bluuebunny/crossref_metadata_2025 huggingface dataset:
Table S1 from Targeting Merkel Cell Carcinoma by Engineered T Cells Specific to T-Antigens of Merkel Cell Polyomavirus
Authors: Gavvovidis Ioannis , Leisegang Matthias , Willimsky Gerald , Miller Natalie , Nghiem Paul , Blankenstein Thomas
Published: April 2023

V-J segment usage as well as CDR3 sequences of TCRs isolated from ABabDII mice after immunization with SMF or KLL epitope petide, respectively.
Supplement figure 4 from Extracellular Vesicles Released by Cardiomyocytes in a Doxorubicin-Induced Cardiac Injury Mouse Model Contain Protein Biomarkers of Early Cardiac Injury
Authors: Yarana Chontida , Carroll Dustin , Chen Jing , Chaiswing Luksana , Zhao Yanming , Noel Teresa , Alstott Michael , Bae Younsoo , Dressler Emily V. , Moscow Jeffrey A. , Butterfield D. Allan , Zhu Haining , St. Clair Daret K.
Published: April 2023

Western blots confirming the existence of PYGB, PYGM, and PYGL in SAL_EVs and DOX_EVs after treatment with proteinase K. Cell lysate was used as a positive control for PYGB, PYGM and PYGL detection. IgG and albumin were measured as a reference for proteinase K efficiency to digest extravesicular proteins.
Supplementary figure 1 from Orthoxenografts of Testicular Germ Cell Tumors Demonstrate Genomic Changes Associated with Cisplatin Resistance and Identify PDMP as a Resensitizing Agent
Authors: Piulats Josep M. , Vidal August , García-Rodríguez Francisco J. , Muñoz Clara , Nadal Marga , Moutinho Catia , Martínez-Iniesta María , Mora Josefina , Figueras Agnés , Guinó Elisabet , Padullés Laura , Aytés Àlvaro , Molleví David G. , Puertas Sara , Martínez-Fernández Carmen , Castillo Wilmar , Juliachs Merce , Moreno Victor , Muñoz Purificación , Stefanovic Milica , Pujana Miguel A. , Condom Enric , Esteller Manel , Germà Josep R. , Capella Gabriel , Farré Lourdes , Morales Albert , Viñals Francesc , García-del-Muro Xavier , Cerón Julián , Villanueva Alberto
Published: April 2023

Short- and long-term CDDP responses at low (2 mg/kg) and high (5 mg/kg) doses of CDDP were characterized in xenografted tumors
Supplementary data from Orthoxenografts of Testicular Germ Cell Tumors Demonstrate Genomic Changes Associated with Cisplatin Resistance and Identify PDMP as a Resensitizing Agent
Authors: Piulats Josep M. , Vidal August , García-Rodríguez Francisco J. , Muñoz Clara , Nadal Marga , Moutinho Catia , Martínez-Iniesta María , Mora Josefina , Figueras Agnés , Guinó Elisabet , Padullés Laura , Aytés Àlvaro , Molleví David G. , Puertas Sara , Martínez-Fernández Carmen , Castillo Wilmar , Juliachs Merce , Moreno Victor , Muñoz Purificación , Stefanovic Milica , Pujana Miguel A. , Condom Enric , Esteller Manel , Germà Josep R. , Capella Gabriel , Farré Lourdes , Morales Albert , Viñals Francesc , García-del-Muro Xavier , Cerón Julián , Villanueva Alberto
Published: April 2023

Supplementary materials and methods, supplementary tables and supplementary figure legends
Supplementary Figures 1-5 from Resistance Mechanisms to Targeted Therapies in ROS1+ and ALK+ Non–small Cell Lung Cancer
Authors: McCoach Caroline E. , Le Anh T. , Gowan Katherine , Jones Kenneth , Schubert Laura , Doak Andrea , Estrada-Bernal Adriana , Davies Kurtis D. , Merrick Daniel T. , Bunn Paul A. , Purcell W. Tom , Dziadziuszko Rafal , Varella-Garcia Marileila , Aisner Dara L. , Camidge D. Ross , Doebele Robert C.
Published: April 2023

Supplementary Figures 1-5
Figure S1 from NY-ESO-1 Vaccination in Combination with Decitabine Induces Antigen-Specific T-lymphocyte Responses in Patients with Myelodysplastic Syndrome
Authors: Griffiths Elizabeth A. , Srivastava Pragya , Matsuzaki Junko , Brumberger Zachary , Wang Eunice S. , Kocent Justin , Miller Austin , Roloff Gregory W. , Wong Hong Yuen , Paluch Benjamin E. , Lutgen-Dunckley Linda G. , Martens Brandon L. , Odunsi Kunle , Karpf Adam R. , Hourigan Christopher S. , Nemeth Michael J.
Published: April 2023

Supplemental Figure 1. Lineages of CD11b+ myeloid cells isolated from MDS patients.
Figure S1 from Pazopanib Exposure Relationship with Clinical Efficacy and Safety in the Adjuvant Treatment of Advanced Renal Cell Carcinoma
Authors: Sternberg Cora N. , Donskov Frede , Haas Naomi B. , Doehn Christian , Russo Paul , Elmeliegy Mohamed , Baneyx Guillaume , Banerjee Hiya , Aimone Paola , Motzer Robert J.
Published: April 2023

Prediction-corrected visual predictive checks of early (A) and late (B) Ctrough in study PROTECT
IRAK1/4i is well-tolerated in mice and synergizes with gemcitabine in inducing apoptosis, suppressing proliferation and fibrosis of PDAC in vivo from Constitutive IRAK4 Activation Underlies Poor Prognosis and Chemoresistance in Pancreatic Ductal Adenocarcinoma
Authors: Zhang Daoxiang , Li Lin , Jiang Hongmei , Knolhoff Brett L. , Lockhart Albert C. , Wang-Gillam Andrea , DeNardo David G. , Ruzinova Marianna B. , Lim Kian-Huat
Published: April 2023

Supplementary Figure 3. IRAK1/4i is well-tolerated in mice and synergizes with gemcitabine in inducing apoptosis, suppressing proliferation and fibrosis of PDAC in vivo.
Supplementary Figure S2 from MITF-High and MITF-Low Cells and a Novel Subpopulation Expressing Genes of Both Cell States Contribute to Intra- and Intertumoral Heterogeneity of Primary Melanoma
Authors: Ennen Marie , Keime Céline , Gambi Giovanni , Kieny Alice , Coassolo Sebastien , Thibault-Carpentier Christelle , Margerin-Schaller Fanny , Davidson Guillaume , Vagne Constance , Lipsker Dan , Davidson Irwin
Published: April 2023

Comparison of gene expression in tumours 1 and 2
Supplementary Figure S1 from MITF-High and MITF-Low Cells and a Novel Subpopulation Expressing Genes of Both Cell States Contribute to Intra- and Intertumoral Heterogeneity of Primary Melanoma
Authors: Ennen Marie , Keime Céline , Gambi Giovanni , Kieny Alice , Coassolo Sebastien , Thibault-Carpentier Christelle , Margerin-Schaller Fanny , Davidson Guillaume , Vagne Constance , Lipsker Dan , Davidson Irwin
Published: April 2023

Differential expression of MITF-high and MITF-low signature genes in cultured melanoma cells
Supplemental Figure 1 from Modifying the Clinical Research Infrastructure at a Dedicated Clinical Trials Unit: Assessment of Trial Development, Activation, and Participant Accrual
Authors: Tang Chad , Hess Kenneth R. , Sanders Dwana , Davis Suzanne E. , Buzdar Aman U. , Kurzrock Razelle , Lee J. Jack , Meric-Bernstam Funda , Hong David S.
Published: April 2023

Number of submitted ICT department trials as a function of time.
Supplementary Data from ER+ Breast Cancers Resistant to Prolonged Neoadjuvant Letrozole Exhibit an E2F4 Transcriptional Program Sensitive to CDK4/6 Inhibitors
Authors: Guerrero-Zotano Angel L. , Stricker Thomas P. , Formisano Luigi , Hutchinson Katherine E. , Stover Daniel G. , Lee Kyung-Min , Schwarz Luis J. , Giltnane Jennifer M. , Estrada Monica V. , Jansen Valerie M. , Servetto Alberto , Gavilá Joaquín , Perez-Fidalgo J. Alejandro , Lluch Ana , Llombart-Cussac Antonio , Bayar Mohamed Amine , Michiels Stefan , André Fabrice , Arnedos Mónica , Guillem Vicente , Ruiz-Simon Amparo , Arteaga Carlos L.
Published: April 2023

Supplementary data information
Figure S4 from ER+ Breast Cancers Resistant to Prolonged Neoadjuvant Letrozole Exhibit an E2F4 Transcriptional Program Sensitive to CDK4/6 Inhibitors
Authors: Guerrero-Zotano Angel L. , Stricker Thomas P. , Formisano Luigi , Hutchinson Katherine E. , Stover Daniel G. , Lee Kyung-Min , Schwarz Luis J. , Giltnane Jennifer M. , Estrada Monica V. , Jansen Valerie M. , Servetto Alberto , Gavilá Joaquín , Perez-Fidalgo J. Alejandro , Lluch Ana , Llombart-Cussac Antonio , Bayar Mohamed Amine , Michiels Stefan , André Fabrice , Arnedos Mónica , Guillem Vicente , Ruiz-Simon Amparo , Arteaga Carlos L.
Published: April 2023

E2F4 gene signature modulation and association with overall survival in ER+/HER2- breast cancer treated with endocrine therapy. a) E2F4 gene signature expression at baseline (pre) and after 2-weeks of aromatase inhibitor treatment (post), data from ACOSOGZ1031b study. Tumors were divided according to the E2F4 score at baseline in high, medium or low tertiles. After two-weeks of aromatase inhibitor treatment, there was a decrease in the E2F4 score in all groups. However, the proportion of tumors still expressing a high post-treatment E2F4 score was greater in patients with a high E2F4 score at baseline (60%) than the other groups. b) Overall survival in patients with ER+ breast cancer treated with adjuvant endocrine therapy in the METABRIC database (n=1498) according to E2F4 signature score tertiles. c) Overall survival in patients with ER+ tumors from METABRIC according to E2F4 score tertiles in Luminal A and d) Luminal B tumors.
Supporting Materials from HER3-Mediated Resistance to Hsp90 Inhibition Detected in Breast Cancer Xenografts by Affibody-Based PET Imaging
Authors: Martins Carlos D. , Da Pieve Chiara , Burley Thomas A. , Smith Rhodri , Ciobota Daniela M. , Allott Louis , Harrington Kevin J. , Oyen Wim J.G. , Smith Graham , Kramer-Marek Gabriela
Published: April 2023

Materials and Methods Fig. S1. Time course of AUY922 treatment in BT-474 and MCF-7 cells. Fig. S2. Effects of AUY922 and PPP treatment in low and high HER2-expressing breast cancer cell lines. Fig. S3. Effect of HRG stimulation in AUY922 and PPP treated MCF-7 cells. Fig. S4. AUY922 and PPP treatment effect on the proliferative and invasive phenotype of BT-474 and MCF-7 breast cancer cells. Fig. S5. HPLC chromatograms of purified DFO-affibody conjugates. Fig. S6. MALDI-MS spectra of purified DFO-ZHER3:8698 (A) and DFO-ZTAQ (B). Fig. S7. Representative radio-ITLC of the crude radiolabelling mixture of 89Zr-DFO-ZHER3:8698. Fig. S8. Representative radio-ITLC of the 89Zr-DFO-ZHER3:8698 serum stability at 0, 3 and 24 h. Fig. S9. In vivo 89Zr-DFO-ZHER3:8698 tumour uptake quantification by image analysis. Fig. S10. Ex vivo biodistribution of 89Zr-DFO-ZHER3:8698 following AUY922 treatment in MCF-7 xenografts. Fig. S11. Microvessel density analysis in response to AUY922 treatment in MCF-7 xenografts. Fig. S12. Tumour volume estimation in response to AUY922 treatment in MCF-7 xenografts. Fig. S13. AUY922 treatment response monitoring in BT-474 xenografts by 89Zr-DFO-ZHER3:8698 PET/CT imaging. Fig. S14. Texture analysis of 89Zr-DFO-ZHER3:8698 PET imaging data following AUY922 treatment in MCF-7 xenografts. Fig. S15. Correlation between %ID/g ratios obtained from 89Zr-DFO-ZHER3:8698 PET images and HER3 protein expression per control and AUY922-treated MCF-7 xenografts. Fig. S16. HER3 intra-tumoral heterogeneity highlighted by histopathological analysis of control and AUY922-treated MCF-7 xenografts. Fig. S17. HER2-HER3 interaction in BT-474 and MCF-7 cells following AUY922 treatment. Fig. S18. Scheme illustrating the proposed effect of AUY922-induced Hsp90 inhibition in MCF-7 breast cancer xenografts. Table S1. Densitometric analysis of Western blots related to the treatment of BT-474, MCF-7, MCF-7 HER2+++ (-dox), and MCF-7 HER2+ (+dox) following 48 h treatment with AUY922 and PPP alone, or in combination. Table S2. Biodistribution results for 89Zr-DFO-ZHER3:8698 and 89Zr-DFO-ZTAQ (3 µg, 7.2-8.1 MBq/mouse) at 3 h after injection. Table S3. Biodistribution results for 89Zr-DFO-ZHER3:8698 at 3 h and 24 h after injection in MCF-7 and MDA-MB-468 tumour-bearing mice. Table S4. Tumour/organ ratios for 89Zr-DFO-ZHER3:8698 at 3 h and 24 h after injection in MCF-7 and MDA-MB-468 tumour-bearing mice. Table S5. HER3 and IGF1R co-occurrence in breast invasive carcinoma samples. Table S6. HER3 and IGF1R alterations lead to a shorter overall survival in breast invasive carcinoma samples. Table S7. HER3 and IGF1R alterations lead to a shorter disease free survival in breast invasive carcinoma samples. Table S8. HER3 and IGF1R co-occurrence in HER2 up-regulated breast invasive carcinoma samples.
Figure S3 from ER+ Breast Cancers Resistant to Prolonged Neoadjuvant Letrozole Exhibit an E2F4 Transcriptional Program Sensitive to CDK4/6 Inhibitors
Authors: Guerrero-Zotano Angel L. , Stricker Thomas P. , Formisano Luigi , Hutchinson Katherine E. , Stover Daniel G. , Lee Kyung-Min , Schwarz Luis J. , Giltnane Jennifer M. , Estrada Monica V. , Jansen Valerie M. , Servetto Alberto , Gavilá Joaquín , Perez-Fidalgo J. Alejandro , Lluch Ana , Llombart-Cussac Antonio , Bayar Mohamed Amine , Michiels Stefan , André Fabrice , Arnedos Mónica , Guillem Vicente , Ruiz-Simon Amparo , Arteaga Carlos L.
Published: April 2023

Distribution of clinically actionable mutations according to PEPI score, PCNA proliferation signature and breast cancer subtypes
Figure S2 from ER+ Breast Cancers Resistant to Prolonged Neoadjuvant Letrozole Exhibit an E2F4 Transcriptional Program Sensitive to CDK4/6 Inhibitors
Authors: Guerrero-Zotano Angel L. , Stricker Thomas P. , Formisano Luigi , Hutchinson Katherine E. , Stover Daniel G. , Lee Kyung-Min , Schwarz Luis J. , Giltnane Jennifer M. , Estrada Monica V. , Jansen Valerie M. , Servetto Alberto , Gavilá Joaquín , Perez-Fidalgo J. Alejandro , Lluch Ana , Llombart-Cussac Antonio , Bayar Mohamed Amine , Michiels Stefan , André Fabrice , Arnedos Mónica , Guillem Vicente , Ruiz-Simon Amparo , Arteaga Carlos L.
Published: April 2023

Variant filtering algorithm and mutation allele frequency distribution a) Variant filter algorithm. b) Mutation Allele Frequency (MAF) histogram of 11861 non-synonymous variants. c) MAF of 330 non-synonymous variants after filtering out potential germline variants.
Movie S1 from HER3-Mediated Resistance to Hsp90 Inhibition Detected in Breast Cancer Xenografts by Affibody-Based PET Imaging
Authors: Martins Carlos D. , Da Pieve Chiara , Burley Thomas A. , Smith Rhodri , Ciobota Daniela M. , Allott Louis , Harrington Kevin J. , Oyen Wim J.G. , Smith Graham , Kramer-Marek Gabriela
Published: April 2023

Representative 3D-rendering of segmented MCF-7, MDA-MB-468 and MDA-MB-231 xenografts following PET/CT image acquisition 3 h after 89Zr-DFO-ZHER3:8698 injection.
supplementary data from A Genetic Polymorphism in CTLA-4 Is Associated with Overall Survival in Sunitinib-Treated Patients with Clear Cell Metastatic Renal Cell Carcinoma
Authors: Liu Xiaoyan , Swen Jesse J. , Diekstra Meta H.M. , Boven Epie , Castellano Daniel , Gelderblom Hans , Mathijssen Ron H.J. , Vermeulen Sita H. , Oosterwijk Egbert , Junker Kerstin , Roessler Max , Alexiusdottir Kristin , Sverrisdottir Asgerdur , Radu Marius T. , Ambert Valentin , Eisen Tim , Warren Anne , Rodríguez-Antona Cristina , García-Donas Jesus , Böhringer Stefan , Koudijs Karel K.M. , Kiemeney Lambertus A.L.M. , Rini Brian I. , Guchelaar Henk-Jan
Published: April 2023

Supplementary Table S1 Selected tagging SNPs Supplementary Figure S1 Kaplan-Meier plot for overall survival by genotype of CTLA-4 rs231775 in discovery cohort (A), validation cohort (B) and combined cohort (C). Supplementary Figure S2 The association of CTLA-4 rs231775 with CTLA-4 gene expression in multiple tissues (A) and in testis tissue (B, p=1.0Ã-10-7) using data from the Genotype-Tissue Expression (GTEx) dataset. Supplementary Figure S3 The survival curve shows the association of CTLA-4 gene expression with overall survival in patients with clear cell renal cell carcinoma (p=0.00255) through OncoLnc, which links The Cancer Genome Atlas (TCGA) survival data to mRNA expression levels (23). (low: lower 50 percentile, high: upper 50 percentile).
Supplementary_Figure_S1-S6_Legends_clean_version from NKG2D-Dependent Antitumor Effects of Chemotherapy and Radiotherapy against Glioblastoma
Authors: Weiss Tobias , Schneider Hannah , Silginer Manuela , Steinle Alexander , Pruschy Martin , Polić Bojan , Weller Michael , Roth Patrick
Published: April 2023

Clean version of Legends to Supplementary Figures
Supplementary Data from A Phase I Clinical Trial of the Poly(ADP-ribose) Polymerase Inhibitor Veliparib and Weekly Topotecan in Patients with Solid Tumors
Authors: Wahner Hendrickson Andrea E. , Menefee Michael E. , Hartmann Lynn C. , Long Harry J. , Northfelt Donald W. , Reid Joel M. , Boakye-Agyeman Felix , Kayode Olumide , Flatten Karen S. , Harrell Maria I. , Swisher Elizabeth M. , Poirier Guy G. , Satele Daniel , Allred Jake , Lensing Janet L. , Chen Alice , Ji Jiuping , Zang Yiping , Erlichman Charles , Haluska Paul , Kaufmann Scott H.
Published: April 2023

Supplementary Data from A Phase I Clinical Trial of the Poly(ADP-ribose) Polymerase Inhibitor Veliparib and Weekly Topotecan in Patients with Solid Tumors
Supplementary figure 2 from CXCR4 Is a Potential Target for Diagnostic PET/CT Imaging in Barrett's Dysplasia and Esophageal Adenocarcinoma
Authors: Fang Hsin-Yu , Münch Natasha Stephens , Schottelius Margret , Ingermann Jonas , Liu Haibo , Schauer Michael , Stangl Stefan , Multhoff Gabriele , Steiger Katja , Gerngroß Carlos , Jesinghaus Moritz , Weichert Wilko , Kühl Anja A. , Sepulveda Antonia R. , Wester Hans-Jürgen , Wang Timothy C. , Quante Michael
Published: April 2023

A trend appears that more CXCR4+proliferating cells are present in high-grade dysplasia mice.
Supplementary Table S3 from A Polymorphism within the Vitamin D Transporter Gene Predicts Outcome in Metastatic Colorectal Cancer Patients Treated with FOLFIRI/Bevacizumab or FOLFIRI/Cetuximab
Authors: Berger Martin D. , Stintzing Sebastian , Heinemann Volker , Cao Shu , Yang Dongyun , Sunakawa Yu , Matsusaka Satoshi , Ning Yan , Okazaki Satoshi , Miyamoto Yuji , Suenaga Mitsukuni , Schirripa Marta , Hanna Diana L. , Soni Shivani , Puccini Alberto , Zhang Wu , Cremolini Chiara , Falcone Alfredo , Loupakis Fotios , Lenz Heinz-Josef
Published: April 2023

Association between GC and VDR SNPs and clinical outcomes in the validation cohort 1 (TRIBE FOLFIRI/bevacizumab arm)
Supplementary Appendix 2 from High Yield of Pathogenic Germline Mutations Causative or Likely Causative of the Cancer Phenotype in Selected Children with Cancer
Authors: Diets Illja J. , Waanders Esmé , Ligtenberg Marjolijn J. , van Bladel Diede A.G. , Kamping Eveline J. , Hoogerbrugge Peter M. , Hopman Saskia , Olderode-Berends Maran J. , Gerkes Erica H. , Koolen David A. , Marcelis Carlo , Santen Gijs W. , van Belzen Martine J. , Mordaunt Dylan , McGregor Lesley , Thompson Elizabeth , Kattamis Antonis , Pastorczak Agata , Mlynarski Wojciech , Ilencikova Denisa , van Silfhout Anneke Vulto- , Gardeitchik Thatjana , de Bont Eveline S. , Loeffen Jan , Wagner Anja , Mensenkamp Arjen R. , Kuiper Roland P. , Hoogerbrugge Nicoline , Jongmans Marjolijn C.
Published: April 2023

This file contains all mutations identified in all patients.
Table S3 from 5-Fluorouracil Enhances Protoporphyrin IX Accumulation and Lesion Clearance during Photodynamic Therapy of Actinic Keratoses: A Mechanism-Based Clinical Trial
Authors: Maytin Edward V. , Anand Sanjay , Riha Margo , Lohser Sara , Tellez Alejandra , Ishak Rim , Karpinski Lauren , Sot Janine , Hu Bo , Denisyuk Anton , Davis Scott C. , Kyei Angela , Vidimos Allison
Published: April 2023

Statistical analysis of AK clearance rates at 3 months and 6 months following PDT
Supplementary Figures from Evolution of Cytogenetically Normal Acute Myeloid Leukemia During Therapy and Relapse: An Exome Sequencing Study of 50 Patients
Authors: Greif Philipp A. , Hartmann Luise , Vosberg Sebastian , Stief Sophie M. , Mattes Raphael , Hellmann Ines , Metzeler Klaus H. , Herold Tobias , Bamopoulos Stefanos A. , Kerbs Paul , Jurinovic Vindi , Schumacher Daniela , Pastore Friederike , Bräundl Kathrin , Zellmeier Evelyn , Ksienzyk Bianka , Konstandin Nikola P. , Schneider Stephanie , Graf Alexander , Krebs Stefan , Blum Helmut , Neumann Martin , Baldus Claudia D. , Bohlander Stefan K. , Wolf Stephan , Görlich Dennis , Berdel Wolfgang E. , Wörmann Bernhard J. , Hiddemann Wolfgang , Spiekermann Karsten
Published: April 2023

Figure S1 Recurrently mutated genes and comparison to TCGA cohort. Figure S2 Stabililty of recurrently mutated genes over disease course. Figure S3 Variant allele frequency plots from diagnosis to relapse for each individual patient. Figure S4 Mutation patterns of individual genes. Lines represent mutations in individual patients. Figure S5 Detection of the pre-existence of gained variants at initial diagnosis. Figure S6 Mutations in AML-associated functional pathways. Figure S7 Deletion of exons 3-10 of the KDM6A gene in the MM-6 cell line. The sister cell line MM-1 is not affected. Deletions were detected by quantitative MLPA analysis and the peak ratio for each KDM6A exon specific probe is shown. Graph represents the results from two independent experiments. Figure S8 H3K27 methylation in the AML cell lines MM-1 and MM-6. The global mono-, di- and tri-methylation of H3K27 in MM-1 and MM-6 was analyzed by Western blot and normalized to H3. The median of three independent experiments is shown. P-Values were calculated using a two-tailed, unpaired Student's t-test. Figure S9 The MM-6 cell line is resistant to cytarabine (Ara-C) but not to Daunorubicin or AC220. Error bars indicate mean {plus minus} s.d. of at least three independent experiments. **P<0.01; unpaired, two-tailed Student's t-test; n.s., not significant . Figure S10 A Correlation of KDM6A expression (low{less than or equal to}25th percentile vs. high>75th percentile) with clinical outcome according to gender in the AMLCG-99 trial (NCT00266136). Figure S11 Proportion of transversions from diagnosis to relapse. Transversion frequencies are shown for lost (blue), stable (orange) and gained (red) mutations. Dots represent individual patients. Figure S12 Median coverage in targeted sequencing of persistent and non-persistent DNMT3A variant positions at complete remission (CR). Figure S13 Clinical outcome according to mutation persistence at remission.
Supplementary Figure 2 from Dual-specific Chimeric Antigen Receptor T Cells and an Indirect Vaccine Eradicate a Variety of Large Solid Tumors in an Immunocompetent, Self-antigen Setting
Authors: Slaney Clare Y. , von Scheidt Bianca , Davenport Alexander J. , Beavis Paul A. , Westwood Jennifer A. , Mardiana Sherly , Tscharke David C. , Ellis Sarah , Prince H. Miles , Trapani Joseph A. , Johnstone Ricky W. , Smyth Mark J. , Teng Michele W. , Ali Aesha , Yu Zhiya , Rosenberg Steven A. , Restifo Nicholas P. , Neeson Paul , Darcy Phillip K. , Kershaw Michael H.
Published: April 2023

High dose IL-2 enables durable tumor regression and proliferation of T cells.
Figure S3 from Therapeutic Drug Monitoring of Carboplatin in High-Dose Protocol (TI-CE) for Advanced Germ Cell Tumors: Pharmacokinetic Results of a Phase II Multicenter Study
Authors: Moeung Sotheara , Chevreau Christine , Broutin Sophie , Guitton Jérôme , Lelièvre Bénédicte , Ciccolini Joseph , Massart Christophe , Fléchon Aude , Delva Rémy , Gravis Gwenaëlle , Lotz Jean-Pierre , Bay Jacques-Olivier , Gross-Goupil Marine , Paci Angelo , Marsili Sabrina , Malard Laurence , Chatelut Etienne , Thomas Fabienne
Published: April 2023

Box plot of total observed carboplatin AUC (when TDM is used) or total predicted AUC (when dose is calculated using solely formula-based method) in cycle 1 of patients having serum creatinine level greater than 120 µM (n=7).
Supplementary Figures 1-2, Supplementary Tables 1-3 from Identification of CCR2 and CD180 as Robust Pharmacodynamic Tumor and Blood Biomarkers for Clinical Use with BRD4/BET Inhibitors
Authors: Yeh Tammie C. , O'Connor Greg , Petteruti Philip , Dulak Austin , Hattersley Maureen , Barrett J. Carl , Chen Huawei
Published: April 2023

Figure S1: Downregulation of CCR2, CD180, MYC and upregulation of HEXIM1 mRNAs by AZD5153 in cells can be detected at 4h; Figure S2: Other BRD4/BET compounds can also downregulate CCR2 and CD180 mRNAs in hematological tumor cell lines; Supplementary Table 1: Description of cell lines used in the RNAseq study; Supplementary Table 2: Information on qPCR assays used in these studies; Supplementary Table 3: More detailed information for each healthy volunteer and patient sample.
Supplementary Data File 1 from Plasma Circulating Tumor DNA in Pancreatic Cancer Patients Is a Prognostic Marker
Authors: Pietrasz Daniel , Pécuchet Nicolas , Garlan Fanny , Didelot Audrey , Dubreuil Olivier , Doat Solène , Imbert-Bismut Francoise , Karoui Mehdi , Vaillant Jean-Christophe , Taly Valérie , Laurent-Puig Pierre , Bachet Jean-Baptiste
Published: April 2023

Supplementary NGS analysis method specifically developed to detect low allele frequency mutations.
Supplement Figure 2 from A Phase II Trial of Abiraterone Combined with Dutasteride for Men with Metastatic Castration-Resistant Prostate Cancer
Authors: McKay Rana R. , Werner Lillian , Mostaghel Elahe A. , Lis Rosina , Voznesensky Olga , Zhang Zhenwei , Marck Brett T. , Matsumoto Alvin M. , Domachevsky Liran , Zukotynski Katherine A. , Bhasin Manoj , Bubley Glenn J. , Montgomery Bruce , Kantoff Philip W. , Balk Steven P. , Taplin Mary-Ellen
Published: April 2023

Black and white figure for supplement.
Figure S1 from Combination Therapy with NHS-muIL12 and Avelumab (anti-PD-L1) Enhances Antitumor Efficacy in Preclinical Cancer Models
Authors: Xu Chunxiao , Zhang Yanping , Rolfe P. Alexander , Hernández Vivian M. , Guzman Wilson , Kradjian Giorgio , Marelli Bo , Qin Guozhong , Qi Jin , Wang Hong , Yu Huakui , Tighe Robert , Lo Kin-Ming , English Jessie M. , Radvanyi Laszlo , Lan Yan
Published: April 2023

NHS-muIL12 and avelumab combination treatment enhanced antitumor efficacy even in well-established tumors.
Supplementary Table S1 from A Strong B-cell Response Is Part of the Immune Landscape in Human High-Grade Serous Ovarian Metastases
Authors: Montfort Anne , Pearce Oliver , Maniati Eleni , Vincent Benjamin G. , Bixby Lisa , Böhm Steffen , Dowe Thomas , Wilkes Edmund H. , Chakravarty Probir , Thompson Richard , Topping Joanne , Cutillas Pedro R. , Lockley Michelle , Serody Jonathan S. , Capasso Melania , Balkwill Frances R.
Published: April 2023

Total patient cohort characteristics reporting the age, disease stage and treatment of patients used in this study
Supplemental Figure 2. Derivation of proposed T-category for Primary Vulvar Melanoma. from Tumor Thickness and Mitotic Rate Robustly Predict Melanoma-Specific Survival in Patients with Primary Vulvar Melanoma: A Retrospective Review of 100 Cases
Authors: Nagarajan Priyadharsini , Curry Jonathan L. , Ning Jing , Piao Jin , Torres-Cabala Carlos A. , Aung Phyu P. , Ivan Doina , Ross Merrick I. , Levenback Charles F. , Frumovitz Michael , Gershenwald Jeffrey E. , Davies Michael A. , Malpica Anais , Prieto Victor G. , Tetzlaff Michael T.
Published: April 2023

(A, B, C) We first assigned patients with PVM to a T-category according to the AJCC for PCM (7th Edition). (A) Shows the AJCC schema and the number of patients assigned to each category. (B) Kaplan Meier DSS curves for patients stratified by AJCC T-categories demonstrate robust prognostic differences for patients with PVM and pT1 and to an extent pT2 disease from those with pT3 and pT4 disease, but less robust stratification among those patients with PVMs {less than or equal to}2.00 mm; pT1 versus pT2 (isolated in C) or >2.0 mm; pT3 and pT4. (D, E, F) Because both tumor thickness and mitotic rate were independent prognostic factors for DSS and because mitotic rate showed a natural prognostic separation at 2 mitotic figures/mm2 (as shown in Figure 1D), we first asked whether a T-category according to the conventional AJCC cut-offs ({less than or equal to}1.0, 1.01-2.0, 2.01-4.0 and >4.0 mm) subsequently modified by mitotic rate (a: <2/mm2 and b: {greater than or equal to}2/mm2) instead of ulceration (as in the AJCC) would effectively stratify patient outcomes. (D) Shows this initial 'alternative T-category' schema and the number of patients assigned to each category. (E) Kaplan Meier DSS curves for patients assigned to the alternative T-categories demonstrate longer DSS for patients with pT1a and pT2a PVM compared to all other patients in the schema. In particular, patients with PVM >2.0 mm (pT3 and pT4) had a short DSS independent of mitotic rate. More importantly, among patients with a tumor thickness {less than or equal to}2.0 mm (pT1 or pT2), only those with mitotic rate {greater than or equal to}2/mm2 had a short DSS, which was essentially superimposable with patients with pT3 and pT4 PVM in this schema. (F) Kaplan-Meier survival curve for patients with pT1 and pT2 PVMs show striking differences in survival according to mitotic rate (<2/mm2 for pT1a or pT2a versus {greater than or equal to}2/mm2 for pT1b and pT2b). (G, H) Combining the above observations together, we concluded that tumor thickness of 2.0 mm represented the ideal cut off to combine with mitotic rate (with <2/mm2 versus {greater than or equal to}2/mm2 as the cut off) to most effectively delineate DSS among patients with PVM. (G) Schema for the proposed T-category and (H) Kaplan-Meier plots of disease-specific survival according to proposed T-categories. (Note: part G and H are identical to Figure 3C and 3D and are only shown here for direct comparison).
Supplementary information from A Positive Feedback Loop of lncRNA-PVT1 and FOXM1 Facilitates Gastric Cancer Growth and Invasion
Authors: Xu Mi-die , Wang Yiqin , Weng Weiwei , Wei Ping , Qi Peng , Zhang Qiongyan , Tan Cong , Ni Shu-juan , Dong Lei , Yang Yusi , Lin Wanrun , Xu Qinghua , Huang Dan , Huang Zhaohui , Ma Yuqing , Zhang Wei , Sheng Weiqi , Du Xiang
Published: April 2023

Supplementary information
Supplementary Figure legends from MUC16 Regulates TSPYL5 for Lung Cancer Cell Growth and Chemoresistance by Suppressing p53
Authors: Lakshmanan Imayavaramban , Salfity Shereen , Seshacharyulu Parthasarathy , Rachagani Satyanarayana , Thomas Abigail , Das Srustidhar , Majhi Prabin D. , Nimmakayala Rama Krishna , Vengoji Raghupathy , Lele Subodh M. , Ponnusamy Moorthy P. , Batra Surinder K. , Ganti Apar Kishor
Published: April 2023

Supplementary Figure legends
Supplemental Figures 1-2 from Tumor-Derived CCL2 Mediates Resistance to Radiotherapy in Pancreatic Ductal Adenocarcinoma
Authors: Kalbasi Anusha , Komar Chad , Tooker Graham M. , Liu Mingen , Lee Jae W. , Gladney Whitney L. , Ben-Josef Edgar , Beatty Gregory L.
Published: April 2023

Supplemental Figure 1: Flow cytometry gating strategy; Supplemental Figure 2: T cell infiltration is not altered by ablative RT
Supplemental Tables from Integrative Development of a TLR8 Agonist for Ovarian Cancer Chemoimmunotherapy
Authors: Monk Bradley J. , Facciabene Andrea , Brady William E. , Aghajanian Carol A. , Fracasso Paula M. , Walker Joan L. , Lankes Heather A. , Manjarrez Kristi L. , Danet-Desnoyers Gwenn-äel H. , Bell-McGuinn Katherine M. , McCourt Carolyn K. , Malykhin Alexander , Hershberg Robert M. , Coukos George
Published: April 2023

Table S1. Subject demographics and baseline characteristics Table S2. Tumor response as assessed by RECIST 1.1 and biochemical response
Supplementary table 1 from Drug-Driven Synthetic Lethality: Bypassing Tumor Cell Genetics with a Combination of AsiDNA and PARP Inhibitors
Authors: Jdey Wael , Thierry Sylvain , Russo Christophe , Devun Flavien , Al Abo Muthana , Noguiez-Hellin Patricia , Sun Jian-Sheng , Barillot Emmanuel , Zinovyev Andrei , Kuperstein Inna , Pommier Yves , Dutreix Marie
Published: April 2023

Supplementary Table 1. Unique genes robustly correlated with survival to AsiDNA or Olaparib in BC cell lines. The values are correlation coefficients (Spearman r; P value <0.005) between gene expression and survival to AsiDNA or Olaparib. Blue: genes involved in DNA repair or cell cycle. (+): positive correlation; (-): negative correlation.
Supplemental Figure Legends from Integrative Development of a TLR8 Agonist for Ovarian Cancer Chemoimmunotherapy
Authors: Monk Bradley J. , Facciabene Andrea , Brady William E. , Aghajanian Carol A. , Fracasso Paula M. , Walker Joan L. , Lankes Heather A. , Manjarrez Kristi L. , Danet-Desnoyers Gwenn-äel H. , Bell-McGuinn Katherine M. , McCourt Carolyn K. , Malykhin Alexander , Hershberg Robert M. , Coukos George
Published: April 2023

Supplemental Figure Legends
Supplementary Information from A Potent In Vivo Antitumor Efficacy of Novel Recombinant Type I Interferon
Authors: Zhang Kang-Jian , Yin Xiao-Fei , Yang Yuan-Qin , Li Hui-Ling , Xu Yan-Ni , Chen Lie-Yang , Liu Xi-Jun , Yuan Su-Jing , Fang Xian-Long , Xiao Jing , Wu Shuai , Xu Hai-Neng , Chu Liang , Katlinski Kanstantsin V. , Katlinskaya Yuliya V. , Guo Rong-Bing , Wei Guang-Wen , Wang Da-Cheng , Liu Xin-Yuan , Fuchs Serge Y.
Published: April 2023

Supplementary methods, tables, figures and legends to figures Supplementary Figure 1. The structure of AB loops for sIFN-I and IFNα-2b and comparison on the sequences for sIFN-I and IFNα-21. Supplementary Figure 2. Quantification of phosphorylaiton of STAT1/3 in Figure 3C Supplementary Figure 3. Analysis of the cell surface IFNAR1 levels in the A549-IFNAR1-KO cell clones by FACS. Supplementary Figure 4. sIFN-I shows potent anti-solid tumor effect in immunocompromised mice models. Supplementary Figure 5. sIFN-I treatment decreases cell proliferation and induces senescence in vivo. Supplementary Figure 6. The antitumor effect of sIFN-I in immunocompetent tumor models. Supplementary Figure 7. FACS analysis of splenocytes from tumor-bearing mice treated with sIFN-I. Supplementary Table 1. Primer sequences used in this study. Supplementary Table 2. Primary antibodies used in this study. Supplementary Table 3. The pharmacokinetic index of human IFNα-2b or sIFN-I administered as in Figure 4B was analyzed by WinNonlin version 6.2 software.
Supplementary information from Downregulation of MicroRNA-644a Promotes Esophageal Squamous Cell Carcinoma Aggressiveness and Stem Cell–like Phenotype via Dysregulation of PITX2
Authors: Zhang Jia-Xing , Chen Zhen-Hua , Xu Yi , Chen Jie-Wei , Weng Hui-Wen , Yun Miao , Zheng Zou-San , Chen Cui , Wu Bing-Li , Li En-Min , Fu Jian-Hua , Ye Sheng , Xie Dan
Published: April 2023

Supplementary Methods, Supplementary Figure legends and Supplementary Table S1 to S4.
Supplementary Table S1 from Hypoxia Causes Downregulation of Dicer in Hepatocellular Carcinoma, Which Is Required for Upregulation of Hypoxia-Inducible Factor 1α and Epithelial–Mesenchymal Transition
Authors: Ibrahim Ahmed Atef , Schmithals Christian , Kowarz Erik , Köberle Verena , Kakoschky Bianca , Pleli Thomas , Kollmar Otto , Nitsch Scarlett , Waidmann Oliver , Finkelmeier Fabian , Zeuzem Stefan , Korf Horst-Werner , Schmid Tobias , Weigert Andreas , Kronenberger Bernd , Marschalek Rolf , Piiper Albrecht
Published: April 2023

Table S1. Clinicopathological parameters of the patients with HCC. HBV, hepatitis B virus; HCV, hepatitis C virus
Supplemental Table S1: PK small-molecule oncology from Clinically Relevant Concentrations of Anticancer Drugs: A Guide for Nonclinical Studies
Authors: Liston Dane R. , Davis Myrtle
Published: April 2023

An Excel file containing all small molecule drugs presented in Tables 1, 2 and 4 of the printed manuscript, including additional fields containing mechanism of action/target, MW, dose schedule, Tmax, Clearance, Volume of distribution, year approved, full references to source data and drug product label, approved indications, additional notes.
Supplementary Materials and Methods from The Immune-microenvironment Confers Chemoresistance of Colorectal Cancer through Macrophage-Derived IL6
Authors: Yin Yuan , Yao Surui , Hu Yaling , Feng Yuyang , Li Min , Bian Zehua , Zhang Jiwei , Qin Yan , Qi Xiaowei , Zhou Leyuan , Fei Bojian , Zou Jian , Hua Dong , Huang Zhaohui
Published: April 2023

Supplementary Materials and Methods Supplemental Table S1. Stage III CRC Patients' information Supplementary Table S2. Primer sequences Supplemental Table S3. CD68 protein levels in three groups of colorectal cancer samples. Supplemental Table S4. P-gp protein levels in three groups of colorectal cancer samples. Supplemental Table S5. Bcl2 protein levels in three groups of colorectal cancer samples. Supplemental Table S6. IL-6 protein levels in three groups of colorectal cancer samples. Supplemental Table S7. RAB22A protein levels in three groups of colorectal cancer samples.
Supplementary Data from Mutation Analysis of Cell-Free DNA and Single Circulating Tumor Cells in Metastatic Breast Cancer Patients with High Circulating Tumor Cell Counts
Authors: Shaw Jacqueline A. , Guttery David S. , Hills Allison , Fernandez-Garcia Daniel , Page Karen , Rosales Brenda M. , Goddard Kate S. , Hastings Robert K. , Luo Jinli , Ogle Olivia , Woodley Laura , Ali Simak , Stebbing Justin , Coombes R. Charles
Published: April 2023

Supplementary data, figures and tables Supplementary Fig. 1. Patient clinical timelines and samples taken. Supplementary Fig. 2. Total cfDNA levels track with CTC counts and CA15-3 in patient CTCM167. Supplementary Table 1: Summary of individual CTCs and WBCs, and respective pools isolated by DEPArray for NGS analysis Supplementary Table 2: Details of PCR amplicons for the custom 30 amplicon NGS panel Supplementary Table 3: Details of PCR amplicons for the Ampli1 Custom Cancer NGS panel showing confirmed mutations in cfDNA and CTCs Supplementary Table 4: Primer sequences of the ESR1 screening assays Supplementary Table 5: Patient details and variables for correlation and survival analyses Supplementary Table 6: Spearman's correlation of each circulating biomarker Supplementary Table 7: Sequencing metrics per panel for each sample Supplementary Table 8: Allelic dropout rate (%) for individual CTCs, WBCs and sample pools by patient Supplementary Table 9: Private mutations detected in single CTCs and WBCs Supplementary Table 10: AF and coverage for each mutation in patient CTCM155 Supplementary Table 11: AF and coverage for each mutation in patient CTCM138 Supplementary Table 12: AF and coverage for each variant in patient CTCM105 Supplementary Table 13: AF and coverage for each mutation in patient CTCM292
Movie S1 from The Second-Generation Exportin-1 Inhibitor KPT-8602 Demonstrates Potent Activity against Acute Lymphoblastic Leukemia
Authors: Vercruysse Thomas , De Bie Jolien , Neggers Jasper E. , Jacquemyn Maarten , Vanstreels Els , Schmid-Burgk Jonathan L. , Hornung Veit , Baloglu Erkan , Landesman Yosef , Senapedis William , Shacham Sharon , Dagklis Antonis , Cools Jan , Daelemans Dirk
Published: April 2023

Movie S1
Supplementary Material from Trajectories of Stress, Depressive Symptoms, and Immunity in Cancer Survivors: Diagnosis to 5 Years
Authors: Andersen Barbara L. , Goyal Neha Godiwala , Westbrook Travis D. , Bishop Brenden , Carson William E.
Published: April 2023

This document contains supplementary methods on assays and additional descriptive and attrition data on participants. Supplementary Table 1. Means of outcome measures at each time point Supplementary Table 2. Attrition Data for Participants by Time Point (N=113) Supplementary Table 3. Adjuvant Treatment Use by Agent or Combination in Reviewed Immunologic Studies
Supplementary Table 3 from Disease Characteristics and Prognostic Implications of Cell-Surface FLT3 Receptor (CD135) Expression in Pediatric Acute Myeloid Leukemia: A Report from the Children's Oncology Group
Authors: Tarlock Katherine , Alonzo Todd A. , Loken Michael R. , Gerbing Robert B. , Ries Rhonda E. , Aplenc Richard , Sung Lillian , Raimondi Susana C. , Hirsch Betsy A. , Kahwash Samir B. , McKenney Amy , Kolb E. Anders , Gamis Alan S. , Meshinchi Soheil
Published: April 2023

Supplementary Table 3. FLT3 mRNA transcript expression and CD135 MFI correlation with clinical and biologic disease features.
Supplementary Figure 2 from Disease Characteristics and Prognostic Implications of Cell-Surface FLT3 Receptor (CD135) Expression in Pediatric Acute Myeloid Leukemia: A Report from the Children's Oncology Group
Authors: Tarlock Katherine , Alonzo Todd A. , Loken Michael R. , Gerbing Robert B. , Ries Rhonda E. , Aplenc Richard , Sung Lillian , Raimondi Susana C. , Hirsch Betsy A. , Kahwash Samir B. , McKenney Amy , Kolb E. Anders , Gamis Alan S. , Meshinchi Soheil
Published: April 2023

Supplementary Figure 2. (A) Correlation of FLT3 mRNA transcript expression (RPKM) and CD135 MFI. (B) Correlation of FLT3mRNA transcript expression and diagnostic WBC.
Supplementary Figure 1 from Disease Characteristics and Prognostic Implications of Cell-Surface FLT3 Receptor (CD135) Expression in Pediatric Acute Myeloid Leukemia: A Report from the Children's Oncology Group
Authors: Tarlock Katherine , Alonzo Todd A. , Loken Michael R. , Gerbing Robert B. , Ries Rhonda E. , Aplenc Richard , Sung Lillian , Raimondi Susana C. , Hirsch Betsy A. , Kahwash Samir B. , McKenney Amy , Kolb E. Anders , Gamis Alan S. , Meshinchi Soheil
Published: April 2023

Supplementary Figure 1. Distribution of CD135 expression. Quantitative CD135 MFI varied among the cohort ranging from 2-232.
Supplementary Figures from Neddylation E2 UBE2F Promotes the Survival of Lung Cancer Cells by Activating CRL5 to Degrade NOXA via the K11 Linkage
Authors: Zhou Weihua , Xu Jie , Li Haomin , Xu Ming , Chen Zhijian J. , Wei Wenyi , Pan Zhenqiang , Sun Yi
Published: April 2023

Figure S1. Expression of UBE2F mRNA in lung cancer tissues and UBE2F overexpression promotes the growth of A427 lung cancer cells. Figure S2. MLN4924 suppressed the growth of lung cancer cells in xenograft model. Figure S3. UBE2F negatively regulates NOXA level in lung cancer cells. Figure S4. CUL5/SAG/UBE2F rather than CUL1/RBX1/UBE2M promotes poly-ubiquitylation of NOXA. Figure S5. Expression of U2OS-shUb-Ub (K11R) causes significant inhibition of cell growth. Figure S6. Analysis of Receiver operating characteristic (ROC) curves for CUL5 and NOXA with indicated cutoff scores.
Supplementary Figure 2 from Unique and Novel Urinary Metabolomic Features in Malignant versus Benign Adrenal Neoplasms
Authors: Patel Dhaval , Thompson Matthew D. , Manna Soumen K. , Krausz Kristopher W. , Zhang Lisa , Nilubol Naris , Gonzalez Frank J. , Kebebew Electron
Published: April 2023

PCA plots showing discrimination between patients with mitotane ingestion (blue) and without mitotane ingestion (red) in HILIC in both (A) ESI and (B) ESI- mode. Supervised OPLS-DA plots showing differences between the two groups in both (C) ESI and (D) ESI- mode. S-plot correlative analysis showing significant variables not correlated with patients with mitotane ingestion (highlighted in red) in both (E) ESI and (F) ESI- mode.
Supplementary Data from Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor–Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002)
Authors: Hua Xin , Bi Xi-Wen , Zhao Jian-Li , Shi Yan-Xia , Lin Ying , Wu Zhi-Yong , Zhang Yuan-Qi , Zhang Le-Hong , Zhang An-Qing , Huang Heng , Liu Xin-Mei , Xu Fei , Guo Ying , Xia Wen , Hong Ruo-Xi , Jiang Kui-Kui , Xue Cong , An Xin , Zhong Yong-Yi , Wang Shu-Sen , Huang Jia-Jia , Yuan Zhong-Yu
Published: April 2023

Supplementary Data from Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor–Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002)
Data from Nuclear Factor-κB-Mediated Transforming Growth Factor-β-Induced Expression of Vimentin Is an Independent Predictor of Biochemical Recurrence after Radical Prostatectomy
Authors: Zhang Qiang , Helfand Brian T. , Jang Thomas L. , Zhu Lihua J. , Chen Lin , Yang Ximing J. , Kozlowski James , Smith Norm , Kundu Shilajit D. , Yang Guangyu , Raji Adekunle A. , Javonovic Borko , Pins Michael , Lindholm Paul , Guo Yinglu , Catalona William J. , Lee Chung
Published: April 2023

Abstract
Purpose: Transforming growth factor-β (TGF-β)-mediated epithelial-to-mesenchymal transition (EMT) has been shown to occur in some cancers; however, the pathway remains controversial and varies with different cancers. In addition, the mechanisms by which TGF-β and the EMT contribute to prostate cancer recurrence are largely unknown. In this study, we elucidated TGF-β-mediated EMT as a predictor of disease recurrence after therapy for prostate cancer, which has not been reported before.

Experimental Design: We analyzed TGF-β-induced EMT using nuclear factor-κB (NF-κB) as an intermediate mediator in prostate cancer cell lines. A total of 287 radical prostatectomy specimens were evaluated using immunohistochemistry in a high-throughput tissue microarray analysis. Levels of TGF-β signaling components and EMT-related factors were analyzed using specific antibodies. Results were expressed as the percentage of cancer cells that stained positive for a given antibody and were correlated with disease recurrence rates at a mean of 7 years following radical prostatectomy.

Results: In prostate cancer cell lines, TGF-β-induced EMT was mediated by NF-κB signaling. Blockade of NF-κB or TGF-β signaling resulted in abrogation of vimentin expression and inhibition of the invasive capability of these cells. There was high risk of biochemical recurrence associated with tumors that displayed high levels of expression of TGF-β1, vimentin, and NF-κB and low level of cytokeratin 18. This was particularly true for vimentin, which is independent of patients' Gleason score.

Conclusions: The detection of NF-κB-mediated TGF-β-induced EMT in primary tumors predicts disease recurrence in prostate cancer patients following radical prostatectomy. The changes in TGF-β signaling and EMT-related factors provide novel molecular markers that may predict prostate cancer outcomes following treatment.
Data from Inhibition of the p53 E3 Ligase HDM-2 Induces Apoptosis and DNA Damage–Independent p53 Phosphorylation in Mantle Cell Lymphoma
Authors: Jones Richard J. , Chen Qing , Voorhees Peter M. , Young Ken H. , Bruey-Sedano Nathalie , Yang Dajun , Orlowski Robert Z.
Published: April 2023

Abstract
Purpose: The ubiquitin-proteasome pathway has been validated as a target in non–Hodgkin's lymphoma through demonstration of the activity of the proteasome inhibitor bortezomib.

Experimental Design: Another potentially attractive target is the human homologue of the murine double minute-2 protein, HDM-2, which serves as the major p53 E3 ubiquitin ligase; we therefore evaluated the activity of a novel agent, MI-63, which disrupts the HDM-2/p53 interaction.

Results: Treatment of wild-type p53 mantle cell lymphoma (MCL) cell lines with MI-63 resulted in a dose- and time-dependent inhibition of proliferation, with an IC50 in the 0.5 to 5.0 μmol/L range. MI-63 induced p53 and HDM-2 accumulation, as well as other downstream p53 targets such as p53 up-regulated modulator of apoptosis and p21Cip1. This was associated with cell cycle arrest at G1-S; activation of caspase-3, caspase-8, and caspase-9; cleavage of poly-(ADP-ribose) polymerase; and loss of E2F1. HDM-2 inhibition caused phosphorylation of p53 at multiple serine residues, including 15, 37, and 392, which coincided with low levels of DNA strand breaks. DNA damage occurred in a small percentage of cells and did not induce phosphorylation of the DNA damage marker H2A.XSer139. Combinations of MI-63 with the molecularly targeted agents bortezomib and rapamycin showed synergistic, sequence-dependent antiproliferative effects. Treatment of primary MCL patient samples resulted in apoptosis and induction of p53 and p21, which was not seen in normal controls.

Conclusions: These findings support the hypothesis that inhibition of the HDM-2/p53 interaction may be a promising approach both by itself and in combination with currently used chemotherapeutics against lymphoid malignancies.