bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure S2 from An Artificial Intelligence–Driven Preoperative Radiomic Subtype for Predicting the Prognosis and Treatment Response of Patients with Papillary Thyroid Carcinoma
Authors: Li Qiang , Zhang Weituo , Liao Tian , Gao Yi , Zhang Yanzhi , Jin Anqi , Ma Ben , Qu Ning , Zhang Huan , Zheng Xiangqian , Li Dapeng , Yun Xinwei , Zhao Jingzhu , Yu Herbert , Gao Ming , Wang Yu , Qian Biyun
Published: January 2025

The difference of TIME and prognosis between molecular subtypes in the external validation set 1.
Supplementary Figure S2 from Integrating Molecular Imaging and Transcriptomic Profiling in Advanced HER2-Positive Breast Cancer Receiving Trastuzumab Emtansine: An Analysis of the ZEPHIR Clinical Trial
Authors: Rediti Mattia , Fimereli Danai , Mileva Magdalena , Wimana Zéna , Venet David , Flamen Patrick , Guiot Thomas , de Vries Elisabeth G.E. , Schröder Carolien P. , Menke-van der Houven van Oordt Catharina Willemien , Maetens Marion , Majjaj Samira , Larsimont Denis , Rothé Françoise , Sotiriou Christos , Gebhart Géraldine
Published: January 2025

CONSORT diagram showing the patient selection for the present analysis in the ZEPHIR trial
Supplementary Table S6 from CD40 Agonist on Patient-Derived Xenograft Mice for the Treatment of B-Cell Acute Lymphoblastic Leukemia
Authors: Bellaye Pierre-Simon , Georgievski Aleksandra , Ballerini Paola , Bouslama Boutheina , Richard Corentin , Boidot Romain , Chevreux Guillaume , Legros Véronique , Guy Julien , Racine Jessica , Collin Bertrand , Garrido Carmen , Quéré Ronan
Published: January 2025

Supplementary Table S6. List of primers used for qPCR on AP-1 target genes.
Supplementary Figure S1 from Phase II Study of Palbociclib in Patients with Tumors with CDK4 or CDK6 Amplification: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1C
Authors: O’Hara Mark H. , Jegede Opeyemi , Dickson Mark A. , DeMichele Angela M. , Piekarz Richard , Gray Robert J. , Wang Victoria , McShane Lisa M. , Rubinstein Lawrence V. , Patton David R. , Williams P. Mickey , Hamilton Stanley R. , Onitilo Adedayo , Tricoli James V. , Conley Barbara A. , Arteaga Carlos L. , Harris Lyndsay N. , O’Dwyer Peter J. , Chen Alice P. , Flaherty Keith T.
Published: January 2025

Supplementary Figure 1: Progression Free and Overall Survival in the Eligible and Treated Population (n=38) Kaplan Meier plots for progression free (A) and overall (B) survival in the eligible and treated population (n=38)
Supplementary Tables S5-S8 from Intestinal Subtype as a Biomarker of Response to Neoadjuvant Immunochemotherapy in Locally Advanced Gastric Adenocarcinoma: Insights from a Prospective Phase II Trial
Authors: Wang Lei , Sun Mengting , Li Jinyang , Wan Linghong , Tan Yuting , Tian Shuoran , Hou Yongying , Wu Linyu , Peng Ziyi , Hu Xiao , Zhang Qihua , Huang Zening , Han Mengyi , Peng Shiyin , Pan Yuwei , Ren Yuanfeng , Zhang Mengsi , Chen Dongfeng , Liu Qin , Li Xianfeng , Qin Zhong-yi , Xiang Junyv , Li Mengxia , Zhu Jianwu , Chen Qiyue , Luo Huiyan , Wang Shunan , Wang Tao , Li Fan , Bian Xiu-wu , Wang Bin
Published: January 2025

Supplementary Table S5 DPH-cohort clinical information Supplementary Table S6 SYSUCC-cohort clinical information Supplementary Table S7 Validation datasets Supplementary Table S8 GC-scRNA clinical information
Supplementary Figure S8 from CD40 Agonist on Patient-Derived Xenograft Mice for the Treatment of B-Cell Acute Lymphoblastic Leukemia
Authors: Bellaye Pierre-Simon , Georgievski Aleksandra , Ballerini Paola , Bouslama Boutheina , Richard Corentin , Boidot Romain , Chevreux Guillaume , Legros Véronique , Guy Julien , Racine Jessica , Collin Bertrand , Garrido Carmen , Quéré Ronan
Published: January 2025

Supplementary Figure S8. The expression of specific markers remains unchanged on residual B-ALL cells following treatment with the CD40 agonist.
Supplementary Table S4 from Intestinal Subtype as a Biomarker of Response to Neoadjuvant Immunochemotherapy in Locally Advanced Gastric Adenocarcinoma: Insights from a Prospective Phase II Trial
Authors: Wang Lei , Sun Mengting , Li Jinyang , Wan Linghong , Tan Yuting , Tian Shuoran , Hou Yongying , Wu Linyu , Peng Ziyi , Hu Xiao , Zhang Qihua , Huang Zening , Han Mengyi , Peng Shiyin , Pan Yuwei , Ren Yuanfeng , Zhang Mengsi , Chen Dongfeng , Liu Qin , Li Xianfeng , Qin Zhong-yi , Xiang Junyv , Li Mengxia , Zhu Jianwu , Chen Qiyue , Luo Huiyan , Wang Shunan , Wang Tao , Li Fan , Bian Xiu-wu , Wang Bin
Published: January 2025

Baseline characteristics associated with pathological response
Supplementary Table S3 from Intestinal Subtype as a Biomarker of Response to Neoadjuvant Immunochemotherapy in Locally Advanced Gastric Adenocarcinoma: Insights from a Prospective Phase II Trial
Authors: Wang Lei , Sun Mengting , Li Jinyang , Wan Linghong , Tan Yuting , Tian Shuoran , Hou Yongying , Wu Linyu , Peng Ziyi , Hu Xiao , Zhang Qihua , Huang Zening , Han Mengyi , Peng Shiyin , Pan Yuwei , Ren Yuanfeng , Zhang Mengsi , Chen Dongfeng , Liu Qin , Li Xianfeng , Qin Zhong-yi , Xiang Junyv , Li Mengxia , Zhu Jianwu , Chen Qiyue , Luo Huiyan , Wang Shunan , Wang Tao , Li Fan , Bian Xiu-wu , Wang Bin
Published: January 2025

Neoadjuvant and adjuvant treatment-related adverse events
Supplementary Figure S6 from CD40 Agonist on Patient-Derived Xenograft Mice for the Treatment of B-Cell Acute Lymphoblastic Leukemia
Authors: Bellaye Pierre-Simon , Georgievski Aleksandra , Ballerini Paola , Bouslama Boutheina , Richard Corentin , Boidot Romain , Chevreux Guillaume , Legros Véronique , Guy Julien , Racine Jessica , Collin Bertrand , Garrido Carmen , Quéré Ronan
Published: January 2025

Supplementary Figure S6. The CD40 agonist does not activate NFκB on B-ALL cells in vivo.
Supplementary Table S2 from Intestinal Subtype as a Biomarker of Response to Neoadjuvant Immunochemotherapy in Locally Advanced Gastric Adenocarcinoma: Insights from a Prospective Phase II Trial
Authors: Wang Lei , Sun Mengting , Li Jinyang , Wan Linghong , Tan Yuting , Tian Shuoran , Hou Yongying , Wu Linyu , Peng Ziyi , Hu Xiao , Zhang Qihua , Huang Zening , Han Mengyi , Peng Shiyin , Pan Yuwei , Ren Yuanfeng , Zhang Mengsi , Chen Dongfeng , Liu Qin , Li Xianfeng , Qin Zhong-yi , Xiang Junyv , Li Mengxia , Zhu Jianwu , Chen Qiyue , Luo Huiyan , Wang Shunan , Wang Tao , Li Fan , Bian Xiu-wu , Wang Bin
Published: January 2025

Surgical and pathological results
Supplementary Table S1 from Intestinal Subtype as a Biomarker of Response to Neoadjuvant Immunochemotherapy in Locally Advanced Gastric Adenocarcinoma: Insights from a Prospective Phase II Trial
Authors: Wang Lei , Sun Mengting , Li Jinyang , Wan Linghong , Tan Yuting , Tian Shuoran , Hou Yongying , Wu Linyu , Peng Ziyi , Hu Xiao , Zhang Qihua , Huang Zening , Han Mengyi , Peng Shiyin , Pan Yuwei , Ren Yuanfeng , Zhang Mengsi , Chen Dongfeng , Liu Qin , Li Xianfeng , Qin Zhong-yi , Xiang Junyv , Li Mengxia , Zhu Jianwu , Chen Qiyue , Luo Huiyan , Wang Shunan , Wang Tao , Li Fan , Bian Xiu-wu , Wang Bin
Published: January 2025

Baseline characteristics
Supplementary Figure S4 from CD40 Agonist on Patient-Derived Xenograft Mice for the Treatment of B-Cell Acute Lymphoblastic Leukemia
Authors: Bellaye Pierre-Simon , Georgievski Aleksandra , Ballerini Paola , Bouslama Boutheina , Richard Corentin , Boidot Romain , Chevreux Guillaume , Legros Véronique , Guy Julien , Racine Jessica , Collin Bertrand , Garrido Carmen , Quéré Ronan
Published: January 2025

Supplementary Figure S4. Agonist CD40 binds primary B-ALL cells.
Supplementary Figure S3 from CD40 Agonist on Patient-Derived Xenograft Mice for the Treatment of B-Cell Acute Lymphoblastic Leukemia
Authors: Bellaye Pierre-Simon , Georgievski Aleksandra , Ballerini Paola , Bouslama Boutheina , Richard Corentin , Boidot Romain , Chevreux Guillaume , Legros Véronique , Guy Julien , Racine Jessica , Collin Bertrand , Garrido Carmen , Quéré Ronan
Published: January 2025

Supplementary Figure S3. CD40 transcription on B-ALL primary samples.
Supplementary Methods S1 from Intestinal Subtype as a Biomarker of Response to Neoadjuvant Immunochemotherapy in Locally Advanced Gastric Adenocarcinoma: Insights from a Prospective Phase II Trial
Authors: Wang Lei , Sun Mengting , Li Jinyang , Wan Linghong , Tan Yuting , Tian Shuoran , Hou Yongying , Wu Linyu , Peng Ziyi , Hu Xiao , Zhang Qihua , Huang Zening , Han Mengyi , Peng Shiyin , Pan Yuwei , Ren Yuanfeng , Zhang Mengsi , Chen Dongfeng , Liu Qin , Li Xianfeng , Qin Zhong-yi , Xiang Junyv , Li Mengxia , Zhu Jianwu , Chen Qiyue , Luo Huiyan , Wang Shunan , Wang Tao , Li Fan , Bian Xiu-wu , Wang Bin
Published: January 2025

Supplementary Information on Materials and Methods
Supplementary Figure S1 from CD40 Agonist on Patient-Derived Xenograft Mice for the Treatment of B-Cell Acute Lymphoblastic Leukemia
Authors: Bellaye Pierre-Simon , Georgievski Aleksandra , Ballerini Paola , Bouslama Boutheina , Richard Corentin , Boidot Romain , Chevreux Guillaume , Legros Véronique , Guy Julien , Racine Jessica , Collin Bertrand , Garrido Carmen , Quéré Ronan
Published: January 2025

Supplementary Figure S1. Flow cytometry plots at diagnosis on B-ALL samples used to generate PDX mice.
Supplementary Figure S3 from Intestinal Subtype as a Biomarker of Response to Neoadjuvant Immunochemotherapy in Locally Advanced Gastric Adenocarcinoma: Insights from a Prospective Phase II Trial
Authors: Wang Lei , Sun Mengting , Li Jinyang , Wan Linghong , Tan Yuting , Tian Shuoran , Hou Yongying , Wu Linyu , Peng Ziyi , Hu Xiao , Zhang Qihua , Huang Zening , Han Mengyi , Peng Shiyin , Pan Yuwei , Ren Yuanfeng , Zhang Mengsi , Chen Dongfeng , Liu Qin , Li Xianfeng , Qin Zhong-yi , Xiang Junyv , Li Mengxia , Zhu Jianwu , Chen Qiyue , Luo Huiyan , Wang Shunan , Wang Tao , Li Fan , Bian Xiu-wu , Wang Bin
Published: January 2025

Identification of malignant and non-malignant epithelial cells in gastric cancer
Supplementary Table S1 from A Translational Study of the ATR Inhibitor Berzosertib as Monotherapy in Four Molecularly Defined Cohorts of Advanced Solid Tumors
Authors: Cote Gregory M. , Kochupurakkal Bose S. , Do Khanh , Bullock Andrea , Cheng Michael L. , Muzikansky Alona , McLoughlin Daniel E. , Cleary James M. , Gao Xin , Parikh Aparna , Park Jong Chul , Weekes Colin D. , Yeku Oladapo , Zou Lee , Shapiro Geoffrey I.
Published: January 2025

Representativeness of Study Participants
Supplemental Table 2 from Phase I/II Investigator-Initiated Study of Olaparib and Temozolomide in SCLC: Final Analysis and CNS Outcomes
Authors: Meador Catherine B. , Digumarthy Subba R. , Yeap Beow Y. , Hung Yin P. , Mino-Kenudson Mari , Farago Anna F. , Heist Rebecca S. , Marcoux J. Paul , Rangachari Deepa , Barbie David A. , Piotrowska Zofia
Published: January 2025

Supplemental Table 2. Representativeness of Study Participants.
Supplementary Table 9 from Genomic, Epigenomic, and Transcriptomic Inter- and Intratumor Heterogeneity in Desmoid Tumors
Authors: De Bellis Chelsea , Vennam Sujay , Eeles Christopher , Rahimizadeh Pegah , Cates Justin , Stricker Thomas , Hoffman Jenny , Ganjoo Kristen , Charville Gregory W. , Haibe-Kains Benjamin , van de Rijn Matt , Przybyl Joanna
Published: January 2025

Supplementary Table 9. Differentially expressed genes between primary desmoid tumors from patients who did and did not develop local recurrence after surgery.
Supplemental Figure 2 from Phase I/II Investigator-Initiated Study of Olaparib and Temozolomide in SCLC: Final Analysis and CNS Outcomes
Authors: Meador Catherine B. , Digumarthy Subba R. , Yeap Beow Y. , Hung Yin P. , Mino-Kenudson Mari , Farago Anna F. , Heist Rebecca S. , Marcoux J. Paul , Rangachari Deepa , Barbie David A. , Piotrowska Zofia
Published: January 2025

Supplemental Figure 2. Study design.
Supplementary Table 8 from Genomic, Epigenomic, and Transcriptomic Inter- and Intratumor Heterogeneity in Desmoid Tumors
Authors: De Bellis Chelsea , Vennam Sujay , Eeles Christopher , Rahimizadeh Pegah , Cates Justin , Stricker Thomas , Hoffman Jenny , Ganjoo Kristen , Charville Gregory W. , Haibe-Kains Benjamin , van de Rijn Matt , Przybyl Joanna
Published: January 2025

Supplementary Table 8. Antibodies used for immunohistochemistry.
Supplemental Figure 1 from Phase I/II Investigator-Initiated Study of Olaparib and Temozolomide in SCLC: Final Analysis and CNS Outcomes
Authors: Meador Catherine B. , Digumarthy Subba R. , Yeap Beow Y. , Hung Yin P. , Mino-Kenudson Mari , Farago Anna F. , Heist Rebecca S. , Marcoux J. Paul , Rangachari Deepa , Barbie David A. , Piotrowska Zofia
Published: January 2025

Supplemental Figure 1. Overview of study participants.
Supplementary Table S5 from Homoharringtonine Added to Venetoclax and Azacitidine Improves Outcome and Mitigates Genetic Impact in Relapsed/Refractory AML: A Multicenter Cohort Study
Authors: Yu Guopan , Zhang Yu , Yu Sijian , Yin Zhao , Weng Guangyang , Xu Na , Du Xin , Lin Dongjun , Xiao Jie , Sun Zhiqiang , Zhang Hongyu , Liang Xinquan , Guo Ziwen , Zhao Weihua , Dai Min , Fan Zhiping , Xuan Li , Liu Hui , Xu Dan , Ye Jieyu , Jiang Xuejie , Shi Pengcheng , Jin Hua , Liu Qifa
Published: January 2025

Supplementary Table S5. The 167-gene next generation sequencing panel.
Supplementary Table S4 from Homoharringtonine Added to Venetoclax and Azacitidine Improves Outcome and Mitigates Genetic Impact in Relapsed/Refractory AML: A Multicenter Cohort Study
Authors: Yu Guopan , Zhang Yu , Yu Sijian , Yin Zhao , Weng Guangyang , Xu Na , Du Xin , Lin Dongjun , Xiao Jie , Sun Zhiqiang , Zhang Hongyu , Liang Xinquan , Guo Ziwen , Zhao Weihua , Dai Min , Fan Zhiping , Xuan Li , Liu Hui , Xu Dan , Ye Jieyu , Jiang Xuejie , Shi Pengcheng , Jin Hua , Liu Qifa
Published: January 2025

Supplementary Table S4. Subgroup analyses of the CRc rate of VAH versus VA based on genetic patterns.
Supplementary Figure S4 from Homoharringtonine Added to Venetoclax and Azacitidine Improves Outcome and Mitigates Genetic Impact in Relapsed/Refractory AML: A Multicenter Cohort Study
Authors: Yu Guopan , Zhang Yu , Yu Sijian , Yin Zhao , Weng Guangyang , Xu Na , Du Xin , Lin Dongjun , Xiao Jie , Sun Zhiqiang , Zhang Hongyu , Liang Xinquan , Guo Ziwen , Zhao Weihua , Dai Min , Fan Zhiping , Xuan Li , Liu Hui , Xu Dan , Ye Jieyu , Jiang Xuejie , Shi Pengcheng , Jin Hua , Liu Qifa
Published: January 2025

Supplementary Figure S4. Survival outcomes in VA and VAH patients depending on FLT3-ITD mutation.
Supplementary Figure S3 from Homoharringtonine Added to Venetoclax and Azacitidine Improves Outcome and Mitigates Genetic Impact in Relapsed/Refractory AML: A Multicenter Cohort Study
Authors: Yu Guopan , Zhang Yu , Yu Sijian , Yin Zhao , Weng Guangyang , Xu Na , Du Xin , Lin Dongjun , Xiao Jie , Sun Zhiqiang , Zhang Hongyu , Liang Xinquan , Guo Ziwen , Zhao Weihua , Dai Min , Fan Zhiping , Xuan Li , Liu Hui , Xu Dan , Ye Jieyu , Jiang Xuejie , Shi Pengcheng , Jin Hua , Liu Qifa
Published: January 2025

Supplementary Figure S3. Prognostic effect of VA and VAH on OS in genetic subgroups.
Supplementary Figure S2 from Homoharringtonine Added to Venetoclax and Azacitidine Improves Outcome and Mitigates Genetic Impact in Relapsed/Refractory AML: A Multicenter Cohort Study
Authors: Yu Guopan , Zhang Yu , Yu Sijian , Yin Zhao , Weng Guangyang , Xu Na , Du Xin , Lin Dongjun , Xiao Jie , Sun Zhiqiang , Zhang Hongyu , Liang Xinquan , Guo Ziwen , Zhao Weihua , Dai Min , Fan Zhiping , Xuan Li , Liu Hui , Xu Dan , Ye Jieyu , Jiang Xuejie , Shi Pengcheng , Jin Hua , Liu Qifa
Published: January 2025

Supplementary Figure S2. Treatment response rates by co-mutations.
Supplementary Figure S1 from Homoharringtonine Added to Venetoclax and Azacitidine Improves Outcome and Mitigates Genetic Impact in Relapsed/Refractory AML: A Multicenter Cohort Study
Authors: Yu Guopan , Zhang Yu , Yu Sijian , Yin Zhao , Weng Guangyang , Xu Na , Du Xin , Lin Dongjun , Xiao Jie , Sun Zhiqiang , Zhang Hongyu , Liang Xinquan , Guo Ziwen , Zhao Weihua , Dai Min , Fan Zhiping , Xuan Li , Liu Hui , Xu Dan , Ye Jieyu , Jiang Xuejie , Shi Pengcheng , Jin Hua , Liu Qifa
Published: January 2025

Supplementary Figure S1. Analysis of pairwise co-mutation and mutual exclusivity in the top 20 most frequently detected gene mutations.
Supplementary Table 1 from Genomic, Epigenomic, and Transcriptomic Inter- and Intratumor Heterogeneity in Desmoid Tumors
Authors: De Bellis Chelsea , Vennam Sujay , Eeles Christopher , Rahimizadeh Pegah , Cates Justin , Stricker Thomas , Hoffman Jenny , Ganjoo Kristen , Charville Gregory W. , Haibe-Kains Benjamin , van de Rijn Matt , Przybyl Joanna
Published: January 2025

Supplementary Table 1. Sequencing statistics and quality control metrics.
Supplementary Figure 2 from Genomic, Epigenomic, and Transcriptomic Inter- and Intratumor Heterogeneity in Desmoid Tumors
Authors: De Bellis Chelsea , Vennam Sujay , Eeles Christopher , Rahimizadeh Pegah , Cates Justin , Stricker Thomas , Hoffman Jenny , Ganjoo Kristen , Charville Gregory W. , Haibe-Kains Benjamin , van de Rijn Matt , Przybyl Joanna
Published: January 2025

Supplementary Figure 2. Validation of the S45F mutation in the CTNNB1 gene in recurrent tumor specimen STT8702 of Patient 3.
Supplementary Data 1 from A Phase II Study of Acimtamig (AFM13) in Patients with CD30-Positive, Relapsed, or Refractory Peripheral T-cell Lymphomas
Authors: Kim Won Seog , Shortt Jake , Zinzani Pier Luigi , Mikhailova Natalia , Radeski Dejan , Ribrag Vincent , Domingo Domenech Eva , Sawas Ahmed , Alexis Karenza , Emig Michael , Elbadri Riham , Hajela Pallavi , Ravenstijn Paulien , Pinto Sheena , Garcia Linta , Overesch Andre , Pietzko Kerstin , Horwitz Steven
Published: January 2025

Supplementary methods including full inclusion/exclusion criteria, Supplementary Tables 1–5 (includes study representativeness table), and Supplementary Figure 1
Supplementary Figure 1 from Genomic, Epigenomic, and Transcriptomic Inter- and Intratumor Heterogeneity in Desmoid Tumors
Authors: De Bellis Chelsea , Vennam Sujay , Eeles Christopher , Rahimizadeh Pegah , Cates Justin , Stricker Thomas , Hoffman Jenny , Ganjoo Kristen , Charville Gregory W. , Haibe-Kains Benjamin , van de Rijn Matt , Przybyl Joanna
Published: January 2025

Supplementary Figure 1. Validation of variable expression of selected candidate prognostic markers at the protein level.
Table 1 from Targeting c-MET for Endoscopic Detection of Dysplastic Lesions within Barrett’s Esophagus Using EMI-137 Fluorescence Imaging
Authors: Huang Yi-Jhih , Rieder Jonas , Tan Kel Vin , Tenditnaya Anna , Vojnovic Borivoj , Gorpas Dimitris , Quante Michael , Vallis Katherine A.
Published: January 2025

Details of L2-IL1β ex vivo IVIS experiment. Average radiant efficiencies of ROIs were calculated from ex vivo IVIS images: left and right squamocolumnar junctions, the junction between the forestomach and the cardiac/corpus of the stomach, and EGJ, with the corresponding background regions located in the corpus of the stomach.
Supplementary Table S1 from Targeting c-MET for Endoscopic Detection of Dysplastic Lesions within Barrett’s Esophagus Using EMI-137 Fluorescence Imaging
Authors: Huang Yi-Jhih , Rieder Jonas , Tan Kel Vin , Tenditnaya Anna , Vojnovic Borivoj , Gorpas Dimitris , Quante Michael , Vallis Katherine A.
Published: January 2025

Supplementary Table S1. Tissue Microarray Metadata (merged data from 4 TMAs used in the study): Correlation between c-MET expression status and patient characteristics and H-score.
Supplementary Information S1 from Targeting c-MET for Endoscopic Detection of Dysplastic Lesions within Barrett’s Esophagus Using EMI-137 Fluorescence Imaging
Authors: Huang Yi-Jhih , Rieder Jonas , Tan Kel Vin , Tenditnaya Anna , Vojnovic Borivoj , Gorpas Dimitris , Quante Michael , Vallis Katherine A.
Published: January 2025

Supplementary Information S1. Details of the Fluorescence Molecular Endoscopy (FME) System; Representative videos with screenshot of FME in L2-IL1b transgenic mice
Supplementary Figure S2 from Targeting c-MET for Endoscopic Detection of Dysplastic Lesions within Barrett’s Esophagus Using EMI-137 Fluorescence Imaging
Authors: Huang Yi-Jhih , Rieder Jonas , Tan Kel Vin , Tenditnaya Anna , Vojnovic Borivoj , Gorpas Dimitris , Quante Michael , Vallis Katherine A.
Published: January 2025

Supplementary Figure S2. Establishment of a dual xenograft mouse model for testing EMI-137.
Supplementary Figure S1 from Targeting c-MET for Endoscopic Detection of Dysplastic Lesions within Barrett’s Esophagus Using EMI-137 Fluorescence Imaging
Authors: Huang Yi-Jhih , Rieder Jonas , Tan Kel Vin , Tenditnaya Anna , Vojnovic Borivoj , Gorpas Dimitris , Quante Michael , Vallis Katherine A.
Published: January 2025

Supplementary Figure S1. c-MET immunostaining of FLO-1 and OE33 cells.
Figure 5 from Targeting c-MET for Endoscopic Detection of Dysplastic Lesions within Barrett’s Esophagus Using EMI-137 Fluorescence Imaging
Authors: Huang Yi-Jhih , Rieder Jonas , Tan Kel Vin , Tenditnaya Anna , Vojnovic Borivoj , Gorpas Dimitris , Quante Michael , Vallis Katherine A.
Published: January 2025

Ex vivo fluorescence imaging of L2-IL1β mice: A, Representative white light and fluorescence images of the excised stomach taken from L2-IL1β mice. The white dotted line shows the SCJ, which is within the stomach in mice. A protruding, irregular lesion is visible at the EGJ and SCJ in the stomach taken from a high-score group mouse, with the corresponding fluorescence image below. B, Upregulation of c-MET in dysplastic lesions from the low-, intermediate-, and high-score groups. C, Correlation between dysplasia score and level of c-MET expression. D, Box-whisker plot of ROI analysis, which shows increasing fluorescence from low- to intermediate- to high-score lesions. E, Quantification of TBR in ex vivo IVIS fluorescence imaging. Range of box-whisker plots indicate minimum to maximum. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001. Eso, esophagus; H&E, hematoxylin and eosin; Max, maximum; Min, minimum; ns, not significant; Sbkg, signal intensities of the background; SJC, squamocolumnar junction; Slesion, signal intensities of the lesion.
Figure 2 from Targeting c-MET for Endoscopic Detection of Dysplastic Lesions within Barrett’s Esophagus Using EMI-137 Fluorescence Imaging
Authors: Huang Yi-Jhih , Rieder Jonas , Tan Kel Vin , Tenditnaya Anna , Vojnovic Borivoj , Gorpas Dimitris , Quante Michael , Vallis Katherine A.
Published: January 2025

EMI-137 binding affinity and specificity: A, Saturation binding assay showing the Kd value of EMI-137 is 8.72 nmol/L. B, Competitive binding assay of EMI-137 indicating the IC50 value of unlabeled EMI-137 is 25 nmol/L. C, Live-cell microscopy FLO-1 cells showing an absence of immunofluorescence staining for c-MET, whereas there is a strong signal in OE33 cells at 2 hours after the addition of EMI-137. Fluorescence in OE33 cells was markedly reduced when cells were exposed to a mixture of 100 nmol/L unlabeled EMI-137 with 10 nmol/L EMI-137. Scale bar, 50 μm. AU, Arbitary unit.
Data from Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1+CD8+ T Cells in Metastatic Ovarian Cancer
Authors: Lanickova Tereza , Hensler Michal , Kasikova Lenka , Vosahlikova Sarka , Angelidou Artemis , Pasulka Josef , Griebler Hannah , Drozenova Jana , Mojzisova Katerina , Vankerckhoven Ann , Laco Jan , Ryska Ales , Dundr Pavel , Kocian Roman , Cibula David , Brtnicky Tomas , Skapa Petr , Jacob Francis , Kovar Marek , Praznovec Ivan , McNeish Iain A. , Halaska Michal J. , Rob Lukas , Coosemans An , Orsulic Sandra , Galluzzi Lorenzo , Spisek Radek , Fucikova Jitka
Published: January 2025

AbstractPurpose:
Patients with high-grade serous ovarian carcinoma (HGSOC) are virtually insensitive to immune checkpoint inhibitors (ICI) employed as standalone therapeutics, at least in part reflecting microenvironmental immunosuppression. Thus, conventional chemotherapeutics and targeted anticancer agents that not only mediate cytotoxic effects but also promote the recruitment of immune effector cells to the HGSOC microenvironment stand out as promising combinatorial partners for ICIs in this oncological indication.
Experimental Design:
We harnessed a variety of transcriptomic, spatial, and functional assays to characterize the differential impact of neoadjuvant paclitaxel-carboplatin on the immunological configuration of paired primary and metastatic HGSOC biopsies as compared to neoadjuvant chemotherapy (NACT)-naïve HGSOC samples from five independent patient cohorts.
Results:
We found NACT-driven endoplasmic reticulum stress and calreticulin exposure in metastatic HGSOC lesions culminates with the establishment of a dense immune infiltrate including follicular T cells (TFH cells), a prerequisite for mature tertiary lymphoid structure (TLS) formation. In this context, TLS maturation was associated with an increased intratumoral density of ICI-sensitive TCF1+PD1+ CD8+ T cells over their ICI-insensitive TIM-3+PD1+ counterparts. Consistent with this notion, chemotherapy coupled with a PD1-targeting ICI provided a significant survival benefit over either therapeutic approach in syngeneic models of HGSOC bearing high (but not low) tumor mutational burden.
Conclusions:
Altogether, our findings suggest that NACT promotes TLS formation and maturation in HGSOC lesions, de facto preserving an intratumoral ICI-sensitive T-cell phenotype. These observations emphasize the role of rational design, especially relative to the administration schedule, for clinical trials testing chemotherapy plus ICIs in patients with HGSOC.

See related commentary by Bravo Melgar and Laoui, p. 10
Data from Germline DNA Damage Repair Variants and Prognosis of Patients with High-Risk or Metastatic Prostate Cancer
Authors: Stopsack Konrad H. , Vijai Joseph , Conry Michael , Berchuck Jacob E. , Kemel Yelena , Vasselman Samantha E. , Freeman Dory A. , Lee Gwo-Shu M. , Mandelker Diana , Solit David B. , Morris Michael J. , Penney Kathryn L. , Abida Wassim , Offit Kenneth , Mucci Lorelei A. , Kantoff Philip W. , Pomerantz Mark M.
Published: January 2025

AbstractPurpose:
Deleterious germline variants in certain DNA repair genes are risk factors for developing aggressive prostate cancer. The objective was to quantify their prognostic impact after prostate cancer diagnosis.
Experimental Design:
Men with prostate cancer, predominantly of European ancestry, were included from four cohorts with long-term follow-up. Pathogenic or likely pathogenic germline variants in 26 DNA repair genes were assessed in relation to metastasis-free survival in high-risk localized prostate cancer and to overall survival in metastatic castration-sensitive prostate cancer (mCSPC) and metastatic castration-resistant prostate cancer (mCRPC).
Results:
Among 3,525 patients initially diagnosed with nonmetastatic prostate cancer, 2,594 had high-risk localized prostate cancer, 429 had mCSPC, and 502 had mCRPC at inclusion. BRCA2 variant carriers did not have worse metastasis-free survival in high-risk localized prostate cancer [hazard ratio (HR), 1.01; 95% confidence interval (CI), 0.69–1.46] or overall survival in mCSPC (HR, 0.46; 95% CI, 0.14–1.45) or mCRPC (HR, 0.60; 95% CI, 0.31–1.17) compared with noncarriers of DNA repair variants. Among 868 additional patients with de novo metastatic (M1) prostate cancer, BRCA2 variant carriers tended to have worse overall survival (HR, 1.59; 95% CI, 1.01–2.51). BRCA2 prognostic associations were not explained by radiation, PARP inhibitor, or platinum therapy. Results for other genes were limited in precision because variants were less common.
Conclusions:
Among patients with high-risk or metastatic prostate cancer who were initially diagnosed with and treated for nonmetastatic tumors, germline DNA repair variants in BRCA2 do not confer a substantially worse prognosis.
Data from An Artificial Intelligence–Driven Preoperative Radiomic Subtype for Predicting the Prognosis and Treatment Response of Patients with Papillary Thyroid Carcinoma
Authors: Li Qiang , Zhang Weituo , Liao Tian , Gao Yi , Zhang Yanzhi , Jin Anqi , Ma Ben , Qu Ning , Zhang Huan , Zheng Xiangqian , Li Dapeng , Yun Xinwei , Zhao Jingzhu , Yu Herbert , Gao Ming , Wang Yu , Qian Biyun
Published: January 2025

AbstractPurpose:
From 8% to 28% of patients with papillary thyroid carcinoma (PTC) experience recurrence, complicating risk stratification and treatment. We previously identified an inflammatory molecular subtype of PTC associated with poor prognosis. Based on this subtype, we aimed to develop and validate a noninvasive radiomic signature to predict prognosis and treatment response in patients with PTC.
Experimental Design:
We collected preoperative ultrasound images from two large independent centers (n = 2,506) to develop and validate a deep learning radiomics signature of inflammation (DLRI) for predicting the inflammatory subtype of PTC, including its correlation with prognosis and anti-inflammatory traditional Chinese medicine (TCM) treatment. Training set 1 (n = 64) and internal validation set 2 (n = 1,108) were from Tianjin Medical University Cancer Institute and Hospital. External validation sets 1 (n = 76) and 2 (n = 1,258) were from Fudan University Shanghai Cancer Center.
Results:
We developed a DLRI to accurately predict PTC’s inflammatory subtype (AUC = 0.97 in training set 1 and AUC = 0.82 in external validation set 1). High-risk DLRI was significantly associated with poor disease-free survival in the first cohort [HR = 16.49, 95% confidence interval (CI), 7.92–34.35, P < 0.001] and second cohort (HR = 5.42, 95% CI, 3.67–8.02, P < 0.001). The DLRI independently predicted disease-free survival, irrespective of clinicopathologic variables (P < 0.001 for all). Furthermore, patients with high-risk DLRI were likely to benefit from anti-inflammatory TCM treatment (HR = 0.19, 95% CI, 0.06–0.55, P = 0.002), whereas those with low-risk DLRI did not.
Conclusions:
DLRI is a reliable noninvasive tool for evaluating prognosis and guiding anti-inflammatory TCM treatment in patients with PTC. Prospective studies are needed to confirm these findings.
Data from Integrating Molecular Imaging and Transcriptomic Profiling in Advanced HER2-Positive Breast Cancer Receiving Trastuzumab Emtansine: An Analysis of the ZEPHIR Clinical Trial
Authors: Rediti Mattia , Fimereli Danai , Mileva Magdalena , Wimana Zéna , Venet David , Flamen Patrick , Guiot Thomas , de Vries Elisabeth G.E. , Schröder Carolien P. , Menke-van der Houven van Oordt Catharina Willemien , Maetens Marion , Majjaj Samira , Larsimont Denis , Rothé Françoise , Sotiriou Christos , Gebhart Géraldine
Published: January 2025

AbstractPurpose:
The ZEPHIR clinical trial evaluated the role of [89Zr]trastuzumab-PET/CT (HER2-PET/CT) and 2-[18F]fluoro-2-deoxy-D-glucose PET/CT ([18F]FDG-PET/CT) in predicting outcomes in patients with advanced HER2-positive breast cancer treated with trastuzumab emtansine (T-DM1). In this study, we combined molecular/metabolic imaging and transcriptomic data to investigate the biological processes associated with [89Zr]trastuzumab and [18F]FDG uptake and to dissect the mechanisms involved in T-DM1 resistance.
Experimental Design:
RNA was extracted from metastasis biopsies obtained in the ZEPHIR trial. HER2-PET/CT and [18F]FDG-PET/CT imaging data of biopsied lesions were integrated with transcriptomic data. Lesions were compared based on the level of [89Zr]trastuzumab uptake as well as on the presence/absence of metabolic response, defined comparing baseline and on-treatment [18F]FDG-PET/CT.
Results:
We analyzed matched transcriptomic and molecular/metabolic imaging data for 24 metastases. Genes and pathways involved in extracellular matrix (ECM) organization and glycosylphosphatidylinositol synthesis were enriched in lesions presenting low [89Zr]trastuzumab uptake. [18F]FDG uptake at baseline correlated with proliferation and immune-related processes. Hypoxia and ECM-related processes were enriched in lesions showing no metabolic response to T-DM1, whereas immune-related processes were associated with high [89Zr]trastuzumab uptake and metabolic response. Gene signatures including differentially expressed genes according to [89Zr]trastuzumab uptake and metabolic response showed predictive value in an external cohort.
Conclusions:
To the best of our knowledge, this study represents the first correlative analysis between [89Zr]trastuzumab tumor uptake and gene expression profiling in humans. Our findings suggest a role for ECM in impairing [89Zr]trastuzumab tumor uptake and T-DM1 metabolic response in advanced HER2-positive breast cancer, highlighting the potential of molecular imaging to depict tumor microenvironment features.
Data from CD40 Agonist on Patient-Derived Xenograft Mice for the Treatment of B-Cell Acute Lymphoblastic Leukemia
Authors: Bellaye Pierre-Simon , Georgievski Aleksandra , Ballerini Paola , Bouslama Boutheina , Richard Corentin , Boidot Romain , Chevreux Guillaume , Legros Véronique , Guy Julien , Racine Jessica , Collin Bertrand , Garrido Carmen , Quéré Ronan
Published: January 2025

AbstractPurpose:
Cluster of differentiation 40 (CD40) is expressed on B-cell acute lymphoblastic leukemia (B-ALL) cases. However, the effect of CD40 activation on B-ALL cells has never been tested in vivo.
Experimental Design:
The aim of our preclinical study was to investigate the therapeutic potential of a CD40 agonist in the treatment of B-ALL using patient-derived xenograft mouse models.
Results:
Intravenous administration of the CD40 agonist significantly impeded B-ALL cell proliferation and growth in vivo, accompanied by rapid activation of the ERK pathway, which led to the induction of apoptosis and disruption of cell-cycle progression. Cotreatment with a specific inhibitor of ERK further demonstrated that CD40 stimulation induced the proapoptosis of B-ALL cells in an ERK-dependent manner. Proteomic analysis revealed alterations in key signaling pathways associated with B-ALL expansion and maintenance. Moreover, the CD40 agonist markedly reduced the frequency of leukemia-initiating cells and leukemia development in patient-derived xenograft mice. Our study showed that the CD40 agonist can be associated with chemotherapeutic agents such as vincristine and dexamethasone, and this combination showed improved effectiveness. Additionally, the CD40 agonist was more effective on pre–B-ALL (EGIL B-III) that expressed CD40 than on common B-ALL (EGIL B-II) that lacked CD40 expression.
Conclusions:
These findings suggest that CD40 agonists are promising immunotherapeutic candidates for pediatric B-ALL, warranting further clinical investigations to improve patient outcomes in CD40-expressing B-ALL.
Data from Phase I/II Investigator-Initiated Study of Olaparib and Temozolomide in SCLC: Final Analysis and CNS Outcomes
Authors: Meador Catherine B. , Digumarthy Subba R. , Yeap Beow Y. , Hung Yin P. , Mino-Kenudson Mari , Farago Anna F. , Heist Rebecca S. , Marcoux J. Paul , Rangachari Deepa , Barbie David A. , Piotrowska Zofia
Published: January 2025

AbstractPurpose:
Temozolomide plus PARP inhibition has shown promise in small cell lung cancer (SCLC). We previously reported outcomes from the first 50 patients (cohort 1) of a phase I/II trial of olaparib/temozolomide in recurrent SCLC. In this study, we report a final analysis of this trial, including a second cohort with an alternate dosing strategy and an exploratory analysis of central nervous system (CNS)–specific outcomes.
Patients and Methods:
This was an open-label phase I/II trial testing the combination of olaparib and temozolomide in relapsed SCLC. The primary endpoint was objective response rate (ORR). Secondary endpoints were safety, progression-free survival, and overall survival. We tested escalating doses of olaparib/temozolomide across two cohorts, both of which had temozolomide dosed on days 1 to 7 of each 21-day cycle. In previously published cohort 1, olaparib was dosed on days 1 to 7; in cohort 2, olaparib was dosed continuously.
Results:
Sixty-six patients were enrolled across the two cohorts: 50 in cohort 1 and 16 in cohort 2. The confirmed ORR of cohort 1 was 41.7% (20/48 evaluable), and the confirmed ORR of cohort 2 was 7% (1/14 evaluable; closed after dose escalation to enrollment for lack of observed efficacy). Among 15/66 patients (22.7%) with untreated brain metastases at enrollment, the best overall intracranial response was complete response in 6/15 patients, partial response in 4/15 patients, and stable disease in 3/15 patients for a CNS disease control rate of 87% (95% confidence interval, 59.5%–98.3%).
Conclusions:
Olaparib/temozolomide may be effective in relapsed SCLC, especially for patients with CNS disease. Ongoing analyses with regard to optimal dosing schedule will inform potential for future use of this combination in SCLC.
Data from Genomic, Epigenomic, and Transcriptomic Inter- and Intratumor Heterogeneity in Desmoid Tumors
Authors: De Bellis Chelsea , Vennam Sujay , Eeles Christopher , Rahimizadeh Pegah , Cates Justin , Stricker Thomas , Hoffman Jenny , Ganjoo Kristen , Charville Gregory W. , Haibe-Kains Benjamin , van de Rijn Matt , Przybyl Joanna
Published: January 2025

AbstractPurpose:
Desmoid tumors are bland fibroblastic tumors that do not metastasize but have a high rate of local recurrence. Previously published studies proposed two different transcriptomic signatures to predict relapse. Molecular heterogeneity has been well established in high-grade sarcomas, but little is known about molecular variability within locally aggressive tumors such as desmoids.
Experimental Design:
We performed transcriptomic profiling of 31 specimens from 20 primary desmoid tumors to identify genes predictive of relapse. We also performed multiomic analysis including DNA methylation, copy-number alterations, point mutations, and gene expression on 24 specimens from different regions of primary and recurrent desmoid tumors from three patients (7–9 specimens per patient).
Results:
We observed highly variable expression of transcriptomic prognostic signatures both in patients who did and did not progress. Signatures associated with favorable and unfavorable outcomes were detected in different regions within the same tumor. Further multiomic studies showed remarkable intra- and intertumor heterogeneity of genomic, epigenomic, and transcriptomic patterns. The transcriptomic profiles showed the highest degree of variability within tumors and between primary and recurrent tumors from the same patient.
Conclusions:
This study shows an unexpected degree of intra- and intertumor heterogeneity in desmoid tumors. Our analysis indicates that molecular analysis of a single-tumor biopsy may underestimate the magnitude of molecular alterations in desmoid tumors. Our study also shows that recurrent desmoid tumors acquire multiple new molecular alterations. Thus, molecular heterogeneity is an important consideration in drug development and validation of prognostic and predictive biomarkers for desmoid tumors.
Supplementary Figure S3 from Automated Breast Density Assessment for Full-Field Digital Mammography and Digital Breast Tomosynthesis
Authors: Jiang Shu , Bennett Debbie L. , Chen Simin , Toriola Adetunji T. , Colditz Graham A.
Published: January 2025

Supplementary Figure S3 shows density estimation by radiologists vs deep learning model for digital breast tomosynthesis
Figure S1 from Black Raspberry Modulates Cecal and Oral Microbiomes at the Early Stage of a Dibenzo[def,p]chrysene-Induced Murine Oral Cancer Model
Authors: Zhao Jingcheng , Sun Yuan-Wan , Chen Kun-Ming , Aliaga Cesar , Bisanz Jordan E. , El-Bayoumy Karam
Published: January 2025

Figure S1: The ASV richness was higher in mouse cecal samples compared to saliva samples.
Data from What Is the Cost: Financial Toxicity and Screening Fatigue in Li–Fraumeni Syndrome
Authors: Underkofler Kaylee A. , Thomas Martha H. , Erickson Sarah H. , Panzer Alayna A. , Fitzgibbon Kara S. , Ring Kari L.
Published: January 2025

Abstract
Patients with Li–Fraumeni syndrome (LFS) are recommended to follow a comprehensive surveillance protocol, but the demanding nature may limit adherence. We sought to identify barriers to adherence and to determine whether screening fatigue and financial hardship are contributors. A 39-item online survey was developed and distributed to patients presenting to a LFS clinic between 2017 and 2022. Of the 39 patients eligible, 20 responded to the survey (51%). Of the respondents, 75% reported they do not skip surveillance tests; however, this was not consistent when asked about specific tests, with only 65% and 40% up to date with colonoscopy and esophagogastroduodenoscopy, respectively. Hundred percent of those diagnosed within the last 5 years said they never skip tests, whereas only 50% of those diagnosed more than 5 years ago reported the same (P = 0.01). Barriers to adherence were reported by 85% and most commonly included finances (40%), time (25%), and difficulty scheduling (25%). Only 21% felt no financial stress, and 63% worried at least somewhat about their future financial situation because of LFS. Even with insurance, 65% felt their share of healthcare costs was too high. Adherence to rigorous cancer surveillance is imperfect and decreases over time among patients with LFS. Whereas number of tests was not a commonly cited barrier, time and difficulty scheduling were common and may contribute to screening fatigue. The degree of financial stress in the affluent population studied should raise even greater concern about financial strain in the LFS population in general.

Prevention Relevance: Li–Fraumeni syndrome (LFS) essentially guarantees a cancer diagnosis in an affected individual’s lifetime. Findings of this study reveal a difficulty for patients with LFS to adhere to recommended rigorous surveillance protocols and question how identified barriers can be broken down to reduce the morbidity and mortality of LFS.
Supplementary Figure 5 from Efficacy of CBP/p300 Dual Inhibitors against Derepression of KREMEN2 in cBAF-Deficient Cancers
Authors: Sasaki Mariko , Kato Daiki , Yoshida Hiroshi , Shimizu Takafumi , Ogiwara Hideaki
Published: January 2025

Downregulation of KREMEN2 through CBP/p300 inhibition in SMARCA4/SMARCA2-deficient and SS18-SSX-fusion cancer cells induces apoptosis via KREMEN1.
Figure 3 from Efficacy of CBP/p300 Dual Inhibitors against Derepression of KREMEN2 in cBAF-Deficient Cancers
Authors: Sasaki Mariko , Kato Daiki , Yoshida Hiroshi , Shimizu Takafumi , Ogiwara Hideaki
Published: January 2025

SMARCA4/SMARCA2 deficiency and SS18–SSX fusion lead to upregulation of KREMEN2 gene expression. A, Expression of KREMEN2 mRNA in SWI/SNF-proficient, SMARCA4/SMARCA2-deficient, and SS18–SSX fusion cell lines (relative to that in DMS114 cells). Data are presented as the mean ± SEM; n = 3 independent experiments. B, Violin plots showing clustered expression of KREMEN2 mRNA in SWI/SNF-WT, SMARCB1-deficient, ARID1A-deficient, PBRM1-deficient, SMARCA4-deficient, SMARCA4/SMARCA2-deficient, and SS18–SSX fusion cell lines based on an analysis of mutations, gene CN, and gene expression data from DepMap (data version 23Q2). SWI/SNF-proficient (n = 1,238), SMARCB1-deficient (n = 19), ARID1A-deficient (n = 52), PBRM1-deficient (n = 23), SMARCA4-deficient (n = 34), SMARCA2-deficient (n = 27), SMARCA4/SMARCA2-deficient (n = 6), and SS18–SSX (n = 5) cell lines were analyzed, and data are presented as the mean ± SEM. n indicates the number of independent samples. C, Localization of signals generated by SMARCA4 and H3K27ac ChIP-seq, ATAC-seq, and RNA-seq around the KREMEN2 locus in SMARCA4/SMARCA2-deficient BIN-67 cells transduced with an SMARCA4 expression vector (+SMARCA4) and in BIN-67 cells without the SMARCA4 expression vector (−SMARCA4). D, Localization of signals generated by SS18, SMARCA4, RNAPII, and SUZ12 ChIP-seq, ATAC-seq, and RNA-seq around the KREMEN2 locus in SS18–SSX-fusion Aska-SS cells depleted of SS18–SSX by SSX-targeting shRNA (shSSX; SS18-WT) and in SS18–SSX fusion Aska-SS cells not depleted of SS18–SSX [i.e., transduced with NT shRNA (shNT; SS18–SSX)].
Data from Efficacy of CBP/p300 Dual Inhibitors against Derepression of KREMEN2 in cBAF-Deficient Cancers
Authors: Sasaki Mariko , Kato Daiki , Yoshida Hiroshi , Shimizu Takafumi , Ogiwara Hideaki
Published: January 2025

Abstract
The SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex is divided into three subcomplexes: cBAF, PBAF, and ncBAF. Constituent genes (e.g., SMARCB1, SMARCA4, SMARCA2, and SS18) of the SWI/SNF complex often harbor genetic abnormalities in various cancers. Previously, we found that histone acetyltransferases CBP/p300 dual inhibitors could be promising treatments for SMARCB1-deficient cancers. We show that treatment with CBP/p300 dual inhibitors causes synthetic lethality in cBAF-deficient cancers such as SMARCA4/SMARCA2-deficient and SS18–SSX fusion cancers. Given the sensitivity to CBP/p300 dual inhibitors and their commonality with SWI/SNF subcomplexes containing each subunit, CBP/p300 dual inhibitors could be promising treatments for cancers harboring abnormalities in constituent genes included in the entire cBAF subcomplex. Because SMARCA4/SMARCA2-deficient and SS18–SSX fusion cancer cells depend on transcriptional upregulation of KREMEN2 due to SMARCA4/SMARCA2 deficiency and SS18–SSX fusion, we clarified that synthetic lethality is induced by repressing expression of KREMEN2 by simultaneous inhibition of CBP/p300. In addition, simultaneous inhibition of CBP/p300 led to transcriptional downregulation of KREMEN2, followed by apoptosis induction via KREMEN1. Furthermore, treatment with CBP/p300 dual inhibitor suppressed the growth of xenografts derived from SMARCA4/SMARCA2-deficient and SS18–SSX fusion cancer cells, resulting from repression of KREMEN2 and induction of apoptosis. Thus, CBP/p300 dual inhibitors could be promising for SMARCA4/SMARCA2-deficient lung cancer and SS18–SSX fusion synovial sarcoma, which are entirely deficient in the cBAF complex.
Significance:
In this study, we clarified that the cBAF subcomplex is deficient in the SWI/SNF complex, resulting in dependency on the CBP/p300 paralog pair. Simultaneous inhibitors of the CBP/p300 paralog pair show promise for cBAF-deficient lung cancer, as well as rare cancers such as malignant rhabdoid tumors, epithelioid sarcomas, and synovial sarcomas.
Paraneoplastic Neurologic Syndrome Associated with Fallopian Tube Cancer: A Case Report
Authors: Wang YingXiang , Wu HaoTian , Gu Jian , Wang Jia
Published: January 2025

Introduction: Paraneoplastic neurological syndrome (PNS) was identified as a rare and unique clinical complication of primary tumors. Paraneoplastic cerebellar degeneration, a subtype of PNS, involved an immune-mediated attack on cerebellar Purkinje cells, resulting in a series of cerebellar symptoms. Case Presentation: We report a case of an elderly female patient who presented with subacute cerebellar symptoms, positive anti-YO antibody, and elevated CA-125 levels. Further examination revealed a fallopian tube malignancy. After surgery, intravenous immunoglobulin and glucocorticoid treatment, the oncological response was satisfactory, but the neurological symptoms did not improve. Conclusion: This case illustrates the importance of considering a paraneoplastic etiology in patients with unexplained neurological manifestations and emphasized the necessity of appropriate management and early treatment of the primary malignancy.