bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Topical Azithromycin versus Systemic Doxycycline in Treatment of Meibomian Gland Dysfunction
Authors: Aly Zaky Marwa , Galal Zaky Adel , Fayez Elsawy Moataz , Fatehy Shehata Kareem , Samy Abd Elaziz Mohamed
Published: August 2023

Background. Ocular surface disease (OSD) is a multifactorial and highly frequent problem. Inadequate or unstable tear film is the main cause, which leads to visual impairments. One of the primary causes of OSD is meibomian gland dysfunction (MGD), with a prevalence of 3.5 to 70%. The aim of this work was to compare the efficacy of azithromycin topical eye drops versus oral doxycycline in MGD individuals. Methods. This prospective comparative cohort research was carried out on 56 patients of both sexes of any age with symptomatic MGD. Randomly, patients were classified into two equal groups: Group 1 was treated twice daily for 4 weeks with topical azithromycin 1% eye drops, while group 2 received oral doxycycline 100 mg capsules twice daily for 4 weeks. Results. In the 1st follow‐up, there was a significant difference between the studied groups in pain and discomfort degree (P value = 0.024) as group 1 showed a higher number of patients with a mild pain degree (P value = 0.013) while group 2 showed a higher number of patients with a severe pain degree (P value = 0.022). There was an insignificant difference between the studied groups in moderate pain degree and lid margin telangiectasia. Conjunctivitis, frothy discharge, and meniscus floaters were significantly higher in group 2 than in group 1 (P value = 0.013, 0.028, and 0.031, respectively). In group 1, the break‐up time test was significantly higher than in group 2 (P value = 0.023). In the 2nd follow up, in group 2 only meniscus floaters were significantly higher than in group 1 (P value = 0.044), while in group 1 break‐up time test was significantly higher than in group 2 (P value = 0.029). Otherwise, there is no significant difference between both the groups. Conclusions. Meibomian gland dysfunction (MGD) could be treated effectively with oral doxycycline and topical azithromycin by improving symptoms, clinical signs, and stabilization of tear film. Moreover, the topical azithromycin group seemed to be superior over the oral doxycycline group in improving the quality of tear film in the short term, having fewer side effects, more compliance, and better tolerability.
Optimal Design of Voltage Reference Circuit and Ring Oscillator Circuit Using Multiobjective Differential Evolution Algorithm
Authors: Dash Sandeep K. , De Bishnu Prasad , Samanta Pravin K. , Appasani Bhargav , Kar Rajib , Mandal Durbadal , Bizon Nicu
Published: August 2023

This paper deals with the optimal design of different VLSI circuits, namely, the CMOS voltage reference circuit and the CMOS ring oscillator (RO). The optimization technique used here is the multiobjective differential evolution algorithm (MDEA). All the circuits are designed for 90 nm technology. The main objective of the CMOS voltage reference circuit is to minimize the voltage variation at the output. The targeted value of the reference voltage is 550 mV. A CMOS ring oscillator (RO) is designed depending on the performance parameters such as power consumption and phase noise. The optimal transistor sizing of each circuit is obtained from MDEA. Each circuit is implemented in SPICE by taking the optimal dimensions of the transistors, and the performance parameters are achieved. The designed voltage reference circuit achieves a reference voltage of 550 mV with 600 nW power dissipation. The reference voltage variation of 8.18% is observed due to temperature variation from −40°C to + 125°C. The MDEA-based optimal design of RO oscillates at 2.001 GHz frequency, has a phase noise of −87 dBc/Hz at 1 MHz offset frequency, and consumes 71 μW power. This work mainly aims to optimize the MOS transistors’ sizes using MDEA for better circuit performance parameters. SPICE simulation has been carried out by using the optimal values of MOS transistor sizes to exhibit the performance parameters of the circuit. Simulation results establish that design specifications are closely met. SPICE results show that MDEA is a better technique for the optimal design of the above-mentioned VLSI circuits.
Polygonatum cyrtonema Hua Polysaccharides with Antiaging and Stress Resistance Efficacies in Caenorhabditis elegans
Authors: Wang Wei , Yang Ying , Hou Ting-ting , Yi Shan-yong , Chen Yan-jun , Li Guo-si , Chen Cun-wu , Han Bang-xing , Ke Jia-ping , Liu Dong , Gao Lei-lei
Published: August 2023

Polygonatum cyrtonema Hua, a source of Polygonati rhizoma, possesses multiple health-promoting properties and is widely used in food and medicine. This study aimed to elucidate the lifespan promotion abilities and potential mechanism of action of P. cyrtonema Hua polysaccharides (PCHPs) on Caenorhabditis elegans. The results revealed that PCHP had a molecular weight distribution of 8.77×103−1.84 × 106 Da and comprised Man, GalA, Glu, Gal, Xyl, and Ara in a molar ratio of 13.8 : 3.5 : 22.7 : 2.7 : 1:1.3. PCHP (5.0 mg/mL) markedly increased the lifespan of C. elegans by 15.78% (

p

 < 0.001), improved motility, and increased the resistance to heat stress, UV irradiation, and oxidative stress. PCHP also promoted healthy aging by attenuating the accumulation of reactive oxygen species (ROS) and lipofuscin. Furthermore, PCHP upregulated the expression of oxidative stress- and aging-related genes, promoted the migration of DAF-16 into the nucleus, and exerted no effect on the lifespan of daf-2, daf-16, age-1, skn-1, and sir-2.1 mutants. These results indicate that the transcription factors DAF-16, SIR-2.1, and SKN-1 are required for PCHP-mediated lifespan extension in C. elegans. In conclusion, PCHP has the potential to attenuate the effects of aging, which can lay the foundation for aging treatment research with P. cyrtonema.
Data from Inter- and intra-metastatic heterogeneity shapes adaptive therapy cycling dynamics
Authors: Gallaher Jill , Strobl Maximilian , West Jeffrey , Gatenby Robert , Zhang Jingsong , Robertson-Tessi Mark , Anderson Alexander R.A.
Published: August 2023

Abstract
Adaptive therapies that alternate between drug applications and drug-free vacations can exploit competition between sensitive and resistant cells to maximize the time to progression. However, optimal dosing schedules depend on the properties of metastases, which are often not directly measurable in clinical practice. Here, we proposed a framework for estimating features of metastases through tumor response dynamics during the first adaptive therapy treatment cycle. Longitudinal PSA levels in sixteen metastatic castration resistant prostate cancer patients undergoing adaptive androgen deprivation treatment were analyzed to investigate relationships between cycle dynamics and clinical variables such as Gleason score, the change in the number of metastases over a cycle, and the total number of cycles over the course of treatment. The first cycle of adaptive therapy, which consists of a response period (applying therapy until 50% PSA reduction), and a regrowth period (removing treatment until reaching initial PSA levels), delineated several features of the computational metastatic system: larger metastases had longer cycles; a higher proportion of drug resistant cells slowed the cycles; and a faster cell turnover rate sped up drug response time and slowed regrowth time. The number of metastases did not affect cycle times, as response dynamics were dominated by the largest tumors rather than the aggregate. In addition, systems with higher inter-metastasis heterogeneity responded better to continuous therapy and correlated with dynamics from patients with high or low Gleason scores. Conversely, systems with higher intra-metastasis heterogeneity responded better to adaptive therapy and correlated with dynamics from patients with intermediate Gleason scores.
Supplementary Table S2 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: August 2023

Recurrent regions of copy number gain and loss together with the candidate genes located within the regions.
Supplemental Figure 6 from Transcriptomic Signatures of MSI-High Metastatic Colorectal Cancer Predict Efficacy of Immune Checkpoint Inhibitors
Authors: Gallois Claire , Landi Matteo , Taieb Julien , Sroussi Marine , Saberzadeh-Ardestani Bahar , Cazelles Antoine , Lonardi Sara , Bergamo Francesca , Intini Rossana , Maddalena Giulia , Pietrantonio Filippo , Corti Francesca , Ambrosini Margherita , Martinetti Antonia , Germani Marco Maria , Boccaccio Chiara , Vetere Guglielmo , Mouillet-Richard Sophie , de Reynies Aurélien , Sinicrope Frank A. , Cremolini Chiara , Laurent-Puig Pierre
Published: August 2023

Survival after recurrence in MSI patients from PETACC8 trial with available 3’RNAseq data
Supplementary Spreadsheet S9 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: August 2023

CRISPR dependency clustering
Supplementary Spreadsheet S7 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: August 2023

Differential expression between normal chr1 and focal gains group MM patients
Supplementary Tables 1 from Poor Outcome in Postpartum Breast Cancer Patients Is Associated with Distinct Molecular and Immunologic Features
Authors: Lefrère Hanne , Moore Kat , Floris Giuseppe , Sanders Joyce , Seignette Iris M. , Bismeijer Tycho , Peters Dennis , Broeks Annegien , Hooijberg Erik , Van Calsteren Kristel , Neven Patrick , Warner Ellen , Peccatori Fedro Alessandro , Loibl Sibylle , Maggen Charlotte , Han Sileny N. , Jerzak Katarzyna J. , Annibali Daniela , Lambrechts Diether , de Visser Karin E. , Wessels Lodewyk , Lenaerts Liesbeth , Amant Frédéric
Published: August 2023

Table S1 - Table S4
Supplementary Spreadsheet S4 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: August 2023

Differential expression between normal chr1 and gain(1q) MM patients
Supplementary Spreadsheet 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: August 2023

Term dictionary
Supplementary Table S4 from Identifying Mechanisms of Resistance by Circulating Tumor DNA in EVOLVE, a Phase II Trial of Cediranib Plus Olaparib for Ovarian Cancer at Time of PARP Inhibitor Progression
Authors: Lheureux Stephanie , Prokopec Stephenie D. , Oldfield Leslie E. , Gonzalez-Ochoa Eduardo , Bruce Jeffrey P. , Wong Derek , Danesh Arnavaz , Torti Dax , Torchia Jonathan , Fortuna Alexander , Singh Sharanjit , Irving Matthew , Marsh Kayla , Lam Bernard , Speers Vanessa , Yosifova Aleksandra , Oaknin Ana , Madariaga Ainhoa , Dhani Neesha C. , Bowering Valerie , Oza Amit M. , Pugh Trevor J.
Published: August 2023

Supplementary Table S4: Targeted Lesions at Baseline. The baseline sum of targeted lesions (mm) for each patient, determined at baseline by CT for RECIST1.1 evaluation.
Supplementary Spreadsheet 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: August 2023

Differentially methylated Illumina HM27 probes in MM vs PC
Supplementary Table S3 from Identifying Mechanisms of Resistance by Circulating Tumor DNA in EVOLVE, a Phase II Trial of Cediranib Plus Olaparib for Ovarian Cancer at Time of PARP Inhibitor Progression
Authors: Lheureux Stephanie , Prokopec Stephenie D. , Oldfield Leslie E. , Gonzalez-Ochoa Eduardo , Bruce Jeffrey P. , Wong Derek , Danesh Arnavaz , Torti Dax , Torchia Jonathan , Fortuna Alexander , Singh Sharanjit , Irving Matthew , Marsh Kayla , Lam Bernard , Speers Vanessa , Yosifova Aleksandra , Oaknin Ana , Madariaga Ainhoa , Dhani Neesha C. , Bowering Valerie , Oza Amit M. , Pugh Trevor J.
Published: August 2023

Supplementary Table S3: Targeted Sequencing Panel. List of regions included in the CHARM+EVOLVE panel used for targeted sequencing; coordinates are for human reference hg38.
Supplementary Spreadsheet S10 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: August 2023

Common dependency pathway analysis
Supplementary Methods S1 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: August 2023

Methods
Supplementary Figure S5 from Identifying Mechanisms of Resistance by Circulating Tumor DNA in EVOLVE, a Phase II Trial of Cediranib Plus Olaparib for Ovarian Cancer at Time of PARP Inhibitor Progression
Authors: Lheureux Stephanie , Prokopec Stephenie D. , Oldfield Leslie E. , Gonzalez-Ochoa Eduardo , Bruce Jeffrey P. , Wong Derek , Danesh Arnavaz , Torti Dax , Torchia Jonathan , Fortuna Alexander , Singh Sharanjit , Irving Matthew , Marsh Kayla , Lam Bernard , Speers Vanessa , Yosifova Aleksandra , Oaknin Ana , Madariaga Ainhoa , Dhani Neesha C. , Bowering Valerie , Oza Amit M. , Pugh Trevor J.
Published: August 2023

Supplementary Figure 5: Sensitivity of variant calling methods on cfDNA
Supplementary Figure 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: August 2023

Co-occurrence of regions of gain(1q) and loss(1p). A. The percentage of patients top and per patient (bottom) with specific region of gain B. A histogram summarising the number of gained regions per patient. C. The percentage of patients top and per patient (bottom) with specific regions of copy number loss D. Histogram summarizing the number of gained regions per patient.
Supplementary Figure S6 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: August 2023

Chromatin state of different SV regions. The CT1 region at 1p36.11-1p34.3 is comprised of greater than 74% A-compartment (range 74-100%); CT2 at 1p33-1p32.3 comprises both inactive (range 35-59%) and active chromatin (range 41-65%) and, CT3 at 1p13.3-1p12, overlaps with TI1, had greater variability with 86% A-compartment in U266 while only 1% in KMS11. TI1 region predominantly laid in B-compartment (range 63-73%) and TI2 lay in an almost entirely active compartment (range 91-100%). NBC=Naïve B-cell, MBC=Memory B-cell, GCBC=Germinal Center B-cell, PC=plasma cell.
Supplementary Figure S18 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: August 2023

Concurrent Hypomethylation and Overexpression Probes. The dot plot (top) displays the distribution of statistically significant CpG probes with difference in group mean methylation beta value, where the greater the value is a proxy for loss of methylation at the CpG probe. The probes are oriented by genomic locus across chromosome 1 with annotations for the midpoint of the recurrent gained regions on the 1q arm. The area graph (bottom) displays the ratio of probes that are significantly differentially methylated in any given 2MB window across chromosome 1. The highlighted region corresponds to the 1q arm.
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: August 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 S14 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: August 2023

Genes with increased dependency in cell lines with gain(1q).
Supplementary Figure S5 from A Phase I/IIa Trial of Yttrium-90 Radioembolization in Combination with Durvalumab for Locally Advanced Unresectable Hepatocellular Carcinoma
Authors: Lee Yun Bin , Nam Joon Yeul , Cho Eun Ju , Lee Jeong-Hoon , Yu Su Jong , Kim Hyo-Cheol , Paeng Jin Chul , Yoon Jung-Hwan , Kim Yoon Jun
Published: August 2023

Supplementary Figure S5. Kaplan–Meier estimates of time to progression and overall survival according to etiology in the per-protocol population. (A) Time to progression. (B) Overall survival. (C) Progression-free survival.
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: August 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 S10 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: August 2023

Correlation between age, telomere length and 1q gain subtype. A. Correlation between telomere length and chromosome 1 rearrangement subtype B. Correlation between age and chromosome 1 rearrangement subtype
Supplementary Figure S1 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: August 2023

Recurrent chromosome 1 mutations. Ninety-five genes on chromosome 1 that are mutated in more than 1% of cases in the Myeloma Genome Project dataset.
Supplementary Table S9 from Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer
Authors: Singh Harshabad , Keller Rachel B. , Kapner Kevin S. , Dilly Julien , Raghavan Srivatsan , Yuan Chen , Cohen Elizabeth F. , Tolstorukov Michael , Andrews Elizabeth , Brais Lauren K. , da Silva Annacarolina , Perez Kimberly , Rubinson Douglas A. , Surana Rishi , Giannakis Marios , Ng Kimmie , Clancy Thomas E. , Yurgelun Matthew B. , Schlechter Benjamin L. , Clark Jeffrey W. , Shapiro Geoffrey I. , Rosenthal Michael H. , Hornick Jason L. , Nardi Valentina , Li Yvonne Y. , Gupta Hersh , Cherniack Andrew D. , Meyerson Matthew , Cleary James M. , Nowak Jonathan A. , Wolpin Brian M. , Aguirre Andrew J.
Published: August 2023

BRAF copynumber LOH
Supplementary Table S6 from Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer
Authors: Singh Harshabad , Keller Rachel B. , Kapner Kevin S. , Dilly Julien , Raghavan Srivatsan , Yuan Chen , Cohen Elizabeth F. , Tolstorukov Michael , Andrews Elizabeth , Brais Lauren K. , da Silva Annacarolina , Perez Kimberly , Rubinson Douglas A. , Surana Rishi , Giannakis Marios , Ng Kimmie , Clancy Thomas E. , Yurgelun Matthew B. , Schlechter Benjamin L. , Clark Jeffrey W. , Shapiro Geoffrey I. , Rosenthal Michael H. , Hornick Jason L. , Nardi Valentina , Li Yvonne Y. , Gupta Hersh , Cherniack Andrew D. , Meyerson Matthew , Cleary James M. , Nowak Jonathan A. , Wolpin Brian M. , Aguirre Andrew J.
Published: August 2023

Mutational frequency KRAS WT vs KRAS MUT
Supplementary Data 2 from Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis
Authors: González-Muñoz Teresa , Di Giannatale Angela , García-Silva Susana , Santos Vanesa , Sánchez-Redondo Sara , Savini Claudia , Graña-Castro Osvaldo , Blanco-Aparicio Carmen , Fischer Suzanne , De Wever Olivier , Creus-Bachiller Edgar , Ortega-Bertran Sara , Pisapia David J. , Rodríguez-Peralto Jose L. , Fernández-Rodríguez Juana , Pérez-Portabella Cleofé Romagosa , Alaggio Rita , Benassi Maria Serena , Pazzaglia Laura , Scotlandi Katia , Ratner Nancy , Yohay Kaleb , Theuer Charles P. , Peinado Héctor
Published: August 2023

Significant deregulated genes in shENG versus shScramble STS26T cells.
Supplementary Table S4 from Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer
Authors: Singh Harshabad , Keller Rachel B. , Kapner Kevin S. , Dilly Julien , Raghavan Srivatsan , Yuan Chen , Cohen Elizabeth F. , Tolstorukov Michael , Andrews Elizabeth , Brais Lauren K. , da Silva Annacarolina , Perez Kimberly , Rubinson Douglas A. , Surana Rishi , Giannakis Marios , Ng Kimmie , Clancy Thomas E. , Yurgelun Matthew B. , Schlechter Benjamin L. , Clark Jeffrey W. , Shapiro Geoffrey I. , Rosenthal Michael H. , Hornick Jason L. , Nardi Valentina , Li Yvonne Y. , Gupta Hersh , Cherniack Andrew D. , Meyerson Matthew , Cleary James M. , Nowak Jonathan A. , Wolpin Brian M. , Aguirre Andrew J.
Published: August 2023

GENIE ID and PANID reference IDs for access to KRAS WT PDAC dataset
Suppl. Figure 6 from Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis
Authors: González-Muñoz Teresa , Di Giannatale Angela , García-Silva Susana , Santos Vanesa , Sánchez-Redondo Sara , Savini Claudia , Graña-Castro Osvaldo , Blanco-Aparicio Carmen , Fischer Suzanne , De Wever Olivier , Creus-Bachiller Edgar , Ortega-Bertran Sara , Pisapia David J. , Rodríguez-Peralto Jose L. , Fernández-Rodríguez Juana , Pérez-Portabella Cleofé Romagosa , Alaggio Rita , Benassi Maria Serena , Pazzaglia Laura , Scotlandi Katia , Ratner Nancy , Yohay Kaleb , Theuer Charles P. , Peinado Héctor
Published: August 2023

Dual inhibition of ENG and MEK efficiently blocks ENG-Smad1/5 and MAPK/ERK pathway activation in ST88-14 cells.
Supplementary Table S3 from Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer
Authors: Singh Harshabad , Keller Rachel B. , Kapner Kevin S. , Dilly Julien , Raghavan Srivatsan , Yuan Chen , Cohen Elizabeth F. , Tolstorukov Michael , Andrews Elizabeth , Brais Lauren K. , da Silva Annacarolina , Perez Kimberly , Rubinson Douglas A. , Surana Rishi , Giannakis Marios , Ng Kimmie , Clancy Thomas E. , Yurgelun Matthew B. , Schlechter Benjamin L. , Clark Jeffrey W. , Shapiro Geoffrey I. , Rosenthal Michael H. , Hornick Jason L. , Nardi Valentina , Li Yvonne Y. , Gupta Hersh , Cherniack Andrew D. , Meyerson Matthew , Cleary James M. , Nowak Jonathan A. , Wolpin Brian M. , Aguirre Andrew J.
Published: August 2023

Organoid Drug Treatment Schedules
Suppl. Figure 4 from Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis
Authors: González-Muñoz Teresa , Di Giannatale Angela , García-Silva Susana , Santos Vanesa , Sánchez-Redondo Sara , Savini Claudia , Graña-Castro Osvaldo , Blanco-Aparicio Carmen , Fischer Suzanne , De Wever Olivier , Creus-Bachiller Edgar , Ortega-Bertran Sara , Pisapia David J. , Rodríguez-Peralto Jose L. , Fernández-Rodríguez Juana , Pérez-Portabella Cleofé Romagosa , Alaggio Rita , Benassi Maria Serena , Pazzaglia Laura , Scotlandi Katia , Ratner Nancy , Yohay Kaleb , Theuer Charles P. , Peinado Héctor
Published: August 2023

Anti-ENG therapy is active against MPNST xenografts.
Supplementary Table S18 from Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer
Authors: Singh Harshabad , Keller Rachel B. , Kapner Kevin S. , Dilly Julien , Raghavan Srivatsan , Yuan Chen , Cohen Elizabeth F. , Tolstorukov Michael , Andrews Elizabeth , Brais Lauren K. , da Silva Annacarolina , Perez Kimberly , Rubinson Douglas A. , Surana Rishi , Giannakis Marios , Ng Kimmie , Clancy Thomas E. , Yurgelun Matthew B. , Schlechter Benjamin L. , Clark Jeffrey W. , Shapiro Geoffrey I. , Rosenthal Michael H. , Hornick Jason L. , Nardi Valentina , Li Yvonne Y. , Gupta Hersh , Cherniack Andrew D. , Meyerson Matthew , Cleary James M. , Nowak Jonathan A. , Wolpin Brian M. , Aguirre Andrew J.
Published: August 2023

Clinical and genomic features of early vs. late onset pancreatic cancer
Supplementary Table S17 from Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer
Authors: Singh Harshabad , Keller Rachel B. , Kapner Kevin S. , Dilly Julien , Raghavan Srivatsan , Yuan Chen , Cohen Elizabeth F. , Tolstorukov Michael , Andrews Elizabeth , Brais Lauren K. , da Silva Annacarolina , Perez Kimberly , Rubinson Douglas A. , Surana Rishi , Giannakis Marios , Ng Kimmie , Clancy Thomas E. , Yurgelun Matthew B. , Schlechter Benjamin L. , Clark Jeffrey W. , Shapiro Geoffrey I. , Rosenthal Michael H. , Hornick Jason L. , Nardi Valentina , Li Yvonne Y. , Gupta Hersh , Cherniack Andrew D. , Meyerson Matthew , Cleary James M. , Nowak Jonathan A. , Wolpin Brian M. , Aguirre Andrew J.
Published: August 2023

Clinical-Genomic Characteristics Of Early Onset (Age <45) KRAS WT Pancreatic Cancer
Suppl. Figure 2 from Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis
Authors: González-Muñoz Teresa , Di Giannatale Angela , García-Silva Susana , Santos Vanesa , Sánchez-Redondo Sara , Savini Claudia , Graña-Castro Osvaldo , Blanco-Aparicio Carmen , Fischer Suzanne , De Wever Olivier , Creus-Bachiller Edgar , Ortega-Bertran Sara , Pisapia David J. , Rodríguez-Peralto Jose L. , Fernández-Rodríguez Juana , Pérez-Portabella Cleofé Romagosa , Alaggio Rita , Benassi Maria Serena , Pazzaglia Laura , Scotlandi Katia , Ratner Nancy , Yohay Kaleb , Theuer Charles P. , Peinado Héctor
Published: August 2023

ENG knockdown leads to downregulation of pro-angiogenic and pro-metastatic gene signatures in MPNST cells.
Supplementary Table S15 from Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer
Authors: Singh Harshabad , Keller Rachel B. , Kapner Kevin S. , Dilly Julien , Raghavan Srivatsan , Yuan Chen , Cohen Elizabeth F. , Tolstorukov Michael , Andrews Elizabeth , Brais Lauren K. , da Silva Annacarolina , Perez Kimberly , Rubinson Douglas A. , Surana Rishi , Giannakis Marios , Ng Kimmie , Clancy Thomas E. , Yurgelun Matthew B. , Schlechter Benjamin L. , Clark Jeffrey W. , Shapiro Geoffrey I. , Rosenthal Michael H. , Hornick Jason L. , Nardi Valentina , Li Yvonne Y. , Gupta Hersh , Cherniack Andrew D. , Meyerson Matthew , Cleary James M. , Nowak Jonathan A. , Wolpin Brian M. , Aguirre Andrew J.
Published: August 2023

List Of Germline Variants In Pancreatic Cancer Cohort
Supplementary Table S14 from Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer
Authors: Singh Harshabad , Keller Rachel B. , Kapner Kevin S. , Dilly Julien , Raghavan Srivatsan , Yuan Chen , Cohen Elizabeth F. , Tolstorukov Michael , Andrews Elizabeth , Brais Lauren K. , da Silva Annacarolina , Perez Kimberly , Rubinson Douglas A. , Surana Rishi , Giannakis Marios , Ng Kimmie , Clancy Thomas E. , Yurgelun Matthew B. , Schlechter Benjamin L. , Clark Jeffrey W. , Shapiro Geoffrey I. , Rosenthal Michael H. , Hornick Jason L. , Nardi Valentina , Li Yvonne Y. , Gupta Hersh , Cherniack Andrew D. , Meyerson Matthew , Cleary James M. , Nowak Jonathan A. , Wolpin Brian M. , Aguirre Andrew J.
Published: August 2023

MAPK pathway gene VUS analysis for oncogenicity in KRAS WT, MAPK Neg
Supplementary Data 1 from Dual Role of CXCL8 in Maintaining the Mesenchymal State of Glioblastoma Stem Cells and M2-Like Tumor-Associated Macrophages
Authors: Yuan Wei , Zhang Qian , Gu Danling , Lu Chenfei , Dixit Deobrat , Gimple Ryan C. , Gao Yisu , Gao Jiancheng , Li Daqi , Shan Danyang , Hu Lang , Li Lu , Li Yangqing , Ci Shusheng , You Hao , Yan Linping , Chen Kexin , Zhao Ningwei , Xu Chuanhai , Lan Jianyun , Liu Dong , Zhang Junxia , Shi Zhumei , Wu Qiulian , Yang Kailin , Zhao Linjie , Qiu Zhixin , Lv Deguang , Gao Wei , Yang Hui , Lin Fan , Wang Qianghu , Man Jianghong , Li Chaojun , Tao Weiwei , Agnihotri Sameer , Qian Xu , Mack Stephen C. , Zhang Nu , You Yongping , Rich Jeremy N. , Sun Guan , Wang Xiuxing
Published: August 2023

Supplementary Figure S1-S7, and Supplementary table S1
Supplementary Table S11 from Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer
Authors: Singh Harshabad , Keller Rachel B. , Kapner Kevin S. , Dilly Julien , Raghavan Srivatsan , Yuan Chen , Cohen Elizabeth F. , Tolstorukov Michael , Andrews Elizabeth , Brais Lauren K. , da Silva Annacarolina , Perez Kimberly , Rubinson Douglas A. , Surana Rishi , Giannakis Marios , Ng Kimmie , Clancy Thomas E. , Yurgelun Matthew B. , Schlechter Benjamin L. , Clark Jeffrey W. , Shapiro Geoffrey I. , Rosenthal Michael H. , Hornick Jason L. , Nardi Valentina , Li Yvonne Y. , Gupta Hersh , Cherniack Andrew D. , Meyerson Matthew , Cleary James M. , Nowak Jonathan A. , Wolpin Brian M. , Aguirre Andrew J.
Published: August 2023

BRAF KRAS co-occurence
Supplementary Table S1 from Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer
Authors: Singh Harshabad , Keller Rachel B. , Kapner Kevin S. , Dilly Julien , Raghavan Srivatsan , Yuan Chen , Cohen Elizabeth F. , Tolstorukov Michael , Andrews Elizabeth , Brais Lauren K. , da Silva Annacarolina , Perez Kimberly , Rubinson Douglas A. , Surana Rishi , Giannakis Marios , Ng Kimmie , Clancy Thomas E. , Yurgelun Matthew B. , Schlechter Benjamin L. , Clark Jeffrey W. , Shapiro Geoffrey I. , Rosenthal Michael H. , Hornick Jason L. , Nardi Valentina , Li Yvonne Y. , Gupta Hersh , Cherniack Andrew D. , Meyerson Matthew , Cleary James M. , Nowak Jonathan A. , Wolpin Brian M. , Aguirre Andrew J.
Published: August 2023

List of genes covered in different OncoPanel versions
Supplementary Figure S9 from Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer
Authors: Singh Harshabad , Keller Rachel B. , Kapner Kevin S. , Dilly Julien , Raghavan Srivatsan , Yuan Chen , Cohen Elizabeth F. , Tolstorukov Michael , Andrews Elizabeth , Brais Lauren K. , da Silva Annacarolina , Perez Kimberly , Rubinson Douglas A. , Surana Rishi , Giannakis Marios , Ng Kimmie , Clancy Thomas E. , Yurgelun Matthew B. , Schlechter Benjamin L. , Clark Jeffrey W. , Shapiro Geoffrey I. , Rosenthal Michael H. , Hornick Jason L. , Nardi Valentina , Li Yvonne Y. , Gupta Hersh , Cherniack Andrew D. , Meyerson Matthew , Cleary James M. , Nowak Jonathan A. , Wolpin Brian M. , Aguirre Andrew J.
Published: August 2023

Dual pan-RAF and MEK inhibition demonstrates synergistic inhibition of pancreatic cancer PDOs harboring BRAF in-frame deletions
Supplementary Figure S8 from Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer
Authors: Singh Harshabad , Keller Rachel B. , Kapner Kevin S. , Dilly Julien , Raghavan Srivatsan , Yuan Chen , Cohen Elizabeth F. , Tolstorukov Michael , Andrews Elizabeth , Brais Lauren K. , da Silva Annacarolina , Perez Kimberly , Rubinson Douglas A. , Surana Rishi , Giannakis Marios , Ng Kimmie , Clancy Thomas E. , Yurgelun Matthew B. , Schlechter Benjamin L. , Clark Jeffrey W. , Shapiro Geoffrey I. , Rosenthal Michael H. , Hornick Jason L. , Nardi Valentina , Li Yvonne Y. , Gupta Hersh , Cherniack Andrew D. , Meyerson Matthew , Cleary James M. , Nowak Jonathan A. , Wolpin Brian M. , Aguirre Andrew J.
Published: August 2023

Germline genetic analysis of KRAS WT versus KRAS mutant pancreatic cancer
Supplementary Figure S5 from Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer
Authors: Singh Harshabad , Keller Rachel B. , Kapner Kevin S. , Dilly Julien , Raghavan Srivatsan , Yuan Chen , Cohen Elizabeth F. , Tolstorukov Michael , Andrews Elizabeth , Brais Lauren K. , da Silva Annacarolina , Perez Kimberly , Rubinson Douglas A. , Surana Rishi , Giannakis Marios , Ng Kimmie , Clancy Thomas E. , Yurgelun Matthew B. , Schlechter Benjamin L. , Clark Jeffrey W. , Shapiro Geoffrey I. , Rosenthal Michael H. , Hornick Jason L. , Nardi Valentina , Li Yvonne Y. , Gupta Hersh , Cherniack Andrew D. , Meyerson Matthew , Cleary James M. , Nowak Jonathan A. , Wolpin Brian M. , Aguirre Andrew J.
Published: August 2023

Pathway-level comparison reveals enrichment of alternative MAPK alterations in KRAS WT pancreatic cancer
Supplementary Figure S3 from Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer
Authors: Singh Harshabad , Keller Rachel B. , Kapner Kevin S. , Dilly Julien , Raghavan Srivatsan , Yuan Chen , Cohen Elizabeth F. , Tolstorukov Michael , Andrews Elizabeth , Brais Lauren K. , da Silva Annacarolina , Perez Kimberly , Rubinson Douglas A. , Surana Rishi , Giannakis Marios , Ng Kimmie , Clancy Thomas E. , Yurgelun Matthew B. , Schlechter Benjamin L. , Clark Jeffrey W. , Shapiro Geoffrey I. , Rosenthal Michael H. , Hornick Jason L. , Nardi Valentina , Li Yvonne Y. , Gupta Hersh , Cherniack Andrew D. , Meyerson Matthew , Cleary James M. , Nowak Jonathan A. , Wolpin Brian M. , Aguirre Andrew J.
Published: August 2023

Focal chromosomal alterations and oncogenic drivers differ between KRAS WT and mutant pancreatic cancer
Supplementary Figure S11 from Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer
Authors: Singh Harshabad , Keller Rachel B. , Kapner Kevin S. , Dilly Julien , Raghavan Srivatsan , Yuan Chen , Cohen Elizabeth F. , Tolstorukov Michael , Andrews Elizabeth , Brais Lauren K. , da Silva Annacarolina , Perez Kimberly , Rubinson Douglas A. , Surana Rishi , Giannakis Marios , Ng Kimmie , Clancy Thomas E. , Yurgelun Matthew B. , Schlechter Benjamin L. , Clark Jeffrey W. , Shapiro Geoffrey I. , Rosenthal Michael H. , Hornick Jason L. , Nardi Valentina , Li Yvonne Y. , Gupta Hersh , Cherniack Andrew D. , Meyerson Matthew , Cleary James M. , Nowak Jonathan A. , Wolpin Brian M. , Aguirre Andrew J.
Published: August 2023

Cox proportional hazard regression shows improved OS for KRAS WT pancreatic cancer after adjusting for patient age and disease stage
Supplementary Figure S10 from Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer
Authors: Singh Harshabad , Keller Rachel B. , Kapner Kevin S. , Dilly Julien , Raghavan Srivatsan , Yuan Chen , Cohen Elizabeth F. , Tolstorukov Michael , Andrews Elizabeth , Brais Lauren K. , da Silva Annacarolina , Perez Kimberly , Rubinson Douglas A. , Surana Rishi , Giannakis Marios , Ng Kimmie , Clancy Thomas E. , Yurgelun Matthew B. , Schlechter Benjamin L. , Clark Jeffrey W. , Shapiro Geoffrey I. , Rosenthal Michael H. , Hornick Jason L. , Nardi Valentina , Li Yvonne Y. , Gupta Hersh , Cherniack Andrew D. , Meyerson Matthew , Cleary James M. , Nowak Jonathan A. , Wolpin Brian M. , Aguirre Andrew J.
Published: August 2023

Additional clinicopathologic/genomic data for KRAS WT patient with SLC4A4-ROS1 fusion
Data from A Phase I, Multicenter, Open-Label, First-in-Human Study of DS-6157a in Patients with Advanced Gastrointestinal Stromal Tumor
Authors: George Suzanne , Heinrich Michael C. , Somaiah Neeta , Oppelt Peter , McLeod Robert , Nishioka Satoshi , Kundu Madan G. , Qian Xiaozhong , Kumar Prasanna , Laadem Abderrahmane , Lau Yvonne , Tran Brittany P. , Fallon Maura , Dosunmu Ololade , Shi Julia , Naito Yoichi
Published: August 2023

AbstractPurpose:
To evaluate DS-6157a, an antibody–drug conjugate targeting G protein–coupled receptor 20 (GPR20), in gastrointestinal stromal tumors (GIST).
Patients and methods:
In this phase I multicenter, open-label, multiple-dose study, patients with previously treated advanced GIST received intravenous DS-6157a on Day 1 of 21-day cycles, with a starting dose of 1.6 mg/kg. The primary objective evaluated the safety and tolerability of DS-6157a, while determining dose-limiting toxicity (DLT) and the MTD. Secondary objectives included plasma pharmacokinetics parameters, plasma antidrug antibodies (ADA), and efficacy.
Results:
A total of 34 patients enrolled. DS-6157a was well tolerated, with DLTs in 4 patients (11.8%) at doses of 6.4 mg/kg, 9.6 mg/kg, and 12.8 mg/kg; the MTD was determined to be 6.4 mg/kg. Treatment-emergent adverse events (TEAE) grade ≥3 occurred in 17 patients (50.0%), including decreased platelet count (23.5%), anemia (20.6%), decreased neutrophil count (14.7%), and decreased white blood cell count (11.8%). Four patients (11.8%) experienced serious adverse events related to DS-6157a. Six patients died with 5 due to disease progression and 1 due to DS-6157a-related TEAE. Tumor shrinkage was observed in 7 patients (20.6%), and 1 patient (2.9%) achieved a partial response. Plasma concentrations and exposure of intact DS-6157a, DXd, and total anti-GPR20 antibody all demonstrated a dose-dependent profile. No treatment-emergent ADAs were observed.
Conclusions:
Targeting GPR20 with DS-6157a was tolerated in patients with advanced GIST with tumor shrinkage demonstrated in KIT/PDGFRA wild-type GIST. However, the study did not proceed further due to lower efficacy outcomes than anticipated.
Data from Transcriptomic Signatures of MSI-high Metastatic Colorectal Cancer Predict Efficacy of Immune Checkpoint Inhibitors
Authors: Gallois Claire , Landi Matteo , Taieb Julien , Sroussi Marine , Saberzadeh-Ardestani Bahar , Cazelles Antoine , Lonardi Sara , Bergamo Francesca , Intini Rossana , Maddalena Giulia , Pietrantonio Filippo , Corti Francesca , Ambrosini Margherita , Martinetti Antonia , Germani Marco Maria. , Boccaccio Chiara , Vetere Guglielmo , Mouillet-Richard Sophie , de Reynies Aurelien , Sinicrope Frank A. , Cremolini Chiara , Laurent-Puig Pierre
Published: August 2023

Abstract
Purpose: Microsatellite instability (MSI) is currently the only predictive biomarker of efficacy of immune checkpoint inhibitors (ICI) in metastatic colorectal cancers (mCRC). However, 10-40% of patients with MSI mCRC will experience a primary resistance to ICI. Experimental design: In 2 cohorts of patients with MSI mCRC treated with ICI (exploratory: N=103, validation: N=35), 3’RNAseq was performed from primary tumors. Previously described single-cell transcriptomic signatures of tumor microenvironment (TME) were analysed. Results: In the exploratory cohort, the unsupervised clustering allowed the identification of three clusters of tumors with distinct transcriptional profiles: cluster A (“stromalHIGH-proliferationLOW”), cluster B (“stromalHIGH-proliferationMED”), and cluster C (“stromalLOW-proliferationHIGH”), with an enrichment of patients progressing at first disease assessment under ICI in the cluster A (30% vs 12% in cluster B and 8.1% in cluster C, p=0.074). Progression-free survival (PFS) was also significantly shorter in patients belonging to cluster A, compared to clusters B or C (p<0.001) with 2-year PFS rates of 33.5%, 80.5% and 78.3%, respectively. In multivariate analysis, PFS was still significantly longer in patients belonging to cluster B (HR: 0.19 95%CI 0.08-0.45, p<0.001) and cluster C (HR: 0.25 95%CI 0.10-0.59, p=0.02), compared to patients belonging to cluster A. The association of this clustering with PFS under ICI was confirmed in the validation cohort. PFS related to non-ICI-based regimens was not significantly different according to cluster. Conclusion: This unsupervised transcriptomic classification identified three groups of MSI mCRCs with different compositions of TME cells and proliferative capacities of TME/tumor cells. The “stromalHIGH-proliferationLOW” cluster is associated with a poorer prognosis with ICI treatment.