bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure 5 from Gastric Adenocarcinomas Express the Glycosphingolipid Gb3/CD77: Targeting of Gastric Cancer Cells with Shiga Toxin B-Subunit
Authors: Geyer Philipp Emanuel , Maak Matthias , Nitsche Ulrich , Perl Markus , Novotny Alexander , Slotta-Huspenina Julia , Dransart Estelle , Holtorf Anne , Johannes Ludger , Janssen Klaus-Peter
Published: April 2023

Control for specificity of intracellular uptake with control (BSA-Cy3)
Supplementary Figure S5 from Interference with the HSF1/HSP70/BAG3 Pathway Primes Glioma Cells to Matrix Detachment and BH3 Mimetic–Induced Apoptosis
Authors: Antonietti Patrick , Linder Benedikt , Hehlgans Stephanie , Mildenberger Iris C. , Burger Michael C. , Fulda Simone , Steinbach Joachim P. , Gessler Florian , Rödel Franz , Mittelbronn Michel , Kögel Donat
Published: April 2023

Apoptosis sensitization after interference with BAG3 occurs independent of survivin and the NF-κB pathway.
Supplementary Figure S3 from Interference with the HSF1/HSP70/BAG3 Pathway Primes Glioma Cells to Matrix Detachment and BH3 Mimetic–Induced Apoptosis
Authors: Antonietti Patrick , Linder Benedikt , Hehlgans Stephanie , Mildenberger Iris C. , Burger Michael C. , Fulda Simone , Steinbach Joachim P. , Gessler Florian , Rödel Franz , Mittelbronn Michel , Kögel Donat
Published: April 2023

Reduced clonogenic survival of U343 BAG3KD cells treated with AT-101.
Supplementary Figure Legends from Vulnerability of Small-Cell Lung Cancer to Apoptosis Induced by the Combination of BET Bromodomain Proteins and BCL2 Inhibitors
Authors: Lam Lloyd T. , Lin Xiaoyu , Faivre Emily J. , Yang Ziping , Huang Xiaoli , Wilcox Denise M. , Bellin Richard J. , Jin Sha , Tahir Stephen K. , Mitten Michael , Magoc Terry , Bhathena Anahita , Kati Warren M. , Albert Daniel H. , Shen Yu , Uziel Tamar
Published: April 2023

Supplemental figure legends
Supplementary Tables 1 and 2 from An HRE-Binding Py-Im Polyamide Impairs Hypoxic Signaling in Tumors
Authors: Szablowski Jerzy O. , Raskatov Jevgenij A. , Dervan Peter B.
Published: April 2023

Supplementary Table 1: Primers used in RT-qPCR experiments; Supplementary Table 2: Percent changes in transcript expression of U251 tumors dosed with 1.
Supplementary Figure S2 from Metformin Synergizes with BCL-XL/BCL-2 Inhibitor ABT-263 to Induce Apoptosis Specifically in p53-Defective Cancer Cells
Authors: Li Xinzhe , Li Bo , Ni Zhenhong , Zhou Peng , Wang Bin , He Jintao , Xiong Haojun , Yang Fan , Wu Yaran , Lyu Xilin , Zhang Yan , Zeng Yijun , Lian Jiqin , He Fengtian
Published: April 2023

Combination of metformin with ABT-263 had no significant growth inhibition effect on HEK-293 cells.
Figure S5 from Vessel-Targeted Chemophototherapy with Cationic Porphyrin-Phospholipid Liposomes
Authors: Luo Dandan , Geng Jumin , Li Nasi , Carter Kevin A. , Shao Shuai , Atilla-Gokcumen G. Ekin , Lovell Jonathan F.
Published: April 2023

Localization of cationic liposomes in tumor microvessels. Intact vessels were stained with intravenous Hoechst's dye administration prior to sacrifice. A scale bar of 100 µm is shown.
Table S1 from Insulin-Mediated Signaling Facilitates Resistance to PDGFR Inhibition in Proneural hPDGFB-Driven Gliomas
Authors: Almiron Bonnin Damian A. , Ran Cong , Havrda Matthew C. , Liu Huan , Hitoshi Yasuyuki , Zhang Zhonghua , Cheng Chao , Ung Matthew , Israel Mark A.
Published: April 2023

Doxycycline-sensitive and doxycycline-resistant TSCs.
Supplementary Figure Legends from Insulin-Mediated Signaling Facilitates Resistance to PDGFR Inhibition in Proneural hPDGFB-Driven Gliomas
Authors: Almiron Bonnin Damian A. , Ran Cong , Havrda Matthew C. , Liu Huan , Hitoshi Yasuyuki , Zhang Zhonghua , Cheng Chao , Ung Matthew , Israel Mark A.
Published: April 2023

Supplementary Figure Legends
Supplementary Figures 1-4. Supplementary Table 1 from Trifluoperazine, a Well-Known Antipsychotic, Inhibits Glioblastoma Invasion by Binding to Calmodulin and Disinhibiting Calcium Release Channel IP3R
Authors: Kang Seokmin , Hong Jinpyo , Lee Jung Moo , Moon Hyo Eun , Jeon Borami , Choi Jungil , Yoon Nal Ae , Paek Sun Ha , Roh Eun Joo , Lee C. Justin , Kang Sang Soo
Published: April 2023

Supplementary Figure S1. TFP induces morphological change of U87MG cells, and cell death; Supplementary Figure S2. Body weight is not changed during TFP injection in in vivo glioblastoma skin xenograft model; Supplementary Figure S3. IP3R1, 2 and 3 shRNA knockdown test by western blot and functional knockdown test using GBL 28 primary glioblastoma cells; Supplementary Figure S4. TFP reduces cell viability of several GBL cells;Supplementary Table S1. IP3R 1, 2, 3 and CaM shRNA sequences
Figure S2 from Insulin-Mediated Signaling Facilitates Resistance to PDGFR Inhibition in Proneural hPDGFB-Driven Gliomas
Authors: Almiron Bonnin Damian A. , Ran Cong , Havrda Matthew C. , Liu Huan , Hitoshi Yasuyuki , Zhang Zhonghua , Cheng Chao , Ung Matthew , Israel Mark A.
Published: April 2023

Relative hPDGFB mRNA levels determined by RT-PCR in doxycycline-sensitive and resistant TSCs cultured in the presence or absence of doxycycline.
Supplementary Figure S3 from Afatinib against Esophageal or Head-and-Neck Squamous Cell Carcinoma: Significance of Activating Oncogenic HER4 Mutations in HNSCC
Authors: Nakamura Yu , Togashi Yosuke , Nakahara Hirokazu , Tomida Shuta , Banno Eri , Terashima Masato , Hayashi Hidetoshi , de Velasco Marco A. , Sakai Kazuko , Fujita Yoshihiko , Okegawa Takatsugu , Nutahara Kikuo , Hamada Suguru , Nishio Kazuto
Published: April 2023

Influence of HER4-knockdown on afatinib sensitivities. The sensitivity of the SAS cell line to afatinib was significantly weakened by HER4-knockdown, while that in the OSC-19 cell line was minimally changed.
Supplementary Figure Legends from Decitabine Priming Enhances Mucin 1 Inhibition Mediated Disruption of Redox Homeostasis in Cutaneous T-Cell Lymphoma
Authors: Jain Salvia , Washington Abigail , Leaf Rebecca Karp , Bhargava Parul , Clark Rachael A. , Kupper Thomas S. , Stroopinsky Dina , Pyzer Athalia , Cole Leandra , Nahas Myrna , Apel Arie , Rosenblatt Jacalyn , Arnason Jon , Kufe Donald , Avigan David
Published: April 2023

All supplementary figure legends are presented here
Supplementary Figure S1 from Afatinib against Esophageal or Head-and-Neck Squamous Cell Carcinoma: Significance of Activating Oncogenic HER4 Mutations in HNSCC
Authors: Nakamura Yu , Togashi Yosuke , Nakahara Hirokazu , Tomida Shuta , Banno Eri , Terashima Masato , Hayashi Hidetoshi , de Velasco Marco A. , Sakai Kazuko , Fujita Yoshihiko , Okegawa Takatsugu , Nutahara Kikuo , Hamada Suguru , Nishio Kazuto
Published: April 2023

Influence of the HRE4 G1109C mutation on other HER family members. The phosphorylation levels of other HER family members (EGFR, HER2, and HER3) in the HEK293/HER4 G1109C and HEK293/HER4 E317K cell lines were elevated compared with those in the HEK293/HER4 WT cell line, which were similar to the phosphorylation of HER4. β-actin was used as an internal control.
Figure S5 from Decitabine Priming Enhances Mucin 1 Inhibition Mediated Disruption of Redox Homeostasis in Cutaneous T-Cell Lymphoma
Authors: Jain Salvia , Washington Abigail , Leaf Rebecca Karp , Bhargava Parul , Clark Rachael A. , Kupper Thomas S. , Stroopinsky Dina , Pyzer Athalia , Cole Leandra , Nahas Myrna , Apel Arie , Rosenblatt Jacalyn , Arnason Jon , Kufe Donald , Avigan David
Published: April 2023

Decitabine and GO-203 combination increases Nox4 and Duox2 mRNA levels
Supplementary Figure 1 from Development of a Novel Antibody–Drug Conjugate for the Potential Treatment of Ovarian, Lung, and Renal Cell Carcinoma Expressing TIM-1
Authors: Thomas Lawrence J. , Vitale Laura , O'Neill Thomas , Dolnick Ree Y. , Wallace Paul K. , Minderman Hans , Gergel Lauren E. , Forsberg Eric M. , Boyer James M. , Storey James R. , Pilsmaker Catherine D. , Hammond Russell A. , Widger Jenifer , Sundarapandiyan Karuna , Crocker Andrea , Marsh Henry C. , Keler Tibor
Published: April 2023

Structure of CDX-014. CDX-014 is a fully human monoclonal antibody specific for TIM-1 covalently linked to the enzyme-cleavable valine-citrulline-p-aminobenzylcarbamate-monomethylauristatin-E (vcMMAE). The drug to antibody (DAR) molar ratio was approximately 4.5.
Figure S4 from Decitabine Priming Enhances Mucin 1 Inhibition Mediated Disruption of Redox Homeostasis in Cutaneous T-Cell Lymphoma
Authors: Jain Salvia , Washington Abigail , Leaf Rebecca Karp , Bhargava Parul , Clark Rachael A. , Kupper Thomas S. , Stroopinsky Dina , Pyzer Athalia , Cole Leandra , Nahas Myrna , Apel Arie , Rosenblatt Jacalyn , Arnason Jon , Kufe Donald , Avigan David
Published: April 2023

A schema of the various CpG locations that were analyzed in the Duox2 promoter of the gene is presented
Supplementary Materials and Methods; Supplementary Tables S1-S3; and Supplementary Figures S1-S3 from Repositioning Dopamine D2 Receptor Agonist Bromocriptine to Enhance Docetaxel Chemotherapy and Treat Bone Metastatic Prostate Cancer
Authors: Yang Yang , Mamouni Kenza , Li Xin , Chen Yanhua , Kavuri Sravan , Du Yuhong , Fu Haian , Kucuk Omer , Wu Daqing
Published: April 2023

Supplementary Materials and Methods; Supplementary Tables (Table S1. Antibodies used in Western blotting, immunoprecipitation and IHC studies. Table S2. Sequences of primers used for real-time PCR analysis. Table S3. Combination index (CI) of bromocriptine and docetaxel treatment in C4-2 cells); Supplementary Figures ( Figure S1. Quantitative PCR analysis of mRNA expression of AR and survivin in C4-2 cells treated with varying concentrations of bromocriptine (24 h). Figure S2. Body weights of athymic nude mice bearing C4-2-Luc tumors and treated with the vehicle control, docetaxel, bromocriptine and the combination. *: p < 0.05. Figure S3. Western blot analysis of p-AR (Ser650) expression in C4-2 cells treated with bromocriptine for varying times)
Supplementary Text from Combined Inhibition of NEDD8-Activating Enzyme and mTOR Suppresses NF2 Loss–Driven Tumorigenesis
Authors: Cooper Jonathan , Xu Qingwen , Zhou Lu , Pavlovic Milica , Ojeda Virginia , Moulick Kamalika , de Stanchina Elisa , Poirier John T. , Zauderer Marjorie , Rudin Charles M. , Karajannis Matthias A. , Hanemann C. Oliver , Giancotti Filippo G.
Published: April 2023

Supplementary Materials and Methods, Supplementary Figure Legends, Supplementary Table 1, Supplementary References
Supplementary Figure S2 from Selective Inhibition of ADAM28 Suppresses Lung Carcinoma Cell Growth and Metastasis
Authors: Mochizuki Satsuki , Shimoda Masayuki , Abe Hitoshi , Miyamae Yuka , Kuramoto Junko , Aramaki-Hattori Noriko , Ishii Ken , Ueno Hideki , Miyakoshi Akira , Kojoh Kanehisa , Okada Yasunori
Published: April 2023

Supplementary Figure S2 shows results of kinetic analysis of the binding interaction between antibody 211-14 and ADAM28s peptide by Biacore system.
Supplementary Figure S1 from Selective Inhibition of ADAM28 Suppresses Lung Carcinoma Cell Growth and Metastasis
Authors: Mochizuki Satsuki , Shimoda Masayuki , Abe Hitoshi , Miyamae Yuka , Kuramoto Junko , Aramaki-Hattori Noriko , Ishii Ken , Ueno Hideki , Miyakoshi Akira , Kojoh Kanehisa , Okada Yasunori
Published: April 2023

Supplementary Figure S1 shows data of immunoblotting analysis of antibody 211-12 and antibody 211-14 in mouse tissue homogenates.
Figure S2 from Discovery of a Highly Selective NAMPT Inhibitor That Demonstrates Robust Efficacy and Improved Retinal Toxicity with Nicotinic Acid Coadministration
Authors: Zhao Genshi , Green Colin F. , Hui Yu-Hua , Prieto Lourdes , Shepard Robert , Dong Sucai , Wang Tao , Tan Bo , Gong Xueqian , Kays Lisa , Johnson Robert L. , Wu Wenjuan , Bhattachar Shobha , Del Prado Miriam , Gillig James R. , Fernandez Maria-Carmen , Roth Ken D. , Buchanan Sean , Kuo Ming-Shang , Geeganage Sandaruwan , Burkholder Timothy P.
Published: April 2023

Addition of NA rescued the inhibitory activity of LSN3154567.
Supp. Figures from Exportin 1 Inhibition Induces Nerve Growth Factor Receptor Expression to Inhibit the NF-κB Pathway in Preclinical Models of Pediatric High-Grade Glioma
Authors: DeSisto John A. , Flannery Patrick , Lemma Rakeb , Pathak Amrita , Mestnik Shelby , Philips Natalie , Bales Natalie J. , Kashyap Trinayan , Moroze Erin , Venkataraman Sujatha , Kung Andrew L. , Carter Bruce D. , Landesman Yosef , Vibhakar Rajeev , Green Adam L.
Published: April 2023

Supplemental Figures 1 - 6
Table S1 from Preclinical Activity of Abemaciclib Alone or in Combination with Antimitotic and Targeted Therapies in Breast Cancer
Authors: O'Brien Neil , Conklin Dylan , Beckmann Richard , Luo Tong , Chau Kevin , Thomas Josh , Mc Nulty Ann , Marchal Christophe , Kalous Ondrej , von Euw Erika , Hurvitz Sara , Mockbee Colleen , Slamon Dennis J.
Published: April 2023

Whole exome sequencing analysis of a panel of 44 breast cancer cell lines, enriched for somatic alterations with functional consequence in cancer
Supplementary Materials and Methods and Figure Legends from Preclinical Activity of Abemaciclib Alone or in Combination with Antimitotic and Targeted Therapies in Breast Cancer
Authors: O'Brien Neil , Conklin Dylan , Beckmann Richard , Luo Tong , Chau Kevin , Thomas Josh , Mc Nulty Ann , Marchal Christophe , Kalous Ondrej , von Euw Erika , Hurvitz Sara , Mockbee Colleen , Slamon Dennis J.
Published: April 2023

Supplementary Data, Supplementary Procedures and Supplementary Figure Legends
Figure S1 from Anti-S100A4 Antibody Therapy Is Efficient in Treating Aggressive Prostate Cancer and Reversing Immunosuppression: Serum and Biopsy S100A4 as a Clinical Predictor
Authors: Ganaie Arsheed A. , Mansini Adrian P. , Hussain Tabish , Rao Arpit , Siddique Hifzur R. , Shabaneh Ashraf , Ferrari Marina G. , Murugan Paari , Klingelhöfer Jörg , Wang Jinhua , Ambartsumian Noona , Warlick Christopher A. , Konety Badrinath R. , Saleem Mohammad
Published: April 2023

(Ai) Box-plot shows the association of copy number of S100A4 gene to Gleason Score of prostate tumors in CaP patients. The graph was generated from the analysis of TCGA clinical data using Oncomine platform. (Aii) Image shows the detection of S100A4 protein in human serum as assessed by immune-Slot blot analyses. The immunoblot data shown here is a representative of experiments conducted three independent times. (Bi) The gel image shows the cloning of s100A4 in pET28a vector using NdeI and Xho I site. (Bii) Immunoblot image shows the detection of S100A4 for different elution fractions of S100A4 protein overexpressed in BL21DE3. (C) Histogram shows the effect of mab6B12 therapy on the rate of proliferation of human CaP cells as assessed by 3[H]thymidine uptake assay. (D) Graph shows the Osterix expression in Bone-mets in CaP patients from Met-CaP Provisional Project 2019 Clinical study as analyzed by cBioportal platform. (E) Heat map shows the gene expression profile of CD4+ T cells Co-cultured with TRAMP-C2 cells in presence and absence of S100A4 protein and mab6B12 antibody.
Supplementary Figures from Dual Mechanisms of Novel CD73-Targeted Antibody and Antibody–Drug Conjugate in Inhibiting Lung Tumor Growth and Promoting Antitumor Immune-Effector Function
Authors: Jin Rui , Liu Liang , Xing Yun , Meng Tao , Ma Lanping , Pei Jinpeng , Cong Ying , Zhang Xuesai , Ren Zhiqiang , Wang Xin , Shen Jingkang , Yu Ker
Published: April 2023

Supplementary Figures and Tables
SupplementaryTable 1 from An Antibody-Tumor Necrosis Factor Fusion Protein that Synergizes with Oxaliplatin for Treatment of Colorectal Cancer
Authors: Bajic Davor , Chester Kerry , Neri Dario
Published: April 2023

Supplementary Table 1 in Word format
Figure S2 from Paternally Expressed Gene 10 (PEG10) Promotes Growth, Invasion, and Survival of Bladder Cancer
Authors: Kawai Yoshihisa , Imada Kenjiro , Akamatsu Shusuke , Zhang Fan , Seiler Roland , Hayashi Tetsutaro , Leong Jeffrey , Beraldi Eliana , Saxena Neetu , Kretschmer Alexander , Oo Htoo Zarni , Contreras-Sanz Alberto , Matsuyama Hideyasu , Lin Dong , Fazli Ladan , Collins Colin C. , Wyatt Alexander W. , Black Peter C. , Gleave Martin E.
Published: April 2023

PEG10 levels are elevated in chemotherapy-resistant cells.
Figure S1 from Paternally Expressed Gene 10 (PEG10) Promotes Growth, Invasion, and Survival of Bladder Cancer
Authors: Kawai Yoshihisa , Imada Kenjiro , Akamatsu Shusuke , Zhang Fan , Seiler Roland , Hayashi Tetsutaro , Leong Jeffrey , Beraldi Eliana , Saxena Neetu , Kretschmer Alexander , Oo Htoo Zarni , Contreras-Sanz Alberto , Matsuyama Hideyasu , Lin Dong , Fazli Ladan , Collins Colin C. , Wyatt Alexander W. , Black Peter C. , Gleave Martin E.
Published: April 2023

PEG10 associates with NE markers in bladder cancer.
Supplementary Figure 5 from High Tumor Mutational Burden Correlates with Longer Survival in Immunotherapy-Naïve Patients with Diverse Cancers
Authors: Riviere Paul , Goodman Aaron M. , Okamura Ryosuke , Barkauskas Donald A. , Whitchurch Theresa J. , Lee Suzanna , Khalid Noor , Collier Rachel , Mareboina Manvita , Frampton Garrett M. , Fabrizio David , Sharabi Andrew B. , Kato Shumei , Kurzrock Razelle
Published: April 2023

Supplementary Figure 5
Figure S5 from Characterization of 7A5: A Human CD137 (4-1BB) Receptor Binding Monoclonal Antibody with Differential Agonist Properties That Promotes Antitumor Immunity
Authors: Kotanides Helen , Sattler Rose Marie , Lebron Maria B. , Carpenito Carmine , Shen Juqun , Li Jingxing , Surguladze David , Haidar Jaafar N. , Burns Colleen , Shen Leyi , Inigo Ivan , Pennello Anthony L. , Forest Amelie , Chen Xinlei , Chin Darin , Sonyi Andreas , Topper Michael , Boucher Lauren , Sharma Prachi , Zhang Yiwei , Burtrum Douglas , Novosiadly Ruslan D. , Ludwig Dale L. , Plowman Gregory D. , Kalos Michael
Published: April 2023

Figure S5 shows body weight graphs of in vivo models
Supplementary Data from ASR490, a Small Molecule, Overrides Aberrant Expression of Notch1 in Colorectal Cancer
Authors: Tyagi Ashish , Chandrasekaran Balaji , Kolluru Venkatesh , Baby Becca V. , Sripathi Cibi A. , Ankem Murali K. , Ramisetti Srinivasa R. , Chirasani Venkat R. , Dokholyan Nikolay V. , Sharma Arun K. , Damodaran Chendil
Published: April 2023

Supplementary Files
Supplementary Figures from The Discovery of SWI/SNF Chromatin Remodeling Activity as a Novel and Targetable Dependency in Uveal Melanoma
Authors: Rago Florencia , Elliott GiNell , Li Ailing , Sprouffske Kathleen , Kerr Grainne , Desplat Aurore , Abramowski Dorothee , Chen Julie T. , Farsidjani Ali , Xiang Kay X. , Bushold Geoffrey , Feng Yun , Shirley Matthew D. , Bric Anka , Vattay Anthony , Möbitz Henrik , Nakajima Katsumasa , Adair Christopher D. , Mathieu Simon , Ntaganda Rukundo , Smith Troy , Papillon Julien P.N. , Kauffmann Audrey , Ruddy David A. , Bhang Hyo-eun C. , Castelletti Deborah , Jagani Zainab
Published: April 2023

Supplementary Figure S1 shows additional shRNA knockdown data in uveal melanoma cell lines. Supplementary Figure S2 shows additional dual BRG1/BRM knockdown data and BRG1 rescue data. Supplementary Figure S3 shows basal SWI/SNF subunit expression, additional caspase activity and viability data in compound treated and shRNA knockdown cell lines, and SWI/SNF mutations in uveal melanoma cells lines. Supplementary Figure S4 shows additional MITF knockdown data and further RNA-Seq and ATAC-Seq data set analyses. Supplementary Figure S5 shows target gene modulation by compound treatment in uveal melanoma cell lines and additional MITF overexpression rescue data. Supplementary Figure S6 shows genomic location of primers used in ChIP-qPCR experiment.
Table S2 from Identification of Predictive ERBB Mutations by Leveraging Publicly Available Cell Line Databases
Authors: Koivu Marika K.A. , Chakroborty Deepankar , Tamirat Mahlet Z. , Johnson Mark S. , Kurppa Kari J. , Elenius Klaus
Published: April 2023

Table S2 shows all ERBB mutation and drug sensitivity data of ERBB mutant cell lines.
Supplementary Video S1 from Development of a MUC16-Targeted Near-Infrared Fluorescent Antibody Conjugate for Intraoperative Imaging of Pancreatic Cancer
Authors: Olson Madeline T. , Wojtynek Nicholas E. , Talmon Geoffrey A. , Caffrey Thomas C. , Radhakrishnan Prakash , Ly Quan P. , Hollingsworth Michael A. , Mohs Aaron M.
Published: April 2023

Supplementary Video S1 shows surgical resection with AR9.6-IRDye800.
Figure S3 from The Indenoisoquinoline LMP517: A Novel Antitumor Agent Targeting both TOP1 and TOP2
Authors: Marzi Laetitia , Sun Yilun , Huang Shar-yin N. , James Amy , Difilippantonio Simone , Pommier Yves
Published: April 2023

The fluoroindenoisoquinoline LMP517 induces DNA damage in all phases of the cell cycle
Supplementary Figure 3 from The Role of Specific ATP-Binding Cassette Transporters in the Acquired Resistance to Pyrrolobenzodiazepine Dimer–Containing Antibody–Drug Conjugates
Authors: Corbett Simon , Huang Shiran , Zammarchi Francesca , Howard Philip W. , van Berkel Patrick H. , Hartley John A.
Published: April 2023

Supplementary Figure 3. Reversing the acquired PBD or PBD-based ADC resistance with ABC drug transporter inhibitors. A. Continuous exposure in vitro growth inhibition of Karpas-299 wt, ADC and PBD resistant cell lines with ADCT-301 and 10 nM Lovastatin. B. Continuous exposure in vitro growth inhibition of NCI-N87 wt, ADC and PBD resistant cell lines with ADCT-502 and 5 µM Lovastatin. Each data point represents the average of at least 3 biological repeats with +/- SD error bars.
Supplementary Data from Optimal Strategy and Benefit of Pulsed Therapy Depend On Tumor Heterogeneity and Aggressiveness at Time of Treatment Initiation
Authors: Mathur Deepti , Taylor Bradford P. , Chatila Walid K. , Scher Howard I. , Schultz Nikolaus , Razavi Pedram , Xavier Joao B.
Published: April 2023

Supplementary Data from Optimal Strategy and Benefit of Pulsed Therapy Depend On Tumor Heterogeneity and Aggressiveness at Time of Treatment Initiation
Figure S2 from Hormone-Dependent Prostate Cancers are Dependent on Rac Signaling for Growth and Survival
Authors: Goka Erik T. , Mesa Lopez Dayrelis T. , Lippman Marc E.
Published: April 2023

Supplementary Figure 2. Cellular proliferation assay of VCaP cells expressing either control shRNA (shNSC) or two independent HACE1 shRNAs (shHACE1 1 and shHACE1 2).
Supplementary Figure from Covalent ERα Antagonist H3B-6545 Demonstrates Encouraging Preclinical Activity in Therapy-Resistant Breast Cancer
Authors: Furman Craig , Puyang Xiaoling , Zhang Zhaojie , Wu Zhenhua J. , Banka Deepti , Aithal Kiran B. , Albacker Lee A. , Hao Ming-Hong , Irwin Sean , Kim Amy , Montesion Meagan , Moriarty Alyssa D. , Murugesan Karthikeyan , Nguyen Tuong-Vi , Rimkunas Victoria , Sahmoud Tarek , Wick Michael J. , Yao Shihua , Zhang Xun , Zeng Hao , Vaillancourt Frédéric H. , Bolduc David M. , Larsen Nicholas , Zheng Guo Zhu , Prajapati Sudeep , Zhu Ping , Korpal Manav
Published: April 2023

Supplementary Figure from Covalent ERα Antagonist H3B-6545 Demonstrates Encouraging Preclinical Activity in Therapy-Resistant Breast Cancer
Supplementary Table 3 from Phosphoproteomics Identifies PI3K Inhibitor–selective Adaptive Responses in Pancreatic Cancer Cell Therapy and Resistance
Authors: Cintas Célia , Douche Thibault , Dantes Zahra , Mouton-Barbosa Emmanuelle , Bousquet Marie-Pierre , Cayron Coralie , Therville Nicole , Pont Frédéric , Ramos-Delgado Fernanda , Guyon Camille , Garmy-Susini Barbara , Cappello Paola , Burlet-Schiltz Odile , Hirsch Emilio , Gomez-Brouchet Anne , Thibault Benoît , Reichert Maximilian , Guillermet-Guibert Julie
Published: April 2023

Supplementary Table 3 contains the location of isoform selective phosphorylations in the protein.
Figure S1 from STimulator of INterferon Genes Agonism Accelerates Antitumor Activity in Poorly Immunogenic Tumors
Authors: Perera Samanthi A. , Kopinja Johnny E. , Ma Yanhong , Muise Eric S. , Laskey Jason , Chakravarthy Kalyan , Chen Yiping , Cui Long , Presland Jeremy , Sathe Manjiri , Javaid Sarah , Minnihan Ellen C. , Ferguson Heidi M. , Piesvaux Jennifer , Pan Bo-Sheng , Zhao Shuxia , Sharma Sharad K. , Woo Hyun Chong , Pucci Vincenzo , Knemeyer Ian , Cemerski Saso , Cumming Jared , Trotter B. Wesley , Tse Archie , Khilnani Anuradha , Ranganath Sheila , Long Brian J. , Bennett David Jonathan , Addona George H.
Published: April 2023

Supplemental Figure 1: Day 10 tumor volume of injected (InjT) and noninjected (Non-injT) tumors following intratumoral (IT) injection with MSA-1
Table S3 from Rapid Resistance of FGFR-driven Gastric Cancers to Regorafenib and Targeted FGFR Inhibitors can be Overcome by Parallel Inhibition of MEK
Authors: Lau David K. , Luk Ian Y. , Jenkins Laura J. , Martin Andrew , Williams David S. , Schoffer Kael L. , Chionh Fiona , Buchert Michael , Sjoquist Katrin , Boussioutas Alex , Hayes Sarah A. , Ernst Matthias , Weickhardt Andrew J. , Pavlakis Nick , Tebbutt Niall C. , Mariadason John M.
Published: April 2023

Supplementary Table 3
Table S1 from Rapid Resistance of FGFR-driven Gastric Cancers to Regorafenib and Targeted FGFR Inhibitors can be Overcome by Parallel Inhibition of MEK
Authors: Lau David K. , Luk Ian Y. , Jenkins Laura J. , Martin Andrew , Williams David S. , Schoffer Kael L. , Chionh Fiona , Buchert Michael , Sjoquist Katrin , Boussioutas Alex , Hayes Sarah A. , Ernst Matthias , Weickhardt Andrew J. , Pavlakis Nick , Tebbutt Niall C. , Mariadason John M.
Published: April 2023

Supplementary Table 1
Figure S2 from Rapid Resistance of FGFR-driven Gastric Cancers to Regorafenib and Targeted FGFR Inhibitors can be Overcome by Parallel Inhibition of MEK
Authors: Lau David K. , Luk Ian Y. , Jenkins Laura J. , Martin Andrew , Williams David S. , Schoffer Kael L. , Chionh Fiona , Buchert Michael , Sjoquist Katrin , Boussioutas Alex , Hayes Sarah A. , Ernst Matthias , Weickhardt Andrew J. , Pavlakis Nick , Tebbutt Niall C. , Mariadason John M.
Published: April 2023

Supplementary Figure 2
Supplementary Figure S5 from NAP1051, a Lipoxin A4 Biomimetic Analogue, Demonstrates Antitumor Activity Against the Tumor Microenvironment
Authors: Dong Tiange , Dave Priyal , Yoo EunJeong , Ebright Brandon , Ahluwalia Kabir , Zhou Eugene , Asante Isaac , Salimova Malika , Pei Hua , Lin Tracey , Mead Andrew , Li Zeyang , Humayun Mark , Petasis Nicos A. , Epstein Alan L. , Louie Stan G.
Published: April 2023

Figure S5 shows secondary antibody controls for immunofluorescence staining and representative images of the CitH3 staining and PAD4/Ly6G staining.
Supplementary Figure S2 from NAP1051, a Lipoxin A4 Biomimetic Analogue, Demonstrates Antitumor Activity Against the Tumor Microenvironment
Authors: Dong Tiange , Dave Priyal , Yoo EunJeong , Ebright Brandon , Ahluwalia Kabir , Zhou Eugene , Asante Isaac , Salimova Malika , Pei Hua , Lin Tracey , Mead Andrew , Li Zeyang , Humayun Mark , Petasis Nicos A. , Epstein Alan L. , Louie Stan G.
Published: April 2023

Figure S2 shows the direct cytotoxicity of NAP1051 and the relative tumor volume of the HCT116 model.
Supplementary Figures from Identification and Characterization of IMD-0354 as a Glutamine Carrier Protein Inhibitor in Melanoma
Authors: Feng Yongmei , Pathria Gaurav , Heynen-Genel Susanne , Jackson Michael , James Brian , Yin Jun , Scott David A. , Ronai Ze'ev A.
Published: April 2023

Supp fig 1-8: Figure S1. Inhibition of SLC1A5 Expression in A431 cells. Figure S2. Screen and Validation of Hits. Figure S3. IMD-0354 inhibited Glutamine Uptake. Figure S4. IMD-0354 Suppresses Glutamine Uptake Independent of IKK-NF- B Signaling Suppression. Figure S5. Profiles of IMD-0354-Treated A375 Cells Matched with Small-Molecule Inhibitors and Melanoma Subtypes. Figure S6. Expression of Glutamine Deprivation-Related Genes. Figure S7. Inhibition of Melanoma Growth with IMD-0354 in combination with LDHA or GLS1 Inhibitors. Figure S8. Immunohistochemistry Staining of Xenograft Tumor Samples.
Supplementary Figures 1-6 from ONC212 is a Novel Mitocan Acting Synergistically with Glycolysis Inhibition in Pancreatic Cancer
Authors: Ferrarini Isacco , Louie Anna , Zhou Lanlan , El-Deiry Wafik S.
Published: April 2023

Supplementary Fig S1. ClpXP expression in normal fibroblasts and pancreatic cancer cells. Supplementary Fig S2. ClpP knockdown affects cell viability and partially restores the expression of ONC212-downregulated OXPHOS proteins. Supplementary Fig S3. ONC212 triggers AMPK activation. Supplementary Fig S4. Glycolysis upregulation in BxPC3 and PANC-1 cells. Supplementary Fig S5. In vivo activity of ONC212 plus 2-DG. Supplementary Fig S6. Tolerability of ONC212 plus 2-DG.
Supplementary Data S3 from SAM-Competitive PRMT5 Inhibitor PF-06939999 Demonstrates Antitumor Activity in Splicing Dysregulated NSCLC with Decreased Liability of Drug Resistance
Authors: Jensen-Pergakes Kristen , Tatlock John , Maegley Karen A. , McAlpine Indrawan J. , McTigue Michele , Xie Tao , Dillon Christopher P. , Wang Yuli , Yamazaki Shinji , Spiegel Noah , Shi Manli , Nemeth Amy , Miller Natalie , Hendrickson Eleanore , Lam Hieu , Sherrill John , Chung Chi-Yeh , McMillan Elizabeth A. , Bryant Shannon Karlicek , Palde Prakash , Braganza John , Brooun Alexei , Deng Ya-Li , Goshtasbi Vesta , Kephart Susan E. , Kumpf Robert A. , Liu Wei , Patman Ryan L. , Rui Eugene , Scales Stephanie , Tran-Dube Michelle , Wang Fen , Wythes Martin , Paul Thomas A.
Published: April 2023

ElasticNet Tables for PF-06939999 in NSCLC
Supplementary Data from Noninvasive Imaging of CD4+ T Cells in Humanized Mice
Authors: Nagle Veronica L. , Hertz Charli Ann J. , Henry Kelly E. , Graham Maya S. , Campos Carl , Pillarsetty Nagavarakishore , Schietinger Andrea , Mellinghoff Ingo K. , Lewis Jason S.
Published: April 2023

Supplementary Data from Noninvasive Imaging of CD4+ T Cells in Humanized Mice
Supplementary Data from Resistance Profile and Structural Modeling of Next-Generation ROS1 Tyrosine Kinase Inhibitors
Authors: Keddy Clare , Shinde Pushkar , Jones Kristen , Kaech Stefanie , Somwar Romel , Shinde Ujwal , Davare Monika A.
Published: April 2023

Supplementary Data
Raw data
Supplementary Figure from Low-Dose JAK3 Inhibition Improves Antitumor T-Cell Immunity and Immunotherapy Efficacy
Authors: Dammeijer Floris , van Gulijk Mandy , Klaase Larissa , van Nimwegen Menno , Bouzid Rachid , Hoogenboom Robin , Joosse Maria E. , Hendriks Rudi W. , van Hall Thorbald , Aerts Joachim G.
Published: April 2023

Supplementary Figure from Low-Dose JAK3 Inhibition Improves Antitumor T-Cell Immunity and Immunotherapy Efficacy
Supplementary figure FS3 from Neoadjuvant Radiation Therapy and Surgery Improves Metastasis-Free Survival over Surgery Alone in a Primary Mouse Model of Soft Tissue Sarcoma
Authors: Patel Rutulkumar , Mowery Yvonne M. , Qi Yi , Bassil Alex M. , Holbrook Matt , Xu Eric S. , Hong Cierra S. , Himes Jonathon E. , Williams Nerissa T. , Everitt Jeffrey , Ma Yan , Luo Lixia , Selitsky Sara R. , Modliszewski Jennifer L. , Gao Junheng , Jung Sin-Ho , Kirsch David G. , Badea Cristian T.
Published: April 2023

Long-term survival of an autochthonous p53/MCA mouse model in immunocompetent 129/SvJae wild-type mice induced by CRISPR/Cas9
Supplementary Table from Inhibition of Integrin αVβ3 Signaling Improves the Antineoplastic Effect of Bexarotene in Cutaneous T-Cell Lymphoma
Authors: Cayrol Florencia , Revuelta Maria V. , Debernardi Mercedes , Paulazo Alejandra , Phillip Jude M. , Zamponi Nahuel , Sterle Helena , Díaz Flaqué María C. , Magro Cynthia , Marullo Rossella , Mulvey Erin , Ruan Jia , Cremaschi Graciela A. , Cerchietti Leandro
Published: April 2023

Supplementary Table from Inhibition of Integrin αVβ3 Signaling Improves the Antineoplastic Effect of Bexarotene in Cutaneous T-Cell Lymphoma
Figure FS8 from Tinengotinib (TT-00420), a Novel Spectrum-Selective Small-Molecule Kinase Inhibitor, Is Highly Active Against Triple-Negative Breast Cancer
Authors: Peng Peng , Qiang Xiaoyan , Li Guoyu , Li Lin , Ni Shumao , Yu Qi , Sourd Laura , Marangoni Elisabetta , Hu Chao , Wang Dong , Wu Di , Wu Frank
Published: April 2023

Tinengotinib is well tolerated through the in vivo studies and body weight curves are shown.
Figure FS1 from Tinengotinib (TT-00420), a Novel Spectrum-Selective Small-Molecule Kinase Inhibitor, Is Highly Active Against Triple-Negative Breast Cancer
Authors: Peng Peng , Qiang Xiaoyan , Li Guoyu , Li Lin , Ni Shumao , Yu Qi , Sourd Laura , Marangoni Elisabetta , Hu Chao , Wang Dong , Wu Di , Wu Frank
Published: April 2023

Tinengotinib highly inhibits TNBC cell by a panel of specific mechanisms.
Supplementary Data from Nonclinical Efficacy and Safety of CX-2029, an Anti-CD71 Probody–Drug Conjugate
Authors: Singh Shweta , Serwer Laura , DuPage Amy , Elkins Kristi , Chauhan Niharika , Ravn Matthew , Buchanan Fritz , Wang Leyu , Krimm Michael , Wong Ken , Sagert Jason , Tipton Kimberly , Moore Stephen J. , Huang Yuanhui , Jang Andrew , Ureno Eric , Miller Adam , Patrick Sarah , Duvur Shanti , Liu Shouchun , Vasiljeva Olga , Li Yingchun , Henriques Tracy , Badagnani Ilaria , Jeffries Shawn , Schleyer Siew , Leanna Rob , Krebber Claus , Viswanathan Sridhar , Desnoyers Luc , Terrett Jonathan , Belvin Marcia , Morgan-Lappe Susan , Kavanaugh W. Michael , Richardson Jennifer
Published: April 2023

Supplementary Data from Nonclinical Efficacy and Safety of CX-2029, an Anti-CD71 Probody–Drug Conjugate
Supplementary Figure from A Novel Enolase-1 Antibody Targets Multiple Interacting Players in the Tumor Microenvironment of Advanced Prostate Cancer
Authors: Chen Mao-Lin , Yuan Ta-Tung , Chuang Chi-Fen , Huang Yung-Tsang , Chung I-Che , Huang Wei-Ching
Published: April 2023

Supplementary Figure from A Novel Enolase-1 Antibody Targets Multiple Interacting Players in the Tumor Microenvironment of Advanced Prostate Cancer
Supplementary Data from Retinoblastoma Expression and Targeting by CDK4/6 Inhibitors in Small Cell Lung Cancer
Authors: Wildey Gary , Shay Ashley M. , McColl Karen S. , Yoon Suzy , Shatat Mohammad A. , Perwez Ahmad , Spainhower Kyle B. , Kresak Adam M. , Lipka MaryBeth , Yang Michael , Behtaj Mohadese , Fu Pingfu , Alahmadi Asrar , Mneimneh Wadad , Abbas Ata , Dowlati Afshin
Published: April 2023

Supplementary Tables
Supplementary Table from Anticancer Activity of ST101, A Novel Antagonist of CCAAT/Enhancer Binding Protein β
Authors: Darvishi Emad , Ghamsari Lila , Leong Siok F. , Ramirez Ricardo , Koester Mark , Gallagher Erin , Yu Miao , Mason Jody M. , Merutka Gene , Kappel Barry J. , Rotolo Jim A.
Published: April 2023

Supplementary Table from Anticancer Activity of ST101, A Novel Antagonist of CCAAT/Enhancer Binding Protein β
Supplementary Table S2 from ER-851, a Novel Selective Inhibitor of AXL, Overcomes Resistance to Antimitotic Drugs
Authors: Tsukamoto Shuntaro , Sugi Naoko Hata , Nishibata Kyoko , Nakazawa Youya , Ito Daisuke , Fukushima Sayo , Nakagawa Takayuki , Ichikawa Kenji , Kato Yu , Kakiuchi Dai , Goto Aya , Itoh-Yagi Machiko , Aota Tomoki , Inoue Satoshi , Yamane Yoshinobu , Murai Norio , Azuma Hiroshi , Nagao Satoshi , Sasai Ken , Akagi Tsuyoshi , Imai Toshio , Matsui Junji , Matsushima Tomohiro
Published: April 2023

Supplementary Table S2
Supplementary Figures and Tables from Preclinical Characterization of XL092, a Novel Receptor Tyrosine Kinase Inhibitor of MET, VEGFR2, AXL, and MER
Authors: Hsu Jeff , Chong Colin , Serrill Jeffrey , Goon Levina , Balayan Joan , Johnson Eric N. , Lorenzana Grachelle , Wu Sharon , Leong Kevin G. , Yun Theodore J. , Wang Yong , Jiang Faming , Bannen Lynne , Lamb Peter , Xu Wei , Yu Peiwen
Published: April 2023

Supplementary Figures and Tables with adjoining Legends
Abstract 1355: Evolution of immune tumor microenvironment (TME) from esophageal dysplasia to esophageal squamous cell carcinoma (ESCC)
Authors: Guo Jhe-Cyuan , Hsu Chia-Lang , Huang Yen-Lin , Wu Tsung-Che , Hsu Chih-Hung
Published: April 2023

Background: Previous studies have revealed esophageal dysplasia, a precancerous lesion of ESCC, harbors similar mutations and markers of genomic instability as ESCC does. This observation suggests that other factors such as evasion of immune surveillance may be involved in the progression of esophageal dysplasia to ESCC. The study aimed to identify the key differences in the immune TME between esophageal dysplasia and ESCC.

Methods: Patients with a history of diagnosing with esophageal dysplasia for at least two times prior to the diagnosis of ESCC were enrolled. Formalin-fixed paraffin-embedded tissues from esophageal dysplasia diagnosed more than 6 months prior to the diagnosis of ESCC (denoted as dysplasia-1), esophageal dysplasia diagnosed within 6 months prior to the diagnosis of ESCC (denoted as dysplasia-2), and ESCC were retrieved. Transcriptomic data of esophageal dysplasia and ESCC tissues were generated by NanoString nCounter platform with Human PanCancer Immune Profiling panel, and were further analyzed for the expression levels of infiltrating immune cells by CIBERSORT.

Results Six ESCC patients (M:F= 6:0), with median age of 56.6 (range: 43.3-79.1) years, were enrolled. The median time between the diagnosis of dysplasia-1 and that of ESCC was 10.2 months (range 6.0-38.6) and the median time between the diagnosis of dysplasia-2 and that of ESCC was 2.3 months (range 0.0-6.0). The analysis of immune cell signatures defined by NanoString platform revealed that multiple cell types were significantly increased in ESCC compared with dysplasia-1 (mast cell, macrophage, CD8 T cell, B cell and dendritic cell, all P < 0.05) and in ESCC compared with dysplasia-2 (macrophage, mast cell, dendritic cell, B cell, T cell, CD4 T cell, regulatory T cell, cytotoxic T cell, NK CD56dim cell, and T helper cell, all P < 0.05). There was no significant difference in the immune cell signatures between dysplasia-1 and dysplasia-2. Immune cells classified by CIBERSORT showed an increase of M2 macrophage and a decrease of M1/M2 ratio in ESCC compared with dysplasia-1 or dysplasia-2 (both P < 0.05).

Conclusions: Our data, showing an increase of M2 macrophage in TME of ESCC compared with its precancerous esophageal dysplasia, suggest that evolution of immune TME may play a role in the progression of esophageal dysplasia to ESCC. (Funded by MOST 108-2314-B-002-076-MY3, MOST 109-2314-B-002-231-, MOHW 111-TDU-B-221-114006, NTUCCS-110-10, and NTUCCS-111-05)

Citation Format: Jhe-Cyuan Guo, Chia-Lang Hsu, Yen-Lin Huang, Tsung-Che Wu, Chih-Hung Hsu. Evolution of immune tumor microenvironment (TME) from esophageal dysplasia to esophageal squamous cell carcinoma (ESCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1355.
Abstract 1451: Cognition-mediated transcriptomic signature associated with androgen deprivation therapy in prostate cancer
Authors: Verma Shiv Shankar , Shankar Eswar , Singh Vaibhav , Krishna Vijay , Gupta Sanjay
Published: April 2023

Androgen deprivation therapy (ADT) is the mainstay treatment for non-metastatic and metastatic hormone-sensitive prostate cancer. Long-term ADT treatment results in adverse side-effects in patients including depression, memory loss, cognitive decline, and dementia. We aimed to identify critical molecules that could provide link between brain-related changes and pathological mechanisms responsible for cognitive decline in prostate cancer patients on ADT protocol. For these studies, gene expression data (GSE150807 and GSE151083) of human prostate cancer cells exposed to enzalutamide emulating ADT protocol was used to identify differential expression of genes at the transcript level. RNA sequencing analysis identified 9409 and 7757 differentially expressed genes (DEGs) in LNCaP and C4-2B enzalutamide exposed cells at p-value < 0.0005 and FDR< 0.05. In both cell lines, neuronal receptor signaling pathway was significantly overrepresented at 0.05 FDR-adjusted p-value (q-value). The genes associated with neuronal receptor signaling pathway belong to the ligand-gated ion channel and G-protein coupled receptors. Validation studies using brain glial cells treated with enzalutamide showed significant upregulation (p-value 0.001) of GABRB1, GABRA3, GABBR2 (GABA receptors/ligand-gated ion channel), BDNF (brain-derived neurotrophic factor), IFNB1 (interferon beta 1), NR3C1 (nuclear receptor subfamily 3 group c member/glucocorticoid receptor), ATGR1 (type-1 angiotensin II receptor), GRIN1 (glutamate ionotropic receptor NMDA type submit 1/ligated-gated ion channel), GRIN2D (glutamate ionotropic receptor NMDA type submit 2D/ligated-gated ion channel). In brain neuronal cells, enzalutamide exposure resulted in increased expression of NR3C1 whereas GABA/ligand-gated ion channel and others were downregulated and/or statistically non-significant. Further analysis using DisGenET (cytoscape) highlighted ATGR1, GABRB1, GRIN1, GRIN2D, and NR3C1 association with neuronal diseases including cognition disorder, forgetfulness, depressive mood, and others. The results of our study provide the first proof of evidence linking cognitive decline, depression, memory loss, and other neurological disorder more likely to develop in prostate cancer patients undergoing long-term androgen deprivation therapy.

Citation Format: Shiv Shankar Verma, Eswar Shankar, Vaibhav Singh, Vijay Krishna, Sanjay Gupta. Cognition-mediated transcriptomic signature associated with androgen deprivation therapy in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1451.
Abstract 1459: Nanocage delivered engineered destabilized 3UTR ARE of cMYC inhibits triple negative breast cancer growth and metastasis in vivo by targeting cMYC and downregulating STAT5A5B
Authors: Awah Chidiebere U. , Mun Joo Sun , Boylu Baris , Paragodaarachchi Alooka , Ochu Chika , Zhang Junfei , Mastui Hiroshi , Ogunwobi Olorunseun
Published: April 2023

c-MYC is a master transcription factor overexpressed in more than 70% of human cancers including breast cancers (TNBC), lung cancers, brain tumors, prostate cancers, lymphomas, pediatrics cancers, pancreatic cancers, colorectal cancers, and ovarian cancers. Yet there is no clinically approved drug that directly targets it. The lack of direct clinically approved inhibitors of c-MYC is a significant biological and clinical question that needs urgent attention, especially in the context of aggressive cancers such as MYC driven triple negative breast cancer. In the USA, TNBC accounts for 10.34% of breast cancers, in China the rate is at 14%, and in African Americans the rate is 40%. We engineered the stable polyU sequences on the 3’UTR of c-MYC into unstable forms and specifically destabilized and degraded c-MYC transcript and protein and controlled primary tumor and metastasis in vivo. We developed three c-MYC destabilizing constructs that were effective in TNBC. They specifically destabilized c-MYC transcript, degraded c-MYC protein and the transcription factors STAT5A/B with increased expression of active caspase 3/7 leading to cancer cell death. In vivo, we delivered nanocage complexed with the MYC destabilizing constructs into TNBC mice bearing tumor and achieved reduction of primary tumor volume by 60-80%, 80% reduction in secondary tumor metastasis and very significant survival outcome (p<0.0001). Mechanistically, the destabilization of c-MYC degraded c-MYC and its super enhancer interacting partner, STAT5A/B, in primary tumors and metastatic tumors. Taken together, we have developed a novel therapy for TNBC and uncovered c-MYC super enhancer STAT5A/B interaction as the target

Citation Format: Chidiebere U. Awah, Joo Sun Mun, Baris Boylu, Alooka Paragodaarachchi, Chika Ochu, Junfei Zhang, Hiroshi Mastui, Olorunseun Ogunwobi. Nanocage delivered engineered destabilized 3UTR ARE of cMYC inhibits triple negative breast cancer growth and metastasis in vivo by targeting cMYC and downregulating STAT5A5B [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1459.
Abstract 1524: Effect of a chimeric antibody targeting CXCL1 in bladder cancer
Authors: Kim Nari , Furuya Hideki , Murakami Kaoru , Rosser Charles J.
Published: April 2023

Introduction and Objectives: Chemokine (C-X-C motif) ligand 1 (CXCL1) plays a crucial role in tumor initiation, promotion, and progression in bladder cancer (BCa) development. Previously, we reported on a monoclonal murine antibody (HL2401) towards CXCL1 which was capable of inhibiting growth in both in vitro and in vivo models. Herein, we have developed a chimeric anti-CXCL1 antibody, which is partially human (cHL2401). In this study, we tested the effect of cHL2401 on tumor growth and angiogenesis in both in vitro and in vivo models.

Methods: We developed chimeric anti-human CXCL1 antibody (cHL2401), and then tested for the following: ability to inhibit in vitro angiogenesis, ability to inhibit cellular proliferation, and tumor growth in cell line-derived xenograft model.

Results: We first performed the tube formation assay to evaluate the effect on angiogenesis. cHL2401 significantly inhibited tube formation in HUVEC, suggesting that cHL2401 inhibits angiogenesis. The inhibitory effect was better than bevacizumab (FDA-approved drug, anti-VEGF antibody). Next, we performed the cell proliferation assay to evaluate the effect on tumor growth in vitro. cHL2401 significantly inhibited the cell proliferation of T24 and 253J cell lines highly expressing CXCL1. Finally, we tested the effect of cHL2401 on tumor growth in an animal model. Both 8 and 32 mg/kg (i.p., twice weekly) significantly inhibited the tumor growth. The final volume of control tumor was 224.5 mm3, while those of 8 and 32 mg/kg were 102.9 and 93.08, respectively.

Conclusions: The chimeric antibody, cHL2401 contains human constant domains and mouse variable domains of mouse HL2401 antibody. Species-matched chimeric antibodies reduce anti-species immune responses in animal models. In this study, we tested whether the effects of mouse HL2401 that we have reported were induced by neutralizing CXCL1 by antibody. Taken together, the results suggest that neutralizing CXCL1 by antibody could be a promising therapeutic agent in BCa.

Citation Format: Nari Kim, Hideki Furuya, Kaoru Murakami, Charles J. Rosser. Effect of a chimeric antibody targeting CXCL1 in bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1524.