bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure S1 from A Pooled Analysis of Treatment-Free Survival in Advanced Renal Cell Carcinoma
Authors: Chang Elaine , Zhou Jiaxi , Song Chi , Gittleman Haley , Fernandes Laura , Weinstock Chana , Atkins Michael B. , Agrawal Sundeep , Sridhara Rajeshwari , Gormley Nicole , Tang Shenghui , Suzman Daniel L. , Amiri-Kordestani Laleh , Kluetz Paul G. , Pazdur Richard , Rini Brian I. , McDermott David F. , Regan Meredith M.
Published: August 2024

Treatment-Free Survival in Advanced Renal Cell Carcinoma Trials Evaluating Immuno-Oncology-VEGF TKI Combinations: Sunitinib Group
Supplementary Table 4 from Sequential Analysis of cfDNA Reveals Clonal Evolution in Patients with Neuroblastoma Receiving ALK-Targeted Therapy
Authors: Bobin Charles , Iddir Yasmine , Butterworth Charlotte , Masliah-Planchon Julien , Saint-Charles Alexandra , Bellini Angela , Bhalshankar Jaydutt , Pierron Gaelle , Combaret Valérie , Attignon Valéry , André Nicolas , Corradini Nadège , Dumont Benoit , Mansuy Ludovic , Khanfar Camille , Klein Sebastien , Briandet Claire , Plantaz Dominique , Millot Frederic , Thouvenin Sandrine , Aerts Isabelle , Ndounga-Diakou Lee Aymar , Laghouati Salim , Abbou Samuel , Jehanno Nina , Tissot Hubert , Renault Shufang , Baulande Sylvain , Raynal Virginie , Bozec Laurence , Bieche Ivan , Delattre Olivier , Berlanga Pablo , Schleiermacher Gudrun
Published: August 2024

Supplementary Table 4
Supplementary Table 2 from Sequential Analysis of cfDNA Reveals Clonal Evolution in Patients with Neuroblastoma Receiving ALK-Targeted Therapy
Authors: Bobin Charles , Iddir Yasmine , Butterworth Charlotte , Masliah-Planchon Julien , Saint-Charles Alexandra , Bellini Angela , Bhalshankar Jaydutt , Pierron Gaelle , Combaret Valérie , Attignon Valéry , André Nicolas , Corradini Nadège , Dumont Benoit , Mansuy Ludovic , Khanfar Camille , Klein Sebastien , Briandet Claire , Plantaz Dominique , Millot Frederic , Thouvenin Sandrine , Aerts Isabelle , Ndounga-Diakou Lee Aymar , Laghouati Salim , Abbou Samuel , Jehanno Nina , Tissot Hubert , Renault Shufang , Baulande Sylvain , Raynal Virginie , Bozec Laurence , Bieche Ivan , Delattre Olivier , Berlanga Pablo , Schleiermacher Gudrun
Published: August 2024

Supplementary Table 2
Supplementary Table 1 from Sequential Analysis of cfDNA Reveals Clonal Evolution in Patients with Neuroblastoma Receiving ALK-Targeted Therapy
Authors: Bobin Charles , Iddir Yasmine , Butterworth Charlotte , Masliah-Planchon Julien , Saint-Charles Alexandra , Bellini Angela , Bhalshankar Jaydutt , Pierron Gaelle , Combaret Valérie , Attignon Valéry , André Nicolas , Corradini Nadège , Dumont Benoit , Mansuy Ludovic , Khanfar Camille , Klein Sebastien , Briandet Claire , Plantaz Dominique , Millot Frederic , Thouvenin Sandrine , Aerts Isabelle , Ndounga-Diakou Lee Aymar , Laghouati Salim , Abbou Samuel , Jehanno Nina , Tissot Hubert , Renault Shufang , Baulande Sylvain , Raynal Virginie , Bozec Laurence , Bieche Ivan , Delattre Olivier , Berlanga Pablo , Schleiermacher Gudrun
Published: August 2024

Supplementary Table 1
Supplementary Table S3 from Evaluating Immune Checkpoint Blockade in Metastatic Castration-Resistant Prostate Cancers with Deleterious CDK12 Alterations in the Phase 2 IMPACT Trial
Authors: Nguyen Charles B. , Reimers Melissa A. , Perera Chamila , Abida Wassim , Chou Jonathan , Feng Felix Y. , Antonarakis Emmanuel S. , McKay Rana R. , Pachynski Russell K. , Zhang Jingsong , Reichert Zachery R. , Palmbos Phillip L. , Caram Megan E.V. , Vaishampayan Ulka N. , Heath Elisabeth I. , Hopkins Alexander C. , Cieslik Marcin P. , Wu Yi-Mi , Robinson Dan R. , Baladandayuthapani Veerabhadran , Chinnaiyan Arul M. , Alva Ajjai S.
Published: August 2024

Supplementary Table S3. Treatment exposure and reasons for discontinuation.
Supplementary Figure S5 from Evaluating Immune Checkpoint Blockade in Metastatic Castration-Resistant Prostate Cancers with Deleterious CDK12 Alterations in the Phase 2 IMPACT Trial
Authors: Nguyen Charles B. , Reimers Melissa A. , Perera Chamila , Abida Wassim , Chou Jonathan , Feng Felix Y. , Antonarakis Emmanuel S. , McKay Rana R. , Pachynski Russell K. , Zhang Jingsong , Reichert Zachery R. , Palmbos Phillip L. , Caram Megan E.V. , Vaishampayan Ulka N. , Heath Elisabeth I. , Hopkins Alexander C. , Cieslik Marcin P. , Wu Yi-Mi , Robinson Dan R. , Baladandayuthapani Veerabhadran , Chinnaiyan Arul M. , Alva Ajjai S.
Published: August 2024

Supplementary Figure S5. Patient-reported quality of life assessments.
Supplementary Figure S3 from Evaluating Immune Checkpoint Blockade in Metastatic Castration-Resistant Prostate Cancers with Deleterious CDK12 Alterations in the Phase 2 IMPACT Trial
Authors: Nguyen Charles B. , Reimers Melissa A. , Perera Chamila , Abida Wassim , Chou Jonathan , Feng Felix Y. , Antonarakis Emmanuel S. , McKay Rana R. , Pachynski Russell K. , Zhang Jingsong , Reichert Zachery R. , Palmbos Phillip L. , Caram Megan E.V. , Vaishampayan Ulka N. , Heath Elisabeth I. , Hopkins Alexander C. , Cieslik Marcin P. , Wu Yi-Mi , Robinson Dan R. , Baladandayuthapani Veerabhadran , Chinnaiyan Arul M. , Alva Ajjai S.
Published: August 2024

Supplementary Figure S3. Unconfirmed PSA50 response.
Supplementary Figure S1 from Evaluating Immune Checkpoint Blockade in Metastatic Castration-Resistant Prostate Cancers with Deleterious CDK12 Alterations in the Phase 2 IMPACT Trial
Authors: Nguyen Charles B. , Reimers Melissa A. , Perera Chamila , Abida Wassim , Chou Jonathan , Feng Felix Y. , Antonarakis Emmanuel S. , McKay Rana R. , Pachynski Russell K. , Zhang Jingsong , Reichert Zachery R. , Palmbos Phillip L. , Caram Megan E.V. , Vaishampayan Ulka N. , Heath Elisabeth I. , Hopkins Alexander C. , Cieslik Marcin P. , Wu Yi-Mi , Robinson Dan R. , Baladandayuthapani Veerabhadran , Chinnaiyan Arul M. , Alva Ajjai S.
Published: August 2024

Supplementary Figure S1. Trial schema design.
Supplementary Figure S4 from Plasma versus Tissue Tumor Mutational Burden as Biomarkers of Durvalumab plus Tremelimumab Response in Patients with Metastatic Colorectal Cancer in the CO.26 Trial
Authors: Loree Jonathan M. , Titmuss Emma , Topham James T. , Kennecke Hagen F. , Feilotter Harriet , Virk Shakeel , Lee Young S. , Banks Kimberly , Quinn Katie , Karsan Aly , Renouf Daniel J. , Jonker Derek J. , Tu Dongsheng , O’Callaghan Chris J. , Chen Eric X.
Published: August 2024

Impact of prior regorafenib on plasma TMB.
Data from Mapping the Single-Cell Differentiation Landscape of Osteosarcoma
Authors: Truong Danh D. , Weistuch Corey , Murgas Kevin A. , Admane Prasad , King Bridgette L. , Chauviere Lee Jes , Lamhamedi-Cherradi Salah-E. , Swaminathan Jyothishmathi , Daw Najat C. , Gordon Nancy , Gopalakrishnan Vidya , Gorlick Richard G. , Somaiah Neeta , Deasy Joseph O. , Mikos Antonios G. , Tannenbaum Allen , Ludwig Joseph
Published: August 2024

AbstractPurpose:
The genetic intratumoral heterogeneity observed in human osteosarcomas poses challenges for drug development and the study of cell fate, plasticity, and differentiation, which are processes linked to tumor grade, cell metastasis, and survival.
Experimental Design:
To pinpoint errors in osteosarcoma differentiation, we transcriptionally profiled 31,527 cells from a tissue-engineered model that directs mesenchymal stem cells toward adipogenic and osteoblastic fates. Incorporating preexisting chondrocyte data, we applied trajectory analysis and non-negative matrix factorization to generate the first human mesenchymal differentiation atlas.
Results:
This “roadmap” served as a reference to delineate the cellular composition of morphologically complex osteosarcoma tumors and quantify each cell’s lineage commitment. Projecting a bulk RNA-sequencing osteosarcoma dataset onto this roadmap unveiled a correlation between a stem-like transcriptomic phenotype and poorer survival outcomes.
Conclusions:
Our study quantifies osteosarcoma differentiation and lineage, a prerequisite to better understanding lineage-specific differentiation bottlenecks that might someday be targeted therapeutically.
First-Line Tyrosine Kinase Inhibitors in Soft-Tissue Sarcomas: A Role for Anlotinib?
Authors: Napolitano Andrea , Huang Paul H. , Jones Robin L.
Published: August 2024

The optimal medical treatment of chemotherapy-ineligible patients affected by advanced soft-tissue sarcomas is unclear. In this population, tyrosine kinase inhibitors represent an appealing alternative treatment strategy. First-line use of the tyrosine kinase inhibitor anlotinib in chemotherapy-ineligible patients with soft-tissue sarcoma showed promising activity across multiple histologies.

See related article by Li et al., p. 4310
Table S5 from A Selective FGFR1/2 PROTAC Degrader with Antitumor Activity
Authors: Kong Ying , Zhao Xinyue , Wang Zhaofu , Yuan Siqi , Chen Sheng , Lou Shidi , Ma Shichao , Li Yunfeng , Wang Xinghao , Ge Yangfeng , Li Guobin , Yang Hongbing , Zhao Mengxi , Li Dandan , Zhang Hailong , Tan Wenfu , Wang Juan
Published: August 2024

Liver microsome metabolic stability data of BR-cpd7.
Supplementary Methods from A Selective FGFR1/2 PROTAC Degrader with Antitumor Activity
Authors: Kong Ying , Zhao Xinyue , Wang Zhaofu , Yuan Siqi , Chen Sheng , Lou Shidi , Ma Shichao , Li Yunfeng , Wang Xinghao , Ge Yangfeng , Li Guobin , Yang Hongbing , Zhao Mengxi , Li Dandan , Zhang Hailong , Tan Wenfu , Wang Juan
Published: August 2024

Supplementary data: experimental section
Figure S5 from A Selective FGFR1/2 PROTAC Degrader with Antitumor Activity
Authors: Kong Ying , Zhao Xinyue , Wang Zhaofu , Yuan Siqi , Chen Sheng , Lou Shidi , Ma Shichao , Li Yunfeng , Wang Xinghao , Ge Yangfeng , Li Guobin , Yang Hongbing , Zhao Mengxi , Li Dandan , Zhang Hailong , Tan Wenfu , Wang Juan
Published: August 2024

Binding affinity of BR-cpd7. A-C, Fluorescence polarization (FP) analysis of BR-cpd7 affinity for purified FGFR1/2/3 (n=3 replicates).
Figure S4 from A Selective FGFR1/2 PROTAC Degrader with Antitumor Activity
Authors: Kong Ying , Zhao Xinyue , Wang Zhaofu , Yuan Siqi , Chen Sheng , Lou Shidi , Ma Shichao , Li Yunfeng , Wang Xinghao , Ge Yangfeng , Li Guobin , Yang Hongbing , Zhao Mengxi , Li Dandan , Zhang Hailong , Tan Wenfu , Wang Juan
Published: August 2024

Molecular dynamics (MD) simulations on the FGFR1/2/3: BR-cpd7: CRBN complexes. A, green-light-blue: CRBN-FGFR1; gray-light-pink: CRBN-FGFR3. B, blue-yellow: CRBN-FGFR2 unphosphorylated; purple-yellow: CRBN-FGFR2 phosphorylated.
Figure S3 from A Selective FGFR1/2 PROTAC Degrader with Antitumor Activity
Authors: Kong Ying , Zhao Xinyue , Wang Zhaofu , Yuan Siqi , Chen Sheng , Lou Shidi , Ma Shichao , Li Yunfeng , Wang Xinghao , Ge Yangfeng , Li Guobin , Yang Hongbing , Zhao Mengxi , Li Dandan , Zhang Hailong , Tan Wenfu , Wang Juan
Published: August 2024

BR-cpd7 selectively degrades FGFR1/2. A-C, Immunoblot analysis of FGFR1/2/3 proteins in DMS114 (A), KATO III (B), and RT112/84 (C) cells treated with BGJ398, BR-cpd7 or BR-cpd7 NC at 10, 100 or 1000 nM for 24 h (n=3 replicates). D and E, HEK293T cells transfected with HiBiT-FGFR1/2/3 were treated with BGJ398 (D) or BR-cpd7 NC (E) for 36 h. FGFR1/2/3 protein levels were quantified with Nano-Glo HiBiT (n=3 replicates). (F) Immunoblot analysis of FGFR1/2/3 levels in DMS114 under comparable exposure time (n=3 replicates).
Figure S1 from A Selective FGFR1/2 PROTAC Degrader with Antitumor Activity
Authors: Kong Ying , Zhao Xinyue , Wang Zhaofu , Yuan Siqi , Chen Sheng , Lou Shidi , Ma Shichao , Li Yunfeng , Wang Xinghao , Ge Yangfeng , Li Guobin , Yang Hongbing , Zhao Mengxi , Li Dandan , Zhang Hailong , Tan Wenfu , Wang Juan
Published: August 2024

H-NMR Spectra for BR-cpd7.
Supplementary Figure S6 from INA03: A Potent Transferrin-Competitive Antibody–Drug Conjugate against CD71 for Safer Acute Leukemia Treatment
Authors: Bratti Manuela , Stubbs Elisa , Kolodych Sergii , Souchet Herve , Kelly Lois , Merlin Johanna , Marchal Michelle , Castellano Remy , Josselin Emmanuelle , Pasquer Hélène , Benajiba Lina , Puissant Alexandre , Koniev Oleksandr , Collette Yves , Belanger Coralie , Hermine Olivier , Monteiro Renato C. , Launay Pierre
Published: August 2024

Figure S6
Supplementary Figure S5 from INA03: A Potent Transferrin-Competitive Antibody–Drug Conjugate against CD71 for Safer Acute Leukemia Treatment
Authors: Bratti Manuela , Stubbs Elisa , Kolodych Sergii , Souchet Herve , Kelly Lois , Merlin Johanna , Marchal Michelle , Castellano Remy , Josselin Emmanuelle , Pasquer Hélène , Benajiba Lina , Puissant Alexandre , Koniev Oleksandr , Collette Yves , Belanger Coralie , Hermine Olivier , Monteiro Renato C. , Launay Pierre
Published: August 2024

Figure S5
Supplemental Table S1 from Enhancing Standard of Care Chemotherapy Efficacy Using DNA-Dependent Protein Kinase (DNA-PK) Inhibition in Preclinical Models of Ewing Sarcoma
Authors: Collins Victor J. , Ludwig Katelyn R. , Nelson Ariana E. , Sundara Rajan Soumya , Yeung Choh , Vulikh Ksenia , Isanogle Kristine A. , Mendoza Arnulfo , Difilippantonio Simone , Karim Baktiar O. , Caplen Natasha J. , Heske Christine M.
Published: August 2024

Reagents
Supplemental Figure S6 from Enhancing Standard of Care Chemotherapy Efficacy Using DNA-Dependent Protein Kinase (DNA-PK) Inhibition in Preclinical Models of Ewing Sarcoma
Authors: Collins Victor J. , Ludwig Katelyn R. , Nelson Ariana E. , Sundara Rajan Soumya , Yeung Choh , Vulikh Ksenia , Isanogle Kristine A. , Mendoza Arnulfo , Difilippantonio Simone , Karim Baktiar O. , Caplen Natasha J. , Heske Christine M.
Published: August 2024

The effect of DNA-PKi and etoposide combinations on non-malignant epithelial cell lines
Supplemental Figure S3 from Enhancing Standard of Care Chemotherapy Efficacy Using DNA-Dependent Protein Kinase (DNA-PK) Inhibition in Preclinical Models of Ewing Sarcoma
Authors: Collins Victor J. , Ludwig Katelyn R. , Nelson Ariana E. , Sundara Rajan Soumya , Yeung Choh , Vulikh Ksenia , Isanogle Kristine A. , Mendoza Arnulfo , Difilippantonio Simone , Karim Baktiar O. , Caplen Natasha J. , Heske Christine M.
Published: August 2024

The synergistic combination of the DNA-PK inhibitor M3814 and etoposide extends to multiple Ewing sarcoma cell lines
Supplemental Figure S2 from Enhancing Standard of Care Chemotherapy Efficacy Using DNA-Dependent Protein Kinase (DNA-PK) Inhibition in Preclinical Models of Ewing Sarcoma
Authors: Collins Victor J. , Ludwig Katelyn R. , Nelson Ariana E. , Sundara Rajan Soumya , Yeung Choh , Vulikh Ksenia , Isanogle Kristine A. , Mendoza Arnulfo , Difilippantonio Simone , Karim Baktiar O. , Caplen Natasha J. , Heske Christine M.
Published: August 2024

Assessment of cell confluency confirms DNA-PK inhibition selectively synergizes with etoposide
Supplemental Figure S1 from Enhancing Standard of Care Chemotherapy Efficacy Using DNA-Dependent Protein Kinase (DNA-PK) Inhibition in Preclinical Models of Ewing Sarcoma
Authors: Collins Victor J. , Ludwig Katelyn R. , Nelson Ariana E. , Sundara Rajan Soumya , Yeung Choh , Vulikh Ksenia , Isanogle Kristine A. , Mendoza Arnulfo , Difilippantonio Simone , Karim Baktiar O. , Caplen Natasha J. , Heske Christine M.
Published: August 2024

A screen of multiple drug combinations demonstrates the selectivity of the synergistic activity of the DNA-PK clinical inhibitor M3814
Figure S1 from Exploiting Metabolic Defects in Glioma with Nanoparticle-Encapsulated NAMPT Inhibitors
Authors: Murray Matthew A. , Noronha Katelyn J. , Wang Yazhe , Friedman Anna P. , Paradkar Sateja , Suh Hee-Won , Sundaram Ranjini K. , Brenner Charles , Saltzman W.M. , Bindra Ranjit S.
Published: August 2024

Validation of PLA-PEG GMX1778 efficacy in an IDH1-R132H model.
Table S5 from Antitumor Activity of a Novel LAIR1 Antagonist in Combination with Anti-PD1 to Treat Collagen-Rich Solid Tumors
Authors: Rodriguez Bertha L. , Huang Jiawei , Gibson Laura , Fradette Jared J. , Chen Hung-I.H. , Koyano Kikuye , Cortez Czrina , Li Betty , Ho Carmence , Ashique Amir M. , Lin Vicky Y. , Crawley Suzanne , Roda Julie M. , Chen Peirong , Fan Bin , Kim Jeong , Sissons James , Sitrin Jonathan , Kaplan Daniel D. , Gibbons Don L. , Rivera Lee B.
Published: August 2024

NGM438 binding to cell-expressed LAIR1.
Table S1 from Antitumor Activity of a Novel LAIR1 Antagonist in Combination with Anti-PD1 to Treat Collagen-Rich Solid Tumors
Authors: Rodriguez Bertha L. , Huang Jiawei , Gibson Laura , Fradette Jared J. , Chen Hung-I.H. , Koyano Kikuye , Cortez Czrina , Li Betty , Ho Carmence , Ashique Amir M. , Lin Vicky Y. , Crawley Suzanne , Roda Julie M. , Chen Peirong , Fan Bin , Kim Jeong , Sissons James , Sitrin Jonathan , Kaplan Daniel D. , Gibbons Don L. , Rivera Lee B.
Published: August 2024

Antibody Information.
Figure S4 from Antitumor Activity of a Novel LAIR1 Antagonist in Combination with Anti-PD1 to Treat Collagen-Rich Solid Tumors
Authors: Rodriguez Bertha L. , Huang Jiawei , Gibson Laura , Fradette Jared J. , Chen Hung-I.H. , Koyano Kikuye , Cortez Czrina , Li Betty , Ho Carmence , Ashique Amir M. , Lin Vicky Y. , Crawley Suzanne , Roda Julie M. , Chen Peirong , Fan Bin , Kim Jeong , Sissons James , Sitrin Jonathan , Kaplan Daniel D. , Gibbons Don L. , Rivera Lee B.
Published: August 2024

Characterization of KP mouse tumor 344SQ.
Figure S3 from Antitumor Activity of a Novel LAIR1 Antagonist in Combination with Anti-PD1 to Treat Collagen-Rich Solid Tumors
Authors: Rodriguez Bertha L. , Huang Jiawei , Gibson Laura , Fradette Jared J. , Chen Hung-I.H. , Koyano Kikuye , Cortez Czrina , Li Betty , Ho Carmence , Ashique Amir M. , Lin Vicky Y. , Crawley Suzanne , Roda Julie M. , Chen Peirong , Fan Bin , Kim Jeong , Sissons James , Sitrin Jonathan , Kaplan Daniel D. , Gibbons Don L. , Rivera Lee B.
Published: August 2024

Anti-murine LAIR1 clone 43H2 blocks murine collagen/LAIR1 engagement.
Supplemental Table 1 from First-in-Human Stage III/IV Melanoma Clinical Trial of Immune Priming Agent IFx-Hu2.0
Authors: Markowitz Joseph , Shamblott Michael , Brohl Andrew S. , Sarnaik Amod A. , Eroglu Zeynep , Khushalani Nikhil I. , Dukes Christopher W. , Chamizo Alejandra , Bastawrous Marina , Garcia Edward T. , Dehlawi Ashraf , Chen Pei-Ling , De Aquino Deanryan B. , Sondak Vernon K. , Tarhini Ahmad A. , Kim Youngchul , Lawman Patricia , Pilon-Thomas Shari
Published: August 2024

Supplemental Table 1: Demographics; related/unrelated adverse events.
Supplemental Figure 7 from First-in-Human Stage III/IV Melanoma Clinical Trial of Immune Priming Agent IFx-Hu2.0
Authors: Markowitz Joseph , Shamblott Michael , Brohl Andrew S. , Sarnaik Amod A. , Eroglu Zeynep , Khushalani Nikhil I. , Dukes Christopher W. , Chamizo Alejandra , Bastawrous Marina , Garcia Edward T. , Dehlawi Ashraf , Chen Pei-Ling , De Aquino Deanryan B. , Sondak Vernon K. , Tarhini Ahmad A. , Kim Youngchul , Lawman Patricia , Pilon-Thomas Shari
Published: August 2024

Supplemental Figure 7: A) Emm55 specific peptides responsible for IgG responses pre and post treatment on individual patients.
Supplemental Figure 4 from First-in-Human Stage III/IV Melanoma Clinical Trial of Immune Priming Agent IFx-Hu2.0
Authors: Markowitz Joseph , Shamblott Michael , Brohl Andrew S. , Sarnaik Amod A. , Eroglu Zeynep , Khushalani Nikhil I. , Dukes Christopher W. , Chamizo Alejandra , Bastawrous Marina , Garcia Edward T. , Dehlawi Ashraf , Chen Pei-Ling , De Aquino Deanryan B. , Sondak Vernon K. , Tarhini Ahmad A. , Kim Youngchul , Lawman Patricia , Pilon-Thomas Shari
Published: August 2024

Supplemental Figure 4: Emm55 specific peptides responsible for IgM responses pre and post treatment on individual patients.
Supplemental Figure 3 from First-in-Human Stage III/IV Melanoma Clinical Trial of Immune Priming Agent IFx-Hu2.0
Authors: Markowitz Joseph , Shamblott Michael , Brohl Andrew S. , Sarnaik Amod A. , Eroglu Zeynep , Khushalani Nikhil I. , Dukes Christopher W. , Chamizo Alejandra , Bastawrous Marina , Garcia Edward T. , Dehlawi Ashraf , Chen Pei-Ling , De Aquino Deanryan B. , Sondak Vernon K. , Tarhini Ahmad A. , Kim Youngchul , Lawman Patricia , Pilon-Thomas Shari
Published: August 2024

Supplemental Figure 3: Cytokine/chemokines increased or decreased after therapy in individual patients with the INF panel.
Supplemental Figure 1 from First-in-Human Stage III/IV Melanoma Clinical Trial of Immune Priming Agent IFx-Hu2.0
Authors: Markowitz Joseph , Shamblott Michael , Brohl Andrew S. , Sarnaik Amod A. , Eroglu Zeynep , Khushalani Nikhil I. , Dukes Christopher W. , Chamizo Alejandra , Bastawrous Marina , Garcia Edward T. , Dehlawi Ashraf , Chen Pei-Ling , De Aquino Deanryan B. , Sondak Vernon K. , Tarhini Ahmad A. , Kim Youngchul , Lawman Patricia , Pilon-Thomas Shari
Published: August 2024

Box plot of genes depicted in Figure 1.
Supplementary Table S3 from Targeting CD33+ Acute Myeloid Leukemia with GLK-33, a Lintuzumab–Auristatin Conjugate with a Wide Therapeutic Window
Authors: Satomaa Tero , Pynnönen Henna , Aitio Olli , Hiltunen Jukka O. , Pitkänen Virve , Lähteenmäki Tuula , Kotiranta Titta , Heiskanen Annamari , Hänninen Anna-Liisa , Niemelä Ritva , Helin Jari , Kuusanmäki Heikki , Vänttinen Ida , Rathod Ramji , Nieminen Anni I. , Yatkin Emrah , Heckman Caroline A. , Kontro Mika , Saarinen Juhani
Published: August 2024

Toxicokinetic parameters of GLK-33 and comparator ADCs in single i.v. dose toxicity studies in Sprague-Dawley rats.
Supplementary Figure S3 from Targeting CD33+ Acute Myeloid Leukemia with GLK-33, a Lintuzumab–Auristatin Conjugate with a Wide Therapeutic Window
Authors: Satomaa Tero , Pynnönen Henna , Aitio Olli , Hiltunen Jukka O. , Pitkänen Virve , Lähteenmäki Tuula , Kotiranta Titta , Heiskanen Annamari , Hänninen Anna-Liisa , Niemelä Ritva , Helin Jari , Kuusanmäki Heikki , Vänttinen Ida , Rathod Ramji , Nieminen Anni I. , Yatkin Emrah , Heckman Caroline A. , Kontro Mika , Saarinen Juhani
Published: August 2024

Ex vivo cytotoxicity assays with leukemia blast samples.
Supplementary Data from Targeting CD33+ Acute Myeloid Leukemia with GLK-33, a Lintuzumab–Auristatin Conjugate with a Wide Therapeutic Window
Authors: Satomaa Tero , Pynnönen Henna , Aitio Olli , Hiltunen Jukka O. , Pitkänen Virve , Lähteenmäki Tuula , Kotiranta Titta , Heiskanen Annamari , Hänninen Anna-Liisa , Niemelä Ritva , Helin Jari , Kuusanmäki Heikki , Vänttinen Ida , Rathod Ramji , Nieminen Anni I. , Yatkin Emrah , Heckman Caroline A. , Kontro Mika , Saarinen Juhani
Published: August 2024

Supplementary Methods and Results
Supplemental Figure 2 from Blockade of Discoidin Domain Receptor Signaling with Sitravatinib Reveals DDR2 as a Mediator of Neuroblastoma Pathogenesis and Metastasis
Authors: Rozen Esteban J. , Frantz William , Wigglesworth Kim , Vessella Theadora , Zhou Hong S. , Shohet Jason M.
Published: August 2024

Tetracycline-inducible DDR2 downregulation confirms the critical role of DDR2 as the central mediator of collagen signaling in neuroblastoma cells.
Supplemental Figure 10 from Blockade of Discoidin Domain Receptor Signaling with Sitravatinib Reveals DDR2 as a Mediator of Neuroblastoma Pathogenesis and Metastasis
Authors: Rozen Esteban J. , Frantz William , Wigglesworth Kim , Vessella Theadora , Zhou Hong S. , Shohet Jason M.
Published: August 2024

Sitravatinib + Lorlatinib combination in neuroblastoma cell proliferation.
Table S7 from TNIK Inhibition Sensitizes TNIK-Overexpressing Lung Squamous Cell Carcinoma to Radiotherapy
Authors: Nguyen Triet , Carrieri Francesca A. , Connis Nick , Lafargue Audrey , Chang Jinhee , Chan Aaron , Shetty Amol C. , Song Yang , Hoang Tung , Jagtap Shreya , Chowdhury Dipanwita D. , Khan Muhammad A. , Gabrielson Kathleen L. , Rezaee Mohammad , Torres-Ayuso Pedro , Brognard John , Hann Christine L. , Tran Phuoc T.
Published: August 2024

DER50 of LSCC cell lines treated with single-agent NCB-0846 (300 nM) or NCB-0846 in combination with KU-55933 (5 µM) or NU7441 (500 nM) for 48h prior to ionizing radiation.
Table S6 from TNIK Inhibition Sensitizes TNIK-Overexpressing Lung Squamous Cell Carcinoma to Radiotherapy
Authors: Nguyen Triet , Carrieri Francesca A. , Connis Nick , Lafargue Audrey , Chang Jinhee , Chan Aaron , Shetty Amol C. , Song Yang , Hoang Tung , Jagtap Shreya , Chowdhury Dipanwita D. , Khan Muhammad A. , Gabrielson Kathleen L. , Rezaee Mohammad , Torres-Ayuso Pedro , Brognard John , Hann Christine L. , Tran Phuoc T.
Published: August 2024

DER50 of LSCC cell lines treated with cisplatin (1 µM), NCB-0846 (300 nM), or both for 48h prior to ionizing radiation.
Table S5 from TNIK Inhibition Sensitizes TNIK-Overexpressing Lung Squamous Cell Carcinoma to Radiotherapy
Authors: Nguyen Triet , Carrieri Francesca A. , Connis Nick , Lafargue Audrey , Chang Jinhee , Chan Aaron , Shetty Amol C. , Song Yang , Hoang Tung , Jagtap Shreya , Chowdhury Dipanwita D. , Khan Muhammad A. , Gabrielson Kathleen L. , Rezaee Mohammad , Torres-Ayuso Pedro , Brognard John , Hann Christine L. , Tran Phuoc T.
Published: August 2024

Synergy scores obtained from LSCC cell lines treated with co-treatment with NCB-0846 and cisplatin/etoposide. Cell viability was evaluated at 48h post-treatment.
Table S2 from TNIK Inhibition Sensitizes TNIK-Overexpressing Lung Squamous Cell Carcinoma to Radiotherapy
Authors: Nguyen Triet , Carrieri Francesca A. , Connis Nick , Lafargue Audrey , Chang Jinhee , Chan Aaron , Shetty Amol C. , Song Yang , Hoang Tung , Jagtap Shreya , Chowdhury Dipanwita D. , Khan Muhammad A. , Gabrielson Kathleen L. , Rezaee Mohammad , Torres-Ayuso Pedro , Brognard John , Hann Christine L. , Tran Phuoc T.
Published: August 2024

Antibodies used in this study.
Figure S2 from TNIK Inhibition Sensitizes TNIK-Overexpressing Lung Squamous Cell Carcinoma to Radiotherapy
Authors: Nguyen Triet , Carrieri Francesca A. , Connis Nick , Lafargue Audrey , Chang Jinhee , Chan Aaron , Shetty Amol C. , Song Yang , Hoang Tung , Jagtap Shreya , Chowdhury Dipanwita D. , Khan Muhammad A. , Gabrielson Kathleen L. , Rezaee Mohammad , Torres-Ayuso Pedro , Brognard John , Hann Christine L. , Tran Phuoc T.
Published: August 2024

Combinations of NCB-0846 with conventional chemotherapeutic agents were either antagonistic or additive.
Figure S1 from TNIK Inhibition Sensitizes TNIK-Overexpressing Lung Squamous Cell Carcinoma to Radiotherapy
Authors: Nguyen Triet , Carrieri Francesca A. , Connis Nick , Lafargue Audrey , Chang Jinhee , Chan Aaron , Shetty Amol C. , Song Yang , Hoang Tung , Jagtap Shreya , Chowdhury Dipanwita D. , Khan Muhammad A. , Gabrielson Kathleen L. , Rezaee Mohammad , Torres-Ayuso Pedro , Brognard John , Hann Christine L. , Tran Phuoc T.
Published: August 2024

Supplementary Figure S1. Coexpression of TNIK with genes associated with CRT resistance mechanisms in LSCC.
Data from A Selective FGFR1/2 PROTAC Degrader with Antitumor Activity
Authors: Kong Ying , Zhao Xinyue , Wang Zhaofu , Yuan Siqi , Chen Sheng , Lou Shidi , Ma Shichao , Li Yunfeng , Wang Xinghao , Ge Yangfeng , Li Guobin , Yang Hongbing , Zhao Mengxi , Li Dandan , Zhang Hailong , Tan Wenfu , Wang Juan
Published: August 2024

Abstract
The aberrant activation of FGFR acts as a potent driver of multiple types of human cancers. Despite the development of several conventional small-molecular FGFR inhibitors, their clinical efficacy is largely compromised because of low selectivity and side effects. In this study, we report the selective FGFR1/2-targeting proteolysis-targeting chimera BR-cpd7 that displays significant isoform specificity to FGFR1/2 with half maximal degradation concentration values around 10 nmol/L while sparing FGFR3. The following mechanistic investigation reveals the reduced FGFR signaling, through which BR-cpd7 induces cell-cycle arrest and consequently blocks the proliferation of multiple FGFR1/2-dependent tumor cells. Importantly, BR-cpd7 has almost no antiproliferative activity against cancer cells without FGFR aberrations, furtherly supporting its selectivity. In vivo, BR-cpd7 exhibits robust antitumor effects in FGFR1-dependent lung cancer at well-tolerated dose schedules, accompanied by complete FGFR1 depletion. Overall, we identify BR-cpd7 as a promising candidate for developing a selective FGFR1/2-targeted agent, thereby offering a new therapeutic strategy for human cancers in which FGFR1/2 plays a critical role.
Data from INA03: A Potent Transferrin-Competitive Antibody–Drug Conjugate against CD71 for Safer Acute Leukemia Treatment
Authors: Bratti Manuela , Stubbs Elisa , Kolodych Sergii , Souchet Herve , Kelly Lois , Merlin Johanna , Marchal Michelle , Castellano Remy , Josselin Emmanuelle , Pasquer Hélène , Benajiba Lina , Puissant Alexandre , Koniev Oleksandr , Collette Yves , Belanger Coralie , Hermine Olivier , Monteiro Renato C. , Launay Pierre
Published: August 2024

Abstract
Innovative strategies for enhancing efficacy and overcoming drug resistance in hematologic cancers, such as using antibody–drug conjugates (ADC), have shifted the paradigm of conventional care by delivering promising outcomes in cancer therapies with a significant reduction in the risk of relapse. Transferrin receptor (TfR1), cluster of differentiation 71 (CD71), is known to be overexpressed in malignant cells and considered a potent antitumor target. Therefore, we developed an anti-CD71 ADC, INA03, a humanized antibody conjugated to monomethyl auristatin E through a 3-arylpropiolonitrile–valine–citrulline linker. In this study, we investigated the potency and safety of INA03, in competition with Transferrin (Tf), the CD71’s natural ligand, as a novel strategy to specifically target highly proliferative cells. The high expression of CD71 was confirmed on different leukemic cell lines, allowing INA03 to bind efficiently. Subsequently, INA03 rapidly internalizes into lysosomal compartments, in which its cytotoxic drug is released following cathepsin B cleavage. Downregulation of CD71 expression using shRNA highlighted that INA03-induced cell death was dependent on CD71 density at the cell surface. INA03 intravenous treatment in acute leukemia mouse models significantly reduced tumor burden, increased mouse survival, and showed no residual disease compared with conventional chemotherapies. Because INA03 competes with human Tf, a double knock-in (human CD71/human Tf) competent mouse model was generated to mimic human pharmacokinetics and pharmacodynamics. INA03 administration in human CD71/hTf mice did not reveal any improper toxicities, even at high doses. Hence, these data demonstrate the promising preclinical efficacy and safety of INA03 and support its development as a novel acute leukemia treatment.

Significance: The Tf receptor is believed to be undruggable because of its ubiquitous expression. By entering into competition with its cognate ligand, the Tf and INA03 ADC can safely achieve potency.
Data from SMG5 Inhibition Restrains Hepatocellular Carcinoma Growth and Enhances Sorafenib Sensitivity
Authors: Fang Nan , Liu Bing , Pan Qiuzhong , Gong Tingting , Zhan Meixiao , Zhao Jingjing , Wang Qijing , Tang Yan , Li Yongqiang , He Jia , Xiang Tong , Sun Fengze , Lu Ligong , Xia Jianchuan
Published: August 2024

Abstract
Hepatocellular carcinoma (HCC) has a pathogenesis that remains elusive with restricted therapeutic strategies and efficacy. This study aimed to investigate the role of SMG5, a crucial component in nonsense-mediated mRNA decay (NMD) that degrades mRNA containing a premature termination codon, in HCC pathogenesis and therapeutic resistance. We demonstrated an elevated expression of SMG5 in HCC and scrutinized its potential as a therapeutic target. Our findings revealed that SMG5 knockdown not only inhibited the migration, invasion, and proliferation of HCC cells but also influenced sorafenib resistance. Differential gene expression analysis between the control and SMG5 knockdown groups showed an upregulation of methionine adenosyltransferase 1A in the latter. High expression of methionine adenosyltransferase 1A, a catalyst for S-adenosylmethionine (SAM) production, as suggested by The Cancer Genome Atlas data, was indicative of a better prognosis for HCC. Further, an ELISA showed a higher concentration of SAM in SMG5 knockdown cell supernatants. Furthermore, we found that exogenous SAM supplementation enhanced the sensitivity of HCC cells to sorafenib alongside changes in the expression of Bax and Bcl-2, apoptosis-related proteins. Our findings underscore the important role of SMG5 in HCC development and its involvement in sorafenib resistance, highlighting it as a potential target for HCC treatment.
Novel Inhibition of Central Carbon Metabolism Pathways by Rac and CDC42 inhibitor MBQ167 and Paclitaxel
Authors: Cruz-Collazo Ailed M. , Katsara Olga , Grafals-Ruiz Nilmary , Colon Gonzalez Jessica , Dorta-Estremera Stephanie , Carlo Victor P. , Chorna Nataliya , Schneider Robert J. , Dharmawardhane Suranganie
Published: August 2024

Triple negative breast cancer (TNBC) represents a therapeutic challenge in which standard chemotherapy is limited to paclitaxel. MBQ167, a clinical stage small molecule inhibitor that targets Rac and Cdc42, inhibits tumor growth and metastasis in mouse models of TNBC. Herein, we investigated the efficacy of MBQ167 in combination with paclitaxel in TNBC preclinical models, as a prelude to safety trials of this combination in patients with advanced breast cancer. Individual MBQ167 or combination therapy with paclitaxel was more effective at reducing TNBC cell viability and increasing apoptosis compared with paclitaxel alone. In orthotopic mouse models of human TNBC (MDA-MB231 and MDA-MB468), individual MBQ167, paclitaxel, or the combination reduced mammary tumor growth with similar efficacy, with no apparent liver toxicity. However, paclitaxel single agent treatment significantly increased lung metastasis, whereas MBQ167, single or combined, reduced lung metastasis. In the syngeneic 4T1/BALB/c model, combined MBQ167 and paclitaxel decreased established lung metastases by ∼80%. To determine the molecular basis for the improved efficacy of the combined treatment on metastasis, 4T1 tumor extracts from BALB/c mice treated with MBQ167, paclitaxel, or the combination were subjected to transcriptomic analysis. Gene set enrichment identified specific downregulation of central carbon metabolic pathways by the combination of MBQ167 and paclitaxel but not individual compounds. Biochemical validation, by immunoblotting and metabolic Seahorse analysis, shows that combined MBQ167 and paclitaxel reduces glycolysis. This study provides a strong rationale for the clinical testing of MBQ167 in combination with paclitaxel as a potential therapeutic for TNBC and identifies a unique mechanism of action.
Supplementary Table 1 from A Linear Relationship between the Number of Cancers among First-Degree Relatives and the Risk of Multiple Primary Cancers
Authors: He Shisi , Barry Kathryn H. , Mitchell Braxton D. , Chen Shuo , Zhang Yuji , Beane Freeman Laura E. , Berndt Sonja I.
Published: August 2024

Supplementary Table 1 shows the risk of multiple primary cancers associated with parental history of cancer in the PLCO Cancer Screening Trial
Supplemental Figure 4 from Stool Protein Mass Spectrometry Identifies Biomarkers for Early Detection of Diffuse-type Gastric Cancer
Authors: Ho Chi-Lee C. , Gilbert Michael B. , Urtecho Guillaume , Lee Hyoungjoo , Drew David A. , Klempner Samuel J. , Cho Jin S. , Ryan Thomas J. , Rustgi Naryan , Lee Hyuk , Lee Jeeyun , Caraballo Alexander , Magicheva-Gupta Marina V. , Rios Carmen , Shin Alice E. , Tseng Yuen-Yi , Davis Jeremy L. , Chung Daniel C. , Chan Andrew T. , Wang Harris H. , Ryeom Sandra
Published: August 2024

Supplemental Figure 4 contains heat maps of stool proteins between various stool donor groups and emphasizes the differential abundance of protein profiles based on donor status.
Supplemental Table 2 from Colon Age: A Metric for Whether and How to Screen Male Veterans for Early-Onset Colorectal Cancer
Authors: Imperiale Thomas F. , Myers Laura J. , Barker Barry C. , Stump Timothy E. , Daggy Joanne K.
Published: August 2024

Supplemental Table 2: Age-adjusted incidence, U.S. population 2014 to 2018 years, for male colon and rectum, 5-year strata
Supplementary Methods File S1 from CLN-617 Retains IL2 and IL12 in Injected Tumors to Drive Robust and Systemic Immune-Mediated Antitumor Activity
Authors: Mehta Naveen K. , Rakhra Kavya , Meetze Kristan A. , Li Bochong , Momin Noor , Chang Jason Y.H. , Wittrup K. Dane , Baeuerle Patrick A. , Michaelson Jennifer S.
Published: August 2024

Statistical Analyses of TCR-β sequencing results
Supplementary Figure 14 from Multifunctional Bispecific Nanovesicles Targeting SLAMF7 Trigger Potent Antitumor Immunity
Authors: Zhu Manman , Wu Yongjian , Zhu Tianchuan , Chen Jian , Chen Zhenxing , Ding Hanxi , Tan Siyi , He Jianzhong , Zeng Qi , Huang Xi
Published: August 2024

Supplementary Figure 14
Supplementary Table S3 from Venetoclax Induces BCL-2–Dependent Treg to TH17 Plasticity to Enhance the Antitumor Efficacy of Anti–PD-1 Checkpoint Blockade
Authors: Liao Rosy , Hsu Jocelyn Y. , Aboelella Nada S. , McKeever Joshua A. , Thomas-Toth Anika T. , Koh Andrew S. , LaBelle James L.
Published: August 2024

Supplementary Table S3
Supplementary Table S1 from Overexpression of an Engineered SERPINB9 Enhances Allogeneic T-cell Persistence and Efficacy
Authors: Teo Pei Y. , Jung Youngrock , Quach David H. , Koh Joanna , Ong Richard W. , Goh Angeline , Tan Alrina , Ng Chee H. , Seh Cheah C. , Tan Kar W. , Horak Ivan D. , Low Lionel
Published: August 2024

Supplementary Table S1. Amino acid sequences of the hinge and reactive center loop of SB9(WT) and its variants. Adapted from Bird et al.
Tables S6-S9 from Improvement of Tumor Neoantigen Detection by High-Field Asymmetric Waveform Ion Mobility Mass Spectrometry
Authors: Meng Wei , Takeuchi Yoshiko , Ward Jeffrey P. , Sultan Hussein , Arthur Cora D. , Mardis Elaine R. , Artyomov Maxim N. , Lichti Cheryl F. , Schreiber Robert D.
Published: August 2024

Table S6: Identification of mLama4 from ICT-naive T3 tumors. Table S7: Identification of mLama4 from ICT-treated T3 tumors. Table S8: Identification of mItgb1 from sorted CD45+ T3 TILs. Table S9: Identification of I-Ab bound peptides from ICT-treated T3 tumors.
Table S5 from Improvement of Tumor Neoantigen Detection by High-Field Asymmetric Waveform Ion Mobility Mass Spectrometry
Authors: Meng Wei , Takeuchi Yoshiko , Ward Jeffrey P. , Sultan Hussein , Arthur Cora D. , Mardis Elaine R. , Artyomov Maxim N. , Lichti Cheryl F. , Schreiber Robert D.
Published: August 2024

Frequency of mItgb1 MS/MS at 45 million T3.CIITA cells.
Table S3 from Improvement of Tumor Neoantigen Detection by High-Field Asymmetric Waveform Ion Mobility Mass Spectrometry
Authors: Meng Wei , Takeuchi Yoshiko , Ward Jeffrey P. , Sultan Hussein , Arthur Cora D. , Mardis Elaine R. , Artyomov Maxim N. , Lichti Cheryl F. , Schreiber Robert D.
Published: August 2024

Frequency of mAlg8 MS/MS.
Table S15 from Improvement of Tumor Neoantigen Detection by High-Field Asymmetric Waveform Ion Mobility Mass Spectrometry
Authors: Meng Wei , Takeuchi Yoshiko , Ward Jeffrey P. , Sultan Hussein , Arthur Cora D. , Mardis Elaine R. , Artyomov Maxim N. , Lichti Cheryl F. , Schreiber Robert D.
Published: August 2024

Twenty-two I-Ab binding F244 neoantigens screened.
Table S10 from Improvement of Tumor Neoantigen Detection by High-Field Asymmetric Waveform Ion Mobility Mass Spectrometry
Authors: Meng Wei , Takeuchi Yoshiko , Ward Jeffrey P. , Sultan Hussein , Arthur Cora D. , Mardis Elaine R. , Artyomov Maxim N. , Lichti Cheryl F. , Schreiber Robert D.
Published: August 2024

Top 20 predicted H-2Kb restricted neoepitopes of 1956 sarcomas.
Figure S6 from Improvement of Tumor Neoantigen Detection by High-Field Asymmetric Waveform Ion Mobility Mass Spectrometry
Authors: Meng Wei , Takeuchi Yoshiko , Ward Jeffrey P. , Sultan Hussein , Arthur Cora D. , Mardis Elaine R. , Artyomov Maxim N. , Lichti Cheryl F. , Schreiber Robert D.
Published: August 2024

Psmd6 and Cs sequences in 1956 subclones.
Figure S2 from Improvement of Tumor Neoantigen Detection by High-Field Asymmetric Waveform Ion Mobility Mass Spectrometry
Authors: Meng Wei , Takeuchi Yoshiko , Ward Jeffrey P. , Sultan Hussein , Arthur Cora D. , Mardis Elaine R. , Artyomov Maxim N. , Lichti Cheryl F. , Schreiber Robert D.
Published: August 2024

Optimal FAIMS CV(s) improve the identification of the mLama4 and mAlg8 peptides.
Supplemental Figure 4 from T-Cell Expression of CXCL13 is Associated with Immunotherapy Response in a Sex-Dependent Manner in Patients with Lung Cancer
Authors: Brennan Michelle , DeBruin David , Nwokolo Chinye , Hunt Katey S. , Piening Alexander , Donlin Maureen J. , Ferris Stephen T. , Teague Ryan M. , DiPaolo Richard J. , Alspach Elise
Published: August 2024

Supplemental Figure 4: TCR repertoire analysis reveals sex-based differences in the association between T cell clonal expansion and expression of CXCL13.
Supplementary Materials File S1 from Low Serum Apolipoprotein A1 Levels Impair Antitumor Immunity of CD8+ T Cells via the HIF-1α–Glycolysis Pathway
Authors: Lv Qiaoying , Su Tong , Liu Wei , Wang Lulu , Hu Jiali , Cheng Yali , Ning Chengcheng , Shan Weiwei , Luo Xuezhen , Chen Xiaojun
Published: August 2024

Supplementary Material Original Western blots and statistics
Data from Low Serum Apolipoprotein A1 Levels Impair Antitumor Immunity of CD8+ T Cells via the HIF-1α–Glycolysis Pathway
Authors: Lv Qiaoying , Su Tong , Liu Wei , Wang Lulu , Hu Jiali , Cheng Yali , Ning Chengcheng , Shan Weiwei , Luo Xuezhen , Chen Xiaojun
Published: August 2024

Abstract
An immunosuppressive microenvironment promotes the occurrence and development of tumors. Low apolipoprotein A1 (ApoA1) is closely related to tumor development, but the underlying mechanisms are unclear. This study investigated the association between serum ApoA1 levels and the immune microenvironment in endometrial, ovarian, and lung cancers. The serum ApoA1 level was decreased significantly in patients with endometrial and ovarian cancers compared with healthy controls. In endometrial cancer (EC) tissues, the low serum ApoA1 level group showed increased CD163+ macrophage infiltration and decreased CD8+ T-cell infiltration compared with the normal serum ApoA1 group. Compromised tumor-infiltrating CD8+ T-cell functions and decreased CD8+ T-cell infiltration also were found in tumor-bearing Apo1-knockout mice. CD8+ T-cell depletion experiments confirmed that ApoA1 exerted its antitumor activity in a CD8+ T-cell–dependent manner. In vitro experiments showed that the ApoA1 mimetic peptide L-4F directly potentiated the antitumor activity of CD8+ T cells via a HIF-1α–mediated glycolysis pathway. Mechanistically, ApoA1 suppressed ubiquitin-mediated degradation of HIF-1α protein by downregulating HIF-1α subunit α inhibitor. This regulatory process maintained the stability of HIF-1α protein and activated the HIF-1α signaling pathway. Tumor-bearing Apoa1 transgenic mice showed an increased response to anti–PD-1 therapy, leading to reduced tumor growth along with increased infiltration of activated CD8+ T cells and enhanced tumor necrosis. The data reported herein demonstrate critical roles for ApoA1 in enhancing CD8+ T-cell immune functions via HIF-1α–mediated glycolysis and support clinical investigation of combining ApoA1 supplementation with anti–PD-1 therapy for treating cancer.
Figure 6 from p300 KAT Regulates SOX10 Stability and Function in Human Melanoma
Authors: Waddell Aaron , Grbic Nicole , Leibowitz Kassidy , Wyant William Austin , Choudhury Sabah , Park Kihyun , Collard Marianne , Cole Philip A. , Alani Rhoda M.
Published: August 2024

p300 KAT activity is essential for the activation of SOX10-repressed EMT markers. A, Diagram depicting the hypothesis that p300 activity is essential for the expression of SOX10-activated genes, but SOX10-repressed genes may also require p300 for their activation. B, Volcano plots of SOX10-repressed genes differentially expressed due to A-485 treatment for IPC-298, CO79, and A375 cells (DEGs defined as FC > |2| and P < 0.05). C, SOX10-repressed genes are enriched for genes involved in the EMT, and similar invasion-related pathways are downregulated by A-485. CAM, cell adhesion molecules; ECM, extracellular matrix. D, Volcano plot of EMT genes differentially expressed due to A-485 treatment for A375 cells. E, Volcano plot of SOX10-regulated EMT genes differentially expressed due to A-485 treatment for A375 cells. F, Volcano plots of genes differentially expressed due to A-485 are shown for various KEGG invasion-related pathways identified in C. Differentially expressed collagen genes are also shown. G, H3K27ac is enriched at the promoters of EMT genes THBS1 and SFRP1 in comparison with a gene desert in invasive 1205Lu cells via ChIP sequencing. H, H3K27ac was confirmed to be enriched at the promoters of THBS1 and SFRP1 in comparison with a gene desert in A375 cells via ChIP-qPCR. I, A-485 decreases H3K27ac enrichment at the promoters of THBS1 and SFRP1, as assessed by ChIP-qPCR. (J) 5 µmol/L A-485 alters the cell morphology of A375 and 1205Lu cells after long-term (12-day) treatment. K, A-485 potently inhibits invasion in A375 and 1205Lu after long-term (12-day) treatment. Representative images of invaded cells are shown on the left, and quantification of invaded cells is shown on the right. *, P < 0.05; **, P < 0.005; ***, P < 0.0005.
Figure 2 from p300 KAT Regulates SOX10 Stability and Function in Human Melanoma
Authors: Waddell Aaron , Grbic Nicole , Leibowitz Kassidy , Wyant William Austin , Choudhury Sabah , Park Kihyun , Collard Marianne , Cole Philip A. , Alani Rhoda M.
Published: August 2024

SOX10 signaling requires p300 KAT activity. (A) A panel of melanoma cell lines were treated with DMSO (D) or 5 µmol/L A-485 (A) for 24 hours. SOX10, MITF, and DCT protein levels were assessed via immunoblotting. B, A panel of EP300/SOX10 co-amplified melanoma cell lines were treated with DMSO (D) or 5 µmol/L A-485 (A) for 24 hours. MITF and DCT expressions were assessed via RT-qPCR. C,MITF, SCD, and MYC expressions were downregulated by SOX10 KD in A375 cells. D, A panel of melanoma cell lines without EP300/SOX10 co-amplifications were treated with DMSO (D) or 5 µmol/L A-485 (A) for 24 hours. MITF, SCD, and MYC expressions were assessed via RT-qPCR. *, P < 0.05; **, P < 0.005; ***, P < 0.0005.
Data from p300 KAT Regulates SOX10 Stability and Function in Human Melanoma
Authors: Waddell Aaron , Grbic Nicole , Leibowitz Kassidy , Wyant William Austin , Choudhury Sabah , Park Kihyun , Collard Marianne , Cole Philip A. , Alani Rhoda M.
Published: August 2024

Abstract
SOX10 is a lineage-specific transcription factor critical for melanoma tumor growth; on the other hand, SOX10 loss-of-function drives the emergence of therapy-resistant, invasive melanoma phenotypes. A major challenge has been developing therapeutic strategies targeting SOX10’s role in melanoma proliferation while preventing a concomitant increase in tumor cell invasion. In this study, we report that the lysine acetyltransferase (KAT) EP300 and SOX10 gene loci on chromosome 22 are frequently co-amplified in melanomas, including UV-associated and acral tumors. We further show that p300 KAT activity mediates SOX10 protein stability and that the p300 inhibitor A-485 downregulates SOX10 protein levels in melanoma cells via proteasome-mediated degradation. Additionally, A-485 potently inhibits proliferation of SOX10+ melanoma cells while decreasing invasion in AXLhigh/MITFlow melanoma cells through downregulation of metastasis-related genes. We conclude that the SOX10/p300 axis is critical to melanoma growth and invasion and that inhibition of p300 KAT activity through A-485 may be a worthwhile therapeutic approach for SOX10-reliant tumors.
Significance:
The p300 KAT inhibitor A-485 blocks SOX10-dependent proliferation and SOX10-independent invasion in hard-to-treat melanoma cells.