bluuebunny/crossref_metadata_2025 huggingface dataset:
Figure S4 from Parallel Signaling through IRE1α and PERK Regulates Pancreatic Neuroendocrine Tumor Growth and Survival
Authors: Moore Paul C. , Qi Jenny Y. , Thamsen Maike , Ghosh Rajarshi , Peng Justin , Gliedt Micah J. , Meza-Acevedo Rosa , Warren Rachel E. , Hiniker Annie , Kim Grace E. , Maly Dustin J. , Backes Bradley J. , Papa Feroz R. , Oakes Scott A.
Published: April 2023

Pharmaceutical inhibitors of IRE1alpha and PERK are effective at inhibiting their kinase targets in vitro
Supplementary Figures from A ceRNA Circuitry Involving the Long Noncoding RNA Klhl14-AS, Pax8, and Bcl2 Drives Thyroid Carcinogenesis
Authors: Credendino Sara C. , Bellone Maria L. , Lewin Nicole , Amendola Elena , Sanges Remo , Basu Swaraj , Sepe Romina , Decaussin-Petrucci Myriam , Tinto Nadia , Fusco Alfredo , De Felice Mario , De Vita Gabriella
Published: April 2023

Supplementary figures S1-S7. Fig S1. Klhl14-AS is down-regulated in thyroid cancer in a MAPK-dependent manner; Fig S2. A. Rat Klhl14-AS alternative transcripts as reported by Ensembl (Rnor_6). B, C Klhl14-AS was knocked-down in FRTL-5 using LNA Gapmers targeting the region indicated in A by the dashed box (Khl14-AS LNA) or control LNA (ctr LNA). Klhl14-AS and Ki67 expression were measured by qRT-pcr. D Human KLHL14-AS transcript as reported by Ensembl (GRCh38.p12). E KLHL14-AS was knocked-down in Nthy-ori 3-1 using LNA Gapmers targeting the region indicated in D by the dashed box (KHL14-AS LNA) or control LNA (ctr LNA). KLHL14-AS expression was measured through qRT-pcr. All data are shown as means {plus minus} SD. *** p < 0.001; Fig S3: miR-182-5p and miR-20a-5p Responsive Elements in the highly conserved region of Klhl14-AS; Fig S4: Klhl14-AS does not bind let7a; Fig S5. Pax8 expression is repressed in thyroid transformaRon models; Fig S6. Pax8 or Bcl2 overexpression have no effects on thyroid differenRaRon gene expression; Fig S7. GEPIA-annotated thyroid cancer data.
Figure S2 from Parallel Signaling through IRE1α and PERK Regulates Pancreatic Neuroendocrine Tumor Growth and Survival
Authors: Moore Paul C. , Qi Jenny Y. , Thamsen Maike , Ghosh Rajarshi , Peng Justin , Gliedt Micah J. , Meza-Acevedo Rosa , Warren Rachel E. , Hiniker Annie , Kim Grace E. , Maly Dustin J. , Backes Bradley J. , Papa Feroz R. , Oakes Scott A.
Published: April 2023

Manipulation of IRE1alpha adaptive vs. apoptotic signaling determines growth of INS1 xenograft tumors
Supplementary Table 1 from Disruption of the Rbm38-eIF4E Complex with a Synthetic Peptide Pep8 Increases p53 Expression
Authors: Lucchesi Christopher A. , Zhang Jin , Ma Buyong , Chen Mingyi , Chen Xinbin
Published: April 2023

Table of peptides used in the study.
Supplementary Figure 6 from Disruption of the Rbm38-eIF4E Complex with a Synthetic Peptide Pep8 Increases p53 Expression
Authors: Lucchesi Christopher A. , Zhang Jin , Ma Buyong , Chen Mingyi , Chen Xinbin
Published: April 2023

IHC for p53 from RKO xenograft tumors.
Supplementary Data from Tumor Angiogenesis Is Differentially Regulated by Phosphorylation of Endothelial Cell Focal Adhesion Kinase Tyrosines-397 and -861
Authors: Pedrosa Ana-Rita , Bodrug Natalia , Gomez-Escudero Jesus , Carter Edward P. , Reynolds Louise E. , Georgiou Paraskivi Natalia , Fernandez Isabelle , Lees Delphine M. , Kostourou Vassiliki , Alexopoulou Annika N. , Batista Silvia , Tavora Bernardo , Serrels Bryan , Parsons Maddy , Iskratsch Thomas , Hodivala-Dilke Kairbaan M.
Published: April 2023

Supplementary data file containing supplementary materials and methods and supplementary figure legends
Supplementary Figure 4 from Disruption of the Rbm38-eIF4E Complex with a Synthetic Peptide Pep8 Increases p53 Expression
Authors: Lucchesi Christopher A. , Zhang Jin , Ma Buyong , Chen Mingyi , Chen Xinbin
Published: April 2023

Pep8 and Pep23 sensitize tumor cells to p53 induction by doxorubicin and etoposide.
Supplementary Figure 2 from Disruption of the Rbm38-eIF4E Complex with a Synthetic Peptide Pep8 Increases p53 Expression
Authors: Lucchesi Christopher A. , Zhang Jin , Ma Buyong , Chen Mingyi , Chen Xinbin
Published: April 2023

Pep8 enhances p53 expression in a Rbm38-dependent manner.
Figure S5 from Tumor Angiogenesis Is Differentially Regulated by Phosphorylation of Endothelial Cell Focal Adhesion Kinase Tyrosines-397 and -861
Authors: Pedrosa Ana-Rita , Bodrug Natalia , Gomez-Escudero Jesus , Carter Edward P. , Reynolds Louise E. , Georgiou Paraskivi Natalia , Fernandez Isabelle , Lees Delphine M. , Kostourou Vassiliki , Alexopoulou Annika N. , Batista Silvia , Tavora Bernardo , Serrels Bryan , Parsons Maddy , Iskratsch Thomas , Hodivala-Dilke Kairbaan M.
Published: April 2023

Supplementary Figure 5. PlGF and bFGF-induced angiogenesis in vivo is significantly reduced in ECCre+;FAKY397F/Y397F but not ECCre+;FAKY861F/Y861F mice
Figure S1 and S2 from Tumor Angiogenesis Is Differentially Regulated by Phosphorylation of Endothelial Cell Focal Adhesion Kinase Tyrosines-397 and -861
Authors: Pedrosa Ana-Rita , Bodrug Natalia , Gomez-Escudero Jesus , Carter Edward P. , Reynolds Louise E. , Georgiou Paraskivi Natalia , Fernandez Isabelle , Lees Delphine M. , Kostourou Vassiliki , Alexopoulou Annika N. , Batista Silvia , Tavora Bernardo , Serrels Bryan , Parsons Maddy , Iskratsch Thomas , Hodivala-Dilke Kairbaan M.
Published: April 2023

Supplementary Figure 1 and 2. Generation and Characterisation of ECCre+;FAKY397F/Y397F and ECCre+;FAKY861F/Y861F mice.
Supplementary Data from The WNT10B Network Is Associated with Survival and Metastases in Chemoresistant Triple-Negative Breast Cancer
Authors: El Ayachi Ikbale , Fatima Iram , Wend Peter , Alva-Ornelas Jackelyn A. , Runke Stephanie , Kuenzinger William L. , Silva Julio , Silva Wendy , Gray Joseph K. , Lehr Stephan , Barch Hilaire C. , Krutilina Raisa I. , White Andrew C. , Cardiff Robert , Yee Lisa D. , Yang Lily , O'Regan Ruth M. , Lowry William E. , Seagroves Tiffany N. , Seewaldt Victoria , Krum Susan A. , Miranda-Carboni Gustavo A.
Published: April 2023

Supplementary Section: 1) Seven supplementary figures and legends: A. Supplementary figure S1: TCGA analysis of WNT10B network. B. Supplementary figure S2: Human IHC analysis of WNT10B, HMGA2 and EZH2. C. Supplementary figure S3: Mouse IHC analysis of HMGA2 and EZH2. D. Supplementary figure S4: ChIP, qPCR and IB analysis on WNT10B/ï�¢CATENIN direct target genes. E. Supplementary figure S5: Characterization of CRISPR HMGA2KO and EZH2KO cells both in vitro and in vivo. F. Supplementary figure S6: Validation of WNT10B network on TNBC PDX tumors. G. Supplementary figure S7: Isobologram curves of ICG-001 and Doxorubicin activity. 2) Supplementary Material & Methods 3) Supplementary Table 1 (ST1) qPCR primers 4) Supplementary Table 2 (ST2) ChIP primers 5) 6) Supplementary Table 3 (ST3) drug combinatorial index
Figure S1 from Comprehensive Benchmarking and Integration of Tumor Microenvironment Cell Estimation Methods
Authors: Jiménez-Sánchez Alejandro , Cast Oliver , Miller Martin L.
Published: April 2023

Figure S1: Additional Analyses: A) Statistical framework benchmark results, each point represents the rank of that statistical framework when compared against the rest for each benchmarking experiment. ConsensusTME gene sets were used for all frameworks. B) Historical benchmark, each consecutive version of consensus contains signature/approach from an additional method, added chronologically. A) Kendall's correlation coefficients (Ï„) of xCell PBMC data based on CyTOF (top left: SDY311 n = 61, top right: SDY420 n = 104) and CIBERSORT PBMC data based on flow cytometry (bottom left, n = 20) vs RNA-derived cell type-specific estimates for the tested methods. The grey box represents correlation coefficients that have a q-value > 0.05 (B-H method). Box plots are sorted according to median correlation coefficient (left to right: decreasing performance).
Supplementary Materials and Methods from Macrophage-Derived IL1β and TNFα Regulate Arginine Metabolism in Neuroblastoma
Authors: Fultang Livingstone , Gamble Laura D. , Gneo Luciana , Berry Andrea M. , Egan Sharon A. , De Bie Fenna , Yogev Orli , Eden Georgina L. , Booth Sarah , Brownhill Samantha , Vardon Ashley , McConville Carmel M. , Cheng Paul N. , Norris Murray D. , Etchevers Heather C. , Murray Jayne , Ziegler David S. , Chesler Louis , Schmidt Ronny , Burchill Susan A. , Haber Michelle , De Santo Carmela , Mussai Francis
Published: April 2023

Supplementary Materials and Methods CLEAN version
Supplementary Figure Legends and Table from Macrophage-Derived IL1β and TNFα Regulate Arginine Metabolism in Neuroblastoma
Authors: Fultang Livingstone , Gamble Laura D. , Gneo Luciana , Berry Andrea M. , Egan Sharon A. , De Bie Fenna , Yogev Orli , Eden Georgina L. , Booth Sarah , Brownhill Samantha , Vardon Ashley , McConville Carmel M. , Cheng Paul N. , Norris Murray D. , Etchevers Heather C. , Murray Jayne , Ziegler David S. , Chesler Louis , Schmidt Ronny , Burchill Susan A. , Haber Michelle , De Santo Carmela , Mussai Francis
Published: April 2023

Supplementary Figure Legends and Tables
Supplementary Table S2 from A Comprehensive PDX Gastric Cancer Collection Captures Cancer Cell–Intrinsic Transcriptional MSI Traits
Authors: Corso Simona , Isella Claudio , Bellomo Sara E. , Apicella Maria , Durando Stefania , Migliore Cristina , Ughetto Stefano , D’Errico Laura , Menegon Silvia , Moya-Rull Daniel , Cargnelutti Marilisa , Capelôa Tânia , Conticelli Daniela , Giordano Jessica , Venesio Tiziana , Balsamo Antonella , Marchiò Caterina , Degiuli Maurizio , Reddavid Rossella , Fumagalli Uberto , De Pascale Stefano , Sgroi Giovanni , Rausa Emanuele , Baiocchi Gian Luca , Molfino Sarah , Pietrantonio Filippo , Morano Federica , Siena Salvatore , Sartore-Bianchi Andrea , Bencivenga Maria , Mengardo Valentina , Rosati Riccardo , Marrelli Daniele , Morgagni Paolo , Rausei Stefano , Pallabazzer Giovanni , De Simone Michele , Ribero Dario , Marsoni Silvia , Sottile Antonino , Medico Enzo , Cassoni Paola , Sapino Anna , Pectasides Eirini , Thorner Aaron R. , Nag Anwesha , Drinan Samantha D. , Wollison Bruce M. , Bass Adam J. , Giordano Silvia
Published: April 2023

Pathological characteristics related to engraftment success of gastric PDXs.
Supplementary Figure 2 from Macrophage-Derived IL1β and TNFα Regulate Arginine Metabolism in Neuroblastoma
Authors: Fultang Livingstone , Gamble Laura D. , Gneo Luciana , Berry Andrea M. , Egan Sharon A. , De Bie Fenna , Yogev Orli , Eden Georgina L. , Booth Sarah , Brownhill Samantha , Vardon Ashley , McConville Carmel M. , Cheng Paul N. , Norris Murray D. , Etchevers Heather C. , Murray Jayne , Ziegler David S. , Chesler Louis , Schmidt Ronny , Burchill Susan A. , Haber Michelle , De Santo Carmela , Mussai Francis
Published: April 2023

Supplementary Figure 2 Cytokine profile of tumour induced macrophages or granulocytes
Supplemental methods, Tables S1, S2, S3,S4, S5, Figures S1, S2, S3, S4. from Inhibition of Notch Signaling Enhances Chemosensitivity in B-cell Precursor Acute Lymphoblastic Leukemia
Authors: Takam Kamga Paul , Dal Collo Giada , Midolo Martina , Adamo Annalisa , Delfino Pietro , Mercuri Angela , Cesaro Simone , Mimiola Elda , Bonifacio Massimiliano , Andreini Angelo , Chilosi Marco , Krampera Mauro
Published: April 2023

Supplemental Methods describes methods that were not thoroughly described in the main manuscript as well as methods used to produce supplemental data. Table S1 describes characteristics of patients involved in the study. Table S2 describes genes potentially damages in 5 B-ALL patients following DNA sequencing. Table S3 describes, epigenetics patterns of ALL patients as obtained following the processing of methylation data publicly available under accession number GSE49031. Table S4 describes Chi Square analysis of the association between Notch expression level and response to therapy. Table S5 describes B-ALL cell survival upon treatment with Notch ligands. Figure S1 describes expression of Notch target genes and Notch active forms in B-ALL samples. This figure also displays the validation of L5C5 antibody in HEK 293T cells. Figures S2 describes the sensitivity (Annexin V) of B-ALL samples to Ara-C, Doxorubicin and Dexamethasone, each used alone or in combination with anti-Notch3 or anti-Notch4. Figure S3 describes the sensitivity (Annexin V) of B-ALL samples to Ara-C, Doxorubicin and Dexamethasone, each used alone or in combination with different Notch inhibitors. The aim is to screen the most active (in term of cell death) association in vitro, that will then be used in vivo. Figures S4 presents how anti-oxidants NAC and BME protect B-ALL cells from cell death induced by drug treatments.
Supplementary Information from Prolactin Promotes Fibrosis and Pancreatic Cancer Progression
Authors: Tandon Manuj , Coudriet Gina M. , Criscimanna Angela , Socorro Mairobys , Eliliwi Mouhanned , Singhi Aatur D. , Cruz-Monserrate Zobeida , Bailey Peter , Lotze Michael T. , Zeh Herbert , Hu Jing , Goffin Vincent , Gittes George K. , Biankin Andrew V. , Esni Farzad
Published: April 2023

Supplementary figure legends and methods.
Figure S5 from Cancer Exacerbates Chemotherapy-Induced Sensory Neuropathy
Authors: Housley Stephen N. , Nardelli Paul , Carrasco Dario I. , Rotterman Travis M. , Pfahl Emily , Matyunina Lilya V. , McDonald John F. , Cope Timothy C.
Published: April 2023

Exemplar Graphical Bayesian Model Validation
Figure S3 from Cancer Exacerbates Chemotherapy-Induced Sensory Neuropathy
Authors: Housley Stephen N. , Nardelli Paul , Carrasco Dario I. , Rotterman Travis M. , Pfahl Emily , Matyunina Lilya V. , McDonald John F. , Cope Timothy C.
Published: April 2023

List of Parameters used for Neurophysiological Analyses
Supplementary Data from Long-Term Gemcitabine Treatment Reshapes the Pancreatic Tumor Microenvironment and Sensitizes Murine Carcinoma to Combination Immunotherapy
Authors: Principe Daniel R. , Narbutis Matthew , Kumar Sandeep , Park Alex , Viswakarma Navin , Dorman Matthew J. , Kamath Suneel D. , Grippo Paul J. , Fishel Melissa L. , Hwang Rosa F. , Thummuri Dinesh , Underwood Patrick W. , Munshi Hidayatullah G. , Trevino Jose G. , Rana Ajay
Published: April 2023

Supplementary Methods, Tables, and Figure Legends.
Figure S8 from Long-Term Gemcitabine Treatment Reshapes the Pancreatic Tumor Microenvironment and Sensitizes Murine Carcinoma to Combination Immunotherapy
Authors: Principe Daniel R. , Narbutis Matthew , Kumar Sandeep , Park Alex , Viswakarma Navin , Dorman Matthew J. , Kamath Suneel D. , Grippo Paul J. , Fishel Melissa L. , Hwang Rosa F. , Thummuri Dinesh , Underwood Patrick W. , Munshi Hidayatullah G. , Trevino Jose G. , Rana Ajay
Published: April 2023

Homozygous loss of TP53 enhances MHC Class 1 expression and T-cell infiltration in murine PDAC, yet increased mutational burden predicts poor outcomes
Figure S7 from Long-Term Gemcitabine Treatment Reshapes the Pancreatic Tumor Microenvironment and Sensitizes Murine Carcinoma to Combination Immunotherapy
Authors: Principe Daniel R. , Narbutis Matthew , Kumar Sandeep , Park Alex , Viswakarma Navin , Dorman Matthew J. , Kamath Suneel D. , Grippo Paul J. , Fishel Melissa L. , Hwang Rosa F. , Thummuri Dinesh , Underwood Patrick W. , Munshi Hidayatullah G. , Trevino Jose G. , Rana Ajay
Published: April 2023

The combination of Gemcitabine, Galunisertib, and anti-PD-1 does not significantly affect T-cell activation in the spleen
Figure S6 from Long-Term Gemcitabine Treatment Reshapes the Pancreatic Tumor Microenvironment and Sensitizes Murine Carcinoma to Combination Immunotherapy
Authors: Principe Daniel R. , Narbutis Matthew , Kumar Sandeep , Park Alex , Viswakarma Navin , Dorman Matthew J. , Kamath Suneel D. , Grippo Paul J. , Fishel Melissa L. , Hwang Rosa F. , Thummuri Dinesh , Underwood Patrick W. , Munshi Hidayatullah G. , Trevino Jose G. , Rana Ajay
Published: April 2023

The combination of Gemcitabine, Galunisertib, and anti-PD-1 restores normal gland architecture and suppresses TGFβ signaling
Figure S5 from Long-Term Gemcitabine Treatment Reshapes the Pancreatic Tumor Microenvironment and Sensitizes Murine Carcinoma to Combination Immunotherapy
Authors: Principe Daniel R. , Narbutis Matthew , Kumar Sandeep , Park Alex , Viswakarma Navin , Dorman Matthew J. , Kamath Suneel D. , Grippo Paul J. , Fishel Melissa L. , Hwang Rosa F. , Thummuri Dinesh , Underwood Patrick W. , Munshi Hidayatullah G. , Trevino Jose G. , Rana Ajay
Published: April 2023

PD-L1/PD-L2 expression is associated with increased immune and TGFβ gene signatures
Figure S17 from Cancer Exacerbates Chemotherapy-Induced Sensory Neuropathy
Authors: Housley Stephen N. , Nardelli Paul , Carrasco Dario I. , Rotterman Travis M. , Pfahl Emily , Matyunina Lilya V. , McDonald John F. , Cope Timothy C.
Published: April 2023

Steps of In Vivo Electrophysiology Analysis
Supplementary Table S1 from Infiltrating Mast Cell–Mediated Stimulation of Estrogen Receptor Activity in Breast Cancer Cells Promotes the Luminal Phenotype
Authors: Majorini Maria Teresa , Cancila Valeria , Rigoni Alice , Botti Laura , Dugo Matteo , Triulzi Tiziana , De Cecco Loris , Fontanella Enrico , Jachetti Elena , Tagliabue Elda , Chiodoni Claudia , Tripodo Claudio , Colombo Mario P. , Lecis Daniele
Published: April 2023

Supplementary Table S1. Genes differentially expressed (FDR < 0.05) between PyMT B6 and PyMT Wsh mice.
Figure S2 from Infiltrating Mast Cell–Mediated Stimulation of Estrogen Receptor Activity in Breast Cancer Cells Promotes the Luminal Phenotype
Authors: Majorini Maria Teresa , Cancila Valeria , Rigoni Alice , Botti Laura , Dugo Matteo , Triulzi Tiziana , De Cecco Loris , Fontanella Enrico , Jachetti Elena , Tagliabue Elda , Chiodoni Claudia , Tripodo Claudio , Colombo Mario P. , Lecis Daniele
Published: April 2023

Heatmap showing genes belonging to the leading edge lists of at least four gene sets of Figure 6F. Leading edge genes drives the significance of the gene sets. The color scale of the heatmap represents the fold change of the gene in the comparison of PyMT B6 versus PyMT Wsh mice. The color bar at the top of the heatmap represents the Spearman's correlation coefficient of the gene with CIBERSORT MC abundance in METABRIC dataset. (B) ER levels in tumors collected from 4 PyMT B6 and 4 PyMT Wsh mice.
Figure S1 from Infiltrating Mast Cell–Mediated Stimulation of Estrogen Receptor Activity in Breast Cancer Cells Promotes the Luminal Phenotype
Authors: Majorini Maria Teresa , Cancila Valeria , Rigoni Alice , Botti Laura , Dugo Matteo , Triulzi Tiziana , De Cecco Loris , Fontanella Enrico , Jachetti Elena , Tagliabue Elda , Chiodoni Claudia , Tripodo Claudio , Colombo Mario P. , Lecis Daniele
Published: April 2023

Characterization of BC cell lines established from spontaneous tumors, commercially available and BMMCs. (A) Western blot to compare the levels of ER and HER2 in cell lines established by us from spontaneous tumors developed in NeuT (N2C), PyMT B6 (PyMT41c) and PyMT Wsh (WPY25F) transgenic mice. (B) Purity of BMMCs employed in co-culture experiments was evaluated by flow cytometry analysis by excluding debris and doublets (FSC-A vs FSC-H) and evaluating the percentage of FceRIβ and cKit double positive cells. (C) WPY25F tumor cells were first gated to include only viable cells (7AA negative), then they were gated on CD45-CD31-Ter119- to exclude leukocytes, endothelial cells and erythrocytes. Gated cells were finally analyzed for the expression of CD49f and EpCAM to define the basal/luminal phenotype as shown in figure 2D. (D) Absolute levels of ESR1 evaluated by Real-Time PCR in both human and mouse cell lines are shown.
Supplementary Table 2 from IL26, a Noncanonical Mediator of DNA Inflammatory Stimulation, Promotes TNBC Engraftment and Progression in Association with Neutrophils
Authors: Trotter Timothy N. , Shuptrine Casey W. , Tsao Li-Chung , Marek Robert D. , Acharya Chaitanya , Wei Jun-Ping , Yang Xiao-Yi , Lei Gangjun , Wang Tao , Lyerly Herbert Kim , Hartman Zachary C.
Published: April 2023

Significant hits identified in CRISPR screen
Supplementary Methods from IL26, a Noncanonical Mediator of DNA Inflammatory Stimulation, Promotes TNBC Engraftment and Progression in Association with Neutrophils
Authors: Trotter Timothy N. , Shuptrine Casey W. , Tsao Li-Chung , Marek Robert D. , Acharya Chaitanya , Wei Jun-Ping , Yang Xiao-Yi , Lei Gangjun , Wang Tao , Lyerly Herbert Kim , Hartman Zachary C.
Published: April 2023

Detailed and supplementary methods
Figure S3 from GPD1 Enhances the Anticancer Effects of Metformin by Synergistically Increasing Total Cellular Glycerol-3-Phosphate
Authors: Xie Jianjiang , Ye Jianheng , Cai Zhiduan , Luo Yong , Zhu Xuejin , Deng Yulin , Feng Yuanfa , Liang Yingke , Liu Ren , Han Zhaodong , Liang Yuxiang , Zheng Yu , Mo Rujun , Zhuo Yangjia , Wu Yongding , Jiang Funeng , Zhu Jianguo , Wu Chin-Lee , Zhong Weide
Published: April 2023

Figure S3 showed the detection of G3P, DHAP and methylglyoxal in cancer cells treated with or without different concentrations of G3P.
Video S5 from ICOS Is an Indicator of T-cell–Mediated Response to Cancer Immunotherapy
Authors: Xiao Zunyu , Mayer Aaron T. , Nobashi Tomomi W. , Gambhir Sanjiv S.
Published: April 2023

Video S5: PD-1 i.p group Day 2 PET image
Video S3 from ICOS Is an Indicator of T-cell–Mediated Response to Cancer Immunotherapy
Authors: Xiao Zunyu , Mayer Aaron T. , Nobashi Tomomi W. , Gambhir Sanjiv S.
Published: April 2023

Video S3: PD-1 i.t group Day 2 PET image
Video S2 from ICOS Is an Indicator of T-cell–Mediated Response to Cancer Immunotherapy
Authors: Xiao Zunyu , Mayer Aaron T. , Nobashi Tomomi W. , Gambhir Sanjiv S.
Published: April 2023

Video S2: STING i.t group Day 2 PET image
TableS1 from FAM46C and FNDC3A Are Multiple Myeloma Tumor Suppressors That Act in Concert to Impair Clearing of Protein Aggregates and Autophagy
Authors: Manfrini Nicola , Mancino Marilena , Miluzio Annarita , Oliveto Stefania , Balestra Matteo , Calamita Piera , Alfieri Roberta , Rossi Riccardo L. , Sassoè-Pognetto Marco , Salio Chiara , Cuomo Alessandro , Bonaldi Tiziana , Manfredi Marcello , Marengo Emilio , Ranzato Elia , Martinotti Simona , Cittaro Davide , Tonon Giovanni , Biffo Stefano
Published: April 2023

Expression data OPM2 with/without wtFAM46C
Supplementary Video 2 from A Circle RNA Regulatory Axis Promotes Lung Squamous Metastasis via CDR1-Mediated Regulation of Golgi Trafficking
Authors: Harrison Emily B. , Porrello Alessandro , Bowman Brittany M. , Belanger Adam R. , Yacovone Gabriella , Azam Salma H. , Windham Ian A. , Ghosh Subrata K. , Wang Menglin , Mckenzie Nicholas , Waugh Trent A. , Van Swearingen Amanda E.D. , Cohen Stephanie M. , Allen Devon G. , Goodwin Tyler J. , Mascenik Teresa , Bear James E. , Cohen Sarah , Randell Scott H. , Massion Pierre P. , Major Michael B. , Huang Leaf , Pecot Chad V.
Published: April 2023

Time lapse imaging of RUSH assay in SK-MES-1-CDR1 cells transfected with Ii-Str_ssSBP-EGFP (green) and Golgi marker mApple-SiT (magenta) beginning 5 min after biotin addition.
Supplementary Data from A Circle RNA Regulatory Axis Promotes Lung Squamous Metastasis via CDR1-Mediated Regulation of Golgi Trafficking
Authors: Harrison Emily B. , Porrello Alessandro , Bowman Brittany M. , Belanger Adam R. , Yacovone Gabriella , Azam Salma H. , Windham Ian A. , Ghosh Subrata K. , Wang Menglin , Mckenzie Nicholas , Waugh Trent A. , Van Swearingen Amanda E.D. , Cohen Stephanie M. , Allen Devon G. , Goodwin Tyler J. , Mascenik Teresa , Bear James E. , Cohen Sarah , Randell Scott H. , Massion Pierre P. , Major Michael B. , Huang Leaf , Pecot Chad V.
Published: April 2023

Supplementary Methods, Figures, and Tables
Figure S1, Figure S2, Figure S3, Figure S4, Table S1, and Table S2 from Combined Blockade of IL6 and PD-1/PD-L1 Signaling Abrogates Mutual Regulation of Their Immunosuppressive Effects in the Tumor Microenvironment
Authors: Tsukamoto Hirotake , Fujieda Koji , Miyashita Azusa , Fukushima Satoshi , Ikeda Tokunori , Kubo Yosuke , Senju Satoru , Ihn Hironobu , Nishimura Yasuharu , Oshiumi Hiroyuki
Published: April 2023

Figure S1 shows that baseline levels of plasma IL-6 before treatment were not associated with responsiveness to Nivolumab in melanoma patients. Figure S2 shows the characterization of PD-1-expressing macrophages in tumor microenvironment. Figure S3 shows the characterization of IL-6-producing cells in tumor tissues. Figure S4 shows the therapeutic effects of combined blockade of IL-6 and PD-L1/PD-1 signals in tumor-bearing mice. Table S1 shows the demographics and disease characteristics of melanoma patients treated with Nivolumab. Table S2 shows the demographics and disease characteristics of melanoma patients receiving surgery.
Supplementary Material & Methods from The MDM2/MDMX-p53 Antagonist PM2 Radiosensitizes Wild-Type p53 Tumors
Authors: Spiegelberg Diana , Mortensen Anja C. , Lundsten Sara , Brown Christopher J. , Lane David P. , Nestor Marika
Published: April 2023

Supplementary Material & Methods
Supplementary Figure 2 from A High-Content Screen Identifies Drugs That Restrict Tumor Cell Extravasation across the Endothelial Barrier
Authors: Hilfenhaus Georg , Mompeón Ana , Freshman Jonathan , Prajapati Divya P. , Hernandez Gloria , Freitas Vanessa M. , Ma Feiyang , Langenbacher Adam D. , Mirkov Snezana , Song Dana , Cho Byoung-Kyu , Goo Young Ah , Pellegrini Matteo , Chen Jau-Nian , Damoiseaux Robert , Iruela-Arispe M. Luisa
Published: April 2023

Summary of the drug screening findings using both MiaPaCa-2 and PaTu-8902 tumor cells
Supplementary Material from Resolution of Spatial and Temporal Heterogeneity in Bevacizumab-Treated Breast Tumors by Eigenspectra Multispectral Optoacoustic Tomography
Authors: Liapis Evangelos , Klemm Uwe , Karlas Angelos , Reber Josefine , Ntziachristos Vasilis
Published: April 2023

Supplementary Material
Supplementary Figure S5 from Resolution of Spatial and Temporal Heterogeneity in Bevacizumab-Treated Breast Tumors by Eigenspectra Multispectral Optoacoustic Tomography
Authors: Liapis Evangelos , Klemm Uwe , Karlas Angelos , Reber Josefine , Ntziachristos Vasilis
Published: April 2023

Supplementary Figure S5
Figure S3 from Dietary Fructose Promotes Prostate Cancer Growth
Authors: Carreño Daniela V. , Corro Néstor B. , Cerda-Infante Javier F. , Echeverría Carolina E. , Asencio-Barría Catalina A. , Torres-Estay Verónica A. , Mayorga-Weber Gonzalo A. , Rojas Pablo A. , Véliz Loreto P. , Cisternas Pedro A. , Montecinos Viviana P. , San Francisco Ignacio F. , Varas-Godoy Manuel A. , Sotomayor Paula C. , Castro Maite A. , Nualart Francisco J. , Inestrosa Nibaldo C. , Godoy Alejandro S.
Published: April 2023

Gene Set Enrichment Analysis (GSEA) from RNA sequencing data of PC3 cells stimulated with fructose or glucose.
Figure S9, Figure S10 from YAP-Mediated Repression of HRK Regulates Tumor Growth, Therapy Response, and Survival Under Tumor Environmental Stress in Neuroblastoma
Authors: Shim Jenny , Lee Jasmine Y. , Jonus Hunter C. , Arnold Amanda , Schnepp Robert W. , Janssen Kaitlyn M. , Maximov Victor , Goldsmith Kelly C.
Published: April 2023

Caspase 9 activity of shYAP model cells in serum starved conditions; Methylation status at HRK promoter region
Supplementary Table S6 from Serine Biosynthesis Is a Metabolic Vulnerability in IDH2-Driven Breast Cancer Progression
Authors: Barnabas Georgina D. , Lee Joo Sang , Shami Tamar , Harel Michal , Beck Lir , Selitrennik Michael , Jerby-Arnon Livnat , Erez Neta , Ruppin Eytan , Geiger Tamar
Published: April 2023

Supplementary Table S6: ANOVA significant proteins in PHGDH and PSAT1 knockout cells with IDH2 overexpression
Supplementary Data from A Genome-Wide Pooled shRNA Screen Identifies PPP2R2A as a Predictive Biomarker for the Response to ATR and CHK1 Inhibitors
Authors: Qiu Zhaojun , Fa Pengyan , Liu Tao , Prasad Chandra B. , Ma Shanhuai , Hong Zhipeng , Chan Ernest R. , Wang Hongbing , Li Zaibo , He Kai , Wang Qi-En , Williams Terence M. , Yan Chunhong , Sizemore Steven T. , Narla Goutham , Zhang Junran
Published: April 2023

Supplementary data.
Dataset S3 from Inhibition of Histone H3K27 Demethylases Inactivates Brachyury (TBXT) and Promotes Chordoma Cell Death
Authors: Cottone Lucia , Cribbs Adam P. , Khandelwal Garima , Wells Graham , Ligammari Lorena , Philpott Martin , Tumber Anthony , Lombard Patrick , Hookway Edward S. , Szommer Tamas , Johansson Catrine , Brennan Paul E. , Pillay Nischalan , Jenner Richard G. , Oppermann Udo , Flanagan Adrienne M.
Published: April 2023

Cottone_Dataset_S3_Chordoma_UCH1_K27Me3_GEA
Supplementary Figure 3 from Loss of ARID1A Promotes Epithelial–Mesenchymal Transition and Sensitizes Pancreatic Tumors to Proteotoxic Stress
Authors: Tomihara Hideo , Carbone Federica , Perelli Luigi , Huang Justin K. , Soeung Melinda , Rose Johnathon L. , Robinson Frederick S. , Lissanu Deribe Yonathan , Feng Ningping , Takeda Mitsunobu , Inoue Akira , Poggetto Edoardo Del , Deem Angela K. , Maitra Anirban , Msaouel Pavlos , Tannir Nizar M. , Draetta Giulio F. , Viale Andrea , Heffernan Timothy P. , Bristow Christopher A. , Carugo Alessandro , Genovese Giannicola
Published: April 2023

Supplementary Figure 3. NVP-AUY922 toxicity in vivo and effect of gemcitabine treatment in ARID1A knock-out PDAC models in vitro and in vivo.
Figure S1 from Insights into the Links between MYC and 3D Chromatin Structure and Epigenetics Regulation: Implications for Cancer Therapy
Authors: Amjadi-Moheb Fatemeh , Paniri Alireza , Akhavan-Niaki Haleh
Published: April 2023

Schematic model for MYC-mediated transcription regulation. MYC potentially regulates the expression of a variety of genes involved in cell growth, apoptosis, proliferation, and immortalization by recruiting a large number of proteins. MYC interacts with two major protein complexes including HATs with GCN5, and Tip60 for ATP-dependent chromatin remodeling. HAT: histone acetyl-transferases; MAX: MYC associated factor X; Tip60: tat interactive protein 60; P300/CBP: p300/CREB-binding protein; GCN5: Gcn5-related N-acetyltransferase: SWI/SNF: SWItch/sucrose non-fermentable SWI/SNF.
Supplementary Table 5 from Bladder Tumor Subtype Commitment Occurs in Carcinoma In Situ Driven by Key Signaling Pathways Including ECM Remodeling
Authors: Wullweber Adrian , Strick Reiner , Lange Fabienne , Sikic Danijel , Taubert Helge , Wach Sven , Wullich Bernd , Bertz Simone , Weyerer Veronika , Stoehr Robert , Breyer Johannes , Burger Maximilian , Hartmann Arndt , Strissel Pamela L. , Eckstein Markus
Published: April 2023

(A)Overview of genes belonging to gene clusters (PanCancer Progression Panel). (B) Most differentially expressed signaling pathways and genes between lesion cluster A and C. (C) Most differentially expressed signaling pathways and genes between lesion cluster A and C.
Supplementary Information from PLEKHA4 Promotes Wnt/β-Catenin Signaling–Mediated G1–S Transition and Proliferation in Melanoma
Authors: Shami Shah Adnan , Cao Xiaofu , White Andrew C. , Baskin Jeremy M.
Published: April 2023

Supplementary Methods; Figure S1 showing PLEKHA4 expression levels in melanoma subtypes; Figure S2 showing RNAi in YUMM1.7 cells; Figure S3 showing Wnt inhibitor effects on proliferation and apoptosis; Figure S4 showing rescue of PLEKHA4 RNAi defects G1/S transition defect; Figure S5 showing partial rescue of PLEKHA4 RNAi apoptosis defects by DVL; Figure S6 showing characterization of PLEKHA4 shRNA in WM266-4 cells; Figure S7 showing characterization of PLEKHA4 shRNA in YUMM1.7 cells; Figure S8 showing characterization of PLEKHA4 shRNA in SK-MEL-2 cells; Table S1 showing siRNA and shRNA sequences; Table S2 showing sources of antibodies; and Supplementary References.
Supplementary Table 2 from Bladder Tumor Subtype Commitment Occurs in Carcinoma In Situ Driven by Key Signaling Pathways Including ECM Remodeling
Authors: Wullweber Adrian , Strick Reiner , Lange Fabienne , Sikic Danijel , Taubert Helge , Wach Sven , Wullich Bernd , Bertz Simone , Weyerer Veronika , Stoehr Robert , Breyer Johannes , Burger Maximilian , Hartmann Arndt , Strissel Pamela L. , Eckstein Markus
Published: April 2023

Reference sequences, gene lists and gene expression distribution of utilized NanoString-assays.
Table S1 from SLFN5 Regulates LAT1-Mediated mTOR Activation in Castration-Resistant Prostate Cancer
Authors: Martinez Rafael S. , Salji Mark J. , Rushworth Linda , Ntala Chara , Rodriguez Blanco Giovanny , Hedley Ann , Clark William , Peixoto Paul , Hervouet Eric , Renaude Elodie , Kung Sonia H.Y. , Galbraith Laura C.A. , Nixon Colin , Lilla Sergio , MacKay Gillian M. , Fazli Ladan , Gaughan Luke , Sumpton David , Gleave Martin E. , Zanivan Sara , Blomme Arnaud , Leung Hing Y.
Published: April 2023

Significantly down-reg genes in SLFN5 KO cells and tumours
Supplementary Information from SLFN5 Regulates LAT1-Mediated mTOR Activation in Castration-Resistant Prostate Cancer
Authors: Martinez Rafael S. , Salji Mark J. , Rushworth Linda , Ntala Chara , Rodriguez Blanco Giovanny , Hedley Ann , Clark William , Peixoto Paul , Hervouet Eric , Renaude Elodie , Kung Sonia H.Y. , Galbraith Laura C.A. , Nixon Colin , Lilla Sergio , MacKay Gillian M. , Fazli Ladan , Gaughan Luke , Sumpton David , Gleave Martin E. , Zanivan Sara , Blomme Arnaud , Leung Hing Y.
Published: April 2023

Figures S1-S2-S3 + Suppl. Fig. legends + Suppl. Methods
Supplementary Figure 1 from Bladder Tumor Subtype Commitment Occurs in Carcinoma In Situ Driven by Key Signaling Pathways Including ECM Remodeling
Authors: Wullweber Adrian , Strick Reiner , Lange Fabienne , Sikic Danijel , Taubert Helge , Wach Sven , Wullich Bernd , Bertz Simone , Weyerer Veronika , Stoehr Robert , Breyer Johannes , Burger Maximilian , Hartmann Arndt , Strissel Pamela L. , Eckstein Markus
Published: April 2023

Comparison of RNAseq and Nanostring-based subtyping in MIBCs from the CCC-EMN cohort with available RNAseq data. The 22 pairs of MIBC/CIS and the WBHM specimen were chosen from this pool of tumors. Subtyping is based on the 21 genes containing MDACC panel (Supplementary Table 2). RNAseq data were generated from FFPE tissues using QuantSeq kits (Lexogen) using 500 ng input RNA. The QuantSeq libraries were sequenced on an Illumina Hiseq platform and generated data were further processed according to the GRCh38, and further normalized. Inter-gene correlations range from 0.78-0.97 (Spearman rank correlations). Comparison of subtype assignment based on average linkage unsupervised hierarchical clustering shows a 100% overlap with no discordant classifications occurring, thus indicating that Nanostring is suitable for subtyping bladder cancer samples compared to RNAseq.
Supplementary Data 5 from SLFN5 Regulates LAT1-Mediated mTOR Activation in Castration-Resistant Prostate Cancer
Authors: Martinez Rafael S. , Salji Mark J. , Rushworth Linda , Ntala Chara , Rodriguez Blanco Giovanny , Hedley Ann , Clark William , Peixoto Paul , Hervouet Eric , Renaude Elodie , Kung Sonia H.Y. , Galbraith Laura C.A. , Nixon Colin , Lilla Sergio , MacKay Gillian M. , Fazli Ladan , Gaughan Luke , Sumpton David , Gleave Martin E. , Zanivan Sara , Blomme Arnaud , Leung Hing Y.
Published: April 2023

ATF4_binding sites
Figure S9 from Pharmacological Disruption of the Notch1 Transcriptional Complex Inhibits Tumor Growth by Selectively Targeting Cancer Stem Cells
Authors: Alvarez-Trotta Annamil , Guerrant William , Astudillo Luisana , Lahiry Mohini , Diluvio Giulia , Shersher Elena , Kaneku Hugo , Robbins David J. , Orton Darren , Capobianco Anthony J.
Published: April 2023

Sorting of OE33 cells by ALDH expression
Data from Mapping Mechanical Properties of the Tumor Microenvironment by Laser Speckle Rheological Microscopy
Authors: Hajjarian Zeinab , Brachtel Elena F. , Tshikudi Diane M. , Nadkarni Seemantini K.
Published: April 2023

Abstract
Altered mechanical properties of the tumor matrix have emerged as both the cause and consequence of breast carcinogenesis. Increased tumor stiffness has traditionally provided a viable metric to screen for malignancies via palpation or imaging. Previous studies have demonstrated that the microscale mechanical properties of the cell substrate influence tumor proliferation and invasive migration in vitro. Nevertheless, the association of the mechanical microenvironment with clinical hallmarks of aggressiveness in human breast tumors, including histopathological subtype, grade, receptor expression status, and lymph node involvement is poorly understood. This is largely due to the lack of tools for mapping tumor viscoelastic properties in clinical specimens with high spatial resolution over a large field of view (FoV). Here we introduce laser Speckle rHEologicAl micRoscopy (SHEAR) that for the first time enables mapping the magnitude viscoelastic or shear modulus, |G*(x,y,ω)|, over a range of frequencies (ω = 1–250 rad/second) in excised tumors within minutes with a spatial resolution of approximately 50 μm, over multiple cm2 FoV. Application of SHEAR in a cohort of 251 breast cancer specimens from 148 patients demonstrated that |G*(x,y,ω)| (ω = 2π rad/second) closely corresponds with histological features of the tumor, and that the spatial gradient of the shear modulus, |∇|G*(x,y,ω)||, is elevated at the tumor invasive front. Multivariate analyses established that the metrics, (|G* |) and (|∇|G* ||), measured by SHEAR are associated with prognosis. These findings implicate the viscoelastic properties of the tumor microenvironment in breast cancer prognosis and likely pave the path for identifying new modifiable targets for treatment.
Significance:
Laser speckle rheological microscopy establishes the links between microscale heterogeneities of viscoelasticity and histopathological subtype, tumor grade, receptor expression, as well as lymph node status in breast carcinoma.
Data from Plastin3 Is a Novel Marker for Circulating Tumor Cells Undergoing the Epithelial–Mesenchymal Transition and Is Associated with Colorectal Cancer Prognosis
Authors: Yokobori Takehiko , Iinuma Hisae , Shimamura Teppei , Imoto Seiya , Sugimachi Keishi , Ishii Hideshi , Iwatsuki Masaaki , Ota Daisuke , Ohkuma Masahisa , Iwaya Takeshi , Nishida Naohiro , Kogo Ryunosuke , Sudo Tomoya , Tanaka Fumiaki , Shibata Kohei , Toh Hiroyuki , Sato Tetsuya , Barnard Graham F. , Fukagawa Takeo , Yamamoto Seiichiro , Nakanishi Hayao , Sasaki Shin , Miyano Satoru , Watanabe Toshiaki , Kuwano Hiroyuki , Mimori Koshi , Pantel Klaus , Mori Masaki
Published: April 2023

Abstract
Circulating tumor cells (CTC) in blood have attracted attention both as potential seeds for metastasis and as biomarkers. However, most CTC detection systems might miss epithelial–mesenchymal transition (EMT)-induced metastatic cells because detection is based on epithelial markers. First, to discover novel markers capable of detecting CTCs in which EMT has not been repressed, microarray analysis of 132 colorectal cancers (CRC) from Japanese patients was conducted, and 2,969 genes were detected that were overexpressed relative to normal colon mucosa. From the detected genes, we selected those that were overexpressed CRC with distant metastasis. Then, we analyzed the CRC metastasis-specific genes (n = 22) to determine whether they were expressed in normal circulation. As a result, PLS3 was discovered as a CTC marker that was expressed in metastatic CRC cells but not in normal circulation. Using fluorescent immunocytochemistry, we validated that PLS3 was expressed in EMT-induced CTC in peripheral blood from patients with CRC with distant metastasis. PLS3-expressing cells were detected in the peripheral blood of approximately one-third of an independent set of 711 Japanese patients with CRC. Multivariate analysis showed that PLS3-positive CTC was independently associated with prognosis in the training set (n = 381) and the validation set [n = 330; HR = 2.17; 95% confidence interval (CI) = 1.38–3.40 and HR = 3.92; 95% CI = 2.27–6.85]. The association between PLS3-positive CTC and prognosis was particularly strong in patients with Dukes B (HR = 4.07; 95% CI = 1.50–11.57) and Dukes C (HR = 2.57; 95% CI = 1.42–4.63). PLS3 is a novel marker for metastatic CRC cells, and it possesses significant prognostic value. Cancer Res; 73(7); 2059–69. ©2012 AACR.
Data from Overcoming Limitations in Nanoparticle Drug Delivery: Triggered, Intravascular Release to Improve Drug Penetration into Tumors
Authors: Manzoor Ashley A. , Lindner Lars H. , Landon Chelsea D. , Park Ji-Young , Simnick Andrew J. , Dreher Matthew R. , Das Shiva , Hanna Gabi , Park Won , Chilkoti Ashutosh , Koning Gerben A. , ten Hagen Timo L.M. , Needham David , Dewhirst Mark W.
Published: April 2023

Abstract
Traditionally, the goal of nanoparticle-based chemotherapy has been to decrease normal tissue toxicity by improving drug specificity to tumors. The enhanced permeability and retention effect can permit passive accumulation into tumor interstitium. However, suboptimal delivery is achieved with most nanoparticles because of heterogeneities of vascular permeability, which limits nanoparticle penetration. Furthermore, slow drug release limits bioavailability. We developed a fast drug-releasing liposome triggered by local heat that has already shown substantial antitumor efficacy and is in human trials. Here, we show that thermally sensitive liposomes (Dox-TSL) release doxorubicin inside the tumor vasculature. Real-time confocal imaging of doxorubicin delivery to murine tumors in window chambers and histologic analysis of flank tumors illustrates that intravascular drug release increases free drug in the interstitial space. This increases both the time that tumor cells are exposed to maximum drug levels and the drug penetration distance, compared with free drug or traditional pegylated liposomes. These improvements in drug bioavailability establish a new paradigm in drug delivery: rapidly triggered drug release in the tumor bloodstream. Cancer Res; 72(21); 5566–75. ©2012 AACR.
Data from Therapeutic Efficacy of Bifunctional siRNA Combining TGF-β1 Silencing with RIG-I Activation in Pancreatic Cancer
Authors: Ellermeier Jonathan , Wei Jiwu , Duewell Peter , Hoves Sabine , Stieg Mareike R. , Adunka Tina , Noerenberg Daniel , Anders Hans-Joachim , Mayr Doris , Poeck Hendrik , Hartmann Gunther , Endres Stefan , Schnurr Max
Published: April 2023

Abstract
Deregulated TGF-β signaling in pancreatic cancer promotes tumor growth, invasion, metastasis, and a potent immunosuppressive network. A strategy for disrupting this tumor-promoting pathway is silencing TGF-β by siRNA. By introducing a triphosphate group at the 5′ end of siRNA (ppp-siRNA), gene silencing can be combined with immune activation via the cytosolic helicase retinoic acid-inducible gene I (RIG-I), a ubiquitously expressed receptor recognizing viral RNA. We validated RIG-I as a therapeutic target by showing that activation of RIG-I in pancreatic carcinoma cells induced IRF-3 phosphorylation, production of type I IFN, the chemokine CXCL10, as well as caspase-9–mediated tumor cell apoptosis. Next, we generated a bifunctional ppp-siRNA that combines RIG-I activation with gene silencing of TGF-β1 (ppp-TGF-β) and studied its therapeutic efficacy in the orthotopic Panc02 mouse model of pancreatic cancer. Intravenous injection of ppp-TGF-β reduced systemic and tumor-associated TGF-β levels. In addition, it induced high levels of type I IFN and CXCL10 in serum and tumor tissue, systemic immune cell activation, and profound tumor cell apoptosis in vivo. Treatment of mice with established tumors with ppp-TGF-β significantly prolonged survival as compared with ppp-RNA or TGF-β siRNA alone. Furthermore, we observed the recruitment of activated CD8+ T cells to the tumor and a reduced frequency of CD11b+ Gr-1+ myeloid cells. Therapeutic efficacy was dependent on CD8+ T cells, whereas natural killer cells were dispensable. In conclusion, combing TGF-β gene silencing with RIG-I signaling confers potent antitumor efficacy against pancreatic cancer by breaking tumor-induced CD8+ T cell suppression. Cancer Res; 73(6); 1709–20. ©2013 AACR.
Data from Evolutionary Approaches to Prolong Progression-Free Survival in Breast Cancer
Authors: Silva Ariosto S. , Kam Yoonseok , Khin Zayar P. , Minton Susan E. , Gillies Robert J. , Gatenby Robert A.
Published: April 2023

Abstract
Many cancers adapt to chemotherapeutic agents by upregulating membrane efflux pumps that export drugs from the cytoplasm, but this response comes at an energetic cost. In breast cancer patients, expression of these pumps is low in tumors before therapy but increases after treatment. While the evolution of therapeutic resistance is virtually inevitable, proliferation of resistant clones is not, suggesting strategies of adaptive therapy. Chemoresistant cells must consume excess resources to maintain resistance mechanisms, so adaptive therapy strategies explicitly aim to maintain a stable population of therapy-sensitive cells to suppress growth of resistant phenotypes through intratumoral competition. We used computational models parameterized by in vitro experiments to illustrate the efficacy of such approaches. Here, we show that low doses of verapamil and 2-deoxyglucose, to accentuate the cost of resistance and to decrease energy production, respectively, could suppress the proliferation of drug-resistant clones in vivo. Compared with standard high-dose-density treatment, the novel treatment we developed achieved a 2-fold to 10-fold increase in time to progression in tumor models. Our findings challenge the existing flawed paradigm of maximum dose treatment, a strategy that inevitably produces drug resistance that can be avoided by the adaptive therapy strategies we describe. Cancer Res; 72(24); 6362–70. ©2012 AACR.
Data from Polyploidization of Murine Mesenchymal Cells Is Associated with Suppression of the Long Noncoding RNA H19 and Reduced Tumorigenicity
Authors: Shoshani Ofer , Massalha Hassan , Shani Nir , Kagan Sivan , Ravid Orly , Madar Shalom , Trakhtenbrot Luba , Leshkowitz Dena , Rechavi Gideon , Zipori Dov
Published: April 2023

Abstract
Mesenchymal stromal cells (MSC) are used extensively in clinical trials; however, the possibility that MSCs have a potential for malignant transformation was raised. We examined the genomic stability versus the tumor-forming capacity of multiple mouse MSCs. Murine MSCs have been shown to be less stable and more prone to malignant transformation than their human counterparts. A large series of independently isolated MSC populations exhibited low tumorigenic potential under syngeneic conditions, which increased in immunocompromised animals. Unexpectedly, higher ploidy correlated with reduced tumor-forming capacity. Furthermore, in both cultured MSCs and primary hepatocytes, polyploidization was associated with a dramatic decrease in the expression of the long noncoding RNA H19. Direct knockdown of H19 expression in diploid cells resulted in acquisition of polyploid cell traits. Moreover, artificial tetraploidization of diploid cancer cells led to a reduction of H19 levels, as well as to an attenuation of the tumorigenic potential. Polyploidy might therefore serve as a protective mechanism aimed at reducing malignant transformation through the involvement of the H19 regulatory long noncoding RNA. Cancer Res; 72(24); 6403–13. ©2012 AACR.