bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure 5 from Identification of Small-Molecule Inhibitors of the Colorectal Cancer Oncogene Krüppel-like Factor 5 Expression by Ultrahigh-Throughput Screening
Authors: Bialkowska Agnieszka B. , Crisp Melissa , Bannister Thomas , He Yuanjun , Chowdhury Sarwat , Schürer Stephan , Chase Peter , Spicer Timothy , Madoux Franck , Tian Chenlu , Hodder Peter , Zaharevitz Daniel , Yang Vincent W.
Published: April 2023

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Supplementary Table 3 from Knockdown of Oncogenic KRAS in Non–Small Cell Lung Cancers Suppresses Tumor Growth and Sensitizes Tumor Cells to Targeted Therapy
Authors: Sunaga Noriaki , Shames David S. , Girard Luc , Peyton Michael , Larsen Jill E. , Imai Hisao , Soh Junichi , Sato Mitsuo , Yanagitani Noriko , Kaira Kyoichi , Xie Yang , Gazdar Adi F. , Mori Masatomo , Minna John D.
Published: April 2023

Supplementary Table 3 from Knockdown of Oncogenic KRAS in Non–Small Cell Lung Cancers Suppresses Tumor Growth and Sensitizes Tumor Cells to Targeted Therapy
Supplementary Table 1 from Inhibition of TGF-β Enhances the In Vivo Antitumor Efficacy of EGF Receptor–Targeted Therapy
Authors: Bedi Atul , Chang Xiaofei , Noonan Kimberly , Pham Vui , Bedi Rishi , Fertig Elana J. , Considine Michael , Califano Joseph A. , Borrello Ivan , Chung Christine H. , Sidransky David , Ravi Rajani
Published: April 2023

PDF file - 256K, Clinical characteristics of patients with HNSCC
Supplementary Data 5 from Direct Role of Adiponectin and Adiponectin Receptors in Endometrial Cancer: In Vitro and Ex Vivo Studies in Humans
Authors: Moon Hyun-Seuk , Chamberland John P. , Aronis Konstantinos , Tseleni-Balafouta Sofia , Mantzoros Christos S.
Published: April 2023

PDF file - 74K, The cell culture and introduction of AdipRs siRNA were performed as described in detail in the "Methods" section. The cells were treated with adiponectin (20 �g/ml) for 24 hr (A) and for 30 min (B). The proliferation assay and Western Blotting were performed as described in detail in the "Methods" section. All data were analyzed using one-way ANOVA followed by post-hoc test for multiple comparisons. Values are means (n=3) � SD. Means with different letters are significantly different, p<0.05.
Supplementary Figure 3 from An Integrated Chemical Biology Approach Identifies Specific Vulnerability of Ewing's Sarcoma to Combined Inhibition of Aurora Kinases A and B
Authors: Winter Georg E. , Rix Uwe , Lissat Andrej , Stukalov Alexey , Müllner Markus K. , Bennett Keiryn L. , Colinge Jacques , Nijman Sebastian M. , Kubicek Stefan , Kovar Heinrich , Kontny Udo , Superti-Furga Giulio
Published: April 2023

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Supplementary Figure Legends 1-3 from Overexpression of Mitotic Centromere–Associated Kinesin Stimulates Microtubule Detachment and Confers Resistance to Paclitaxel
Authors: Ganguly Anutosh , Yang Hailing , Cabral Fernando
Published: April 2023

Supplementary Figure Legends 1-3 from Overexpression of Mitotic Centromere–Associated Kinesin Stimulates Microtubule Detachment and Confers Resistance to Paclitaxel
Supplementary Table 1 from High-Risk Endometrial Carcinoma Profiling Identifies TGF-β1 as a Key Factor in the Initiation of Tumor Invasion
Authors: Muinelo-Romay Laura , Colas Eva , Barbazan Jorge , Alonso-Alconada Lorena , Alonso-Nocelo Marta , Bouso Marta , Curiel Teresa , Cueva Juan , Anido Urbano , Forteza Jeronimo , Gil-Moreno Antonio , Reventos Jaume , Lopez-Lopez Rafael , Abal Miguel
Published: April 2023

Supplementary Table 1 from High-Risk Endometrial Carcinoma Profiling Identifies TGF-β1 as a Key Factor in the Initiation of Tumor Invasion
Supplementary Video 6 from Determinants of Mitotic Catastrophe on Abrogation of the G2 DNA Damage Checkpoint by UCN-01
Authors: On Kin Fan , Chen Yue , Tang Ma Hoi , Chow Jeremy P.H. , Poon Randy Y.C.
Published: April 2023

Supplementary Video 6 from Determinants of Mitotic Catastrophe on Abrogation of the G2 DNA Damage Checkpoint by UCN-01
Supplementary Figures 1 - 7, Table 1 from Impact of Tumor Vascularity on Responsiveness to Antiangiogenesis in a Prostate Cancer Stem Cell-Derived Tumor Model
Authors: Zhang Kexiong , Waxman David J.
Published: April 2023

PDF file - 6346K, Supplemental Figure 1. Immunohistochemical staining of PC3/2G7 and PC3 tumors using anti-human-specific CD31 antibody. ; Supplemental Figure 2. Staining of paraffin-embedded PC3/2G7 and PC3 tumor sections, with and without 12 days axitinib treatment, as shown in Fig. 2. ; Supplemental Figure 3. Cell growth inhibition assay. ; Supplemental Figure 4. Effects of daily sorafenib treatment on growth of PC3 and PC3/2G7 tumors. ; Supplemental Figure 5. Impact of DC101 treatment on growth of PC3 and PC3/2G7 tumors. ; Supplemental Figure 6. Expression of VEGFC (A) and interleukin-8 (IL8) (B) in PC3/2G7 and PC3 tumors, determined by qPCR. ; Supplemental Figure 7. Images showing increased CD31 immunostained microvessel density in PC3/2G7 tumors after 58 days axitinib treatment, as in Fig. 6D, right. ; Supplemental Table 1. Primer sequences used for quantitative real-time PCR (qPCR) analysis.
Supplementary Figure Legend from RETRACTED: Combining PARP-1 Inhibition and Radiation in Ewing Sarcoma Results in Lethal DNA Damage
Authors: Lee Hae-June , Yoon Changhwan , Schmidt Benjamin , Park Do Joong , Zhang Alexia Y. , Erkizan Hayriye V. , Toretsky Jeffrey A. , Kirsch David G. , Yoon Sam S.
Published: April 2023

PDF - 51KB
Supplementary Figure 1 from Induction of Endoplasmic Reticulum Stress by Sorafenib and Activation of NF-κB by Lestaurtinib as a Novel Resistance Mechanism in Hodgkin Lymphoma Cell Lines
Authors: Holz Meike Stefanie , Janning Angela , Renné Christoph , Gattenlöhner Stefan , Spieker Tilmann , Bräuninger Andreas
Published: April 2023

PDF file - 28K, Supplementary Figure S1. Effect of sorafenib treatment on GADD34 and GADD153 mRNA expression in different cell lines.
Supplementary Materials and Methods from A Monoclonal Antibody against Human Notch1 Ligand–Binding Domain Depletes Subpopulation of Putative Breast Cancer Stem–like Cells
Authors: Sharma Ankur , Paranjape Anurag N. , Rangarajan Annapoorni , Dighe Rajan R.
Published: April 2023

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Supplementary Figure 3 from A Monoclonal Antibody against Human Notch1 Ligand–Binding Domain Depletes Subpopulation of Putative Breast Cancer Stem–like Cells
Authors: Sharma Ankur , Paranjape Anurag N. , Rangarajan Annapoorni , Dighe Rajan R.
Published: April 2023

PDF file - 1.9MB
Supplmentary Figures 1-3 from ALK Inhibitor PF02341066 (Crizotinib) Increases Sensitivity to Radiation in Non–Small Cell Lung Cancer Expressing EML4-ALK
Authors: Sun Yunguang , Nowak Kamila A. , Zaorsky Nicholas G. , Winchester Chia-Lin , Dalal Kunal , Giacalone Nicholas J. , Liu Ningbo , Werner-Wasik Maria , Wasik Mariusz A. , Dicker Adam P. , Lu Bo
Published: April 2023

PDF File - 501K, PF02341066 is well tolerated in female athymic nude mice.
Supplementary Table 3 from A High-Throughput Panel for Identifying Clinically Relevant Mutation Profiles in Melanoma
Authors: Dutton-Regester Ken , Irwin Darryl , Hunt Priscilla , Aoude Lauren G. , Tembe Varsha , Pupo Gulietta M. , Lanagan Cathy , Carter Candace D. , O'Connor Linda , O'Rourke Michael , Scolyer Richard A. , Mann Graham J. , Schmidt Christopher W. , Herington Adrian , Hayward Nicholas K.
Published: April 2023

PDF file - 381K, Results of Melanoma Specific Mutation Panel.
Supplementary Figure Legends 1-2 from Targeting Interleukin-4 Receptor α with Hybrid Peptide for Effective Cancer Therapy
Authors: Yang Liying , Horibe Tomohisa , Kohno Masayuki , Haramoto Mari , Ohara Koji , Puri Raj K. , Kawakami Koji
Published: April 2023

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Supplementary Figure 1 from Targeting Interleukin-4 Receptor α with Hybrid Peptide for Effective Cancer Therapy
Authors: Yang Liying , Horibe Tomohisa , Kohno Masayuki , Haramoto Mari , Ohara Koji , Puri Raj K. , Kawakami Koji
Published: April 2023

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Supplementary Figure 1 from Inducible Silencing of Protein Kinase D3 Inhibits Secretion of Tumor-Promoting Factors in Prostate Cancer
Authors: LaValle Courtney R. , Zhang Liyong , Xu Shuping , Eiseman Julie L. , Wang Q. Jane
Published: April 2023

PDF file, 170KB, Knockdown of PKD3 by multiple siRNAs and its effect on cell survival.
Supplementary Figure 2 from Therapeutic Mechanism and Efficacy of the Antibody–Drug Conjugate BAY 79-4620 Targeting Human Carbonic Anhydrase 9
Authors: Petrul Heike M. , Schatz Christoph A. , Kopitz Charlotte C. , Adnane Lila , McCabe Timothy J. , Trail Pamela , Ha Sha , Chang Yong S. , Voznesensky Andrei , Ranges Gerald , Tamburini Paul P.
Published: April 2023

PDF file - 65K, Targeted tubulin disruption by BAY 79-4620.
Supplementary Figure Legend from Reversing Effect of Ring Finger Protein 43 Inhibition on Malignant Phenotypes of human Hepatocellular Carcinoma
Authors: Xing Chunyang , Zhou Wuhua , Ding Songming , Xie Haiyang , Zhang Wu , Yang Zhe , Wei Bajin , Chen Kangjie , Su Rong , Cheng Jun , Zheng Shusen , Zhou Lin
Published: April 2023

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Supplementary Figure 1 from Reversing Effect of Ring Finger Protein 43 Inhibition on Malignant Phenotypes of human Hepatocellular Carcinoma
Authors: Xing Chunyang , Zhou Wuhua , Ding Songming , Xie Haiyang , Zhang Wu , Yang Zhe , Wei Bajin , Chen Kangjie , Su Rong , Cheng Jun , Zheng Shusen , Zhou Lin
Published: April 2023

PDF file - 16459K, RNF43 expression in human Hepatocellular carcinoma tissues. Representative images (magnification � 100) of RNF43 stained tumors with (A) more than 75% positive tumor cells (+2), (B) 5-75% positive tumor cells (+1), and (C) less than 5% RNF43-positive tumor cells (0). (D) Adjacent noncancerous liver tissues.
Supplementary Tables 1 and 2 from Attenuation of Argininosuccinate Lyase Inhibits Cancer Growth via Cyclin A2 and Nitric Oxide
Authors: Huang Hau-Lun , Hsu Hui-Ping , Shieh Shu-Chu , Chang Yung-Sheng , Chen Wei-Ching , Cho Chien-Yu , Teng Chiao-Fang , Su Ih-Jen , Hung Wen-Chun , Lai Ming-Derg
Published: April 2023

PDF - 50KB, Supplementary Table S1: Primers for RT-PCR, and Supplementary Table S2: Antibody list
Supplementary Figure 3 from CBS9106-Induced CRM1 Degradation Is Mediated by Cullin Ring Ligase Activity and the Neddylation Pathway
Authors: Saito Naoya , Sakakibara Keiichi , Sato Takuji , Friedman Jonathan M. , Kufe Donald W. , VonHoff Daniel D. , Kawabe Takumi
Published: April 2023

Supplementary Figure 3: The cell growth inhibition and apoptosis by CBS9106 is suppressed by MLN4924 in MM.1S cells. (A) MM.1S cells are treated with the indicated concentration of CBS9106 and/or MLN4924 for 72 hours (n = 6). Cell viability is determined by cell counting kit-8. (B) Cells are treated with CBS9106 (50 nM) and/or MLN4924 (10 or 100 nM) for indicated period (48-96 hours, n = 6). Cell growth is determined by cell counting kit-8. (C) The apoptotic population (indicated by sub-G1) is measured by flow cytometry after staining with propidium iodide. MM.1S cells are treated with CBS9106 (50 or 100 nM), LMB (1 nM), or MLN4924 (1, 2, 5, 10, or 50 nM) either alone or in combination for 24 hours (n = 3). Data are expressed as the mean {plus minus} SD. *P<0.05.
Supplementary Materials and Methods and Supplementary Figure Legends from miR200c Attenuates P-gp–Mediated MDR and Metastasis by Targeting JNK2/c-Jun Signaling Pathway in Colorectal Cancer
Authors: Sui Hua , Cai Guo-Xiang , Pan Shu-Fang , Deng Wan-Li , Wang Yu-Wei , Chen Zhe-Sheng , Cai San-Jun , Zhu Hui-Rong , Li Qi
Published: April 2023

Supplementary Materials and Methods and Figure Legends.
Supplementary Figure 4 from miR200c Attenuates P-gp–Mediated MDR and Metastasis by Targeting JNK2/c-Jun Signaling Pathway in Colorectal Cancer
Authors: Sui Hua , Cai Guo-Xiang , Pan Shu-Fang , Deng Wan-Li , Wang Yu-Wei , Chen Zhe-Sheng , Cai San-Jun , Zhu Hui-Rong , Li Qi
Published: April 2023

Supplementary Figure 4: miR-200c modifies the chemo-drug sensitivity of HCT116/MDR cells and the growth activity.
Supplementary Tables 1-4 from Development of Human Serine Protease-Based Therapeutics Targeting Fn14 and Identification of Fn14 as a New Target Overexpressed in TNBC
Authors: Zhou Hong , Mohamedali Khalid A. , Gonzalez-Angulo Ana Maria , Cao Yu , Migliorini Mary , Cheung Lawrence H. , LoBello Janine , Lei Xiudong , Qi Yuan , Hittelman Walter N. , Winkles Jeffrey A. , Tran Nhan L. , Rosenblum Michael G.
Published: April 2023

Supplementary Tables 1-4. Supplementary Table 1: In vitro cytotoxicity of GrB-TWEAK Supplementary Table 2: TNBC cell lines are highly sensitive to GrB-Fc-IT4 cytotoxicity Supplementary Table 3: GrB-TWEAK and GrB-Fc-IT4 circumvent MDR1-mediated multidrug resistance Supplementary Table 4: Patient characteristics stratified by Fn14 groups
Supplementary Figures 1-5 from Near Infrared Photoimmunotherapy in the Treatment of Disseminated Peritoneal Ovarian Cancer
Authors: Sato Kazuhide , Hanaoka Hirofumi , Watanabe Rira , Nakajima Takahito , Choyke Peter L. , Kobayashi Hisataka
Published: April 2023

Supplementary Figures 1-5. Video Captions (Video 1 and 2) Supplementary Figure 1. Targeted necrotic cell death observed after NIR-PIT in vitro. Supplementary Figure 2. Necrotic cell death evaluated on serial bioluminescence imaging after NIR-PIT Supplementary Figure 3.In vivo tumor inhibition by NIR-PIT in flank model Supplementary Figure 4. In vivo fluorescence imaging of tumor bearing mice before and after NIRPIT Supplementary Figure 5. Mesothelin targeted necrotic cell death observed after NIR-PIT in vitro
Supplementary Table 1 from Significance of Polypyrimidine Tract–Binding Protein 1 Expression in Colorectal Cancer
Authors: Takahashi Hidekazu , Nishimura Junichi , Kagawa Yoshinori , Kano Yoshihiro , Takahashi Yusuke , Wu Xin , Hiraki Masayuki , Hamabe Atsushi , Konno Masamitsu , Haraguchi Naotsugu , Takemasa Ichiro , Mizushima Tsunekazu , Ishii Masaru , Mimori Koshi , Ishii Hideshi , Doki Yuichiro , Mori Masaki , Yamamoto Hirofumi
Published: April 2023

Primers and probes used for qRT-PCR in this study.
Supplementary Figure 9 from Significance of Polypyrimidine Tract–Binding Protein 1 Expression in Colorectal Cancer
Authors: Takahashi Hidekazu , Nishimura Junichi , Kagawa Yoshinori , Kano Yoshihiro , Takahashi Yusuke , Wu Xin , Hiraki Masayuki , Hamabe Atsushi , Konno Masamitsu , Haraguchi Naotsugu , Takemasa Ichiro , Mizushima Tsunekazu , Ishii Masaru , Mimori Koshi , Ishii Hideshi , Doki Yuichiro , Mori Masaki , Yamamoto Hirofumi
Published: April 2023

Survival rate after surgery of two groups divided according to CD44v8-10 mRNA expression. The high CD44v8-10 expression group had significantly poor prognosis (P = 0.0264).
Supplementary Figure 8 from Significance of Polypyrimidine Tract–Binding Protein 1 Expression in Colorectal Cancer
Authors: Takahashi Hidekazu , Nishimura Junichi , Kagawa Yoshinori , Kano Yoshihiro , Takahashi Yusuke , Wu Xin , Hiraki Masayuki , Hamabe Atsushi , Konno Masamitsu , Haraguchi Naotsugu , Takemasa Ichiro , Mizushima Tsunekazu , Ishii Masaru , Mimori Koshi , Ishii Hideshi , Doki Yuichiro , Mori Masaki , Yamamoto Hirofumi
Published: April 2023

(A) Survival rate after surgery of two groups divided according to PTBP1 mRNA expression. The high PTBP1 mRNA group had significantly poorer prognosis (P = 0.0138, log-rank test). (B) Disease-free rate after curative surgery in the two groups divided according to PTBP1 mRNA expression. The high PTBP1 mRNA group had significantly poorer prognosis (P = 0.0083, log-rank test).
Supplementary Table 5 from Structure-Based Screen Identifies a Potent Small Molecule Inhibitor of Stat5a/b with Therapeutic Potential for Prostate Cancer and Chronic Myeloid Leukemia
Authors: Liao Zhiyong , Gu Lei , Vergalli Jenny , Mariani Samanta A. , De Dominici Marco , Lokareddy Ravi K. , Dagvadorj Ayush , Purushottamachar Puranik , McCue Peter A. , Trabulsi Edouard , Lallas Costas D. , Gupta Shilpa , Ellsworth Elyse , Blackmon Shauna , Ertel Adam , Fortina Paolo , Leiby Benjamin , Xia Guanjun , Rui Hallgeir , Hoang David T. , Gomella Leonard G. , Cingolani Gino , Njar Vincent , Pattabiraman Nagarajan , Calabretta Bruno , Nevalainen Marja T.
Published: April 2023

Supplementary Table 5: IST5-002 regulation of known Stat5 target genes in K562 cells.
Supplemental Table 1 from Structure-Based Screen Identifies a Potent Small Molecule Inhibitor of Stat5a/b with Therapeutic Potential for Prostate Cancer and Chronic Myeloid Leukemia
Authors: Liao Zhiyong , Gu Lei , Vergalli Jenny , Mariani Samanta A. , De Dominici Marco , Lokareddy Ravi K. , Dagvadorj Ayush , Purushottamachar Puranik , McCue Peter A. , Trabulsi Edouard , Lallas Costas D. , Gupta Shilpa , Ellsworth Elyse , Blackmon Shauna , Ertel Adam , Fortina Paolo , Leiby Benjamin , Xia Guanjun , Rui Hallgeir , Hoang David T. , Gomella Leonard G. , Cingolani Gino , Njar Vincent , Pattabiraman Nagarajan , Calabretta Bruno , Nevalainen Marja T.
Published: April 2023

Supplemental Table 1: Structure-Activity-Relationship analysis.
Supplement Figure S4 from Aromatase Inhibitor–Mediated Downregulation of INrf2 (Keap1) Leads to Increased Nrf2 and Resistance in Breast Cancer
Authors: Khatri Raju , Shah Preeti , Guha Rupa , Rassool Feyruz V. , Tomkinson Alan E. , Brodie Angela , Jaiswal Anil K.
Published: April 2023

Supplement Figure S4. Expression of Nrf2 and ERα in MCF-7Ca, LTLTCa and LTLTCa+Nrf2shRNA (LTLTCa-Nrf2KD) cells.
Supplementary Figure 3 from Lipid Catabolism via CPT1 as a Therapeutic Target for Prostate Cancer
Authors: Schlaepfer Isabel R. , Rider Leah , Rodrigues Lindsey Ulkus , Gijón Miguel A. , Pac Colton T. , Romero Lina , Cimic Adela , Sirintrapun S. Joseph , Glodé L. Michael , Eckel Robert H. , Cramer Scott D.
Published: April 2023

Supplementary figure 3: Cleaved Caspase 3 expression in LNCaP and BPH-1 cells: Cells were treated with etomoxir over a 16 hour period and the activation of caspase 3 was examined by western blot in the cell lysates. Supplements Figure 3.
Supplementary Figure legends from Daurinol Enhances the Efficacy of Radiotherapy in Lung Cancer via Suppression of Aurora Kinase A/B Expression
Authors: Woo Jong Kyu , Kang Ju-Hee , Shin DongYun , Park Seong-Hyeok , Kang Kyungsu , Nho Chu Won , Seong Je Kyung , Lee Sang-Jin , Oh Seung Hyun
Published: April 2023

Legends for supplementary figures
Supplementary Figure S3 from Daurinol Enhances the Efficacy of Radiotherapy in Lung Cancer via Suppression of Aurora Kinase A/B Expression
Authors: Woo Jong Kyu , Kang Ju-Hee , Shin DongYun , Park Seong-Hyeok , Kang Kyungsu , Nho Chu Won , Seong Je Kyung , Lee Sang-Jin , Oh Seung Hyun
Published: April 2023

Supplementary Figure S3. Expression and cellular sub-localization of Aurora kinase B binding partners
Supplementary Figure 10 from Targeting the Replication Checkpoint Using SCH 900776, a Potent and Functionally Selective CHK1 Inhibitor Identified via High Content Screening
Authors: Guzi Timothy J. , Paruch Kamil , Dwyer Michael P. , Labroli Marc , Shanahan Frances , Davis Nicole , Taricani Lorena , Wiswell Derek , Seghezzi Wolfgang , Penaflor Ervin , Bhagwat Bhagyashree , Wang Wei , Gu Danling , Hsieh Yunsheng , Lee Suining , Liu Ming , Parry David
Published: April 2023

Supplementary Figure 10 from Targeting the Replication Checkpoint Using SCH 900776, a Potent and Functionally Selective CHK1 Inhibitor Identified via High Content Screening
Supplementary Figures 1 through 3 from The Tyrosine Kinase Inhibitors Imatinib and Dasatinib Reduce Myeloid Suppressor Cells and Release Effector Lymphocyte Responses
Authors: Christiansson Lisa , Söderlund Stina , Mangsbo Sara , Hjorth-Hansen Henrik , Höglund Martin , Markevärn Berit , Richter Johan , Stenke Leif , Mustjoki Satu , Loskog Angelica , Olsson-Strömberg Ulla
Published: April 2023

The supplementary Figures 1 to 3 demonstrate the gating procedure post flow cytomety analysis.
Supplementary Figure 1 from Radiosensitization of Head and Neck Squamous Cell Carcinoma by a SMAC-Mimetic Compound, SM-164, Requires Activation of Caspases
Authors: Yang Jie , McEachern Donna , Li Wenyan , Davis Mary A. , Li Hua , Morgan Meredith A. , Bai Longchuan , Sebolt Jonathan T. , Sun Haiying , Lawrence Theodore S. , Wang Shaomeng , Sun Yi
Published: April 2023

Supplementary Figure 1 from Radiosensitization of Head and Neck Squamous Cell Carcinoma by a SMAC-Mimetic Compound, SM-164, Requires Activation of Caspases
Supplemental Figures S1-S12 from Inhibition of the GTPase Rac1 Mediates the Antimigratory Effects of Metformin in Prostate Cancer Cells
Authors: Dirat Béatrice , Ader Isabelle , Golzio Muriel , Massa Fabienne , Mettouchi Amel , Laurent Kathiane , Larbret Frédéric , Malavaud Bernard , Cormont Mireille , Lemichez Emmanuel , Cuvillier Olivier , Tanti Jean François , Bost Frédéric
Published: April 2023

Supplemental Figures S1-S12. Figure S1: Metformin does not affect mouse weight an insulinemia; Figure S2: Metformin does not induce apoptosis in prostate cancer cells; Figure S3: Metformin does not affect P69 cell migration; Figure S4: Metformin blocks cell migration out of the spheroid; Figure S5: Metformin inhibits cell motility; Figure S6: Metformin effects on actin and fascin levels; Figure S7: Metformin does not affect Rho GTP levels; Figure S8: A rac1 inhibitor affects cytoskeletal organisation; Figure S9: Metformin does not affect cAMP levels in PC3 cells; Figure S10: Metformin increases P CREB in DU145 cells; Figure S11: dbcAMP decreases Rac1GTP levels; Figure S12: Metformin decreases CXCR4 at the cell surface
Supplementary Tables S1-S5 from Inhibition of PI3K Pathway Reduces Invasiveness and Epithelial-to-Mesenchymal Transition in Squamous Lung Cancer Cell Lines Harboring PIK3CA Gene Alterations
Authors: Bonelli Mara A. , Cavazzoni Andrea , Saccani Francesca , Alfieri Roberta R. , Quaini Federico , La Monica Silvia , Galetti Maricla , Cretella Daniele , Caffarra Cristina , Madeddu Denise , Frati Caterina , Lagrasta Costanza Annamaria , Falco Angela , Rossetti Pietro , Fumarola Claudia , Tiseo Marcello , Petronini Pier Giorgio , Ardizzoni Andrea
Published: April 2023

Supplementary Tables S1-S5. Table S1: Antiproliferative effects of PI3K inhibitors on SKMES-1 and PIK3CA amplified/mutated clones Tables S2-S4: densitometric analysis of Western blotting of Figure 1D Table S5: Antiproliferative effects of PI3K inhibitors on H596 and HCC2450 cells
Supplementary Materials and Methods from Inhibition of PI3K Pathway Reduces Invasiveness and Epithelial-to-Mesenchymal Transition in Squamous Lung Cancer Cell Lines Harboring PIK3CA Gene Alterations
Authors: Bonelli Mara A. , Cavazzoni Andrea , Saccani Francesca , Alfieri Roberta R. , Quaini Federico , La Monica Silvia , Galetti Maricla , Cretella Daniele , Caffarra Cristina , Madeddu Denise , Frati Caterina , Lagrasta Costanza Annamaria , Falco Angela , Rossetti Pietro , Fumarola Claudia , Tiseo Marcello , Petronini Pier Giorgio , Ardizzoni Andrea
Published: April 2023

Supplementary Materials and Methods. List of antibodies used in the Western blotting and description of Tumor spheroid-based migration assay.
Supplemental Table 1 from Dual PI3K/mTOR Inhibitors, GSK2126458 and PKI-587, Suppress Tumor Progression and Increase Radiosensitivity in Nasopharyngeal Carcinoma
Authors: Liu Tongxin , Sun Quanquan , Li Qi , Yang Hua , Zhang Yuqin , Wang Rong , Lin Xiaoshan , Xiao Dong , Yuan Yawei , Chen Longhua , Wang Wei
Published: April 2023

Supplementary Table 1: Radiosensitivity parameters of nasopharyngeal carcinoma cell lines
Supplementary Figure 4 from Anticancer Activity of a Novel Selective CYP17A1 Inhibitor in Preclinical Models of Castrate-Resistant Prostate Cancer
Authors: Toren Paul J. , Kim Soojin , Pham Steven , Mangalji Azzra , Adomat Hans , Guns Emma S. Tomlinson , Zoubeidi Amina , Moore William , Gleave Martin E.
Published: April 2023

Supplementary Figure 4: Supplementary AR degradation studies.
Supplementary Figure S5. Trastuzumab produced by oncolytic adenovirus in vivo binds to HER2-positive N87 cancer cells from Oncolytic Adenovirus Expressing Monoclonal Antibody Trastuzumab for Treatment of HER2-Positive Cancer
Authors: Liikanen Ilkka , Tähtinen Siri , Guse Kilian , Gutmann Theresia , Savola Paula , Oksanen Minna , Kanerva Anna , Hemminki Akseli
Published: April 2023

Serum from mice treated with Ad5/3-Î"24-tras in MDA-MB-436 experiment or commercial trastuzumab was added on HER2-expressing N87 gastric cancer cells, followed by washing and incubation in FITC-conjugated secondary anti-human IgG antibody. Flow cytometry analysis of the washed single cell suspensions showed binding of in vivo virus-produced trastuzumab to HER2-positive cells (red curve) over background signal (grey curve, secondary antibody alone). Commercial trastuzumab (green curve), used as an in vitro positive control, showed high fluorescence intensity due to saturation of HER2 binding sites on N87 cells. Of note, virus-produced trastuzumab levels in mouse serum (Fig. 4C) remained ca. 4-fold below the concentration reported for adequate saturation of HER2 binding sites of N87 cells (27), likely contributing to the relatively lower fluorescence intensity than positive control.
Supplementary Figure S2: ATF3 knockdown via siATF3 inhibits apoptosis in VCaP cells after AD and edelfosine treatment. from Edelfosine Promotes Apoptosis in Androgen-Deprived Prostate Tumors by Increasing ATF3 and Inhibiting Androgen Receptor Activity
Authors: Udayakumar Thirupandiyur S. , Stoyanova Radka , Shareef Mohammed M. , Mu Zhaomei , Philip Sakhi , Burnstein Kerry L. , Pollack Alan
Published: April 2023

Cells were harvested after 24 hours following treatment and caspase 3/7 assay was carried out. For ATF3 knockdown, VCaP were transfected with control siRNA or siATF3 (10 nM), followed by treatment with edelfosine (5 µM). Data shown represent the mean values ({plus minus} SEM) from three independent experiments. *p < 0.05, compared to control siRNA + edelfosine (one way ANOVA).
Supplementary Figure S2. Oncolytic adenovirus coding for trastuzumab shows superior cell killing efficacy when dosed according to functional titers from Oncolytic Adenovirus Expressing Monoclonal Antibody Trastuzumab for Treatment of HER2-Positive Cancer
Authors: Liikanen Ilkka , Tähtinen Siri , Guse Kilian , Gutmann Theresia , Savola Paula , Oksanen Minna , Kanerva Anna , Hemminki Akseli
Published: April 2023

Breast cancer cell lines BT-474, SKBR3, JIMT-1, and MDA-MB-436 were infected with indicated viruses at increasing plaque-forming units per cell (pfu/cell). The pfu-titers were first determined for each virus in a standard tissue culture infectious dose 50 (TCID50) assay. Ad5/3-Î"24-tras mediated significantly higher cancer cell killing as compared to its oncolytic control virus Ad5/3-Î"24 (P<0.001, P<0.001, P<0.05, and P<0.01, in BT-474, SKBR3, JIMT-1, and MDA-MB-436 cells, respectively). Improved efficacy was especially apparent in HER2-positive trastuzumab sensitive BT-474 and SKBR3 cells, but interestingly, HER2-negative MDA-MB-436 cells were also more susceptible to trastuzumab-coding oncolytic adenovirus. Thus, despite the slower replication rate due to large genome size (Supplementary Fig. S1), the oncolytic potency of the engineered adenovirus was not impaired by the insertion of trastuzumab transgene. ***, P<0.001; **, P<0.01; *, P<0.05; all Student's T tests.
Supplemental Fig. S1. Effect of the experimental conditions on cancer cells viability after OCR measurements from A Fast Hydrogen Sulfide–Releasing Donor Increases the Tumor Response to Radiotherapy
Authors: De Preter Géraldine , Deriemaeker Caroline , Danhier Pierre , Brisson Lucie , Cao Pham Thanh Trang , Grégoire Vincent , Jordan Bénédicte F. , Sonveaux Pierre , Gallez Bernard
Published: April 2023

Viability of MDA-MB-231 and SiHa cancer cells was measured in vitro using trypan blue exclusion after OCR measurements. (A-B) Cancer cells treated with 50 µM NaHS or vehicle (NaCl 0.9 %) in the presence of different pHe values. (C-D) Cancer cells treated with increasing NaHS concentration or vehicle in the presence of pHe = 6.5. No significant cell death was found in any of the experimental conditions.
Supplementary Figure Legends from Wee-1 Kinase Inhibition Overcomes Cisplatin Resistance Associated with High-Risk TP53 Mutations in Head and Neck Cancer through Mitotic Arrest Followed by Senescence
Authors: Osman Abdullah A. , Monroe Marcus M. , Ortega Alves Marcus V. , Patel Ameeta A. , Katsonis Panagiotis , Fitzgerald Alison L. , Neskey David M. , Frederick Mitchell J. , Woo Sang Hyeok , Caulin Carlos , Hsu Teng-Kuei , McDonald Thomas O. , Kimmel Marek , Meyn Raymond E. , Lichtarge Olivier , Myers Jeffrey N.
Published: April 2023

The Wee-1 inhibitor, MK-1775 Synergizes with cisplatin in vitro in established HNSCC cell lines with known TP53 mutational status; Dual phospho-H3 staining and PI flow cytometric analysis (FACS); The synergy between cisplatin and MK-1775 in HNSCC is not mediated by apoptosis.
Supplementary Figure S3 from Tumor-Associated Hyaluronan Limits Efficacy of Monoclonal Antibody Therapy
Authors: Singha Netai C. , Nekoroski Tara , Zhao Chunmei , Symons Rebecca , Jiang Ping , Frost Gregory I. , Huang Zhongdong , Shepard H. Michael
Published: April 2023

ADCC on adherent monolayer SKBR3 cells is CD16 dependent.
Supplementary Figure 2 from Reversible Action of Diaminothiazoles in Cancer Cells Is Implicated by the Induction of a Fast Conformational Change of Tubulin and Suppression of Microtubule Dynamics
Authors: Thomas Nisha E. , Thamkachy Reshma , Sivakumar Krishnankutty C. , Sreedevi Krishnakumar J. , Louis Xavier Lieben , Thomas Sannu A. , Kumar Rohith , Rajasekharan Kallikat N. , Cassimeris Lynne , Sengupta Suparna
Published: April 2023

PDF - 3904KB, Supplemental Fig S2: Reversible action of DAT1 on mitotic block and cell morphology in HeLa cells.
Supplementary Table 1 from Anti–B-cell Maturation Antigen Chimeric Antigen Receptor T cell Function against Multiple Myeloma Is Enhanced in the Presence of Lenalidomide
Authors: Works Melissa , Soni Neha , Hauskins Collin , Sierra Catherine , Baturevych Alex , Jones Jon C. , Curtis Wendy , Carlson Patrick , Johnstone Timothy G. , Kugler David , Hause Ronald J. , Jiang Yue , Wimberly Lindsey , Clouser Christopher R. , Jessup Heidi K. , Sather Blythe , Salmon Ruth A. , Ports Michael O.
Published: April 2023

anti-BCMA CAR T amino acid sequence
Data from A Correlative Analysis of PD-L1, PD-1, PD-L2, EGFR, HER2, and HER3 Expression in Oropharyngeal Squamous Cell Carcinoma
Authors: Steuer Conor E. , Griffith Christopher C. , Nannapaneni Sreenivas , Patel Mihir R. , Liu Yuan , Magliocca Kelly R. , El-Deiry Mark W. , Cohen Cynthia , Owonikoko Taofeek K. , Shin Dong M. , Chen Zhuo G. , Saba Nabil F.
Published: April 2023

Abstract
We explored potential associations of the PD-1/PD-L1/PD-L2 pathway with clinical characteristics, outcome, and expression of EGFR, HER2, HER3 in oropharyngeal squamous cell carcinoma (OPSCC) using an institutional database. Protein expression was assessed by IHC on tissue microarray sections (EGFR, HER2, HER3) or whole tissue sections (PD-1/PD-L1/PD-L2). Expression of EGFR, HER2, HER3, PD-L1, and PD-L2 was quantified on tumor cells. Maximum density of PD-1 positive lymphocytes was measured on a scale of 0 to 4 within the tumor mass and peritumoral stroma. Associations between biomarkers and patient outcomes were tested using descriptive and inferential statistics, logistic regression, and Cox proportional hazards models. We analyzed tissue samples from 97 OPSCC cases: median age 59 years, p16+ (71%), male (83.5%), never smokers (18%), stage 3 to 4 disease (77%). Twenty-five percent of cases were PD-L1 positive. The proportion of PD-L1+ tumors was higher in p16+ (29%) than p16− OPSCC (11%, P = 0.047). There was no correlation between PD-L1, PD-L2, PD-1, EGFR, HER2, or HER3 expression. Positive PD-L1 status correlated with advanced nodal disease on multivariate analysis (OR 5.53; 95% CI, 1.06–28.77; P = 0.042). Negative PD-L2 expression was associated with worse survival (HR 3.99; 95% CI, 1.37–11.58; P = 0.011) in p16− OPSCC. Lower density of PD-1 positive lymphocytes in peritumoral stroma was associated with significantly increased risk of death on multivariate analysis (HR 3.17; 95% CI, 1.03–9.78; P = 0.045) after controlling for prognostic factors such as stage and p16 status. PD-L1 expression on tumor cells correlates with p16 status and advanced nodal status in OPSCC. PD-1 positive lymphocytes in peritumoral stroma serve as an independent prognostic factor for overall survival. Mol Cancer Ther; 17(3); 710–6. ©2018 AACR.
Data from CD44 Facilitates Epithelial-to-Mesenchymal Transition Phenotypic Change at Acquisition of Resistance to EGFR Kinase Inhibitors in Lung Cancer
Authors: Suda Kenichi , Murakami Isao , Yu Hui , Kim Jihye , Tan Aik-Choon , Mizuuchi Hiroshi , Rozeboom Leslie , Ellison Kim , Rivard Christopher J. , Mitsudomi Tetsuya , Hirsch Fred R.
Published: April 2023

Abstract
Epithelial-to-mesenchymal transition (EMT) is one of the acquired resistance mechanisms to EGFR tyrosine kinase inhibitors (TKI) in lung cancers. Because EMT is related to tumor invasion, metastases, and resistance to various treatments, it is important to prevent the emergence of EMT. However, molecular mechanism(s) underlying EMT phenotypic changes, as well as biomarker(s) that predict the emergence of EMT in EGFR-mutated lung cancers, are unclear to date. Through the comparison of expression data between isogenic lung cancer cell lines that acquired resistance to EGFR-TKI(s), we identified that high CD44 expression is related to a mesenchymal phenotype and that shRNA-mediated knockdown of CD44 reversed the EMT change. High membranous CD44 expression was identified in lesions with mesenchymal phenotype that were obtained from lung cancer patients who developed acquired resistance to gefitinib or afatinib, whereas isogenic lesions without EMT change showed negative/weak staining for CD44. Immunohistochemistry for treatment-naïve lung cancer cell lines with EGFR mutations found those that acquire resistance to EGFR-TKIs via EMT (HCC4006 and H1975 cells) had strong membranous CD44 expression compared with non–EMT-transforming lines which demonstrated negative or weak staining (Fisher exact test P value = 0.036). shRNA-mediated CD44 knockdown in HCC4006 cells prevented the emergence of EMT after chronic exposure to osimertinib. These results suggest that upregulation of CD44 facilitates EMT-phenotypic change in lung cancers with EGFR mutations when treated with EGFR-TKIs. In addition, our results suggest that CD44 can be a useful biomarker to predict the emergence of EMT upon EGFR-TKI monotherapy. Mol Cancer Ther; 17(10); 2257–65. ©2018 AACR.
Data from Characterization of the Anti–PD-1 Antibody REGN2810 and Its Antitumor Activity in Human PD-1 Knock-In Mice
Authors: Burova Elena , Hermann Aynur , Waite Janelle , Potocky Terra , Lai Venus , Hong Seongwon , Liu Matt , Allbritton Omaira , Woodruff Amy , Wu Qi , D’Orvilliers Amanda , Garnova Elena , Rafique Ashique , Poueymirou William , Martin Joel , Huang Tammy , Skokos Dimitris , Kantrowitz Joel , Popke Jon , Mohrs Markus , MacDonald Douglas , Ioffe Ella , Olson William , Lowy Israel , Murphy Andrew , Thurston Gavin
Published: April 2023

Abstract
The Programmed Death-1 (PD-1) receptor delivers inhibitory checkpoint signals to activated T cells upon binding to its ligands PD-L1 and PD-L2 expressed on antigen-presenting cells and cancer cells, resulting in suppression of T-cell effector function and tumor immune evasion. Clinical antibodies blocking the interaction between PD-1 and PD-L1 restore the cytotoxic function of tumor antigen-specific T cells, yielding durable objective responses in multiple cancers. This report describes the preclinical characterization of REGN2810, a fully human hinge-stabilized IgG4(S228P) high-affinity anti–PD-1 antibody that potently blocks PD-1 interactions with PD-L1 and PD-L2. REGN2810 was characterized in a series of binding, blocking, and functional cell-based assays, and preclinical in vivo studies in mice and monkeys. In cell-based assays, REGN2810 reverses PD-1–dependent attenuation of T-cell receptor signaling in engineered T cells and enhances responses of human primary T cells. To test the in vivo activity of REGN2810, which does not cross-react with murine PD-1, knock-in mice were generated to express a hybrid protein containing the extracellular domain of human PD-1, and transmembrane and intracellular domains of mouse PD-1. In these mice, REGN2810 binds the humanized PD-1 receptor and inhibits growth of MC38 murine tumors. As REGN2810 binds to cynomolgus monkey PD-1 with high affinity, pharmacokinetic and toxicologic assessment of REGN2810 was performed in cynomolgus monkeys. High doses of REGN2810 were well tolerated, without adverse immune-related effects. These preclinical studies validate REGN2810 as a potent and promising candidate for cancer immunotherapy. Mol Cancer Ther; 16(5); 861–70. ©2017 AACR.
Data from KDM6B Counteracts EZH2-Mediated Suppression of IGFBP5 to Confer Resistance to PI3K/AKT Inhibitor Treatment in Breast Cancer
Authors: Wang Wenyu , Lim Keng Gat , Feng Min , Bao Yi , Lee Puay Leng , Cai Yu , Chen Yufeng , Zhang Hao , Marzese Diego , Hoon Dave S.B. , Yu Qiang
Published: April 2023

Abstract
Despite showing promise against PIK3CA-mutant breast cancers in preclinical studies, PI3K/AKT pathway inhibitors demonstrate limited clinical efficacy as monotherapy. Here, we found that histone H3K27me3 demethylase KDM6B-targeted IGFBP5 expression provides a protective mechanism for PI3K/AKT inhibitor-induced apoptosis in breast cancer cells. We found that overexpression of KDM6B and IGFBP5 in luminal breast cancer are positively associated with poorer disease outcomes. Mechanistically, KDM6B promotes IGFBP5 expression by antagonizing EZH2-mediated repression, and pharmacologic inhibition of KDM6B augments apoptotic response to PI3K/AKT inhibitor treatment. Moreover, the IGFBP5 expression is upregulated upon acquired resistance to the PI3K inhibitor GDC-0941, which is associated with an epigenetic switch from H3K27me3 to H3K27Ac at the IGFBP5 gene promoter. Intriguingly, GDC-0941–resistant breast cancer cells remained sensitive to KDM6B or IGFBP5 inhibition, indicating the dependency on the KDM6B–IGFBP5 axis to confer the survival advantage in GDC-0941–resistant cells. Our study reveals an epigenetic mechanism associated with resistance to targeted therapy and demonstrates that therapeutic targeting of KDM6B-mediated IGFBP5 expression may provide a useful approach to mitigate both intrinsic and acquired resistance to the PI3K inhibitor in breast cancer. Mol Cancer Ther; 17(9); 1973–83. ©2018 AACR.
Data from Induction of Thioredoxin-Interacting Protein by a Histone Deacetylase Inhibitor, Entinostat, Is Associated with DNA Damage and Apoptosis in Esophageal Adenocarcinoma
Authors: Feingold Paul L. , Surman Deborah R. , Brown Kate , Xu Yuan , McDuffie Lucas A. , Shukla Vivek , Reardon Emily S. , Crooks Daniel R. , Trepel Jane B. , Lee Sunmin , Lee Min-Jung , Gao Shaojian , Xi Sichuan , McLoughlin Kaitlin C. , Diggs Laurence P. , Beer David G. , Nancarrow Derek J. , Neckers Leonard M. , Davis Jeremy L. , Hoang Chuong D. , Hernandez Jonathan M. , Schrump David S. , Ripley R. Taylor
Published: April 2023

Abstract
In 2017, an estimated 17,000 individuals were diagnosed with esophageal adenocarcinoma (EAC), and less than 20% will survive 5 years. Positron emission tomography avidity is indicative of high glucose utilization and is nearly universal in EAC. TXNIP blocks glucose uptake and exhibits proapoptotic functions. Higher expression in EAC has been associated with improved disease-specific survival, lack of lymph node involvement, reduced perineural invasion, and increased tumor differentiation. We hypothesized that TXNIP may act as a tumor suppressor that sensitizes EAC cells to standard chemotherapeutics. EAC cell lines and a Barrett epithelial cell line were used. qRT-PCR, immunoblot, and immunofluorescence techniques evaluated gene expression. TXNIP was stably overexpressed or knocked down using lentiviral RNA transduction techniques. Murine xenograft methods examined growth following overexpression of TXNIP. Apoptosis and DNA damage were measured by annexin V and γH2AX assays. Activation of the intrinsic apoptosis was quantitated with green fluorescence protein-caspase 3 reporter assay. In cultured cells and an esophageal tissue array, TXNIP expression was higher in Barrett epithelia and normal tissue compared with EAC. Constitutive overexpression of TXNIP decreased proliferation, clonogenicity, and tumor xenograft growth. TXNIP overexpression increased, whereas knockdown abrogated, DNA damage and apoptosis following cisplatin treatment. An HDAC inhibitor, entinostat (currently in clinical trials), upregulated TXNIP and synergistically increased cisplatin-mediated DNA damage and apoptosis. TXNIP is a tumor suppressor that is downregulated in EACC. Its reexpression dramatically sensitizes these cells to cisplatin. Our findings support phase I/II evaluation of “priming” strategies to enhance the efficacy of conventional chemotherapeutics in EAC. Mol Cancer Ther; 17(9); 2013–23. ©2018 AACR.
Data from Restricted Delivery of Talazoparib Across the Blood–Brain Barrier Limits the Sensitizing Effects of PARP Inhibition on Temozolomide Therapy in Glioblastoma
Authors: Kizilbash Sani H. , Gupta Shiv K. , Chang Kenneth , Kawashima Ryo , Parrish Karen E. , Carlson Brett L. , Bakken Katrina K. , Mladek Ann C. , Schroeder Mark A. , Decker Paul A. , Kitange Gaspar J. , Shen Yuqiao , Feng Ying , Protter Andrew A. , Elmquist William F. , Sarkaria Jann N.
Published: April 2023

Abstract
Poly ADP-ribose polymerase (PARP) inhibitors, including talazoparib, potentiate temozolomide efficacy in multiple tumor types; however, talazoparib-mediated sensitization has not been evaluated in orthotopic glioblastoma (GBM) models. This study evaluates talazoparib ± temozolomide in clinically relevant GBM models. Talazoparib at 1–3 nmol/L sensitized T98G, U251, and GBM12 cells to temozolomide, and enhanced DNA damage signaling and G2–M arrest in vitro. In vivo cyclical therapy with talazoparib (0.15 mg/kg twice daily) combined with low-dose temozolomide (5 mg/kg daily) was well tolerated. This talazoparib/temozolomide regimen prolonged tumor stasis more than temozolomide alone in heterotopic GBM12 xenografts [median time to endpoint: 76 days versus 50 days temozolomide (P = 0.005), 11 days placebo (P < 0.001)]. However, talazoparib/temozolomide did not accentuate survival beyond that of temozolomide alone in corresponding orthotopic xenografts [median survival 37 vs. 30 days with temozolomide (P = 0.93), 14 days with placebo, P < 0.001]. Average brain and plasma talazoparib concentrations at 2 hours after a single dose (0.15 mg/kg) were 0.49 ± 0.07 ng/g and 25.5±4.1 ng/mL, respectively. The brain/plasma distribution of talazoparib in Bcrp−/− versus wild-type (WT) mice did not differ, whereas the brain/plasma ratio in Mdr1a/b−/− mice was higher than WT mice (0.23 vs. 0.02, P < 0.001). Consistent with the in vivo brain distribution, overexpression of MDR1 decreased talazoparib accumulation in MDCKII cells. These results indicate that talazoparib has significant MDR1 efflux liability that may restrict delivery across the blood–brain barrier, and this may explain the loss of talazoparib-mediated temozolomide sensitization in orthotopic versus heterotopic GBM xenografts. Mol Cancer Ther; 16(12); 2735–46. ©2017 AACR.
Data from Pharmacologic Inhibition of the Menin–MLL Interaction Leads to Transcriptional Repression of PEG10 and Blocks Hepatocellular Carcinoma
Authors: Kempinska Katarzyna , Malik Bhavna , Borkin Dmitry , Klossowski Szymon , Shukla Shirish , Miao Hongzhi , Wang Jingya , Cierpicki Tomasz , Grembecka Jolanta
Published: April 2023

Abstract
Hepatocellular carcinoma (HCC) accounts for approximately 85% of malignant liver tumors and results in 600,000 deaths each year, emphasizing the need for new therapies. Upregulation of menin was reported in HCC patients and high levels of menin correlate with poor patient prognosis. The protein–protein interaction between menin and histone methyltransferase mixed lineage leukemia 1 (MLL1) plays an important role in the development of HCC, implying that pharmacologic inhibition of this interaction could lead to new therapeutic strategy for the HCC patients. Here, we demonstrate that the menin–MLL inhibitor MI-503 shows antitumor activity in in vitro and in vivo models of HCC and reveals the potential mechanism of menin contribution to HCC. Treatment with MI-503 selectively kills various HCC cell lines and this effect is significantly enhanced by a combination of MI-503 with sorafenib, the standard-of-care therapy for HCC. Furthermore, MI-503 reduces sphere formation and cell migration in in vitro HCC models. When applied in vivo, MI-503 gives a strong antitumor effect both as a single agent and in combination with sorafenib in mice xenograft models of HCC. Mechanistically, treatment with MI-503 downregulates expression of several genes known to play a critical role in proliferation and migration of HCC cells, including PEG10, and displaces the menin–MLL1 complex from the PEG10 promoter, resulting in reduced H3K4 methylation and transcriptional repression. Overall, our studies reveal a mechanistic link between menin and genes involved in HCC and demonstrate that pharmacologic inhibition of the menin–MLL interaction might represent a promising therapeutic approach for HCC. Mol Cancer Ther; 17(1); 26–38. ©2017 AACR.
Data from SKLB-23bb, A HDAC6-Selective Inhibitor, Exhibits Superior and Broad-Spectrum Antitumor Activity via Additionally Targeting Microtubules
Authors: Wang Fang , Zheng Li , Yi Yuyao , Yang Zhuang , Qiu Qiang , Wang Xiaoyan , Yan Wei , Bai Peng , Yang Jianhong , Li Dan , Pei Heying , Niu Ting , Ye Haoyu , Nie Chunlai , Hu Yiguo , Yang Shengyong , Wei Yuquan , Chen Lijuan
Published: April 2023

Abstract
Our previous study reported that SKLB-23bb, an orally bioavailable HDAC6-selective inhibitor, exhibited superior antitumor efficiency both in vitro and in vivo in comparison with ACY1215, a HDAC6-selective inhibitor recently in phase II clinical trial. This study focused on the mechanism related to the activity of SKLB-23bb. We discovered that despite having HDAC6-selective inhibition equal to ACY1215, SKLB-23bb showed cytotoxic effects against a panel of solid and hematologic tumor cell lines at the low submicromolar level. Interestingly, in contrast to the reported HDAC6-selective inhibitors, SKLB-23bb was more efficient against solid tumor cells. Utilizing HDAC6 stably knockout cell lines constructed by CRISPR–Cas9 gene editing, we illustrated that SKLB-23bb could remain cytotoxic independent of HDAC6 status. Investigation of the mechanism confirmed that SKLB-23bb exerted its cytotoxic activity by additionally targeting microtubules. SKLB-23bb could bind to the colchicine site in β-tubulin and act as a microtubule polymerization inhibitor. Consistent with its microtubule-disrupting ability, SKLB-23bb also blocked tumor cell cycle at G2–M phase and triggered cellular apoptosis. In solid tumor xenografts, oral administration of SKLB-23bb efficiently inhibited tumor growth. These results suggested that SKLB-23bb was an orally bioavailable HDAC6 and microtubule dual targeting agent. The microtubule targeting profile enhanced the antitumor activity and expanded the antitumor spectrum of SKLB-23bb, thus breaking through the limitation of HDAC6 inhibitors. Mol Cancer Ther; 17(4); 763–75. ©2018 AACR.