bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure S6 from Clinical and Molecular Features of Long-term Response to Immune Checkpoint Inhibitors in Patients with Advanced Non–Small Cell Lung Cancer
Authors: Thummalapalli Rohit , Ricciuti Biagio , Bandlamudi Chaitanya , Muldoon Daniel , Rizvi Hira , Elkrief Arielle , Luo Jia , Alessi Joao V. , Pecci Federica , Lamberti Giuseppe , Di Federico Alessandro , Hong Lingzhi , Zhang Jianjun , Heymach John V. , Gibbons Don L. , Plodkowski Andrew J. , Ravichandran Vignesh , Donoghue Mark T.A. , Vanderbilt Chad , Ladanyi Marc , Rudin Charles M. , Kris Mark G. , Riely Gregory J. , Chaft Jamie E. , Hellmann Matthew D. , Vokes Natalie I. , Awad Mark M. , Schoenfeld Adam J.
Published: November 2023

Univariable analyses of association of clinical characteristics with long-term response (LTR) compared to short-term response (STR), non-LTR, and progressive disease (PD).
Table S1, Table S2, Table S3 from Adavosertib Enhances Antitumor Activity of Trastuzumab Deruxtecan in HER2-Expressing Cancers
Authors: DiPeri Timothy P. , Evans Kurt W. , Raso Maria Gabriela , Zhao Ming , Rizvi Yasmeen Q. , Zheng Xiaofeng , Wang Bailiang , Kirby Bryce P. , Kong Kathleen , Kahle Michael , Yap Timothy A. , Dumbrava Ecaterina E. , Ajani Jaffer A. , Fu Siqing , Keyomarsi Khandan , Meric-Bernstam Funda
Published: November 2023

Supplemental Tables 1 - 3
Supplementary Figure S10 from Clinical and Molecular Features of Long-term Response to Immune Checkpoint Inhibitors in Patients with Advanced Non–Small Cell Lung Cancer
Authors: Thummalapalli Rohit , Ricciuti Biagio , Bandlamudi Chaitanya , Muldoon Daniel , Rizvi Hira , Elkrief Arielle , Luo Jia , Alessi Joao V. , Pecci Federica , Lamberti Giuseppe , Di Federico Alessandro , Hong Lingzhi , Zhang Jianjun , Heymach John V. , Gibbons Don L. , Plodkowski Andrew J. , Ravichandran Vignesh , Donoghue Mark T.A. , Vanderbilt Chad , Ladanyi Marc , Rudin Charles M. , Kris Mark G. , Riely Gregory J. , Chaft Jamie E. , Hellmann Matthew D. , Vokes Natalie I. , Awad Mark M. , Schoenfeld Adam J.
Published: November 2023

Genomic features of patients with long-term response (LTR) compared to non-LTR and progressive disease (PD).
Supplementary Figure S1 from Clinical and Molecular Features of Long-term Response to Immune Checkpoint Inhibitors in Patients with Advanced Non–Small Cell Lung Cancer
Authors: Thummalapalli Rohit , Ricciuti Biagio , Bandlamudi Chaitanya , Muldoon Daniel , Rizvi Hira , Elkrief Arielle , Luo Jia , Alessi Joao V. , Pecci Federica , Lamberti Giuseppe , Di Federico Alessandro , Hong Lingzhi , Zhang Jianjun , Heymach John V. , Gibbons Don L. , Plodkowski Andrew J. , Ravichandran Vignesh , Donoghue Mark T.A. , Vanderbilt Chad , Ladanyi Marc , Rudin Charles M. , Kris Mark G. , Riely Gregory J. , Chaft Jamie E. , Hellmann Matthew D. , Vokes Natalie I. , Awad Mark M. , Schoenfeld Adam J.
Published: November 2023

Frequency of patients with long-term response (LTR), short-term response (STR), and progressive disease (PD) from individual clinical sites.
Supplementary Table S5 from SPOP Mutations Target STING1 Signaling in Prostate Cancer and Create Therapeutic Vulnerabilities to PARP Inhibitor–Induced Growth Suppression
Authors: Geng Chuandong , Zhang Man-Chao , Manyam Ganiraju C. , Vykoukal Jody V. , Fahrmann Johannes F. , Peng Shan , Wu Cheng , Park Sanghee , Kondraganti Shakuntala , Wang Daoqi , Robinson Brian D. , Loda Massimo , Barbieri Christopher E. , Yap Timothy A. , Corn Paul G. , Hanash Samir , Broom Bradley M. , Pilié Patrick G. , Thompson Timothy C.
Published: November 2023

Supplementary Table S5. Complete listing and details of siRNA targeting sequences used for gene knockdown in Fig. 4A and Extended Data Fig. 3.
Supplementary Table S12 from SPOP Mutations Target STING1 Signaling in Prostate Cancer and Create Therapeutic Vulnerabilities to PARP Inhibitor–Induced Growth Suppression
Authors: Geng Chuandong , Zhang Man-Chao , Manyam Ganiraju C. , Vykoukal Jody V. , Fahrmann Johannes F. , Peng Shan , Wu Cheng , Park Sanghee , Kondraganti Shakuntala , Wang Daoqi , Robinson Brian D. , Loda Massimo , Barbieri Christopher E. , Yap Timothy A. , Corn Paul G. , Hanash Samir , Broom Bradley M. , Pilié Patrick G. , Thompson Timothy C.
Published: November 2023

Supplemental Table S12. Quantification of each protein-specific band normalized to vinculin (RM-1-BM–derived models, Fig 4E).
Supplementary Table S10 from SPOP Mutations Target STING1 Signaling in Prostate Cancer and Create Therapeutic Vulnerabilities to PARP Inhibitor–Induced Growth Suppression
Authors: Geng Chuandong , Zhang Man-Chao , Manyam Ganiraju C. , Vykoukal Jody V. , Fahrmann Johannes F. , Peng Shan , Wu Cheng , Park Sanghee , Kondraganti Shakuntala , Wang Daoqi , Robinson Brian D. , Loda Massimo , Barbieri Christopher E. , Yap Timothy A. , Corn Paul G. , Hanash Samir , Broom Bradley M. , Pilié Patrick G. , Thompson Timothy C.
Published: November 2023

Supplementary Table S10. Quantification of each protein-specific band normalized to vinculin (Dox-inducible RM-1-BM–derived models, Fig. 4D, lower panel).
Supplementary Methods S1 from SPOP Mutations Target STING1 Signaling in Prostate Cancer and Create Therapeutic Vulnerabilities to PARP Inhibitor–Induced Growth Suppression
Authors: Geng Chuandong , Zhang Man-Chao , Manyam Ganiraju C. , Vykoukal Jody V. , Fahrmann Johannes F. , Peng Shan , Wu Cheng , Park Sanghee , Kondraganti Shakuntala , Wang Daoqi , Robinson Brian D. , Loda Massimo , Barbieri Christopher E. , Yap Timothy A. , Corn Paul G. , Hanash Samir , Broom Bradley M. , Pilié Patrick G. , Thompson Timothy C.
Published: November 2023

Supplementary Methods
Supplementary Figure S9 from SPOP Mutations Target STING1 Signaling in Prostate Cancer and Create Therapeutic Vulnerabilities to PARP Inhibitor–Induced Growth Suppression
Authors: Geng Chuandong , Zhang Man-Chao , Manyam Ganiraju C. , Vykoukal Jody V. , Fahrmann Johannes F. , Peng Shan , Wu Cheng , Park Sanghee , Kondraganti Shakuntala , Wang Daoqi , Robinson Brian D. , Loda Massimo , Barbieri Christopher E. , Yap Timothy A. , Corn Paul G. , Hanash Samir , Broom Bradley M. , Pilié Patrick G. , Thompson Timothy C.
Published: November 2023

Supplementary Fig. S9. MALDI-TOF mass spectrometry analysis of ubiquitinated STING1 protein at K347 from in vivo ubiquitination sample co-transfected with SPOPwt shown in Fig. 3D.
Supplementary Figure S5 from SPOP Mutations Target STING1 Signaling in Prostate Cancer and Create Therapeutic Vulnerabilities to PARP Inhibitor–Induced Growth Suppression
Authors: Geng Chuandong , Zhang Man-Chao , Manyam Ganiraju C. , Vykoukal Jody V. , Fahrmann Johannes F. , Peng Shan , Wu Cheng , Park Sanghee , Kondraganti Shakuntala , Wang Daoqi , Robinson Brian D. , Loda Massimo , Barbieri Christopher E. , Yap Timothy A. , Corn Paul G. , Hanash Samir , Broom Bradley M. , Pilié Patrick G. , Thompson Timothy C.
Published: November 2023

Supplementary Fig. S5. Original unedited IB images for representative Western blots experiments (n-2) used in Figure 3C.
Supplementary Figure S4 from SPOP Mutations Target STING1 Signaling in Prostate Cancer and Create Therapeutic Vulnerabilities to PARP Inhibitor–Induced Growth Suppression
Authors: Geng Chuandong , Zhang Man-Chao , Manyam Ganiraju C. , Vykoukal Jody V. , Fahrmann Johannes F. , Peng Shan , Wu Cheng , Park Sanghee , Kondraganti Shakuntala , Wang Daoqi , Robinson Brian D. , Loda Massimo , Barbieri Christopher E. , Yap Timothy A. , Corn Paul G. , Hanash Samir , Broom Bradley M. , Pilié Patrick G. , Thompson Timothy C.
Published: November 2023

Supplementary Fig. S4. Original unedited IB images for representative Western blots experiments (n-2) used in Figure 3B.
Supplementary Figure S3 from SPOP Mutations Target STING1 Signaling in Prostate Cancer and Create Therapeutic Vulnerabilities to PARP Inhibitor–Induced Growth Suppression
Authors: Geng Chuandong , Zhang Man-Chao , Manyam Ganiraju C. , Vykoukal Jody V. , Fahrmann Johannes F. , Peng Shan , Wu Cheng , Park Sanghee , Kondraganti Shakuntala , Wang Daoqi , Robinson Brian D. , Loda Massimo , Barbieri Christopher E. , Yap Timothy A. , Corn Paul G. , Hanash Samir , Broom Bradley M. , Pilié Patrick G. , Thompson Timothy C.
Published: November 2023

Supplementary Fig. S3. Original unedited IB images for representative Western blots experiments (n-3) used in Figure 3A.
Supplementary Figure S21 from SPOP Mutations Target STING1 Signaling in Prostate Cancer and Create Therapeutic Vulnerabilities to PARP Inhibitor–Induced Growth Suppression
Authors: Geng Chuandong , Zhang Man-Chao , Manyam Ganiraju C. , Vykoukal Jody V. , Fahrmann Johannes F. , Peng Shan , Wu Cheng , Park Sanghee , Kondraganti Shakuntala , Wang Daoqi , Robinson Brian D. , Loda Massimo , Barbieri Christopher E. , Yap Timothy A. , Corn Paul G. , Hanash Samir , Broom Bradley M. , Pilié Patrick G. , Thompson Timothy C.
Published: November 2023

Supplementary Fig. S21. Double immunofluorescence staining analysis of cleaved caspase 3 and PARP1 in
C4-2b-empty vector and C4-2b-SPOPF133V xenograft tumors treated with talazoparib (TALA) or control vehicle
Supplementary Figure S2 from SPOP Mutations Target STING1 Signaling in Prostate Cancer and Create Therapeutic Vulnerabilities to PARP Inhibitor–Induced Growth Suppression
Authors: Geng Chuandong , Zhang Man-Chao , Manyam Ganiraju C. , Vykoukal Jody V. , Fahrmann Johannes F. , Peng Shan , Wu Cheng , Park Sanghee , Kondraganti Shakuntala , Wang Daoqi , Robinson Brian D. , Loda Massimo , Barbieri Christopher E. , Yap Timothy A. , Corn Paul G. , Hanash Samir , Broom Bradley M. , Pilié Patrick G. , Thompson Timothy C.
Published: November 2023

Supplementary Fig. S2. Original unedited IB images for representative Western blots experiments used in Figure 2B and 2C
Supplementary Figure S15 from SPOP Mutations Target STING1 Signaling in Prostate Cancer and Create Therapeutic Vulnerabilities to PARP Inhibitor–Induced Growth Suppression
Authors: Geng Chuandong , Zhang Man-Chao , Manyam Ganiraju C. , Vykoukal Jody V. , Fahrmann Johannes F. , Peng Shan , Wu Cheng , Park Sanghee , Kondraganti Shakuntala , Wang Daoqi , Robinson Brian D. , Loda Massimo , Barbieri Christopher E. , Yap Timothy A. , Corn Paul G. , Hanash Samir , Broom Bradley M. , Pilié Patrick G. , Thompson Timothy C.
Published: November 2023

Supplementary Fig. S15. Original unedited IB images for representative Western blots experiments (n-3) used in Figure 4D lower panels (RM-1-BM-EV/ inducible SPOPmuts)
Supplementary Figure S14 from SPOP Mutations Target STING1 Signaling in Prostate Cancer and Create Therapeutic Vulnerabilities to PARP Inhibitor–Induced Growth Suppression
Authors: Geng Chuandong , Zhang Man-Chao , Manyam Ganiraju C. , Vykoukal Jody V. , Fahrmann Johannes F. , Peng Shan , Wu Cheng , Park Sanghee , Kondraganti Shakuntala , Wang Daoqi , Robinson Brian D. , Loda Massimo , Barbieri Christopher E. , Yap Timothy A. , Corn Paul G. , Hanash Samir , Broom Bradley M. , Pilié Patrick G. , Thompson Timothy C.
Published: November 2023

Supplementary Fig. S14. Original unedited IB images for representative Western blots experiments (n-3) used in Figure 4D upper panels (C4-2b-EV/ inducible SPOPmuts).
Supplementary Figure S13 from SPOP Mutations Target STING1 Signaling in Prostate Cancer and Create Therapeutic Vulnerabilities to PARP Inhibitor–Induced Growth Suppression
Authors: Geng Chuandong , Zhang Man-Chao , Manyam Ganiraju C. , Vykoukal Jody V. , Fahrmann Johannes F. , Peng Shan , Wu Cheng , Park Sanghee , Kondraganti Shakuntala , Wang Daoqi , Robinson Brian D. , Loda Massimo , Barbieri Christopher E. , Yap Timothy A. , Corn Paul G. , Hanash Samir , Broom Bradley M. , Pilié Patrick G. , Thompson Timothy C.
Published: November 2023

Supplementary Fig. S13. Original unedited IB images for representative Western blots experiments (n-3) used in Supplementary Figure S12
Data from Inhibition of NAD+-Dependent Metabolic Processes Induces Cellular Necrosis and Tumor Regression in Rhabdomyosarcoma Models
Authors: McKay-Corkum Grace B. , Collins Victor J. , Yeung Choh , Ito Takeshi , Issaq Sameer H. , Holland David , Vulikh Ksenia , Zhang Yiping , Lee Unsun , Lei Haiyan , Mendoza Arnulfo , Shern Jack F. , Yohe Marielle E. , Yamamoto Kazutoshi , Wilson Kelli , Ji Jiuping , Karim Baktiar O. , Thomas Craig J. , Krishna Murali C. , Neckers Leonard M. , Heske Christine M.
Published: November 2023

AbstractPurpose:
Deregulated metabolism in cancer cells represents a vulnerability that may be therapeutically exploited to benefit patients. One such target is nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD+ salvage pathway. NAMPT is necessary for efficient NAD+ production and may be exploited in cells with increased metabolic demands. We have identified NAMPT as a dependency in rhabdomyosarcoma (RMS), a malignancy for which novel therapies are critically needed. Here we describe the effect of NAMPT inhibition on RMS proliferation and metabolism in vitro and in vivo.
Experimental Design:
Assays of proliferation and cell death were used to determine the effects of pharmacologic NAMPT inhibition in a panel of ten molecularly diverse RMS cell lines. Mechanism of the clinical NAMPTi OT-82 was determined using measures of NAD+ and downstream NAD+-dependent functions, including energy metabolism. We used orthotopic xenograft models to examine tolerability, efficacy, and drug mechanism in vivo.
Results:
Across all ten RMS cell lines, OT-82 depleted NAD+ and inhibited cell growth at concentrations ≤1 nmol/L. Significant impairment of glycolysis was a universal finding, with some cell lines also exhibiting diminished oxidative phosphorylation. Most cell lines experienced profound depletion of ATP with subsequent irreversible necrotic cell death. Importantly, loss of NAD and glycolytic activity were confirmed in orthotopic in vivo models, which exhibited complete tumor regressions with OT-82 treatment delivered on the clinical schedule.
Conclusions:
RMS is highly vulnerable to NAMPT inhibition. These findings underscore the need for further clinical study of this class of agents for this malignancy.
Data from Exercise Training Reduces the Inflammatory Response and Promotes Intestinal Mucosa-Associated Immunity in Lynch Syndrome
Authors: Deng Nan , Reyes-Uribe Laura , Fahrmann Johannes F. , Thoman Whittney S. , Munsell Mark F. , Dennison Jennifer B. , Murage Eunice , Wu Ranran , Hawk Ernest T. , Thirumurthi Selvi , Lynch Patrick M. , Dieli-Conwright Christina M. , Lazar Alexander J. , Jindal Sonali , Chu Khoi , Chelvanambi Manoj , Basen-Engquist Karen , Li Yisheng , Wargo Jennifer A. , McAllister Florencia , Allison James P. , Sharma Padmanee , Sinha Krishna M. , Hanash Samir , Gilchrist Susan C. , Vilar Eduardo
Published: November 2023

AbstractPurpose:
Lynch syndrome (LS) is a hereditary condition with a high lifetime risk of colorectal and endometrial cancers. Exercise is a non-pharmacologic intervention to reduce cancer risk, though its impact on patients with LS has not been prospectively studied. Here, we evaluated the impact of a 12-month aerobic exercise cycling intervention in the biology of the immune system in LS carriers.
Patients and Methods:
To address this, we enrolled 21 patients with LS onto a non-randomized, sequential intervention assignation, clinical trial to assess the effect of a 12-month exercise program that included cycling classes 3 times weekly for 45 minutes versus usual care with a one-time exercise counseling session as control. We analyzed the effects of exercise on cardiorespiratory fitness, circulating, and colorectal-tissue biomarkers using metabolomics, gene expression by bulk mRNA sequencing, and spatial transcriptomics by NanoString GeoMx.
Results:
We observed a significant increase in oxygen consumption (VO2peak) as a primary outcome of the exercise and a decrease in inflammatory markers (prostaglandin E) in colon and blood as the secondary outcomes in the exercise versus usual care group. Gene expression profiling and spatial transcriptomics on available colon biopsies revealed an increase in the colonic mucosa levels of natural killer and CD8+ T cells in the exercise group that were further confirmed by IHC studies.
Conclusions:
Together these data have important implications for cancer interception in LS, and document for the first-time biological effects of exercise in the immune system of a target organ in patients at-risk for cancer.
Data from Circulating microRNAs and Cytokines as Prognostic Biomarkers for Doxorubicin-Induced Cardiac Injury and for Evaluating the Effectiveness of an Exercise Intervention
Authors: Jeyabal Prince , Bhagat Anchit , Wang Fei , Roth Michael , Livingston J. Andrew , Gilchrist Susan C. , Banchs Jose , Hildebrandt Michelle A.T. , Chandra Joya , Deswal Anita , Koutroumpakis Efstratios , Wang Jian , Daw Najat C. , Honey Theresa A. , Kleinerman Eugenie S.
Published: November 2023

AbstractPurpose:
To define a set of biomarkers that can be used to identify patients at high risk of developing late doxorubicin (DOX)-induced cardiac morbidity with the goal of focused monitoring and early interventions.
Experimental Design:
Mice received phosphate buffered saline or DOX 2.5 mg/kg 2x/week for 2 weeks. Blood samples were obtained before and after therapy for quantification of miRNAs (6 and 24 hours), cytokines (24 hours), and troponin (24 hours, 4 and 6 weeks). Cardiac function was evaluated using echocardiography before and 24 hours after therapy. To assess the effectiveness of exercise intervention in preventing DOX-induced cardiotoxicity blood samples were collected from mice treated with DOX or DOX + exercise. Plasma samples from 13 DOX-treated patients with sarcoma were also evaluated before and 24 hours after therapy.
Results:
Elevations in plasma miRNA-1, miRNA-499 and IL1α, IL1β, and IL6 were seen in DOX-treated mice with decreased ejection fraction and fractional shortening 24 hours after DOX therapy. Troponin levels were not elevated until 4 weeks after therapy. In mice treated with exercise during DOX, there was no elevation in these biomarkers and no change in cardiac function. Elevations in these biomarkers were seen in 12 of 13 patients with sarcoma treated with DOX.
Conclusions:
These findings define a potential set of biomarkers to identify and predict patients at risk for developing acute and late cardiovascular diseases with the goal of focused monitoring and early intervention. Further studies are needed to confirm the predictive value of these biomarkers in late cardiotoxicity.
Data from Regorafenib plus Vincristine and Irinotecan in Pediatric Patients with Recurrent/Refractory Solid Tumors: An Innovative Therapy for Children with Cancer Study
Authors: Casanova Michela , Bautista Francisco , Campbell-Hewson Quentin , Makin Guy , Marshall Lynley V. , Verschuur Arnauld C. , Cañete Nieto Adela , Corradini Nadège , Ploeger Bart A. , Brennan Barbara J. , Mueller Udo , Zebger-Gong Hong , Chung John W. , Geoerger Birgit
Published: November 2023

AbstractPurpose:
This phase Ib study defined the safety, MTD, and recommended phase II dose (RP2D) of regorafenib combined with vincristine and irinotecan (VI). Secondary objectives were evaluation of antitumor activity and pharmacokinetics (PK) of regorafenib and irinotecan.
Patients and Methods:
Patients aged 6 months to <18 years with relapsed/refractory solid malignancies [≥50% with rhabdomyosarcoma (RMS)] received regorafenib (starting dose 72 mg/m2/day) concomitantly or sequentially with vincristine 1.5 mg/m2 on days 1 and 8, and irinotecan 50 mg/m2 on days 1–5 (21-day cycle). Adverse events (AE) and tumor response were assessed. PK (regorafenib and irinotecan) were evaluated using a population PK model.
Results:
We enrolled 21 patients [median age, 10 years; 12, RMS; 5, Ewing sarcoma (EWS)]. The MTD/RP2D of regorafenib in the sequential schedule was 82 mg/m2. The concomitant dosing schedule was discontinued because of dose-limiting toxicities in 2 of 2 patients treated. Most common grade 3/4 (>30% of patients) AEs were neutropenia, anemia, thrombocytopenia, and leukopenia. The overall response rate was 48% and disease control rate [complete response (CR)/partial response/stable disease/non-CR/non-progressive disease] was 86%. Median progression-free survival was 7.0 months [95% confidence interval (CI), 2.9–14.8] and median overall survival was 8.7 months (95% CI, 5.5–16.3). When combined with VI, regorafenib PK was similar to single-agent PK in children and adults (treated with regorafenib 160 mg/day).
Conclusions:
Regorafenib can be combined sequentially with standard dose VI in pediatric patients with relapsed/refractory solid tumors with appropriate dose modifications. Clinical activity was observed in patients with RMS and EWS (ClinicalTrials.gov NCT02085148).
Data from Clinical and molecular features of long-term response to immune checkpoint inhibitors in patients with advanced non-small cell lung cancer
Authors: Thummalapalli Rohit , Ricciuti Biagio , Bandlamudi Chaitanya , Muldoon Daniel , Rizvi Hira , Elkrief Arielle , Luo Jia , Alessi Joao V. , Pecci Federica , Lamberti Giuseppe , Di Federico Alessandro , Hong Lingzhi , Zhang Jianjun , Heymach John V. , Gibbons Don L. , Plodkowski Andrew J. , Ravichandran Vignesh , Donoghue Mark T.A. , Vanderbilt Chad , Ladanyi Marc , Rudin Charles M. , Kris Mark G. , Riely Gregory J. , Chaft Jamie E. , Hellmann Matthew D. , Vokes Natalie I. , Awad Mark M. , Schoenfeld Adam J.
Published: November 2023

Abstract
Purpose: We sought to identify features of patients with advanced non-small cell lung cancer (NSCLC) who achieve long-term response (LTR) to immune checkpoint inhibitors (ICIs), and how these might differ from features predictive of short-term response (STR). Experimental Design: We performed a multicenter retrospective analysis of patients with advanced NSCLC treated with ICIs over ten years. LTR and STR were defined as response ≥ 24 months and response < 12 months, respectively. Tumor PD-L1 expression, mutational burden (TMB), next-generation sequencing, and whole exome sequencing data were analyzed to identify characteristics enriched in patients achieving LTR compared to STR and non-LTR. Results: Among 3118 patients, 8% achieved LTR and 7% achieved STR, with 5-year overall survival of 81% and 18% among LTR and STR patients respectively. High TMB (≥ 50th percentile) enriched for LTR compared to STR (P = 0.001) and non-LTR (P < 0.001). Whereas PD-L1 ≥ 50% enriched for LTR compared to non-LTR (P < 0.001); PD-L1 ≥ 50% did not enrich for LTR compared to STR (P = 0.181). Non-squamous histology (P = 0.040) and increasing depth of response (median best overall response [BOR] -65% vs -46%, P < 0.001) also associated with LTR compared to STR; no individual genomic alterations were uniquely enriched among LTR patients. Conclusions: Among advanced NSCLC patients treated with ICIs, distinct features including high TMB, non-squamous histology, and depth of radiographic improvement distinguish patients poised to achieve long-term response compared to initial response followed by progression, whereas high PD-L1 does not.
Data from ATM-Inhibitor AZD1390 Is a Radiosensitizer for Breast Cancer CNS Metastasis
Authors: Tew Ben Yi , Kalfa Alex J. , Yang Zeyi , Hurth Kyle M. , Simon Thomas , Abnoosian Eric , Durant Stephen T. , Hamerlik Petra , Salhia Bodour
Published: November 2023

AbstractPurpose:
Limited effective treatments are currently available for central nervous system (CNS) metastasis (CM). This is largely driven by the inability of current therapeutics to penetrate the blood brain barrier (BBB) and the lack of preclinical models for testing new therapies. Here we study the efficacy of AZD1390, a BBB penetrating ataxia-telangiectasia mutated inhibitor, as a radiosensitizer for breast cancer CM treatment.
Experimental Design:
Three patient-derived xenograft (PDX) tumors including 2 HER2+ and 1 triple-negative breast cancer harboring DNA damage response (DDR) gene mutations, were implanted subcutaneously in the flank of mice to assess tumor growth inhibition by AZD1390 combined with radiation. Animal survival was further assessed by implanting the best responding PDX model orthotopically in the brain.
Results:
Pretreatment with AZD1390 followed by radiation therapy inhibited growth of PDX tumors implanted in the flank, and improved survival in orthotopic models with average survival of 222 days compared with 123 days in controls. Administration of AZD1390 posttreatment for 21 days had no further benefits. While the combination therapy resulted in sustained tumor inhibition, sporadic regrowth was observed in some mice 50 to 100 days posttreatment in all models. Gene expression comparing these tumors with complete responders demonstrated changes in upregulation of oncogenic proteins, which are potential drivers of tumor growth after treatment.
Conclusions:
Our results demonstrate that AZD1390 effectively sensitizes breast cancer CM to radiation therapy in DDR mutant tumors. This study demonstrates the potential of using AZD1390 as a novel therapeutic agent for patients with breast cancer CM.
Data from SPOP Mutations Target STING1 Signaling in Prostate Cancer and Create Therapeutic Vulnerabilities to PARP Inhibitor–Induced Growth Suppression
Authors: Geng Chuandong , Zhang Man-Chao , Manyam Ganiraju C. , Vykoukal Jody V. , Fahrmann Johannes F. , Peng Shan , Wu Cheng , Park Sanghee , Kondraganti Shakuntala , Wang Daoqi , Robinson Brian D. , Loda Massimo , Barbieri Christopher E. , Yap Timothy A. , Corn Paul G. , Hanash Samir , Broom Bradley M. , Pilié Patrick G. , Thompson Timothy C.
Published: November 2023

AbstractPurpose:
Speckle-type POZ protein (SPOP) is important in DNA damage response (DDR) and maintenance of genomic stability. Somatic heterozygous missense mutations in the SPOP substrate-binding cleft are found in up to 15% of prostate cancers. While mutations in SPOP predict for benefit from androgen receptor signaling inhibition (ARSi) therapy, outcomes for patients with SPOP-mutant (SPOPmut) prostate cancer are heterogeneous and targeted treatments for SPOPmut castrate-resistant prostate cancer (CRPC) are lacking.
Experimental Design:
Using in silico genomic and transcriptomic tumor data, proteomics analysis, and genetically modified cell line models, we demonstrate mechanistic links between SPOP mutations, STING signaling alterations, and PARP inhibitor vulnerabilities.
Results:
We demonstrate that SPOP mutations are associated with upregulation of a 29-gene noncanonical (NC) STING (NC-STING) signature in a subset of SPOPmut, treatment-refractory CRPC patients. We show in preclinical CRPC models that SPOP targets and destabilizes STING1 protein, and prostate cancer–associated SPOP mutations result in upregulated NC-STING–NF-κB signaling and macrophage- and tumor microenvironment (TME)–facilitated reprogramming, leading to tumor cell growth. Importantly, we provide in vitro and in vivo mechanism-based evidence that PARP inhibitor (PARPi) treatment results in a shift from immunosuppressive NC-STING–NF-κB signaling to antitumor, canonical cGAS–STING–IFNβ signaling in SPOPmut CRPC and results in enhanced tumor growth inhibition.
Conclusions:
We provide evidence that SPOP is critical in regulating immunosuppressive versus antitumor activity downstream of DNA damage–induced STING1 activation in prostate cancer. PARPi treatment of SPOPmut CRPC alters this NC-STING signaling toward canonical, antitumor cGAS–STING–IFNβ signaling, highlighting a novel biomarker-informed treatment strategy for prostate cancer.
Table S1 from Cotargeting Phosphoinositide 3-Kinase and Focal Adhesion Kinase Pathways Inhibits Proliferation of NF2 Schwannoma Cells
Authors: Hardin Haley M. , Dinh Christine T. , Huegel Julianne , Petrilli Alejandra M. , Bracho Olena , Allaf Abdulrahman M. , Karajannis Matthias A. , Griswold Anthony J. , Ivan Michael E. , Morcos Jacques , Gultekin Sakir H. , Telischi Fred F. , Liu Xue Zhong , Fernandez-Valle Cristina
Published: November 2023

Supplemental Table 1. PI3K/mTOR and FAK/Src Inhibitors Assessed in Combination.
Supplementary Table S3 from Targeting Aggressive B-cell Lymphomas through Pharmacological Activation of the Mitochondrial Protease OMA1
Authors: Schwarzer Adrian , Oliveira Matheus , Kleppa Marc-Jens , Slattery Scott D. , Anantha Andy , Cooper Alan , Hannink Mark , Schambach Axel , Dörrie Anneke , Kotlyarov Alexey , Gaestel Matthias , Hembrough Todd , Levine Jedd , Luther Michael , Stocum Michael , Stiles Linsey , Weinstock David M. , Liesa Marc , Kostura Matthew J.
Published: November 2023

Biomarker Identification based on cell line screening data results
Figure S3 from Cotargeting Phosphoinositide 3-Kinase and Focal Adhesion Kinase Pathways Inhibits Proliferation of NF2 Schwannoma Cells
Authors: Hardin Haley M. , Dinh Christine T. , Huegel Julianne , Petrilli Alejandra M. , Bracho Olena , Allaf Abdulrahman M. , Karajannis Matthias A. , Griswold Anthony J. , Ivan Michael E. , Morcos Jacques , Gultekin Sakir H. , Telischi Fred F. , Liu Xue Zhong , Fernandez-Valle Cristina
Published: November 2023

Figure S3. Drug Response Relative to Phospho-Protein Levels in VS samples.
Supplementary Data from Targeting Aggressive B-cell Lymphomas through Pharmacological Activation of the Mitochondrial Protease OMA1
Authors: Schwarzer Adrian , Oliveira Matheus , Kleppa Marc-Jens , Slattery Scott D. , Anantha Andy , Cooper Alan , Hannink Mark , Schambach Axel , Dörrie Anneke , Kotlyarov Alexey , Gaestel Matthias , Hembrough Todd , Levine Jedd , Luther Michael , Stocum Michael , Stiles Linsey , Weinstock David M. , Liesa Marc , Kostura Matthew J.
Published: November 2023

Compiled RNAseq data from HCT-116 cells treated with BTM-3528.
Table S3 from Use of Payload Binding Selectivity Enhancers to Improve Therapeutic Index of Maytansinoid–Antibody–Drug Conjugates
Authors: Nguyen Toan D. , Bordeau Brandon M. , Balthasar Joseph P.
Published: November 2023

Supplemental table 3: Anti-DM4 sdAb, Effects on DM4 / DM4-ADC cytotoxicity and binding data
Table S1 from Use of Payload Binding Selectivity Enhancers to Improve Therapeutic Index of Maytansinoid–Antibody–Drug Conjugates
Authors: Nguyen Toan D. , Bordeau Brandon M. , Balthasar Joseph P.
Published: November 2023

Supplemental table 1: model parameters
Supplementary Data from Use of Payload Binding Selectivity Enhancers to Improve Therapeutic Index of Maytansinoid–Antibody–Drug Conjugates
Authors: Nguyen Toan D. , Bordeau Brandon M. , Balthasar Joseph P.
Published: November 2023

Supplementary methods and results
Figure S4 from Use of Payload Binding Selectivity Enhancers to Improve Therapeutic Index of Maytansinoid–Antibody–Drug Conjugates
Authors: Nguyen Toan D. , Bordeau Brandon M. , Balthasar Joseph P.
Published: November 2023

DM4-ADC cytotoxicity data
Supplementary Table S6 from Combination Therapies to Improve the Efficacy of Immunotherapy in Triple-negative Breast Cancer
Authors: Alečković Maša , Li Zheqi , Zhou Ningxuan , Qiu Xintao , Lulseged Bethlehem , Foidart Pierre , Huang Xiao-Yun , Garza Kodie , Shu Shaokun , Kesten Nikolas , Li Rong , Lim Klothilda , Garrido-Castro Ana C. , Guerriero Jennifer L. , Qi Jun , Long Henry W. , Polyak Kornelia
Published: November 2023

Motifs enriched in gained ATAC sites.
Supplementary Table S3 from Combination Therapies to Improve the Efficacy of Immunotherapy in Triple-negative Breast Cancer
Authors: Alečković Maša , Li Zheqi , Zhou Ningxuan , Qiu Xintao , Lulseged Bethlehem , Foidart Pierre , Huang Xiao-Yun , Garza Kodie , Shu Shaokun , Kesten Nikolas , Li Rong , Lim Klothilda , Garrido-Castro Ana C. , Guerriero Jennifer L. , Qi Jun , Long Henry W. , Polyak Kornelia
Published: November 2023

Genes differentially expressed in CD45- tumor-enriched cells.
Supplementary Fig. S5 from Combination Therapies to Improve the Efficacy of Immunotherapy in Triple-negative Breast Cancer
Authors: Alečković Maša , Li Zheqi , Zhou Ningxuan , Qiu Xintao , Lulseged Bethlehem , Foidart Pierre , Huang Xiao-Yun , Garza Kodie , Shu Shaokun , Kesten Nikolas , Li Rong , Lim Klothilda , Garrido-Castro Ana C. , Guerriero Jennifer L. , Qi Jun , Long Henry W. , Polyak Kornelia
Published: November 2023

Supplementary Fig. S5 shows additional ATAC-seq data analyses.
Supplementary Table 1 from Cancer-Immunity Marker RNA Expression Levels across Gynecologic Cancers: Implications for Immunotherapy
Authors: Jou Jessica , Kato Shumei , Miyashita Hirotaka , Thangathurai Kartheeswaran , Pabla Sarabjot , DePietro Paul , Nesline Mary K. , Conroy Jeffrey M. , Rubin Eitan , Eskander Ramez N. , Kurzrock Razelle
Published: November 2023

Supplemental Table 1 includes information on how biomarkers participate in the immune microenvironment.
Supplemental Figure 1 from Cancer-Immunity Marker RNA Expression Levels across Gynecologic Cancers: Implications for Immunotherapy
Authors: Jou Jessica , Kato Shumei , Miyashita Hirotaka , Thangathurai Kartheeswaran , Pabla Sarabjot , DePietro Paul , Nesline Mary K. , Conroy Jeffrey M. , Rubin Eitan , Eskander Ramez N. , Kurzrock Razelle
Published: November 2023

Immunograms of individual cancer types
Supplementary Fig. S2 from Preclinical Development of Brain Permeable ERβ Agonist for the Treatment of Glioblastoma
Authors: Pratap Uday P. , Tidwell Michael , Balinda Henriette U. , Clanton Nicholas A. , Yang Xue , Viswanadhapalli Suryavathi , Sareddy Gangadhara R. , Liang Dong , Xie Huan , Chen Yidong , Lai Zhao , Tekmal Rajeshwar R. , McHardy Stanton F. , Brenner Andrew J. , Vadlamudi Ratna K.
Published: November 2023

Supplementary Fig.S2 shows data shows specificity of CIDD-0149897 using ER beta KO cells.
Supplementary Fig. S1 from Preclinical Development of Brain Permeable ERβ Agonist for the Treatment of Glioblastoma
Authors: Pratap Uday P. , Tidwell Michael , Balinda Henriette U. , Clanton Nicholas A. , Yang Xue , Viswanadhapalli Suryavathi , Sareddy Gangadhara R. , Liang Dong , Xie Huan , Chen Yidong , Lai Zhao , Tekmal Rajeshwar R. , McHardy Stanton F. , Brenner Andrew J. , Vadlamudi Ratna K.
Published: November 2023

Supplementary Fig.S1 shows scheme for synthesis of ER beta agonist CIDD-0149897
Supplementary Figure S6 from Efficacy and Safety of Glycosphingolipid SSEA-4 Targeting CAR-T Cells in an Ovarian Carcinoma Model
Authors: Monzo Hector J. , Kalander Kerttu , Hyytiäinen Marko M. , Elbasani Endrit , Wall Johanna , Moyano-Galceran Lidia , Tanjore Ramanathan Jayendrakishore , Jukonen Joonas , Laakkonen Pirjo , Ristimäki Ari , Carlson Joseph W. , Lehti Kaisa , Salehi Sahar , Puolakkainen Pauli , Haglund Caj , Seppänen Hanna , Leppä Sirpa , Ojala Päivi M.
Published: November 2023

Supplementary Figure S6. Expression of SSEA-4 in normal mouse tissues. Immunofluorescence detection of SSEA-4 (green) in the indicated tissues of healthy 10 weeks old (C57BL/6) mouse using anti-SSEA-4 antibody.
Data from Cancer-Immunity Marker RNA Expression Levels across Gynecologic Cancers: Implications for Immunotherapy
Authors: Jou Jessica , Kato Shumei , Miyashita Hirotaka , Thangathurai Kartheeswaran , Pabla Sarabjot , DePietro Paul , Nesline Mary K. , Conroy Jeffrey M. , Rubin Eitan , Eskander Ramez N. , Kurzrock Razelle
Published: November 2023

Abstract
Our objective was to characterize cancer-immunity marker expression in gynecologic cancers and compare immune landscapes between gynecologic tumor subtypes and with nongynecologic solid tumors. RNA expression levels of 51 cancer-immunity markers were analyzed in patients with gynecologic cancers versus nongynecologic cancers, and normalized to a reference population of 735 control cancers, ranked from 0 to 100, and categorized as low (0–24), moderate (25–74), or high (75–100) percentile rank. Of the 72 patients studied, 43 (60%) had ovarian, 24 (33%) uterine, and 5 (7%) cervical cancer. No two immune profiles were identical according to expression rank (0–100) or rank level (low, moderate, or high). Patients with cervical cancer had significantly higher expression level ranks of immune activating, proinflammatory, tumor-infiltrating lymphocyte markers, and checkpoints than patients with uterine or ovarian cancer (P < 0.001 for all comparisons). However, there were no significant differences in immune marker expression between uterine and ovarian cancers. Tumors with PD-L1 tumor proportional score (TPS) ≥1% versus 0% had significantly higher expression levels of proinflammatory markers (58 vs. 49%, P = 0.0004). Compared to patients with nongynecologic cancers, more patients with gynecologic cancers express high levels of IDO-1 (44 vs. 13%, P < 0.001), LAG3 (35 vs. 21%, P = 0.008), and IL10 (31 vs. 15%, P = 0.002.) Patients with gynecologic cancers have complex and heterogeneous immune landscapes that are distinct from patient to patient and from other solid tumors. High levels of IDO1 and LAG3 suggest that clinical trials with IDO1 inhibitors or LAG3 inhibitors, respectively, may be warranted in gynecologic cancers.
Supplementary Data File S3 from USP1 Expression Driven by EWS::FLI1 Transcription Factor Stabilizes Survivin and Mitigates Replication Stress in Ewing Sarcoma
Authors: Mallard Halle J. , Wan Shibiao , Nidhi Prakriti , Hanscom-Trofy Yvan D. , Mohapatra Bhopal , Woods Nicholas T. , Lopez-Guerrero Jose Antonio , Llombart-Bosch Antonio , Machado Isidro , Scotlandi Katia , Kreiling Natasha F. , Perry Megan C. , Mirza Sameer , Coulter Donald W. , Band Vimla , Band Hamid , Ghosal Gargi
Published: November 2023

Page 1: RT-qPCR primers used for DUB array; Page 2: Primers used for ChIP-qPCR analysis; Page 3: shRNA sequences used for EWS::FLI1 and USP1 knockdown cell line generation; Page 4: gRNA sequences used for USP1 knockout cell line generation; Page 5: List of working dilutions for antibodies used in this study; Page 6: List of reagents, with product information and RRIDs, used in this study; Page 7: List of biological resources, with product information and RRIDs, used in this study
Figure S3 from USP1 Expression Driven by EWS::FLI1 Transcription Factor Stabilizes Survivin and Mitigates Replication Stress in Ewing Sarcoma
Authors: Mallard Halle J. , Wan Shibiao , Nidhi Prakriti , Hanscom-Trofy Yvan D. , Mohapatra Bhopal , Woods Nicholas T. , Lopez-Guerrero Jose Antonio , Llombart-Bosch Antonio , Machado Isidro , Scotlandi Katia , Kreiling Natasha F. , Perry Megan C. , Mirza Sameer , Coulter Donald W. , Band Vimla , Band Hamid , Ghosal Gargi
Published: November 2023

Figure S3 shows USP1 knockdown or inhibition induces apoptotic cell death.
Table S6 from CBF-Beta Mitigates PI3K-Alpha–Specific Inhibitor Killing through PIM1 in PIK3CA-Mutant Gastric Cancer
Authors: Stanland Lyla J. , Ang Hazel X. , Hoj Jacob P. , Chu Yunqiang , Tan Patrick , Wood Kris C. , Luftig Micah A.
Published: November 2023

Sequences of guide RNAs used to generate genetic knockouts
Supplementary Materials and Methods from Exon Junction Complex Mediates the Cap-Independent Translation of Circular RNA
Authors: Lin Hui-Hsuan , Chang Chiu-Yuan , Huang Yi-Ren , Shen Che-Hung , Wu Yu-Chen , Chang Kai-Li , Lee Yueh-Chun , Lin Ya-Chi , Ting Wen-Chien , Chien Han-Ju , Zheng Yi-Feng , Lai Chien-Chen , Hsiao Kuei-Yang
Published: November 2023

Supplementary Materials and Methods
Supplementary Table 1 from Podoplanin Drives Amoeboid Invasion in Canine and Human Mucosal Melanoma
Authors: Shinada Masahiro , Kato Daiki , Motegi Tomoki , Tsuboi Masaya , Ikeda Namiko , Aoki Susumu , Iguchi Takaaki , Li Toshio , Kodera Yuka , Ota Ryosuke , Hashimoto Yuko , Takahashi Yosuke , Chambers James , Uchida Kazuyuki , Kato Yukinari , Nishimura Ryohei , Nakagawa Takayuki
Published: November 2023

Clinical information of dogs used for the survival analysis.
Table S5 from Stromal DDR2 Promotes Ovarian Cancer Metastasis through Regulation of Metabolism and Secretion of Extracellular Matrix Proteins
Authors: Schab Angela M. , Greenwade Molly M. , Stock Elizabeth , Lomonosova Elena , Cho Kevin , Grither Whitney R. , Noia Hollie , Wilke Daniel , Mullen Mary M. , Hagemann Andrea R. , Hagemann Ian S. , Thaker Premal H. , Kuroki Lindsay M. , McCourt Carolyn K. , Khabele Dineo , Powell Matthew A. , Mutch David G. , Zhao Peinan , Shriver Leah P. , Patti Gary J. , Longmore Gregory D. , Fuh Katherine C.
Published: November 2023

Secretome
Supplementary Figure 9 from Podoplanin Drives Amoeboid Invasion in Canine and Human Mucosal Melanoma
Authors: Shinada Masahiro , Kato Daiki , Motegi Tomoki , Tsuboi Masaya , Ikeda Namiko , Aoki Susumu , Iguchi Takaaki , Li Toshio , Kodera Yuka , Ota Ryosuke , Hashimoto Yuko , Takahashi Yosuke , Chambers James , Uchida Kazuyuki , Kato Yukinari , Nishimura Ryohei , Nakagawa Takayuki
Published: November 2023

PDPN promotes distant colonization.
Supplementary Figure 7 from Podoplanin Drives Amoeboid Invasion in Canine and Human Mucosal Melanoma
Authors: Shinada Masahiro , Kato Daiki , Motegi Tomoki , Tsuboi Masaya , Ikeda Namiko , Aoki Susumu , Iguchi Takaaki , Li Toshio , Kodera Yuka , Ota Ryosuke , Hashimoto Yuko , Takahashi Yosuke , Chambers James , Uchida Kazuyuki , Kato Yukinari , Nishimura Ryohei , Nakagawa Takayuki
Published: November 2023

ROCK inhibition leads to cell cycle arrest and cellular senescence.
Supplementary Figure 5 from Podoplanin Drives Amoeboid Invasion in Canine and Human Mucosal Melanoma
Authors: Shinada Masahiro , Kato Daiki , Motegi Tomoki , Tsuboi Masaya , Ikeda Namiko , Aoki Susumu , Iguchi Takaaki , Li Toshio , Kodera Yuka , Ota Ryosuke , Hashimoto Yuko , Takahashi Yosuke , Chambers James , Uchida Kazuyuki , Kato Yukinari , Nishimura Ryohei , Nakagawa Takayuki
Published: November 2023

ROCK inhibition suppresses cell proliferation, survival, and migration.
Figure S5 from Stromal DDR2 Promotes Ovarian Cancer Metastasis through Regulation of Metabolism and Secretion of Extracellular Matrix Proteins
Authors: Schab Angela M. , Greenwade Molly M. , Stock Elizabeth , Lomonosova Elena , Cho Kevin , Grither Whitney R. , Noia Hollie , Wilke Daniel , Mullen Mary M. , Hagemann Andrea R. , Hagemann Ian S. , Thaker Premal H. , Kuroki Lindsay M. , McCourt Carolyn K. , Khabele Dineo , Powell Matthew A. , Mutch David G. , Zhao Peinan , Shriver Leah P. , Patti Gary J. , Longmore Gregory D. , Fuh Katherine C.
Published: November 2023

Stromal cell expression of DDR2 is critical for migration and invasion of ovarian cancer cells, related to Figure 7
Supplementary Figure 2 from Podoplanin Drives Amoeboid Invasion in Canine and Human Mucosal Melanoma
Authors: Shinada Masahiro , Kato Daiki , Motegi Tomoki , Tsuboi Masaya , Ikeda Namiko , Aoki Susumu , Iguchi Takaaki , Li Toshio , Kodera Yuka , Ota Ryosuke , Hashimoto Yuko , Takahashi Yosuke , Chambers James , Uchida Kazuyuki , Kato Yukinari , Nishimura Ryohei , Nakagawa Takayuki
Published: November 2023

PDPN regulates canine mucosal melanoma proliferation, survival, migration, and invasion.
Figure S4 from Stromal DDR2 Promotes Ovarian Cancer Metastasis through Regulation of Metabolism and Secretion of Extracellular Matrix Proteins
Authors: Schab Angela M. , Greenwade Molly M. , Stock Elizabeth , Lomonosova Elena , Cho Kevin , Grither Whitney R. , Noia Hollie , Wilke Daniel , Mullen Mary M. , Hagemann Andrea R. , Hagemann Ian S. , Thaker Premal H. , Kuroki Lindsay M. , McCourt Carolyn K. , Khabele Dineo , Powell Matthew A. , Mutch David G. , Zhao Peinan , Shriver Leah P. , Patti Gary J. , Longmore Gregory D. , Fuh Katherine C.
Published: November 2023

Inhibition of DDR2 in OF 206 decreases HIF-1 and hexokinase transcription in response to collagen stimulation and does not alter cell viability, related to Figure 6
Supplementary Figure 10 from Podoplanin Drives Amoeboid Invasion in Canine and Human Mucosal Melanoma
Authors: Shinada Masahiro , Kato Daiki , Motegi Tomoki , Tsuboi Masaya , Ikeda Namiko , Aoki Susumu , Iguchi Takaaki , Li Toshio , Kodera Yuka , Ota Ryosuke , Hashimoto Yuko , Takahashi Yosuke , Chambers James , Uchida Kazuyuki , Kato Yukinari , Nishimura Ryohei , Nakagawa Takayuki
Published: November 2023

Canine mucosal melanomas with PDPN high expression demonstrate enrichment of gene signatures associated with amoeboid invasion.
Data from Telomerase Upregulation Induces Progression of Mouse BrafV600E-Driven Thyroid Cancers and Triggers Nontelomeric Effects
Authors: Landa Iñigo , Thornton Caitlin E.M. , Xu Bin , Haase Jacob , Krishnamoorthy Gnana P. , Hao Jingzhu , Knauf Jeffrey A. , Herbert Zachary T. , Martínez Paula , Blasco María A. , Ghossein Ronald , Fagin James A.
Published: November 2023

Abstract
Mutations in the promoter of the telomerase reverse transcriptase (TERT) gene are the paradigm of a cross-cancer alteration in a noncoding region. TERT promoter mutations (TPM) are biomarkers of poor prognosis in cancer, including thyroid tumors. TPMs enhance TERT transcription, which is otherwise silenced in adult tissues, thus reactivating a bona fide oncoprotein. To study TERT deregulation and its downstream consequences, we generated a Tert mutant promoter mouse model via CRISPR/Cas9 engineering of the murine equivalent locus (Tert−123C>T) and crossed it with thyroid-specific BrafV600E-mutant mice. We also employed an alternative model of Tert overexpression (K5-Tert). Whereas all BrafV600E animals developed well-differentiated papillary thyroid tumors, 29% and 36% of BrafV600E+Tert−123C>T and BrafV600E+K5-Tert mice progressed to poorly differentiated cancers at week 20, respectively. Tert-upregulated tumors showed increased mitosis and necrosis in areas of solid growth, and older animals displayed anaplastic-like features, that is, spindle cells and macrophage infiltration. Murine TPM increased Tert transcription in vitro and in vivo, but temporal and intratumoral heterogeneity was observed. RNA-sequencing of thyroid tumor cells showed that processes other than the canonical Tert-mediated telomere maintenance role operate in these specimens. Pathway analysis showed that MAPK and PI3K/AKT signaling, as well as processes not previously associated with this tumor etiology, involving cytokine, and chemokine signaling, were overactivated. These models constitute useful preclinical tools to understand the cell-autonomous and microenvironment-related consequences of Tert-mediated progression in advanced thyroid cancers and other aggressive tumors carrying TPMs.
Implications:
Telomerase-driven cancer progression activates pathways that can be dissected and perhaps therapeutically exploited.
Supplementary Table 1 from Polymorphisms in Cyclooxygenase, Lipoxygenase, and TP53 Genes Predict Colorectal Polyp Risk Reduction by Aspirin in the seAFOod Polyp Prevention Trial
Authors: Davies John R. , Mell Tracey , Fuller Harriett , Harland Mark , Saleh Rasha N.M. , Race Amanda D. , Rees Colin J. , Brown Louise C. , Loadman Paul M. , Downing Amy , Minihane Anne Marie , Williams Elizabeth A. , Hull Mark A.
Published: November 2023

Supplementary Table 1 shows the list of SNPs that were analysed by the Fluidigm assay.
Supplementary Table S1 from Dynamic Risk Prediction of Treatment Discontinuation Using Patient-Reported Outcomes Data in the Phase III NSABP B-35 Trial
Authors: Calsavara Vinicius F. , Henry Norah L. , Hays Ron D. , Kim Sungjin , Luu Michael , Diniz Márcio A. , Gresham Gillian , Cecchini Reena S. , Yothers Greg , Ganz Patricia A. , Rogatko André , Tighiouart Mourad
Published: November 2023

Supplementary Table S1 outlines all predictors employed to predict treatment discontinuation, including the predictor variable name, variable description, variable type, and whether the data was collected over time or only at baseline.
Supplementary Figure S6 from Dynamic Risk Prediction of Treatment Discontinuation Using Patient-Reported Outcomes Data in the Phase III NSABP B-35 Trial
Authors: Calsavara Vinicius F. , Henry Norah L. , Hays Ron D. , Kim Sungjin , Luu Michael , Diniz Márcio A. , Gresham Gillian , Cecchini Reena S. , Yothers Greg , Ganz Patricia A. , Rogatko André , Tighiouart Mourad
Published: November 2023

Supplementary Figure S6 (a) shows the actual eight PROs of patient 1 at two time points, baseline, and 6 months (shown by the black dotted line). This patient is also overweight at baseline (25 < BMI < 30). In the clinical data set, this patient discontinued treatment at 14 months, but this information was not used in the model. Supplementary Figure S6 (b) shows the estimated probability of treatment discontinuation for patient 1 anytime after 6 months but before 18 months. Supplementary Figure S6 (c) shows similar information for patient 2 who is also overweight. However, patient 2 completed treatment by 60 months. Supplementary Figure S6 (d) shows the estimated probability of treatment discontinuation for patient 2 anytime after 6 months but before 18 months.