Tsay Yeou-Guang , Liao Yung-Feng , Hsieh Fon-Jou
Published: April 2023

Abstract
Purpose: Neuroblastoma (NB) is a heterogeneous neoplasm. Detailed biological discrimination is critical for the effective treatment of this disease. Because the tumor behavior of NB is closely associated with the histologic state of differentiation, we thus aimed to identify novel differentiation-associated markers of NB with prognostic implication.

Experimental Design: A human NB cell line SH-SY5Y was used as a model system to explore potential biomarkers for the differentiation of NB by proteomic analyses. Seventy-two NB tumor tissues were subsequently investigated by immunohistochemistry to validate the correlations between the expression of a novel prognostic marker, various clinicopathologic and biological factors, and patient survival.

Results: Using two-dimensional differential gel electrophoresis, we found a total of 24 spots of proteins in SH-SY5Y cells whose expression was enhanced following differentiation. Glucose-regulated protein 75 (GRP75) was unambiguously identified as one of the five proteins that were dramatically up-regulated following differentiation. Immunohistochemical analyses of 72 NB tumor tissues further revealed that positive GRP75 immunostaining is strongly correlated with differentiated histologies (P < 0.001), mass-screened tumors (P = 0.016), and early clinical stages (P < 0.001) but inversely correlated with MYCN amplification (P = 0.010). Univariate and multivariate survival analyses showed that GRP75 expression is an independent favorable prognostic factor.

Conclusions: The present findings clearly showed that our proteomics-based novel experimental paradigm could be a powerful tool to uncover novel biomarkers associated with the differentiation of NB. Our data also substantiate an essential role of GRP75 in the differentiation of NB.
Data from Deregulated GSK3 Sustains Gastrointestinal Cancer Cells Survival by Modulating Human Telomerase Reverse Transcriptase and Telomerase
Authors: Mai Wei , Kawakami Kazuyuki , Shakoori Abbas , Kyo Satoru , Miyashita Katsuyoshi , Yokoi Kenji , Jin Mingji , Shimasaki Takeo , Motoo Yoshiharu , Minamoto Toshinari
Published: April 2023

Abstract
Purpose: Glycogen synthase kinase-3 (GSK3) regulates multiple cell signaling pathways and has been implicated in glucose intolerance, neurodegenerative disorders, and inflammation. We investigated the expression, activity, and putative pathologic role of GSK3 in gastrointestinal, pancreatic, and liver cancers.

Experimental Design: Colon, stomach, pancreatic, and liver cancer cell lines; nonneoplastic HEK293 cells; and matched pairs of normal and tumor tissues of stomach and colon cancer patients were examined for GSK3 expression and its phosphorylation at serine 9 (inactive form) and tyrosine 216 (active form) by Western immunoblotting and for GSK3 activity by in vitro kinase assay. The effects of small-molecule GSK3 inhibitors and of RNA interference on cell survival, proliferation, and apoptosis were examined in vitro and on human colon cancer cell xenografts in athymic mice. The effects of GSK3 inhibition on human telomerase reverse transcriptase (hTERT) expression and telomerase activity were compared between colon cancer and HEK293 cells.

Results: Cancer cell lines and most cancer tissues showed increased GSK3 expression and increased tyrosine 216 phosphorylation and activity but decreased serine 9 phosphorylation compared with HEK293 cells and nonneoplastic tissues. Inhibition of GSK3 resulted in attenuated cell survival and proliferation and increased apoptosis in most cancer cell lines and in HT-29 xenografts in rodents but not in HEK293 cells. GSK3 inhibition in colon cancer cells was associated with decreased hTERT expression and telomerase activity.

Conclusion: The results indicate that deregulated GSK3 sustains gastrointestinal cancer cells survival through modulation of hTERT and telomerase. (Clin Cancer Res 2009;15(22):68109)