bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Sex-Specific Associations between Adiponectin and Leptin Signaling and Pancreatic Cancer Survival
Authors: Babic Ana , Wang Qiao-Li , Lee Alice A. , Yuan Chen , Rifai Nader , Luo Juhua , Tabung Fred K. , Shadyab Aladdin H. , Wactawski-Wende Jean , Saquib Nazmus , Kim Jihye , Kraft Peter , Sesso Howard D. , Buring Julie E. , Giovannucci Edward L. , Manson JoAnn E. , Stampfer Meir J. , Ng Kimmie , Fuchs Charles S. , Wolpin Brian M.
Published: October 2023

AbstractBackground:
Circulating adiponectin and leptin have been associated with risk of pancreatic cancer. However, the relationship between long-term exposure to these adipokines in the prediagnostic period with patient survival has not been investigated.
Methods:
Adipokine levels were measured in prospectively collected samples from 472 patients with pancreatic cancer. Because of sex-specific differences in adipokine levels, associations were evaluated separately for men and women. In a subset of 415 patients, we genotyped 23 SNPs in adiponectin receptor genes (ADIPOR1 and ADIPOR2) and 30 SNPs in the leptin receptor gene (LEPR).
Results:
Adiponectin levels were inversely associated with survival in women [HR, 1.71; 95% confidence interval (CI), 1.15–2.54]; comparing top with bottom quartile but not in men (HR, 0.89; 95% CI, 0.46–1.70). The SNPs rs10753929 and rs1418445 in ADIPOR1 were associated with survival in the combined population (per minor allele HR, 0.66; 95% CI, 0.51–0.84, and HR, 1.33; 95% CI, 1.12–1.58, respectively). Among SNPs in LEPR, rs12025906, rs3790431, and rs17127601 were associated with survival in the combined population [HRs, 1.54 (95% CI, 1.25–1.90), 0.72 (95% CI, 0.59–0.88), and 0.70 (95% CI, 0.56–0.89), respectively], whereas rs11585329 was associated with survival in men only (HR, 0.39; 95% CI, 0.23–0.66; Pinteraction = 0.0002).
Conclusions:
High levels of adiponectin in the prediagnostic period were associated with shorter survival among women, but not among men with pancreatic cancer. Several polymorphisms in ADIPOR1 and LEPR are associated with patient survival.
Impact:
Our findings reveal the association between adipokine signaling and pancreatic cancer survival and demonstrate the importance of examining obesity-associated pathways in relation to pancreatic cancer in a sex-specific manner.
Data from Heritable Traits and Lung Cancer Risk: A Two-Sample Mendelian Randomization Study
Authors: Pettit Rowland W. , Byun Jinyoung , Han Younghun , Ostrom Quinn T. , Coarfa Cristian , Bondy Melissa L. , Amos Christopher I.
Published: October 2023

AbstractIntroduction:
Lung cancer is a complex polygenic disorder. Analysis with Mendelian randomization (MR) allows for genetically predicted risks to be estimated between exposures and outcomes.
Methods:
We analyzed 345 heritable traits from the United Kingdom Biobank and estimated their associated effects on lung cancer outcomes using two sample MR. In addition to estimating effects with overall lung cancer, adenocarcinoma, small cell lung cancer, and squamous cell lung cancers, we performed conditional effect modeling with multivariate MR (MVMR) and the traits of alcohol use, smoking initiation, average pre-tax income, and educational attainment.
Results:
Univariate MR provided evidence for increased age at first sexual intercourse (OR, 0.55; P = 6.15 × 10−13), educational attainment (OR, 0.24; P = 1.07 × 10−19), average household income (OR, 0.58; P = 7.85 × 10−05), and alcohol usually taken with meals (OR, 0.19; P = 1.06 × 10−06) associating with decreased odds of overall lung cancer development. In contrast, a lack of additional educational attainment (OR, 8.00; P = 3.48 × 10−12), body mass index (OR, 1.28; P = 9.00 × 10−08), pack years smoking as a proportion of life span (OR, 9.93; P = 7.96 × 10−12), and weekly beer intake (OR, 3.48; P = 4.08 × 10−07) were associated with an increased risk of overall lung cancer development.
Conclusions:
Many heritable traits associated with an increased or inverse risk of lung cancer development. Effects vary based on histologic subtype and conditional third trait exposures.
Impact:
We identified several heritable traits and presented their genetically predictable impact on lung cancer development, providing valuable insights for consideration.
Data from The Association of Kidney Function and Inflammatory Biomarkers with Epithelial Ovarian Cancer Risk
Authors: Hathaway Cassandra A. , Townsend Mary K. , Sklar Elliot M. , Thomas-Purcell Kamilah B. , Terry Kathryn L. , Trabert Britton , Tworoger Shelley S.
Published: October 2023

Abstract
Background: One of the mechanisms of ovarian tumorigenesis is through inflammation. Kidney dysfunction is associated with increased inflammation; thus we assessed its relationship with ovarian cancer risk.
Methods: In prospectively collected samples, we evaluated the association of kidney function markers and C reactive protein (CRP) with ovarian cancer risk in the UK Biobank. We used multivariable-adjusted Cox proportional hazards models to evaluate quartiles of serum and urine markers with ovarian cancer risk overall and by histology. We assessed effect modification by CRP (≤3.0, >3.0 mg/L).
Results: Among 232,908 women (1,110 ovarian cancer cases diagnosed from 2006-2020), we observed no association between estimated glomerular filtration rate and ovarian cancer risk (Q4 vs. Q1: Hazard Ratio: 1.00, 95% Confidence Intervals: 0.83,1.22). Potassium was associated with endometrioid (Q4 vs. Q1: 0.33 [0.11,0.98]) and clear cell (4.74 [1.39,16.16]) tumors. Poor kidney function was associated with a non-significant increase in ovarian cancer risk among women with CRP >3.0 mg/L (e.g., uric acid Q4 vs. Q1. 1.23 [0.81,1.86]), but not CRP ≤3.0 mg/L (0.83 [0.66,1.05]). Other associations did not vary across CRP categories.
Conclusions: Kidney function was not clearly associated with ovarian cancer risk. Larger studies are needed to evaluate possible histology specific associations. Given the suggestive trend for increased ovarian cancer risk in women with poor kidney function and high CRP, future work is needed, particularly in populations with a high prevalence of inflammatory conditions.
Impact: This study provided the first evaluation of markers of kidney function in relation to ovarian cancer risk.
Data from The Association of Kidney Function and Inflammatory Biomarkers with Epithelial Ovarian Cancer Risk
Authors: Hathaway Cassandra A. , Townsend Mary K. , Sklar Elliot M. , Thomas-Purcell Kamilah B. , Terry Kathryn L. , Trabert Britton , Tworoger Shelley S.
Published: October 2023

AbstractBackground:
One of the mechanisms of ovarian tumorigenesis is through inflammation. Kidney dysfunction is associated with increased inflammation; thus, we assessed its relationship with ovarian cancer risk.
Methods:
In prospectively collected samples, we evaluated the association of kidney function markers and C-reactive protein (CRP) with ovarian cancer risk in the UK Biobank. We used multivariable-adjusted Cox proportional hazards models to evaluate quartiles of serum and urine markers with ovarian cancer risk overall and by histology. We assessed effect modification by CRP (≤3.0, >3.0 mg/L).
Results:
Among 232,908 women (1,110 ovarian cancer cases diagnosed from 2006–2020), we observed no association between estimated glomerular filtration rate and ovarian cancer risk (Q4 vs. Q1: HR, 1.00; 95% confidence intervals, 0.83–1.22). Potassium was associated with endometrioid (Q4 vs. Q1: 0.33, 0.11–0.98) and clear cell (4.74, 1.39–16.16) tumors. Poor kidney function was associated with a nonsignificant increase in ovarian cancer risk among women with CRP>3.0 mg/L (e.g., uric acid Q4 vs. Q1; 1.23, 0.81–1.86), but not CRP≤3.0 mg/L (0.83, 0.66–1.05). Other associations did not vary across CRP categories.
Conclusions:
Kidney function was not clearly associated with ovarian cancer risk. Larger studies are needed to evaluate possible histology specific associations. Given the suggestive trend for increased ovarian cancer risk in women with poor kidney function and high CRP, future work is needed, particularly in populations with a high prevalence of inflammatory conditions.
Impact:
This study provided the first evaluation of markers of kidney function in relation to ovarian cancer risk.
Data from Dietary fish and n-3 polyunsaturated fatty acid consumption, and renal cell carcinoma risk in Japan: The Japan Public Health Center-based Prospective Study
Authors: Takahashi Michiko , Sobue Tomotaka , Zha Ling , Kitamura Tetsuhisa , Iwasaki Motoki , Inoue Manami , Yamaji Taiki , Tsugane Shoichiro , Sawada Norie
Published: October 2023

Abstract
Background: Previous epidemiological studies found inconsistent associations between fish consumption and renal cell carcinoma (RCC). Although the consumption of n-3 polyunsaturated fatty acids (n-3 PUFA) was reported to protect against the development of some types of cancer, little is known regarding its association with RCC.
Methods: We investigated the association between fish and n-3 PUFA consumption and RCC risk using the Japan Public Health Center-based Prospective Study. We examined data from 84,063 eligible Japanese participants aged 45–74 years who responded to a validated food frequency questionnaire for Cohort I in 1995 and Cohort II in 1998. The participants were followed-up until 2013. HRs and 95% confidence intervals (CIs) were estimated using a multivariable-adjusted Cox proportional hazard model, and the exposure level was categorized into quartiles.
Results: Among the 1,272,298 person-years of follow-up, 262 cases of newly diagnosed RCC were identified. The multivariate-adjusted HRs for the highest vs. lowest quartile of fish, including shellfish, were [HR=1.43, 95% CI (0.98–2.07)] and the individual marine n-3 PUFAs were [HR=1.56, 95% CI (1.07–2.28) Ptrend=0.09] for eicosapentenoic acid, [HR=1.81, 95% CI (1.27–2.59) Ptrend=0.01] for docosapentaenoic acid, and [HR=1.56, 95% CI (1.07–2.27) Ptrend=0.09] for docosahexaenoic acid. RCC were further categorized based on diagnosis methods and cancer stage, and the positive correlation did not change substantially.
Conclusion: We demonstrated that high consumption of n-3PUFA is associated with RCC risk.
Impact: The positive association between n-3 PUFA and RCC risk was observed in Japanese who consume higher amounts of fish than Western populations.
Table S1 from A Phase II Study of Durvalumab for Bacillus Calmette-Guerin (BCG) Unresponsive Urothelial Carcinoma In Situ of the Bladder
Authors: Li Roger , Sexton Wade J. , Dhillon Jasreman , Berglund Anders , Naidu Shreyas , Borjas Gustavo , Rose Kyle , Kim Youngchul , Wang Xuefeng , Conejo-Garcia Jose R. , Jain Rohit K. , Poch Michael A. , Spiess Philippe E. , Pow-Sang Julio , Gilbert Scott M. , Zhang Jingsong
Published: October 2023

Study Representativeness Table
Supplementary Table S2 from Safety and Efficacy of Anlotinib Hydrochloride Plus Temozolomide in Patients with Recurrent Glioblastoma
Authors: Xu Qingsheng , Huang Kaiyuan , Meng Xiangqi , Weng Yuxiang , Zhang Luyuan , Bu Linghao , Zheng Xiujue , Cai Jinquan , Zhan Renya , Chen Qun
Published: October 2023

Supplementary Table S2. Representativeness of Study Participants
Supplementary Figure S2 from Safety and Efficacy of Anlotinib Hydrochloride Plus Temozolomide in Patients with Recurrent Glioblastoma
Authors: Xu Qingsheng , Huang Kaiyuan , Meng Xiangqi , Weng Yuxiang , Zhang Luyuan , Bu Linghao , Zheng Xiujue , Cai Jinquan , Zhan Renya , Chen Qun
Published: October 2023

Axial, sagittal and coronal gadolinium-enhanced and FLAIR MRI at pre-baseline (A-D). Three months later, MRI demonstrated progressive disease after anlotinib plus temozolomide (E-H).
Supplementary Spreadsheet S8 from Multiomic Mapping of Acquired Chromosome 1 Copy-Number and Structural Variants to Identify Therapeutic Vulnerabilities in Multiple Myeloma
Authors: Boyle Eileen M. , Blaney Patrick , Stoeckle James H. , Wang Yubao , Ghamlouch Hussein , Gagler Dylan , Braunstein Marc , Williams Louis , Tenenbaum Avital , Siegel Ariel , Chen Xiaoyi , Varma Gaurav , Avigan Jason , Li Alexander , Jinsi Monica , Kaminetzsky David , Arbini Arnaldo , Montes Lydia , Corre Jill , Rustad Even H. , Landgren Ola , Maura Francesco , Walker Brian A. , Bauer Michael , Bruno Benedetto , Tsirigos Aristotelis , Davies Faith E. , Morgan Gareth J.
Published: October 2023

Supplemental Spreadsheet 8: Differential expression between normal chr1 and whole-arm gains group MM patients
Supplementary Spreadsheet S12 from Multiomic Mapping of Acquired Chromosome 1 Copy-Number and Structural Variants to Identify Therapeutic Vulnerabilities in Multiple Myeloma
Authors: Boyle Eileen M. , Blaney Patrick , Stoeckle James H. , Wang Yubao , Ghamlouch Hussein , Gagler Dylan , Braunstein Marc , Williams Louis , Tenenbaum Avital , Siegel Ariel , Chen Xiaoyi , Varma Gaurav , Avigan Jason , Li Alexander , Jinsi Monica , Kaminetzsky David , Arbini Arnaldo , Montes Lydia , Corre Jill , Rustad Even H. , Landgren Ola , Maura Francesco , Walker Brian A. , Bauer Michael , Bruno Benedetto , Tsirigos Aristotelis , Davies Faith E. , Morgan Gareth J.
Published: October 2023

Differentially hypomethylated and concurrently overexpressed genes in gain(1q) MM patients
Supplementary Figure S3 from Multiomic Mapping of Acquired Chromosome 1 Copy-Number and Structural Variants to Identify Therapeutic Vulnerabilities in Multiple Myeloma
Authors: Boyle Eileen M. , Blaney Patrick , Stoeckle James H. , Wang Yubao , Ghamlouch Hussein , Gagler Dylan , Braunstein Marc , Williams Louis , Tenenbaum Avital , Siegel Ariel , Chen Xiaoyi , Varma Gaurav , Avigan Jason , Li Alexander , Jinsi Monica , Kaminetzsky David , Arbini Arnaldo , Montes Lydia , Corre Jill , Rustad Even H. , Landgren Ola , Maura Francesco , Walker Brian A. , Bauer Michael , Bruno Benedetto , Tsirigos Aristotelis , Davies Faith E. , Morgan Gareth J.
Published: October 2023

Hi-C interaction and TAD map of G7 region. The chromatin confirmation of the G7 region across the 3 HMCLs (U266, RPMI8226, and KMS11) and PC for comparison. The local TAD structure around the ABL2 locus appears conserved across the samples suggesting the additional gene dosage as a result of the CNV gain is likely the cause of the overexpression.
Supplementary Figure S16 from Multiomic Mapping of Acquired Chromosome 1 Copy-Number and Structural Variants to Identify Therapeutic Vulnerabilities in Multiple Myeloma
Authors: Boyle Eileen M. , Blaney Patrick , Stoeckle James H. , Wang Yubao , Ghamlouch Hussein , Gagler Dylan , Braunstein Marc , Williams Louis , Tenenbaum Avital , Siegel Ariel , Chen Xiaoyi , Varma Gaurav , Avigan Jason , Li Alexander , Jinsi Monica , Kaminetzsky David , Arbini Arnaldo , Montes Lydia , Corre Jill , Rustad Even H. , Landgren Ola , Maura Francesco , Walker Brian A. , Bauer Michael , Bruno Benedetto , Tsirigos Aristotelis , Davies Faith E. , Morgan Gareth J.
Published: October 2023

Methylation probe intensity across chromosome 1. Heatmap representation of the beta value for all probes across chromosome 1, the probes a presented in a genomic coordinate sorted fashion. The recurrent regions of deletion, gain, templated insertion, and chromothripsis have be highlighted along with the cytoband information for reference.
Supplementary Figure S15 from Multiomic Mapping of Acquired Chromosome 1 Copy-Number and Structural Variants to Identify Therapeutic Vulnerabilities in Multiple Myeloma
Authors: Boyle Eileen M. , Blaney Patrick , Stoeckle James H. , Wang Yubao , Ghamlouch Hussein , Gagler Dylan , Braunstein Marc , Williams Louis , Tenenbaum Avital , Siegel Ariel , Chen Xiaoyi , Varma Gaurav , Avigan Jason , Li Alexander , Jinsi Monica , Kaminetzsky David , Arbini Arnaldo , Montes Lydia , Corre Jill , Rustad Even H. , Landgren Ola , Maura Francesco , Walker Brian A. , Bauer Michael , Bruno Benedetto , Tsirigos Aristotelis , Davies Faith E. , Morgan Gareth J.
Published: October 2023

Genes with increased dependency in cell lines with del(1p) [part A] Genes with increased dependency in cell lines with del(1p) [part B]
Supplementary Figure S13 from Multiomic Mapping of Acquired Chromosome 1 Copy-Number and Structural Variants to Identify Therapeutic Vulnerabilities in Multiple Myeloma
Authors: Boyle Eileen M. , Blaney Patrick , Stoeckle James H. , Wang Yubao , Ghamlouch Hussein , Gagler Dylan , Braunstein Marc , Williams Louis , Tenenbaum Avital , Siegel Ariel , Chen Xiaoyi , Varma Gaurav , Avigan Jason , Li Alexander , Jinsi Monica , Kaminetzsky David , Arbini Arnaldo , Montes Lydia , Corre Jill , Rustad Even H. , Landgren Ola , Maura Francesco , Walker Brian A. , Bauer Michael , Bruno Benedetto , Tsirigos Aristotelis , Davies Faith E. , Morgan Gareth J.
Published: October 2023

CRISPR dependencies on chromosome 1. Nineteen myeloma cell lines and 15 random non-myeloma cell lines were identified and CERES dependencies for genes located on chr1 recorded. A total of 1701 genes were analyzed. Cell lines did not cluster according to their copy number profile but tended to clutter according to disease type. Common dependencies genes with gene dependencies< -1 clustered together and comprised proteasome subunit coding genes (PSMA5, PSMB2, PSMB4), three regulators of ubiquitin-protein transferase activity (RPL5, RPL11, CDC20), splicing factors (SF3B4, SF3A3, SFPQ, RNPC3, SRNPE, PRPF38A, PRPF38B) and DTL. The second clade could be further subdivided into two clades (n2.1=125 and n2.2=1594). The second of these two clades could further be divided into two clades (n2.2.1=105 and n2.2.2=1489). Clades 2.1 and 2.2.0 included genes with significant dependencies in some cell lines but not the others. Genes in these clusters include suspected drivers such as ADAR alongside more unexpected genes such as CD30. The tumor suppressor genes commonly found in deleted regions on 1p such as CDKN2C, or FAF1 were commonly found in clade with no dependency.
Supplementary Figure S12 from Multiomic Mapping of Acquired Chromosome 1 Copy-Number and Structural Variants to Identify Therapeutic Vulnerabilities in Multiple Myeloma
Authors: Boyle Eileen M. , Blaney Patrick , Stoeckle James H. , Wang Yubao , Ghamlouch Hussein , Gagler Dylan , Braunstein Marc , Williams Louis , Tenenbaum Avital , Siegel Ariel , Chen Xiaoyi , Varma Gaurav , Avigan Jason , Li Alexander , Jinsi Monica , Kaminetzsky David , Arbini Arnaldo , Montes Lydia , Corre Jill , Rustad Even H. , Landgren Ola , Maura Francesco , Walker Brian A. , Bauer Michael , Bruno Benedetto , Tsirigos Aristotelis , Davies Faith E. , Morgan Gareth J.
Published: October 2023

Gene set enrichment analysis highlighting pathway associated with A. Gain 1q in all patients (all genes) B. Gain 1q in all patients (restricted to genes on chromosome 1) C. Gain 1q in t(4;14) patients D. Gain 1q in t(11;14) E. Focal versus whole arm 1q gain.
Supplementary Figure S11 from Multiomic Mapping of Acquired Chromosome 1 Copy-Number and Structural Variants to Identify Therapeutic Vulnerabilities in Multiple Myeloma
Authors: Boyle Eileen M. , Blaney Patrick , Stoeckle James H. , Wang Yubao , Ghamlouch Hussein , Gagler Dylan , Braunstein Marc , Williams Louis , Tenenbaum Avital , Siegel Ariel , Chen Xiaoyi , Varma Gaurav , Avigan Jason , Li Alexander , Jinsi Monica , Kaminetzsky David , Arbini Arnaldo , Montes Lydia , Corre Jill , Rustad Even H. , Landgren Ola , Maura Francesco , Walker Brian A. , Bauer Michael , Bruno Benedetto , Tsirigos Aristotelis , Davies Faith E. , Morgan Gareth J.
Published: October 2023

Differential expression between patients with no 1q gain and those with a gain(1q:CKS1B). A. All genes that are differentially expressed
Supplementary appendix S2 from Liquid Biopsies with Circulating Plasma HPV–DNA Measurements—A Clinically Applicable Surveillance Tool for Patients with HPV-Positive Oropharyngeal Cancer
Authors: Jakobsen Kathrine K. , Bendtsen Simone K. , Pallisgaard Niels , Friborg Jeppe , Lelkaitis Giedrius , Grønhøj Christian , von Buchwald Christian
Published: October 2023

Comparing included patients to the OPSCC database
Figure S4 from Liquid Biopsies with Circulating Plasma HPV–DNA Measurements—A Clinically Applicable Surveillance Tool for Patients with HPV-Positive Oropharyngeal Cancer
Authors: Jakobsen Kathrine K. , Bendtsen Simone K. , Pallisgaard Niels , Friborg Jeppe , Lelkaitis Giedrius , Grønhøj Christian , von Buchwald Christian
Published: October 2023

Overall survival of patients in the OPSCC database compared to patients included in the project
Supplementary Data 1 from A Phase II Study of Optimized Individualized Adaptive Radiotherapy for Hepatocellular Carcinoma
Authors: Herr Daniel J. , Wang Chang , Mendiratta-Lala Mishal , Matuszak Martha , Mayo Charles S. , Cao Yue , Parikh Neehar D. , Ten Haken Randy , Owen Dawn , Evans Joseph R. , Stanescu Teodor , Yan Michael , Dawson Laura A. , Schipper Matthew , Lawrence Theodore S. , Cuneo Kyle C.
Published: October 2023

Supplemental Tables
Supplementary Tables 1-2 from Neoadjuvant Cabazitaxel plus Abiraterone/Leuprolide Acetate in Patients with High-Risk Prostate Cancer: ACDC-RP Phase II Trial
Authors: Fleshner Neil E. , Sayyid Rashid K. , Hansen Aaron R. , Chin Joseph L.K. , Fernandes Ricardo , Winquist Eric , van der Kwast Theodorus , Sweet Joan , Lajkosz Katherine , Kenk Miran , Hersey Karen , Veloso Rosette , Berlin Doron , Herrera-Caceres Jaime O. , Sridhar Srikala , Moussa Madeleine , Finelli Antonio , Hamilton Robert J. , Kulkarni Girish S. , Zlotta Alexandre R. , Joshua Anthony M.
Published: October 2023

Supplementary Tables 1-2
Supplementary Figure S7 from Prognostic Markers of DNA Methylation and Next-Generation Sequencing in Progressive Glioblastoma from the EORTC-26101 Trial
Authors: Kessler Tobias , Schrimpf Daniel , Doerner Laura , Hai Ling , Kaulen Leon D. , Ito Jakob , van den Bent Martin , Taphoorn Martin , Brandes Alba A. , Idbaih Ahmed , Dômont Julien , Clement Paul M. , Campone Mario , Bendszus Martin , von Deimling Andreas , Sahm Felix , Platten Michael , Wick Wolfgang , Wick Antje
Published: October 2023

Supplementary Figure 7: Exceptional survivors of the EORTC-26101 study (n = 78).
Supplementary Figure S4 from Prognostic Markers of DNA Methylation and Next-Generation Sequencing in Progressive Glioblastoma from the EORTC-26101 Trial
Authors: Kessler Tobias , Schrimpf Daniel , Doerner Laura , Hai Ling , Kaulen Leon D. , Ito Jakob , van den Bent Martin , Taphoorn Martin , Brandes Alba A. , Idbaih Ahmed , Dômont Julien , Clement Paul M. , Campone Mario , Bendszus Martin , von Deimling Andreas , Sahm Felix , Platten Michael , Wick Wolfgang , Wick Antje
Published: October 2023

Supplementary Figure 4: Multivariate analysis. Baselines were MGMT = “methylated” and Classifier = “GBM MES”. Classifier assignment is based on the v12.5 version (n = 380).
Supplementary Figure S2 from Prognostic Markers of DNA Methylation and Next-Generation Sequencing in Progressive Glioblastoma from the EORTC-26101 Trial
Authors: Kessler Tobias , Schrimpf Daniel , Doerner Laura , Hai Ling , Kaulen Leon D. , Ito Jakob , van den Bent Martin , Taphoorn Martin , Brandes Alba A. , Idbaih Ahmed , Dômont Julien , Clement Paul M. , Campone Mario , Bendszus Martin , von Deimling Andreas , Sahm Felix , Platten Michael , Wick Wolfgang , Wick Antje
Published: October 2023

Supplementary Figure 2: Overall (A) and progression-free (B) survival in the EORTC-26101 clinical study (n = 596) and EORTC-26101 biomarker cohort (n = 380).
Supplementary Figure S4 from Autocrine 17-β-Estradiol/Estrogen Receptor-α Loop Determines the Response to Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer
Authors: Anobile Dario P. , Salaroglio Iris C. , Tabbò Fabrizio , La Vecchia Sofia , Akman Muhlis , Napoli Francesca , Bungaro Maristella , Benso Federica , Aldieri Elisabetta , Bironzo Paolo , Kopecka Joanna , Passiglia Francesco , Righi Luisella , Novello Silvia , Scagliotti Giorgio V. , Riganti Chiara
Published: October 2023

Disaggregated data of PD-L1 and ERα in non-small cell lung cancer patients, according to ages, tumor stages and smoking habits.
Expression of PD-L1 (panel a) and ERα (panel b) mRNA, measured by RT-PCR (technical triplicates) in tumor samples of 35 NSCLC patients, according to pathological classification (T: primary tumors; N: lymph nodes involved; M: metastasis), clinical stages (III-IV stage), smoking habits (never smoker: NSm; former smoker: FSm; current smoker: CSm). *p<0.05, **p<0.01, ***p<0.001: T versus N+M, III vs IV, NSM+FSm vs CSm (ANOVA).
Supplementary Figure S3 from Autocrine 17-β-Estradiol/Estrogen Receptor-α Loop Determines the Response to Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer
Authors: Anobile Dario P. , Salaroglio Iris C. , Tabbò Fabrizio , La Vecchia Sofia , Akman Muhlis , Napoli Francesca , Bungaro Maristella , Benso Federica , Aldieri Elisabetta , Bironzo Paolo , Kopecka Joanna , Passiglia Francesco , Righi Luisella , Novello Silvia , Scagliotti Giorgio V. , Riganti Chiara
Published: October 2023

Outcome of non-small cell lung cancer patients in LUAD TCGA cohort.
a. OS of patients of lung adenocarcinoma (LUAD) dataset of The Cancer Genome Atlas (TCGA), stratified according to the gender. F: females; M: males. b-c. OS of LUAD TCGA female and male patients, stratified according to the median expression value of CD274/PD-L1 mRNA. d-e. OS of LUAD TCGA female and male patients, stratified according to the median expression value of ESR1/ERα mRNA. f-g. OS of LUAD TCGA female and male patients, stratified according to the co-expression phenotypes: CD274high/ESR1high, CD274high/ESR1low, CD274low/ESR1high, CD274low/ESR1low. P:0.005 for CD274high/ESR1high versus CD274low/ESR1low group. h. Expression of ERα mRNA, plotted versus PD-L1 mRNA, both measured by RT-PCR (technical triplicates) in the tumor samples from F and M patients.
Supplementary Figure S13 from Autocrine 17-β-Estradiol/Estrogen Receptor-α Loop Determines the Response to Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer
Authors: Anobile Dario P. , Salaroglio Iris C. , Tabbò Fabrizio , La Vecchia Sofia , Akman Muhlis , Napoli Francesca , Bungaro Maristella , Benso Federica , Aldieri Elisabetta , Bironzo Paolo , Kopecka Joanna , Passiglia Francesco , Righi Luisella , Novello Silvia , Scagliotti Giorgio V. , Riganti Chiara
Published: October 2023

Switch-off/on EGFR activity in NCI-H1385 cells.
a. Experimental scheme: Low EGFR activitywild-type NCI-H1385 cells were knocked-out (KO) for endogenous EGFR by a CRISPR/Cas vector, then stably transfected with an expression vector encoding L858R EGFR. b. Immunoblot of EGFR in wild-type (wt) NCI-H1385 cells and in clones subjected to two (#1, #2) EGFR-CRISPR/Cas vectors. Tubulin is included as control of equal protein loading. The image is representative of one of three experiments. c. L858R EGFR mRNA levels in wt NCI-H1385 cells and in cells stably transfected with the L858R EGFR-expression vector, measured by RT-PCR (technical triplicates). Data are means + SD (n=3, biological replicates). ***p<0.001: L858R cells versus wt cells (ANOVA). d. Immunoblot of EGFR in wt and L858R NCI-H1385 cells. Tubulin is included as control of equal protein loading. The image is representative of one of three experiments. e. EGFR kinase activity, measured in wt and L858R NCI-H1385 cells by a chemiluminescence-based assay in technical duplicates. Data are means+SD (n=3, biological replicates). ***p<0.001: L858R cells versus wt cells (ANOVA).
Supplementary Figure S2 from Novel Genomic Risk Stratification Model for Primary Gastrointestinal Stromal Tumors (GIST) in the Adjuvant Therapy Era
Authors: Dermawan Josephine K. , Kelly Ciara , Gao Zhidong , Smith Shaleigh , Jadeja Bhumika , Singer Samuel , Tap William D. , Chi Ping , Antonescu Cristina R.
Published: October 2023

Supplementary Figure 2. Multivariate Cox regression survival analysis for primary gastric and small bowel GISTs represented by forest plots.
Supplementary table 2 from Unique Spectrum of Activating BRAF Alterations in Prostate Cancer
Authors: Chehrazi-Raffle Alex , Tukachinsky Hanna , Toye Eamon , Sivakumar Smruthy , Schrock Alexa B. , Bergom Hannah E. , Ebrahimi Hedyeh , Pal Sumanta , Dorff Tanya , Agarwal Neeraj , Mahal Brandon A. , Oxnard Geoffrey R. , Hwang Justin , Antonarakis Emmanuel S.
Published: October 2023

Supplementary table 2
Supplementary Table S9 from Comprehensive Analysis of Tumor Microenvironment Reveals Prognostic ceRNA Network Related to Immune Infiltration in Sarcoma
Authors: Leng Dongliang , Yang Ziyi , Sun Heng , Song Chengcheng , Huang Chen , Ip Ka U. , Chen Guokai , Deng Chu-Xia , Zhang Xiaohua Douglas , Zhao Qi
Published: October 2023

Supplementary Table S9. DE miRNAs in C2 (High) compared with C1 (Low).
Supplementary Table S4 from Comprehensive Analysis of Tumor Microenvironment Reveals Prognostic ceRNA Network Related to Immune Infiltration in Sarcoma
Authors: Leng Dongliang , Yang Ziyi , Sun Heng , Song Chengcheng , Huang Chen , Ip Ka U. , Chen Guokai , Deng Chu-Xia , Zhang Xiaohua Douglas , Zhao Qi
Published: October 2023

Supplementary Table S4. DE genes in C3 (Moderate) compared with C1 (Low) subtype.
Supplementary Table S10 from Comprehensive Analysis of Tumor Microenvironment Reveals Prognostic ceRNA Network Related to Immune Infiltration in Sarcoma
Authors: Leng Dongliang , Yang Ziyi , Sun Heng , Song Chengcheng , Huang Chen , Ip Ka U. , Chen Guokai , Deng Chu-Xia , Zhang Xiaohua Douglas , Zhao Qi
Published: October 2023

Supplementary Table S10. Survival analysis for DEmiRNA.
Supplementary Table S1 from Comprehensive Analysis of Tumor Microenvironment Reveals Prognostic ceRNA Network Related to Immune Infiltration in Sarcoma
Authors: Leng Dongliang , Yang Ziyi , Sun Heng , Song Chengcheng , Huang Chen , Ip Ka U. , Chen Guokai , Deng Chu-Xia , Zhang Xiaohua Douglas , Zhao Qi
Published: October 2023

Supplementary Table S1. PCR primers of the 10 genes in the subnetwork for cell line experiments.
Supplementary Figure S9 from Comprehensive Analysis of Tumor Microenvironment Reveals Prognostic ceRNA Network Related to Immune Infiltration in Sarcoma
Authors: Leng Dongliang , Yang Ziyi , Sun Heng , Song Chengcheng , Huang Chen , Ip Ka U. , Chen Guokai , Deng Chu-Xia , Zhang Xiaohua Douglas , Zhao Qi
Published: October 2023

Supplementary Figure S9. Flow cytometry and immunohistochemical (IHC) analysis of CD4+/CD8+ T cells for tumor tissues of S180 bearing mice with TSA administration.
Supplementary Figure S5 from Comprehensive Analysis of Tumor Microenvironment Reveals Prognostic ceRNA Network Related to Immune Infiltration in Sarcoma
Authors: Leng Dongliang , Yang Ziyi , Sun Heng , Song Chengcheng , Huang Chen , Ip Ka U. , Chen Guokai , Deng Chu-Xia , Zhang Xiaohua Douglas , Zhao Qi
Published: October 2023

Supplementary Figure S5. Characteristics of prognosis-related ceRNA network.
Supplementary Data 2 from Uncoupling CD4+ TIL-Mediated Tumor Killing from JAK-Signaling in Melanoma
Authors: Draghi Arianna , Presti Mario , Jensen Agnete W.P. , Chamberlain Christopher A. , Albieri Benedetta , Rasmussen Anne-Christine K. , Andersen Mads H. , Crowther Michael D. , Svane Inge Marie , Donia Marco
Published: October 2023

CD4+ TIL-mediated killing is dependent on MHC Class II expression (TCL#17)
Data from Safety and Efficacy of Anlotinib Hydrochloride Plus Temozolomide in Patients with Recurrent Glioblastoma
Authors: Xu Qingsheng , Huang Kaiyuan , Meng Xiangqi , Weng Yuxiang , Zhang Luyuan , Bu Linghao , Zheng Xiujue , Cai Jinquan , Zhan Renya , Chen Qun
Published: October 2023

AbstractPurpose:
Glioblastoma (GBM) is a highly vascularized tumor with few treatment options after disease recurrence. Here, we report the efficacy and safety of anlotinib hydrochloride plus temozolomide in patients with recurrent GBM.
Patients and Methods:
Patients with first definite postsurgical progression of histologically confirmed GBM preceded by standard radiotherapy and temozolomide chemotherapy were eligible for inclusion. All patients received temozolomide (150–200 mg/m2, orally, every day (QD) d1–5/4 wk) and anlotinib (10 mg, orally, QD, d1–14/3 wk) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed 6-month progression-free survival (PFS) rate by the Response Assessment in Neuro-Oncology (RANO) criteria.
Results:
Twenty-one patients were enrolled between May 2020 and July 2021, with a median age of 55 (range 27–68) years old. According to the Response Assessment in Neuro-Oncology (RANO) criteria, tumor response occurred in 17 patients, of which 9 patients had a complete response, and the objective response rate was 81.0% [95% confidence interval (CI), 62.6–99.3]. The disease control rate was 95.2% (95% CI, 76.2–99.9), with three additional patients achieving a stable disease without tumor progression. The median PFS was 7.3 months (95% CI, 4.9–9.7), and the 6-month PFS rate was 61.9% (95% CI, 39.3–84.6). The median overall survival was 16.9 months (95% CI, 7.8–26.0). The most common adverse events were leukocytopenia (66.7%), thrombocytopenia (38.1%), and hypertriglyceridemia (38.1%). Five patients had nine grade 3 adverse events, with a 23.8% incidence rate. Two patients discontinued therapy due to ischemic stroke (grade 3) and wound dehiscence (grade 1), respectively. No grade 4 or treatment-related deaths occurred in this study.
Conclusions:
Anlotinib combined with temozolomide is efficacious and tolerated in patients with recurrent GBM.
Data from Prognostic Markers of DNA Methylation and Next-Generation Sequencing in Progressive Glioblastoma from the EORTC-26101 Trial
Authors: Kessler Tobias , Schrimpf Daniel , Doerner Laura , Hai Ling , Kaulen Leon D. , Ito Jakob , van den Bent Martin , Taphoorn Martin , Brandes Alba A. , Idbaih Ahmed , Dômont Julien , Clement Paul M. , Campone Mario , Bendszus Martin , von Deimling Andreas , Sahm Felix , Platten Michael , Wick Wolfgang , Wick Antje
Published: October 2023

AbstractPurpose:
The EORTC-26101 study was a randomized phase II and III clinical trial of bevacizumab in combination with lomustine versus lomustine alone in progressive glioblastoma. Other than for progression-free survival (PFS), there was no benefit from addition of bevacizumab for overall survival (OS). However, molecular data allow for the rare opportunity to assess prognostic biomarkers from primary surgery for their impact in progressive glioblastoma.
Experimental Design:
We analyzed DNA methylation array data and panel sequencing from 170 genes of 380 tumor samples of the EORTC-26101 study. These patients were comparable with the overall study cohort in regard to baseline characteristics, study treatment, and survival.
Results:
Of patients' samples, 295/380 (78%) were classified into one of the main glioblastoma groups, receptor tyrosine kinase (RTK)1, RTK2 and mesenchymal. There were 10 patients (2.6%) with isocitrate dehydrogenase mutant tumors in the biomarker cohort. Patients with RTK1 and RTK2 classified tumors had lower median OS compared with mesenchymal (7.6 vs. 9.2 vs. 10.5 months). O6-methylguanine DNA-methyltransferase (MGMT) promoter methylation was prognostic for PFS and OS. Neurofibromin (NF)1 mutations were predictive of response to bevacizumab treatment.
Conclusions:
Thorough molecular classification is important for brain tumor clinical trial inclusion and evaluation. MGMT promoter methylation and RTK1 classifier assignment were prognostic in progressive glioblastoma. NF1 mutation may be a predictive biomarker for bevacizumab treatment.
Data from Novel Genomic Risk Stratification Model for Primary Gastrointestinal Stromal Tumors (GIST) in the Imatinib and Adjuvant Therapy Era
Authors: Dermawan Josephine K. , Kelly Ciara , Gao Zhidong , Smith Shaleigh , Jadeja Bhumika , Singer Samuel , Tap William D. , Chi Ping , Antonescu Cristina R.
Published: October 2023

Abstract
Purpose: Traditional risk stratification schemes in gastrointestinal stromal tumors (GIST) had been defined in the pre-imatinib era and rely solely on clinicopathologic metrics. We hypothesize that genomic-based risk stratification is prognostically relevant in the current era of tyrosine kinase inhibitor (TKI) therapeutics. Experimental Design: Comprehensive mutational and copy number profiling using MSK-IMPACT was performed. We integrated clinicopathologic and genomic parameters and utilized an elastic-net penalized Cox proportional hazards machine learning model for outcome risk stratification. Results: A 3-tier genomic risk stratification model for recurrence-free survival (RFS) in 152 primary localized gastric and 80 small bowel GISTs was proposed. Gastric GISTs were classified as high risk if chr1p deletion or SDHB loss was present, and intermediate risk if chr14q deletion was present or KIT exon 11 mutation was absent. Small bowel GISTs were classified as high risk if MAX/MGA/MYC, CDKN2A or RB1 alterations was present, and intermediate risk if chr1p deletion or chr5q amplification was present. Compared to conventional risk stratification, genomic risk stratification both upgrades and downgrades, suggesting that conventional risk stratification may underestimate or overtreat some high-risk and low-risk patients, respectively. Longitudinal sequencing detected most KIT-independent genomic alterations at baseline. Subanalysis in 26 SDH-deficient GISTs revealed that presence of TP53 mutations or chr1q amplifications portends worse RFS and disease-free survival. Conclusions: We developed a novel, next-generation genomic risk stratification model for primary gastric and small bowel GISTs, complementing traditional clinicopathologic models. Future independent validation of our model in external cohorts is essential.
Figure S9 from Intratumoral IL15 Improves Efficacy of Near-Infrared Photoimmunotherapy
Authors: Fukushima Hiroshi , Furusawa Aki , Kato Takuya , Wakiyama Hiroaki , Takao Seiichiro , Okuyama Shuhei , Choyke Peter L. , Kobayashi Hisataka
Published: October 2023

Supplementary Fig. S9. In vivo therapeutic efficacy of intratumoral IL-15 injection combined with CD44-targeted NIR-PIT against MC38 tumors using T cell-deficient athymic nude mice.
Figure S12 from Intratumoral IL15 Improves Efficacy of Near-Infrared Photoimmunotherapy
Authors: Fukushima Hiroshi , Furusawa Aki , Kato Takuya , Wakiyama Hiroaki , Takao Seiichiro , Okuyama Shuhei , Choyke Peter L. , Kobayashi Hisataka
Published: October 2023

Supplementary Fig. S12. Therapeutic efficacy of in vivo CD44-targeted NIR-PIT in a bilateral tumor mouse model (R: MC38 tumor, L: MC38 tumor).
Supplementary Fig. S6 from Dual Targeting of the PDZ1 and PDZ2 Domains of MDA-9/Syntenin Inhibits Melanoma Metastasis
Authors: Pradhan Anjan K. , Modi Jinkal , Maji Santanu , Kumar Amit , Bhoopathi Praveen , Mannangatti Padmanabhan , Guo Chunqing , Afosah Daniel K. , Mochel Mark C. , Mukhopadhyay Nitai D. , Kirkwood John M. , Wang Xiang-Yang , Desai Umesh R. , Sarkar Devanand , Emdad Luni , Das Swadesh K. , Fisher Paul B.
Published: October 2023

IVMT-Rx-3 inhibited invasion in murine melanoma cells
Supplementary Fig. S5 from Dual Targeting of the PDZ1 and PDZ2 Domains of MDA-9/Syntenin Inhibits Melanoma Metastasis
Authors: Pradhan Anjan K. , Modi Jinkal , Maji Santanu , Kumar Amit , Bhoopathi Praveen , Mannangatti Padmanabhan , Guo Chunqing , Afosah Daniel K. , Mochel Mark C. , Mukhopadhyay Nitai D. , Kirkwood John M. , Wang Xiang-Yang , Desai Umesh R. , Sarkar Devanand , Emdad Luni , Das Swadesh K. , Fisher Paul B.
Published: October 2023

IVMT-Rx-3 inhibited MDA-9/Src signaling cascade
Supplementary Fig. S2 from Dual Targeting of the PDZ1 and PDZ2 Domains of MDA-9/Syntenin Inhibits Melanoma Metastasis
Authors: Pradhan Anjan K. , Modi Jinkal , Maji Santanu , Kumar Amit , Bhoopathi Praveen , Mannangatti Padmanabhan , Guo Chunqing , Afosah Daniel K. , Mochel Mark C. , Mukhopadhyay Nitai D. , Kirkwood John M. , Wang Xiang-Yang , Desai Umesh R. , Sarkar Devanand , Emdad Luni , Das Swadesh K. , Fisher Paul B.
Published: October 2023

Specificity of IVMT-Rx-3
Figure S1 from A Multivalent Peptoid Conjugate Modulates Androgen Receptor Transcriptional Activity to Inhibit Therapy-resistant Prostate Cancer
Authors: Habault Justine , Schneider Jeffrey A. , Ha Susan , Ruoff Rachel , Pereira Luiza D. , Puccini Joseph , Ranieri Michela , Ayasun Ruveyda , Deng Jiehui , Kasper Amanda C. , Bar-Sagi Dafna , Wong Kwok-Kin , Zoubeidi Amina , Claessens Frank , Wise David R. , Logan Susan K. , Kirshenbaum Kent , Garabedian Michael J.
Published: October 2023

Chemical structures and IC50 of the multivalent ethisterone-peptoid conjugate
Supplementary Fig.S8 from MTX-13, a Novel PTK7-Directed Antibody–Drug Conjugate with Widened Therapeutic Index Shows Sustained Tumor Regressions for a Broader Spectrum of PTK7-Positive Tumors
Authors: Kong Chao , Pu Junyi , Zhao Qianqian , Weng Weining , Ma Linjie , Qian Yu , Hu Wenhao , Meng Xun , Meng Tao
Published: October 2023

Supplementary Fig.S8 shows MTX-13 prevents metastasis in vivo in an orthotopic colon cancer xenograft model
Supplementary Fig.S3 from MTX-13, a Novel PTK7-Directed Antibody–Drug Conjugate with Widened Therapeutic Index Shows Sustained Tumor Regressions for a Broader Spectrum of PTK7-Positive Tumors
Authors: Kong Chao , Pu Junyi , Zhao Qianqian , Weng Weining , Ma Linjie , Qian Yu , Hu Wenhao , Meng Xun , Meng Tao
Published: October 2023

Supplementary Fig.S3 shows PTK7 expression in tumor tissues and cell lines
Supplementary Fig.S2 from MTX-13, a Novel PTK7-Directed Antibody–Drug Conjugate with Widened Therapeutic Index Shows Sustained Tumor Regressions for a Broader Spectrum of PTK7-Positive Tumors
Authors: Kong Chao , Pu Junyi , Zhao Qianqian , Weng Weining , Ma Linjie , Qian Yu , Hu Wenhao , Meng Xun , Meng Tao
Published: October 2023

Supplementary Fig.S2 shows PTK7 expression in normal human tissues surveyed by mAb13
Supplementary Fig.S1 from MTX-13, a Novel PTK7-Directed Antibody–Drug Conjugate with Widened Therapeutic Index Shows Sustained Tumor Regressions for a Broader Spectrum of PTK7-Positive Tumors
Authors: Kong Chao , Pu Junyi , Zhao Qianqian , Weng Weining , Ma Linjie , Qian Yu , Hu Wenhao , Meng Xun , Meng Tao
Published: October 2023

Supplementary Fig.S1 shows the development and characterization of Ab13, a PTK7-targeting antibody
Supplementary Table 2 from Conditional Dependency of LP-184 on Prostaglandin Reductase 1 is Synthetic Lethal in Pancreatic Cancers with DNA Damage Repair Deficiencies
Authors: Restifo Diana , McDermott Joseph R. , Cvetkovic Dusica , Dos Santos Troy , Ogier Charline , Surumbayeva Aizhan , Handorf Elizabeth A. , Schimke Caleb , Ma Charlie , Cai Kathy Q. , Olszanski Anthony J. , Kathad Umesh , Bhatia Kishor , Sharma Panna , Kulkarni Aditya , Astsaturov Igor
Published: October 2023

Characteristics of PDX models
Supplementary Table 1 from Conditional Dependency of LP-184 on Prostaglandin Reductase 1 is Synthetic Lethal in Pancreatic Cancers with DNA Damage Repair Deficiencies
Authors: Restifo Diana , McDermott Joseph R. , Cvetkovic Dusica , Dos Santos Troy , Ogier Charline , Surumbayeva Aizhan , Handorf Elizabeth A. , Schimke Caleb , Ma Charlie , Cai Kathy Q. , Olszanski Anthony J. , Kathad Umesh , Bhatia Kishor , Sharma Panna , Kulkarni Aditya , Astsaturov Igor
Published: October 2023

IC50 and PTGR1 expression
Supplementary Figure 1 from Conditional Dependency of LP-184 on Prostaglandin Reductase 1 is Synthetic Lethal in Pancreatic Cancers with DNA Damage Repair Deficiencies
Authors: Restifo Diana , McDermott Joseph R. , Cvetkovic Dusica , Dos Santos Troy , Ogier Charline , Surumbayeva Aizhan , Handorf Elizabeth A. , Schimke Caleb , Ma Charlie , Cai Kathy Q. , Olszanski Anthony J. , Kathad Umesh , Bhatia Kishor , Sharma Panna , Kulkarni Aditya , Astsaturov Igor
Published: October 2023

Supplementary Figure 1
Data from A Multivalent Peptoid Conjugate Modulates Androgen Receptor Transcriptional Activity to Inhibit Therapy-resistant Prostate Cancer
Authors: Habault Justine , Schneider Jeffrey A. , Ha Susan , Ruoff Rachel , Pereira Luiza D. , Puccini Joseph , Ranieri Michela , Ayasun Ruveyda , Deng Jiehui , Kasper Amanda C. , Bar-Sagi Dafna , Wong Kwok-Kin , Zoubeidi Amina , Claessens Frank , Wise David R. , Logan Susan K. , Kirshenbaum Kent , Garabedian Michael J.
Published: October 2023

Abstract
Prostate cancers adapt to androgen receptor (AR) pathway inhibitors and progress to castration resistance due to ongoing AR expression and function. To counter this, we developed a new approach to modulate the AR and inhibit castration-resistant prostate cancer (CRPC) using multivalent peptoid conjugates (MPC) that contain multiple copies of the AR-targeting ligand ethisterone attached to a peptidomimetic scaffold. Here, we investigated the antitumor effects of compound MPC309, a trivalent display of ethisterone conjugated to a peptoid oligomer backbone that binds to the AR with nanomolar affinity. MPC309 exhibited potent antiproliferative effects on various enzalutamide-resistant prostate cancer models, including those with AR splice variants, ligand-binding mutations, and noncanonical AR gene expression programs, as well as mouse prostate organoids harboring defined genetic alterations that mimic lethal human prostate cancer subtypes. MPC309 is taken up by cells through macropinocytosis, an endocytic process more prevalent in cancer cells than in normal ones, thus providing an opportunity to target tumors selectively. MPC309 triggers a distinct AR transcriptome compared with DHT and enzalutamide, a clinically used antiandrogen. Specifically, MPC309 enhances the expression of differentiation genes while reducing the expression of genes needed for cell division and metabolism. Mechanistically, MPC309 increases AR chromatin occupancy and alters AR interactions with coregulatory proteins in a pattern distinct from DHT. In xenograft studies, MPC309 produced significantly greater tumor suppression than enzalutamide. Altogether, MPC309 represents a promising new AR modulator that can combat resistant disease by promoting an AR antiproliferative gene expression program.
Data from MTX-13, a novel PTK7-directed antibody-drug conjugate with widened therapeutic index shows sustained tumor regressions for a broader spectrum of PTK7-positive tumors
Authors: Kong Chao , Pu Junyi , Zhao Qianqian , Weng Weining , Ma Linjie , Qian Yu , Hu Wenhao , Meng Xun , Meng Tao
Published: October 2023

Abstract
Protein tyrosine kinase 7 (PTK7) is a Wnt signaling pathway protein implicated in cancer development and metastasis. When using a potent microtubule inhibitor (Aur0101), PTK7-targeting antibody-drug conjugate (ADC), h6M24-vc0101 (PF-06647020/Cofetuzumab pelidotin) is efficacious only in limited tumor types with low response rates in a phase I trial. To improve patient response and to expand responding tumor types, we designed MTX-13, a PTK7-targeting ADC consisting of a novel antibody (Ab13) conjugated to eight molecules of Topoisomerase I inhibitor exatecan through T1000, a novel self-immolative moiety. MTX-13 exhibited PTK7-specific cell binding, efficient internalization and exatecan release to cause cytotoxic activity through DNA damage and apoptosis induction, and a strong bystander killing. MTX-13 displayed potent antitumor activities on CDX and PDX models from a wide range of solid tumors, significantly outperforming h6M24-vc0101. PTK7 was shown to be an actionable target in small cell lung cancer for which MTX-13 showed complete and durable responses. With a consistent overexpression of PTK7 in squamous cell carcinomas derived from diverse anatomic sites, strong potency of MTX-13 in this group of heterogenous tumors suggested a common treatment strategy. Finally, MTX-13 inhibited tumor growth and metastasis in an orthotopic colon cancer xenograft model. MTX-13 displayed a favorable pharmacokinetic and safety profile in monkey with a highest non-severely toxic dose (HNSTD) of >30 mg/kg, significantly higher than 3-5 mg/kg of HNSTD for h6M24-vc0101. The higher therapeutic index of MTX-13 bodes well for its clinical translation with a potential to expand responding patient population beyond that of current PTK7-targeting ADCs.
Supplementary Table 2 from TRIM50 Inhibits Gastric Cancer Progression by Regulating the Ubiquitination and Nuclear Translocation of JUP
Authors: Hu Jiajia , Huang Runjie , Liang Chengcai , Wang Yingnan , Wang Min , Chen Yanxing , Wu Chenyi , Zhang Jinling , Liu Zekun , Zhao Qi , Liu Zexian , Wang Feng , Yuan Shuqiang
Published: October 2023

The raw data of 1B.