bluuebunny/crossref_metadata_2025 huggingface dataset:
The Significance of Paying Attention to Medical Emergencies in Medical Diagnostic Laboratories in Iran
Authors: Yousefi Mohammad Javad , Soltani Mansoor , Mezginejad Fatemeh , Yousefi Kosar , Takhviji Mahdi , Soltani Mohammad Hossein
Published: December 2024

Background: Medical diagnostic laboratories as high‐risk environments are often exposed to unpredictable situations such as patient fainting, blood pressure drops, chemical spills, and burns. These life‐threatening events defined as medical emergencies and necessitate urgent actions. Hence, determining the most common medical emergencies in medical laboratories, so understanding and planning strategies to effective management seems to be crucial.

Objective: This study aimed to investigate medical crises in Iranian medical laboratories.

Methods: In this cross‐sectional study, data collection was performed by a simple random sampling method through electronic and paper questionnaires filled by personnel in private and hospital laboratories in different provinces.

Results: The most frequent medical emergencies were patient fainting, staff needle stick, and patient’s blood pressure dropping. The occurrence of medical emergencies was 24% and 76% in men and women, respectively. Out of all, treatment was administered at the scene of the accident in 37.1% of cases, and 28.1% were discharged after sampling. Moreover, 51% of the medical diagnostic laboratories had a trolley code, with injection devices and angiocaths as available tools. In 81% of the laboratories, practicing for probable medical emergencies was not possible. A significant relationship was found between the type of client (laboratory personnel or the referring person) and the type of emergency event (p < 0.05).

Conclusions: Considering the prevalence and importance of handling medical emergencies in a short time, it is necessary to design training courses for laboratory personnel and expert them to encountering with unpredictable threats in order to help affected individuals.
Supplementary figure 6 from Targeting NTRK1 Enhances Immune Checkpoint Inhibitor Efficacy in NTRK1 Wild-Type Non–Small Cell Lung Cancer
Authors: Smith Margaret R. , Dixon Caroline B. , Wang Yuezhu , Liu Yin , D’Agostino Ralph , Ruiz Jimmy , Oliver George , Miller Lance D. , Topaloglu Umit , Chan Michael D. , Farris Michael , Su Jing , Mileham Kathryn F. , Zhao Dawen , Li Wencheng , Sexton Tammy , Lycan Thomas , Haas Karen M. , Grayson Jason M. , Xing Fei
Published: December 2024

Supplementary figure 6
Supplementary figure 2 from Targeting NTRK1 Enhances Immune Checkpoint Inhibitor Efficacy in NTRK1 Wild-Type Non–Small Cell Lung Cancer
Authors: Smith Margaret R. , Dixon Caroline B. , Wang Yuezhu , Liu Yin , D’Agostino Ralph , Ruiz Jimmy , Oliver George , Miller Lance D. , Topaloglu Umit , Chan Michael D. , Farris Michael , Su Jing , Mileham Kathryn F. , Zhao Dawen , Li Wencheng , Sexton Tammy , Lycan Thomas , Haas Karen M. , Grayson Jason M. , Xing Fei
Published: December 2024

Supplementary figure 2
Supplementary Data from B7-H3–Targeted CAR-Vδ1T Cells Exhibit Potent Broad-Spectrum Activity against Solid Tumors
Authors: Jiang Licui , You Fengtao , Wu Hai , Qi Changsong , Xiang Shufen , Zhang Ping , Meng Huimin , Wang Min , Huang Jiequn , Li Yafen , Chen Dan , An Gangli , Yang Nan , Zhang Bozhen , Shen Lin , Yang Lin
Published: December 2024

All the supplementary data
Supplementary figure 2 from Single-Cell Transcriptomic Analysis Identifies Senescent Osteocytes That Trigger Bone Destruction in Breast Cancer Metastasis
Authors: Kaur Japneet , Adhikari Manish , Sabol Hayley M. , Anloague Aric , Khan Sharmin , Kurihara Noriyoshi , Diaz-delCastillo Marta , Andreasen Christina Møller , Barnes Charles Lowry , Stambough Jeffrey B. , Palmieri Michela , Reyes-Castro Olivia , Zarrer Jennifer , Taipaleenmäki Hanna , Ambrogini Elena , Almeida Maria , O’Brien Charles A. , Nookaw Intawat , Delgado-Calle Jesus
Published: December 2024

Supplementary figure 2
Supplementary figure 17 from Single-Cell Transcriptomic Analysis Identifies Senescent Osteocytes That Trigger Bone Destruction in Breast Cancer Metastasis
Authors: Kaur Japneet , Adhikari Manish , Sabol Hayley M. , Anloague Aric , Khan Sharmin , Kurihara Noriyoshi , Diaz-delCastillo Marta , Andreasen Christina Møller , Barnes Charles Lowry , Stambough Jeffrey B. , Palmieri Michela , Reyes-Castro Olivia , Zarrer Jennifer , Taipaleenmäki Hanna , Ambrogini Elena , Almeida Maria , O’Brien Charles A. , Nookaw Intawat , Delgado-Calle Jesus
Published: December 2024

Supplementary figure 17
Supplementary figure 10 from Single-Cell Transcriptomic Analysis Identifies Senescent Osteocytes That Trigger Bone Destruction in Breast Cancer Metastasis
Authors: Kaur Japneet , Adhikari Manish , Sabol Hayley M. , Anloague Aric , Khan Sharmin , Kurihara Noriyoshi , Diaz-delCastillo Marta , Andreasen Christina Møller , Barnes Charles Lowry , Stambough Jeffrey B. , Palmieri Michela , Reyes-Castro Olivia , Zarrer Jennifer , Taipaleenmäki Hanna , Ambrogini Elena , Almeida Maria , O’Brien Charles A. , Nookaw Intawat , Delgado-Calle Jesus
Published: December 2024

Supplementary figure 10
Table S1 from Fitness Screens Map State-Specific Glioblastoma Stem Cell Vulnerabilities
Authors: MacLeod Graham , Molaei Fatemeh , Haider Shahan , Almeida Maira P. , Lin Sichun , Kushida Michelle , Sureshkumar Haresh , Bhatti Jasmine K. , Lu Jack Q. , Schramek Daniel , Dirks Peter B. , Angers Stephane
Published: December 2024

Sequence of gRNAs used in this study
Supplementary Table S1 from Asymptomatic Incidence of Monoclonal Gammopathy of Undetermined Significance and Preclinical Duration to Myeloma Diagnosis: A Modeling Study
Authors: Ji Mengmeng , Shih Yi-Hsuan , Huber John H. , Wang Mei , Feuer Eric J. , Etzioni Ruth , Wang Shi-Yi , Chang Su-Hsin
Published: December 2024

Supplementary Table S1 shows the intermediate results of calculations used to estimate the age-specific incidence of asymptomatic MGUS for non-Hispanic white population aged 50 to 84.
Supplementary Figure S1 from Asymptomatic Incidence of Monoclonal Gammopathy of Undetermined Significance and Preclinical Duration to Myeloma Diagnosis: A Modeling Study
Authors: Ji Mengmeng , Shih Yi-Hsuan , Huber John H. , Wang Mei , Feuer Eric J. , Etzioni Ruth , Wang Shi-Yi , Chang Su-Hsin
Published: December 2024

Supplementary Figure S1 shows the MGUS incidence estimates derived from our prior simulation model. The consistency between two models indicates the robustness of our estimates.
Supplementary Table S3 from Identification of High-Incidence Populations in the United States for Anti–Epstein-Barr Virus Serologic Screening for Nasopharyngeal Carcinoma
Authors: Clark Payton E. , Taparra Kekoa , Miller Jacob A.
Published: December 2024

Table S3. Cost of Diagnosis, Work-up, and Treatment in United States
Supplementary Table S2 from Identification of High-Incidence Populations in the United States for Anti–Epstein-Barr Virus Serologic Screening for Nasopharyngeal Carcinoma
Authors: Clark Payton E. , Taparra Kekoa , Miller Jacob A.
Published: December 2024

Table S2. Modeled Transition Probabilities, Management Assumptions, Health Utilities, and Costs with Parameter Ranges for Deterministic and Probabilistic Sensitivity Analyses
Supplementary Table S1 from Cervical Cancer Screening Utilization among Kidney Transplant Recipients, 2001 to 2018
Authors: Hsu Christine D. , Yu Xiaoying , Guo Fangjian , Adekanmbi Victor , Kuo Yong-Fang , Westra Jordan , Berenson Abbey B.
Published: December 2024

Supplementary Table S1 lists the diagnoses and procedure codes used in the study.
Supplementary Table 2 from Cervical Cancer Screening Utilization among Kidney Transplant Recipients, 2001 to 2018
Authors: Hsu Christine D. , Yu Xiaoying , Guo Fangjian , Adekanmbi Victor , Kuo Yong-Fang , Westra Jordan , Berenson Abbey B.
Published: December 2024

Supplementary Table 2 shows the detailed race/ethnicity distributions before combining race/ethnicity groups.
Supplementary Table S8 from Associations of Prostate Tumor Immune Landscape with Vigorous Physical Activity and Prostate Cancer Progression
Authors: Huang Lanshan , Winter Sarah J. , Olsson Linnea T. , Hamilton Alina M. , Halliday Sophia R. , Kirk Erin L. , Farnan Laura , Gerstel Adrian , Craig Stephanie G. , Finn Stephen P. , LaBonte Wilson Melissa , Jain Suneil , Troester Melissa A. , Butler Eboneé N. , Bensen Jeannette T. , Wobker Sara E. , Allott Emma H.
Published: December 2024

Supplementary Table S8. Hazard ratios and 95% confidence intervals for associations between immune cell types and risk of prostate cancer progression in the FASTMAN, overall and stratified by ERG expression.
Supplementary Table S7 from Associations of Prostate Tumor Immune Landscape with Vigorous Physical Activity and Prostate Cancer Progression
Authors: Huang Lanshan , Winter Sarah J. , Olsson Linnea T. , Hamilton Alina M. , Halliday Sophia R. , Kirk Erin L. , Farnan Laura , Gerstel Adrian , Craig Stephanie G. , Finn Stephen P. , LaBonte Wilson Melissa , Jain Suneil , Troester Melissa A. , Butler Eboneé N. , Bensen Jeannette T. , Wobker Sara E. , Allott Emma H.
Published: December 2024

Supplementary Table S7. Hazard ratios and 95% confidence intervals for associations between immune cell types and risk of prostate cancer progression in the UNC CSC, overall and stratified by ERG expression.
Supplementary Table S6 from Hepatocellular Carcinoma Etiology Drives Survival Outcomes: A Population-Based Analysis
Authors: Cranford Hannah M. , Jones Patricia D. , Wong Robert J. , Liu Qinran , Kobetz Erin N. , Reis Isildinha M. , Koru-Sengul Tulay , Pinheiro Paulo S.
Published: December 2024

6. Supplementary Table S6 shows age-adjusted Cox proportional hazards regression models in which HCC-specific survival is assessed by etiology for HCC cases with complete variables.
Supplementary Table S5 from Hepatocellular Carcinoma Etiology Drives Survival Outcomes: A Population-Based Analysis
Authors: Cranford Hannah M. , Jones Patricia D. , Wong Robert J. , Liu Qinran , Kobetz Erin N. , Reis Isildinha M. , Koru-Sengul Tulay , Pinheiro Paulo S.
Published: December 2024

5. Supplementary Table S5 shows age-adjusted 5-year HCC-specific survival by single etiology or select dual etiology groups, a sensitivity analysis for all HCC cases and for complete HCC cases.
Supplementary Figure S4 from Associations of Prostate Tumor Immune Landscape with Vigorous Physical Activity and Prostate Cancer Progression
Authors: Huang Lanshan , Winter Sarah J. , Olsson Linnea T. , Hamilton Alina M. , Halliday Sophia R. , Kirk Erin L. , Farnan Laura , Gerstel Adrian , Craig Stephanie G. , Finn Stephen P. , LaBonte Wilson Melissa , Jain Suneil , Troester Melissa A. , Butler Eboneé N. , Bensen Jeannette T. , Wobker Sara E. , Allott Emma H.
Published: December 2024

Supplementary Figure S4. Boxplots comparing gene expression-based immune cell types in men with high tumor aggressiveness reporting any vs. no vigorous recreational activity. A. Gleason score ≥4 + 3. B. Clinical stage III-IV.
Supplementary Table S2 from Racial, Ethnic, and Socioeconomic Disparities in Meeting Physical Activity Guidelines among Female Breast Cancer Survivors in the United States
Authors: Wojcik Kaitlyn M. , Wilson Oliver W.A. , Shiels Meredith S. , Sheppard Vanessa B. , Jayasekera Jinani
Published: December 2024

Supplementary Table S2: Sensitivity Analysis: National-level (weighted) Estimates and Absolute Differences among Female Breast Cancer Survivors and Adult Women without Cancer Who Met Aerobic Physical Activity Guidelines
Supplementary Table S3 from High Gastric Cancer Mortality and Years of Life Lost in Nicaragua: A Population-Based Study 1997 to 2012
Authors: Peña-Galo Edgar M. , Palacios-Navarro Guillermo , Pastora-Membreño Javier , Torres-Herman Tatiana , Norwood Dalton A. , Montalvan-Sanchez Eleazar E. , Beasley Timothy , Bravo Luis E. , Morgan Douglas R.
Published: December 2024

Supplementary Table S3 presents cross-sectional age-specific gastric cancer rates, detailing the rates per 100,000 population for each age group, along with the corresponding lower and upper 95% confidence intervals.
Supplemental Table 2 from Adiposity throughout Adulthood and Risk of Young-Onset Breast Cancer Tumor Subtypes in the Young Women’s Health History Study
Authors: Marcus Post Lydia , Pathak Dorothy R. , Hamilton Ann S. , Hirko Kelly A. , Houang Richard T. , Guseman Emily H. , Sanfelippo Dan , Bohme Carnegie Nicole , Olson L. Karl , Rui Hallgeir , Schwartz Ann G. , Velie Ellen M.
Published: December 2024

Supplemental Table 2 shows associations between body size throughout adulthood and odds of YOBC subtypes, stratified by race.
Supplementary Table S4 from Cancer Mortality among Hispanic Groups in the United States by Birthplace (2003–2017)
Authors: He Yuelin , Pinheiro Paulo S. , Tripathi Osika , Nguyen Helen , Srinivasan Malathi , Palaniappan Latha P. , Thompson Caroline A.
Published: December 2024

Supplementary Table S4 summarises results from Joinpoint trend analysis annual percentage change and 95% confidence intervals (CI) among Mexicans.
Supplementary Table S3 from Cancer Mortality among Hispanic Groups in the United States by Birthplace (2003–2017)
Authors: He Yuelin , Pinheiro Paulo S. , Tripathi Osika , Nguyen Helen , Srinivasan Malathi , Palaniappan Latha P. , Thompson Caroline A.
Published: December 2024

Supplementary Table S3 summarises results from Joinpoint trend analysis 3-year percentage change and 95% confidence intervals (CI) among Cuban, Puerto Rican, and Central or South Americans.
Data from Asymptomatic Incidence of Monoclonal Gammopathy of Undetermined Significance and Preclinical Duration to Myeloma Diagnosis: A Modeling Study
Authors: Ji Mengmeng , Shih Yi-Hsuan , Huber John H. , Wang Mei , Feuer Eric J. , Etzioni Ruth , Wang Shi-Yi , Chang Su-Hsin
Published: December 2024

AbstractBackground:
Monoclonal gammopathy of undetermined significance (MGUS) is the premalignant condition of multiple myeloma. Given a lack of population-based screening for MGUS and its asymptomatic nature, the epidemiology of MGUS remains unknown. This study estimated age- and race/ethnicity-specific MGUS incidence and preclinical duration from MGUS to multiple myeloma in the United States.
Methods:
A previously published modeling approach was used to calculate national MGUS incidence using estimates of MGUS prevalence, multiple myeloma incidence, multiple myeloma–specific and all-cause mortality, and population age distribution from the National Health and Nutrition Examination Survey, 1999 to 2004, and Surveillance, Epidemiology, and End Results, 2000 to 2021. The estimated MGUS prevalence was divided by MGUS incidence to obtain preclinical duration of multiple myeloma.
Results:
MGUS incidence for non-Hispanic White (NHW) populations was 52, 86, 142, and 181 and for non-Hispanic Black (NHB) population was 110, 212, 392, and 570 per 100,000 person-years at ages 50, 60, 70, and 80 years, respectively. The average preclinical duration was 20.5 (95% confidence interval, CI, 16.5–26.1) years for the NHW population and 14.2 (95% CI, 11.5–17.6) years for the NHB population. The cumulative risk of developing MGUS in age 50 to 85 was 2.8% (95% CI, 1.7%–4.2%) for the NHW population and 6.1% (95% CI, 3.8%–10.0%) for the NHB population.
Conclusions:
NHB populations had a higher MGUS incidence rate at all ages and a shorter preclinical duration of multiple myeloma compared to their NHW counterparts.
Impact:
This study provides insights into the epidemiology of MGUS and enhances our understanding of the natural history of multiple myeloma.

See related In the Spotlight, p. 1547
Data from Cervical Cancer Screening Utilization among Kidney Transplant Recipients, 2001 to 2018
Authors: Hsu Christine D. , Yu Xiaoying , Guo Fangjian , Adekanmbi Victor , Kuo Yong-Fang , Westra Jordan , Berenson Abbey B.
Published: December 2024

AbstractBackground:
Kidney transplant recipients (KTR) have elevated risks of cervical precancers and cancers and guidelines recommend more frequent cervical cancer screening exams. However, little is known about current trends in cervical cancer screening in this unique population. We described patterns in the uptake of cervical cancer screening exams among female KTRs and identified factors associated with screening utilization.
Methods:
This retrospective cohort study included female KTRs between 20 and 65 years old, with Texas Medicare fee-for-service coverage, who received a transplant between January 1, 2001, and December 31, 2017. We determined the cumulative incidence of receiving cervical cancer screening post-transplant using ICD-9, ICD-10, and CPT codes and assessed factors associated with screening utilization, using the Fine and Gray model to account for competing events. Subdistribution hazard models were used to assess factors associated with screening uptake.
Results:
Among 2,653 KTRs meeting the inclusion and exclusion criteria, the 1-, 2-, and 3-year cumulative incidences of initiating a cervical cancer screening exam post-transplant were 31.7% [95% confidence interval (CI), 30.0%–33.6%], 48.0% (95% CI, 46.2%–49.9%), and 58.5% (95% CI, 56.7%–60.3%), respectively. KTRs who were 55 to 64 years old (vs. <45 years old) and those with a higher Charlson Comorbidity Score post-transplant were less likely to receive cervical cancer screening post-transplant.
Conclusions:
Cervical cancer screening uptake is low in the years immediately following a kidney transplant.
Impact:
Our findings highlight a need for interventions to improve cervical cancer screening utilization among kidney transplant recipients.

See related In the Spotlight, p. 1554
Figure 6 from Preclinical Evaluation of AZD6422, an Armored Chimeric Antigen Receptor T Cell Targeting CLDN18.2 in Gastric, Pancreatic, and Esophageal Cancers
Authors: Barrett Allison M. , Britton Zachary T. , Carrasco Rosa A. , Breen Shannon , Broggi Maria A.S. , Hatke Amanda L. , Clark Benjamin , Yang Chunning , Phipps Sandrina , Ortiz Lorenzo , Janocha Brianna , Zanvit Peter , Giraldo Nicolas A. , Martin Philip L. , Lapointe Jean-Martin , Harder Nathalie , Cornish Georgina H. , Attili Bala N.N.R. , Mazor Yariv , Damschroder Melissa , Cobbold Mark , Moody Gordon , Bosco Emily E.
Published: December 2024

In vivo antitumor activity of AZD6422 in PDX models of gastric cancer, PDAC, and esophageal adenocarcinoma. Activity and tolerability of AZD6422 are shown in various PDX models of esophageal adenocarcinoma (A, ES11085; D, ES_9500), gastric cancer (E, GA_9275), and PDAC (B, PANC_22; C, PANC_12; F, PANC_24). Each model was selected to represent a range of CLDN18.2 (shown at 10× scan) and TGFβ expression. NSG MHC-DKO mice received a single tail-vein infusion of 1e6 AZD6422, donor-matched UT, or vehicle when the average tumor volume reached 150 mm3. Tumor volumes and body weights were measured biweekly until study completion on day 35, and blood was collected for cytokine analysis on days 7 and 14. Data are shown as mean ± SEM (n = 5).
Figure 4 from Preclinical Evaluation of AZD6422, an Armored Chimeric Antigen Receptor T Cell Targeting CLDN18.2 in Gastric, Pancreatic, and Esophageal Cancers
Authors: Barrett Allison M. , Britton Zachary T. , Carrasco Rosa A. , Breen Shannon , Broggi Maria A.S. , Hatke Amanda L. , Clark Benjamin , Yang Chunning , Phipps Sandrina , Ortiz Lorenzo , Janocha Brianna , Zanvit Peter , Giraldo Nicolas A. , Martin Philip L. , Lapointe Jean-Martin , Harder Nathalie , Cornish Georgina H. , Attili Bala N.N.R. , Mazor Yariv , Damschroder Melissa , Cobbold Mark , Moody Gordon , Bosco Emily E.
Published: December 2024

Rationale for selection of TGFβ armoring and proof of mechanism in vitro and in vivo. A, Quantitative analysis of intensity and prevalence and representative images of TGFβ staining in a subset of patient tumor samples [gastric cancer (GC), n = 130; esophageal adenocarcinoma (EAc), n = 15; PDAC, n = 71]. Data represent the pooled scores of tumor and stromal compartments. B, Schematic representation of second-generation CAR-T lentivirus design, including an IgG4P hinge, CD28 transmembrane, CD28 costimulatory domain, and CD3z (unarmored CAR-T cells) or additional T2A self-cleaving peptide and dnTGFβRII (armored CAR-T cells). Average fold expansion across multiple healthy donors is shown. There was no significant difference in expansion across groups (one-way ANOVA). Representative FC plots show CAR and TGFβRII surface expression at day 10 after lentivirus transduction compared with UT control. C, FACS-purified, serum-starved CAR-T cells were stimulated with 1 ng/mL rhTGFβ for various time periods. Western blotting was used to determine protein levels of p-SMAD2/3 and total SMAD2/3; β-actin was used as the loading control. D, Percent cytolysis of BxPC3 + CLDN18.2 cells as determined by xCELLigence RTCA assay after 72 hours of co-culture at a 1:1 ratio with CLDN18.2 CAR-T cells in the presence or absence of 10 ng/mL rhTGFβ. Results were analyzed by using paired t tests. E, NSG mice bearing pancreatic PDX (PANC22, H-score = 225, TGFβ intermediate) were dosed by tail vein with 3e6 CAR+ unarmored or dnTGFβRII CLDN18.2 CAR-T cells; the total T-cell infusion number was matched across groups. Tumor volume and body weight were measured biweekly (n = 5). Serum levels of IFNγ were measured at 7 and 14 days after infusion (n = 3). Representative images of CLDN18.2 and TGFβ staining IHC expression (20× scan) are shown. All data represent mean ± SEM of replicate experiments or animals.
Supplementary Table S3 from Reduced Platelet Activation in Triple-Negative Essential Thrombocythemia Compared with JAK2V617F-Mutated Essential Thrombocythemia
Authors: Dong Huan , Chen Jia , Zhang Jing , Xue Feng , Li Huiyuan , Zhang Donglei , Zhou Hu , Zhang Xian , Huang Yueting , Liu Xiaofan , Chen Yunfei , Liu Wei , Chi Ying , Wang Wentian , Sun Ting , Ju Mankai , Dai Xinyue , Gu Wenjing , Yang Renchi , Fu Rongfeng , Zhang Lei
Published: December 2024

Supplementary Table S3. Non-canonical mutations of ET patients.
Supplementary Table S1 from Reduced Platelet Activation in Triple-Negative Essential Thrombocythemia Compared with JAK2V617F-Mutated Essential Thrombocythemia
Authors: Dong Huan , Chen Jia , Zhang Jing , Xue Feng , Li Huiyuan , Zhang Donglei , Zhou Hu , Zhang Xian , Huang Yueting , Liu Xiaofan , Chen Yunfei , Liu Wei , Chi Ying , Wang Wentian , Sun Ting , Ju Mankai , Dai Xinyue , Gu Wenjing , Yang Renchi , Fu Rongfeng , Zhang Lei
Published: December 2024

Supplementary Table S1. Basic characteristics of ET patients and healthy donors.
Supplementary Figure S1 from Pilot Trial of Perampanel on Peritumoral Hyperexcitability in Newly Diagnosed High-grade Glioma
Authors: Tobochnik Steven , Regan Michael S. , Dorotan Maria K.C. , Reich Dustine , Lapinskas Emily , Hossain Md Amin , Stopka Sylwia , Meredith David M. , Santagata Sandro , Murphy Melissa M. , Arnaout Omar , Bi Wenya Linda , Chiocca E. Antonio , Golby Alexandra J. , Mooney Michael A. , Smith Timothy R. , Ligon Keith L. , Wen Patrick Y. , Agar Nathalie Y.R. , Lee Jong Woo
Published: December 2024

Supplementary Figure 1. MALDI Calibration Curves. (A) 15N1 – glutamate, normalized to internal standard (IS) D5 - glutamate. (B,C) Levetiracetam; low concentration (B) and high concentration (C), normalized to IS D6 – levetiracetam. (D) Perampanel, normalized to IS panobinostat. All calibration curves were calculated using a weighted linear regression (1/x2).
Supplementary Figure S2 from Association of Tumor Mutational Burden and PD-L1 with the Efficacy of Pembrolizumab with or without Chemotherapy versus Chemotherapy in Advanced Urothelial Carcinoma
Authors: Fléchon Aude , Morales-Barrera Rafael , Powles Thomas , Alva Ajjai , Özgüroğlu Mustafa , Csöszi Tibor , Loriot Yohann , Rodriguez-Vida Alejo , Géczi Lajos , Cheng Susanna Y. , Fradet Yves , Oudard Stéphane , Vulsteke Christof , Gunduz Seyda , Mamtani Ronac , Yu Evan Y. , Montesa Pino Alvaro , Anido Urbano , Sendur Mehmet A.N. , Gravis Gwenaelle , Révész János , Kostorov Vladimir , Huillard Olivier , Ma Junshui , Rajasagi Mohini , Vajdi Amir , Lunceford Jared , Cristescu Razvan , Imai Kentaro , Homet Moreno Blanca , Matsubara Nobuaki
Published: December 2024

Supplementary Figure 2. Joint effect of TMB and PD-L1 CPS on ORR by treatment arm
Supplementary Figure S1 from Association of Tumor Mutational Burden and PD-L1 with the Efficacy of Pembrolizumab with or without Chemotherapy versus Chemotherapy in Advanced Urothelial Carcinoma
Authors: Fléchon Aude , Morales-Barrera Rafael , Powles Thomas , Alva Ajjai , Özgüroğlu Mustafa , Csöszi Tibor , Loriot Yohann , Rodriguez-Vida Alejo , Géczi Lajos , Cheng Susanna Y. , Fradet Yves , Oudard Stéphane , Vulsteke Christof , Gunduz Seyda , Mamtani Ronac , Yu Evan Y. , Montesa Pino Alvaro , Anido Urbano , Sendur Mehmet A.N. , Gravis Gwenaelle , Révész János , Kostorov Vladimir , Huillard Olivier , Ma Junshui , Rajasagi Mohini , Vajdi Amir , Lunceford Jared , Cristescu Razvan , Imai Kentaro , Homet Moreno Blanca , Matsubara Nobuaki
Published: December 2024

Supplementary Figure 1. OncoPrint showing biomarker distribution and most frequently mutated genes.
Supplementary Methods1 from Nivolumab in Patients with Metastatic Castration-Resistant Prostate Cancer with and without DNA Repair Defects
Authors: Isaacsson Velho Pedro , Bastos Diogo Assed , Saint’ana Pedro Tofani , Rigatti Brenda , da Costa Emily Tonin , Muniz David Q.B. , Andreis Felipe , Ferreira Rafael Dal Ponte , Giongo Pedrotti Luana , Maistro Simone , Katayama Maria Lucia Hirata , Folgueira Maria Aparecida Azevedo Koike , Morelle Alessandra , Leal Alessandro , de Castro Gilberto
Published: December 2024

Supplementary Methods
Supplementary Figure 4B from Nivolumab in Patients with Metastatic Castration-Resistant Prostate Cancer with and without DNA Repair Defects
Authors: Isaacsson Velho Pedro , Bastos Diogo Assed , Saint’ana Pedro Tofani , Rigatti Brenda , da Costa Emily Tonin , Muniz David Q.B. , Andreis Felipe , Ferreira Rafael Dal Ponte , Giongo Pedrotti Luana , Maistro Simone , Katayama Maria Lucia Hirata , Folgueira Maria Aparecida Azevedo Koike , Morelle Alessandra , Leal Alessandro , de Castro Gilberto
Published: December 2024

Supplementary Figure 4B: KM curve of rPFS in patients with and without PD-L1 expression.
Supplementary Figure 2C from Nivolumab in Patients with Metastatic Castration-Resistant Prostate Cancer with and without DNA Repair Defects
Authors: Isaacsson Velho Pedro , Bastos Diogo Assed , Saint’ana Pedro Tofani , Rigatti Brenda , da Costa Emily Tonin , Muniz David Q.B. , Andreis Felipe , Ferreira Rafael Dal Ponte , Giongo Pedrotti Luana , Maistro Simone , Katayama Maria Lucia Hirata , Folgueira Maria Aparecida Azevedo Koike , Morelle Alessandra , Leal Alessandro , de Castro Gilberto
Published: December 2024

Supplementary Figure 2C: KM curve of OS by TMB
Study Participants1 from Nivolumab in Patients with Metastatic Castration-Resistant Prostate Cancer with and without DNA Repair Defects
Authors: Isaacsson Velho Pedro , Bastos Diogo Assed , Saint’ana Pedro Tofani , Rigatti Brenda , da Costa Emily Tonin , Muniz David Q.B. , Andreis Felipe , Ferreira Rafael Dal Ponte , Giongo Pedrotti Luana , Maistro Simone , Katayama Maria Lucia Hirata , Folgueira Maria Aparecida Azevedo Koike , Morelle Alessandra , Leal Alessandro , de Castro Gilberto
Published: December 2024

Representativeness of Study Participants
Supplementary Data 1 from The Tumor Immune Microenvironment Drives Survival Outcomes and Therapeutic Response in an Integrated Molecular Analysis of Gastric Adenocarcinoma
Authors: Skubleny Daniel , Purich Kieran , McLean David R. , Martins-Filho Sebastiao N. , Buttenschoen Klaus , Haase Erika , McCall Michael , Ghosh Sunita , Spratlin Jennifer L. , Schiller Dan E. , Rayat Gina R.
Published: December 2024

Supplemental Methods and Figures
Supplementary Table S7 from Determination of MYD88 and CXCR4 Mutations for Clinical Detection and Their Significance in Waldenström Macroglobulinemia
Authors: Yan Yuting , Yu Ying , Xiong Wenjie , Wang Jun , Yao Yao , Jia Yujiao , Huang Yanshan , Li Yuxi , Wang Tingyu , Lyu Rui , Sun Hao , Wang Haoxu , Wang Qi , Liu Wei , An Gang , Sui Weiwei , Xu Yan , Huang Wenyang , Yu Zhen , Zou Dehui , Hao Mu , Xiao Zhijian , Wang Jianxiang , Qiu Lugui , Yi Shuhua
Published: December 2024

Supplementary Table 7. The concordance of three methods for CXCR4 mutation detection
Supplementary Figure S7 from Combinations of HDAC Inhibitor and PPAR Agonist Induce Ferroptosis of Leukemic Stem Cell–like Cells in Acute Myeloid Leukemia
Authors: Zhou Hui , Qin Dongmei , Xie Chendi , Zhou Jie , Jia Shuman , Zhou Ziwei , Qiu Yi , Xu Bing , Zha Jie
Published: December 2024

Supplementary Figure S7. (A) Knockdown of HDAC3 enhanced the endogenous lipid peroxidation levels in KG-1α and Kasumi-1cells, and the lipid peroxidation was detected by flow cytometry using C11-BODIPY staining. (B-C) The glutamate release (B) and intracellular GSH (C) were detected in HDAC3 knockdown KG-1α and Kasumi-1 cells. (D) Cell viability was counted in HDAC3 knockdown KG-1α and Kasumi-1 cells after treatments Ferr-1 (2 μM) for 72 h. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.
Supplementary Table S4 from Determination of MYD88 and CXCR4 Mutations for Clinical Detection and Their Significance in Waldenström Macroglobulinemia
Authors: Yan Yuting , Yu Ying , Xiong Wenjie , Wang Jun , Yao Yao , Jia Yujiao , Huang Yanshan , Li Yuxi , Wang Tingyu , Lyu Rui , Sun Hao , Wang Haoxu , Wang Qi , Liu Wei , An Gang , Sui Weiwei , Xu Yan , Huang Wenyang , Yu Zhen , Zou Dehui , Hao Mu , Xiao Zhijian , Wang Jianxiang , Qiu Lugui , Yi Shuhua
Published: December 2024

Supplementary Table 4. The concordance of four methods for MYD88 mutation detection
Supplementary Table S3 from Determination of MYD88 and CXCR4 Mutations for Clinical Detection and Their Significance in Waldenström Macroglobulinemia
Authors: Yan Yuting , Yu Ying , Xiong Wenjie , Wang Jun , Yao Yao , Jia Yujiao , Huang Yanshan , Li Yuxi , Wang Tingyu , Lyu Rui , Sun Hao , Wang Haoxu , Wang Qi , Liu Wei , An Gang , Sui Weiwei , Xu Yan , Huang Wenyang , Yu Zhen , Zou Dehui , Hao Mu , Xiao Zhijian , Wang Jianxiang , Qiu Lugui , Yi Shuhua
Published: December 2024

Supplementary Table 3. The test performance of four methods in detection of MYD88 mutations.
Supplementary Table S10 from Determination of MYD88 and CXCR4 Mutations for Clinical Detection and Their Significance in Waldenström Macroglobulinemia
Authors: Yan Yuting , Yu Ying , Xiong Wenjie , Wang Jun , Yao Yao , Jia Yujiao , Huang Yanshan , Li Yuxi , Wang Tingyu , Lyu Rui , Sun Hao , Wang Haoxu , Wang Qi , Liu Wei , An Gang , Sui Weiwei , Xu Yan , Huang Wenyang , Yu Zhen , Zou Dehui , Hao Mu , Xiao Zhijian , Wang Jianxiang , Qiu Lugui , Yi Shuhua
Published: December 2024

Supplementary Table 10. The response rate by MYD88/CXCR4 genotype during first-line BTKi-based therapy.
Supplementary Figure S1 from Combinations of HDAC Inhibitor and PPAR Agonist Induce Ferroptosis of Leukemic Stem Cell–like Cells in Acute Myeloid Leukemia
Authors: Zhou Hui , Qin Dongmei , Xie Chendi , Zhou Jie , Jia Shuman , Zhou Ziwei , Qiu Yi , Xu Bing , Zha Jie
Published: December 2024

Supplementary Figure S1. (A-B) The CD34+CD38−cell population was sorted from LSC-like cell lines KG-1α (A) and Kasumi-1 (B) and was further identified by flow cytometry using CD123, CD96, CD47, CD44, CD32, and CD25 antibodies. (C) Flow cytometric plots show the gating strategy to determine the percentages of cell death.
Supplementary Methods S1 from Determination of MYD88 and CXCR4 Mutations for Clinical Detection and Their Significance in Waldenström Macroglobulinemia
Authors: Yan Yuting , Yu Ying , Xiong Wenjie , Wang Jun , Yao Yao , Jia Yujiao , Huang Yanshan , Li Yuxi , Wang Tingyu , Lyu Rui , Sun Hao , Wang Haoxu , Wang Qi , Liu Wei , An Gang , Sui Weiwei , Xu Yan , Huang Wenyang , Yu Zhen , Zou Dehui , Hao Mu , Xiao Zhijian , Wang Jianxiang , Qiu Lugui , Yi Shuhua
Published: December 2024

supplementary methods
Supplementary Figure S1 from Determination of MYD88 and CXCR4 Mutations for Clinical Detection and Their Significance in Waldenström Macroglobulinemia
Authors: Yan Yuting , Yu Ying , Xiong Wenjie , Wang Jun , Yao Yao , Jia Yujiao , Huang Yanshan , Li Yuxi , Wang Tingyu , Lyu Rui , Sun Hao , Wang Haoxu , Wang Qi , Liu Wei , An Gang , Sui Weiwei , Xu Yan , Huang Wenyang , Yu Zhen , Zou Dehui , Hao Mu , Xiao Zhijian , Wang Jianxiang , Qiu Lugui , Yi Shuhua
Published: December 2024

Supplementary Figure 1. Mutation rates of MYD88 in patients with different tumor load detected by (A) Sanger sequencing; (B) next generation sequencing (NGS); (C) real-time allele specific polymerase chain reaction (AS-PCR); (D) droplet digital polymerase chain reaction (ddPCR). ns, no significance; ***P < 0.001.
Data from Neoadjuvant Intratumoral Plasmid IL-12 Electro-Gene-Transfer and Nivolumab in Patients with Operable, Locoregionally Advanced Melanoma
Authors: Tarhini Ahmad A. , Eroglu Zeynep , Eljilany Islam , Zager Jonathan S. , Gonzalez Ricardo J. , Sarnaik Amod A. , Cruse Carl Wayne , Khushalani Nikhil I. , De Aquino Deanryan B. , Abraham Edith , Acevedo Diana M. , Richards Allison , Schell Michael J. , Kalos Denise , Chen Pei-Ling , Messina Jane L. , Canton David A. , Sondak Vernon K.
Published: December 2024

AbstractPurpose:
Intratumoral tavokinogene telseplasmid delivered by electroporation (TAVO-EP) results in localized expression of IL-12 within the tumor microenvironment (TME). This study evaluated neoadjuvant TAVO-EP combined with intravenous nivolumab followed by surgery and adjuvant nivolumab in patients with operable, locoregionally advanced melanoma.
Patients and Methods:
The neoadjuvant phase comprised up to 3 × 4-week cycles during which TAVO-EP was given intratumorally on days 1, 8, and 15 (optional) concurrently with 480 mg nivolumab intravenously on day 8 of each 4-week cycle. Surgery followed, and adjuvant nivolumab was initiated after surgery. The primary endpoint was pathologic complete response (pCR). Secondary endpoints included major pathologic response (MPR; pCR or near pCR).
Results:
Sixteen patients were enrolled, and the preoperative radiological response rate was 63%. One patient declined surgery after experiencing a significant clinical response. Among the remaining 15 patients, the pCR rate was 60% and the MPR was 80%. No patient with MPR has had disease recurrence with a median follow-up from the date of surgery of 15.4 months. At baseline, most patients exhibited low CD8+ tumor-infiltrating lymphocytes, PD-L1, and IFN-γ gene expression signature. There was enhanced immune activation following treatment in the TME and blood, including increased immune-related gene expression, CD8+ tumor-infiltrating lymphocytes, and proliferating immune cell subsets.
Conclusions:
The clinical efficacy of neoadjuvant intratumoral TAVO-EP + nivolumab is promising with 80% of patients achieving an MPR. Evidence of potent immune activation both systemically and within the TME along with a favorable safety profile supports the activity of local IL-12 and anti–PD-1 based regimens.
Data from Efficacy and Safety of the Anti-IL1RAP Antibody Nadunolimab (CAN04) in Combination with Gemcitabine and Nab-Paclitaxel in Patients with Advanced/Metastatic Pancreatic Cancer
Authors: Van Cutsem Eric , Collignon Joelle , Eefsen Rikke L. , Ochsenreither Sebastian , Zvirbule Zanete , Ivanauskas Audrius , Arnold Dirk , Baltruskeviciene Edita , Pfeiffer Per , Yachnin Jeffrey , Magnusson Susanne , Rydberg Millrud Camilla , Sanfridson Annika , Losic Nedjad , Garcia-Ribas Ignacio , Tersago Dominique , Awada Ahmad
Published: December 2024

AbstractPurpose:
IL1 pathway upregulation is implicated in pancreatic ductal adenocarcinoma (PDAC) progression, therapy resistance, and survival. Nadunolimab is an IL1 receptor accessory protein (IL1RAP)–targeting antibody with enhanced antibody-dependent cellular cytotoxicity that blocks IL1α/IL1β signaling. We investigated efficacy and safety of nadunolimab in PDAC, in combination with gemcitabine/nab-paclitaxel (GN).
Patients and Methods:
Patients with previously untreated locally advanced/metastatic PDAC received nadunolimab (1.0–7.5 mg/kg) every 2 weeks with standard GN. The primary objective was safety; secondary objectives were antitumor response, progression-free survival, and overall survival (OS). Correlations between serum and tumor biomarkers and clinical response were explored.
Results:
Seventy-six patients were enrolled; the median age was 63 years (range, 43–89), 42% were female, 97% had metastatic disease, and 9% had received adjuvant chemotherapy. The most frequent grade ≥3 adverse event was neutropenia (66%), typically during cycle 1. Infusion-related reactions occurred in 29% (grade 3, 3%). Only 1 of the 76 patients had grade 3 or above peripheral neuropathy. No marked dose-dependent differences in safety or efficacy were observed among the four dose groups. The median OS was 13.2 months (95% confidence interval, 11.0–15.6), and the 1-year survival rate was 58%. The median immune PFS (immune Response Evaluation Criteria in Solid Tumours) was 7.1 months (95% confidence interval, 5.2–7.4). Treatment efficacy was higher in patients with high versus low tumor baseline IL1RAP expression (OS 14.2 vs. 10.6 months; P = 0.012). A reduction in serum IL8 on treatment correlated with prolonged OS.
Conclusions:
Nadunolimab combined with GN shows promising efficacy and manageable safety in locally advanced/metastatic PDAC. Higher tumor baseline IL1RAP expression correlated with better outcome.
Data from Characterization of FGFR Alterations and Activation in Patients with High-Risk Non–Muscle-Invasive Bladder Cancer
Authors: Eisner Joel R. , de Jong Florus C. , Shibata Yoichiro , Mayhew Gregory M. , Davison James M. , Carcione Jenna , Pappan Kirk L. , Thomas Shibu , Triantos Spyros , Santiago-Walker Ademi , Baig Mahadi , Milburn Michael V. , Beebe Kirk D. , Zuiverloon Tahlita C.M.
Published: December 2024

AbstractPurpose:
The Genomic Analysis of High-Risk Non–Muscle-Invasive Bladder Cancer (GARNER) study investigated FGFR alteration (ALT) frequency and the clinical outcome relationship with Bacillus Calmette–Guérin (BCG) treatment in high-risk non–muscle-invasive bladder cancer (HR-NMIBC). An FGFR predictive response signature (FGFR-PRS) was discovered that identifies patients with an activated FGFR pathway who could potentially benefit from FGFR-targeted therapy beyond those who are FGFR ALT (+).
Experimental Design:
Pretreatment tumor samples and clinical data were analyzed from 582 BCG-treated patients with HR-NMIBC. FGFR-PRS was discovered using a separate bladder cancer dataset and applied to the GARNER and other bladder cancer cohorts. FGFR-PRS was also applied to in vitro data from urothelial cancer cell lines treated with FGFR-active agents.
Results:
A total of 31% of pretreatment GARNER HR-NMIBC tumors were FGFR ALT (+), but this was not significantly associated with BCG response. For the subset of patients with paired pre- and post-BCG treatment samples, nearly one-third of pretreatment ALT (+) patients were ALT (−) posttreatment. FGFR-PRS identified patients with an activated FGFR pathway and identified approximately twofold additional patients compared with ALT status alone, and this increase was similar across tumor stage. A positive relationship between tumor growth inhibition and FGFR-PRS score was shown in bladder cancer in vitro models treated with FGFR-active agents.
Conclusions:
These data provide support for FGFR-targeted therapy use in FGFR ALT (+) HR-NMIBC and describe tumors with shared FGFR pathway–activated biology that is FGFR ALT (−) but FGFR-PRS (+). The latter suggests a broader potential patient population for FGFR-targeted therapy, which will require subsequent validation in patients treated with FGFR-targeted therapy.
Data from A Preoperative Window-of-Opportunity Study of Oral SERD, Imlunestrant, in Newly Diagnosed ER-Positive, HER2-Negative Early Breast Cancer: Results from the EMBER-2 Study
Authors: Neven Patrick , Stahl Nicole , Vidal Maria , Martín Miguel , Kaufman Peter A. , Harbeck Nadia , Hunt Kelly K. , Carter Stacey , Bidard Francois-Clement , Fasching Peter A. , Aftimos Philippe , Wheatley Duncan , Hamilton Erika , Aft Rebecca , Kulkarni Swati , Schmid Peter , Bhave Manali , Ismail-Khan Roohi , Karacsonyi Claudia , Estrem Shawn T. , Nguyen Bastien , Ozbek Umut , Yuen Eunice , Rodrik-Outmezguine Vanessa , Ciruelos Eva
Published: December 2024

AbstractPurpose:
Imlunestrant is an oral selective estrogen receptor degrader with favorable safety and preliminary efficacy in patients with advanced breast cancer. Pharmacodynamic (PD) biomarker data can optimize drug dosing; in this study, we present PD data from the EMBER-2 study.
Patients and Methods:
Postmenopausal women with untreated, operable estrogen receptor (ER)–positive, HER2-negative early breast cancer were randomized to 400 versus 800 mg of imlunestrant daily for ∼2 weeks before surgery. A single arm study tested a daily dose of 200 mg. PD biomarker changes (ER, progesterone receptor, Ki-67 by IHC, and mRNA expression of ER-related genes) were evaluated in paired tumor samples (pre-/posttreatment). Safety and pharmacokinetics were also assessed.
Results:
Among evaluable paired samples (n = 75), PD profiles demonstrated consistent ER targeting between 400- and 800-mg doses, with less toxicity at the 400-mg dose. Although inducing the lowest rate of complete cell-cycle arrest, PD and pharmacokinetic results were similar for the 200-mg dose.
Conclusions:
EMBER-2 combined with existing phase I data has identified 400 mg as the optimal imlunestrant dose.
Data from Multidimensional Immunotyping of Human NF1-Associated Peripheral Nerve Sheath Tumors Uncovers Tumor-Associated Macrophages as Key Drivers of Immune Evasion in the Tumor Microenvironment
Authors: Zhang Lindy , Maalouf Alexandre , Makri Stavriani C. , Banerjee Jineta , Suru Aditya , Tam Ada J. , Calizo Ana , Pollard Kai , Wang Jiawan , Danilova Ludmila , Ioannou Maria , Levin Adam S. , Morris Carol D. , Rhee Daniel S. , Belzberg Allan J. , Blakeley Jaishri O. , Ladle Brian H. , Pardoll Drew M. , Lucas Calixto-Hope G. , Rodriguez Fausto J. , Gross John M. , Anders Robert A. , Pratilas Christine A. , Llosa Nicolas J.
Published: December 2024

AbstractPurpose:
Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft-tissue sarcomas and the leading cause of mortality in individuals with neurofibromatosis type 1 (NF1). Despite many clinical trials, outcomes for patients with MPNST have remained stagnant, and most succumb to their disease; thus, novel therapeutic approaches are needed. A better understanding of the MPNST immune ecosystem will aid in the development of strategies to activate the immune system against the tumor. In this study, we profile the tumor immune microenvironment (TIME) in NF1-associated peripheral nerve sheath tumors (PNST) to discover insights on the role played by tumor-infiltrating immune cells in malignant transformation.
Experimental Design:
Using fresh and formalin-fixed paraffin-embedded tissue from patients diagnosed with NF1-PNST, we dissected the TIME through IHC, multiparameter flow cytometry, and comparative transcriptomic studies.
Results:
Immunophenotyping confirmed increased immune cell infiltration during malignant progression, with a predominance of infiltrating myeloid cells, particularly CD163+ tumor-associated macrophages (TAM). The T cells within MPNST exhibited signs of tumor activation, characterized by high programmed cell death 1 expression. Additionally, MPNST specimens demonstrated elevated levels of immunosuppressive TAM, with heightened PD-L1 expression. The proportion of CD163+ myeloid cells within the TIME correlated with poorer progression-free survival. Notably, loss of H3K27 trimethylation correlated with low immune cell infiltration in MPNST.
Conclusions:
Malignant transformation of NF1-PNST is characterized by an immunosuppressive microenvironment comprising TAM with high expression of PD-L1, which is associated with inferior outcomes. These findings suggest the clinical potential of immune-modulating therapeutics that can unleash an antitumor immune response.
The Prostaglandin EP4 Antagonist Vorbipiprant Combined with PD-1 Blockade for Refractory Microsatellite-Stable Metastatic Colorectal Cancer: A Phase Ib/IIa Trial
Authors: Pietrantonio Filippo , Morano Federica , Niger Monica , Ghelardi Filippo , Chiodoni Claudia , Palazzo Michele , Nichetti Federico , Manca Paolo , Cristarella Eleonora , Doldi Valentina , Zaffaroni Nadia , Sabella Giovanna , Brambilla Nadia , Benincasa Elena , Giacovelli Giampaolo , Vitalini Cristina , Girolami Federica , Rovati Lucio C.
Published: December 2024

Purpose:

Novel combinations are required to overcome resistance to immune checkpoint inhibitors in proficient mismatch repair (pMMR) or microsatellite-stable (MSS) metastatic colorectal cancer (mCRC). We aimed to determine whether vorbipiprant, a prostaglandin E2 receptor EP4 subtype antagonist, can convert immune-resistant mCRC into a tumor responsive to anti–PD-1 inhibition.

Patients and Methods:

This phase Ib/IIa prospective, open-label, single-arm trial followed a 3 + 3 dose-escalation and dose-optimization design. A total of 28 patients with chemorefractory pMMR/MSS mCRC were given dose-escalated oral vorbipiprant (30, 90, or 180 mg twice daily), along with biweekly intravenous balstilimab (3 mg/kg), an anti–PD-1 antibody. The primary endpoints included safety and the disease control rate (DCR). Secondary endpoints were the overall response rate, duration of response, progression-free survival, and overall survival.

Results:

No dose-limiting toxicities were observed. Of the 28 patients, seven (25%) experienced serious adverse events, but only one was attributed to vorbipiprant and one to balstilimab. The trial achieved a DCR of 50% observed across the entire cohort. In the subgroup of patients with liver metastases (n = 12), the DCR was 25%. The overall response rate was 11%, with three patients showing a partial response (median duration of response, 7.4 months). The median progression-free survival was 2.6 months, and the median overall survival was 14.2 months. Translational exploratory analyses suggested that vorbipiprant may boost response to anti–PD-1 in patients with immunogenic tumors.

Conclusions:

The combination of vorbipiprant and a PD-1 inhibitor (balstilimab) yielded sufficient activity in refractory pMMR/MSS mCRC, which is worthy of confirmation in future clinical trials in biomarker-enriched populations.
Table S6 from RNA Shielding of p65 Is Required to Potentiate Oncogenic Inflammation in TET2-Mutated Clonal Hematopoiesis
Authors: Ben-Crentsil Nana Adjoa , Mohammed Ismail Wazim , Balasis Maria E. , Newman Hannah , Quintana Ariel , Binder Moritz , Kruer Traci , Neupane Surendra , Ferrall-Fairbanks Meghan C. , Fernandez Jenna , Lasho Terra L. , Finke Christy M. , Ibrahim Mohammed L. , McGraw Kathy L. , Wysota Michael , Aldrich Amy L. , Ryder Christopher B. , Letson Christopher T. , Traina Joshua , McLemore Amy F. , Droin Nathalie , Shastri Aditi , Yun Seongseok , Solary Eric , Sallman David A. , Beg Amer A. , Ma Li , Gaspar-Maia Alexandre , Patnaik Mrinal M. , Padron Eric
Published: December 2024

guide RNA for T7 knockdown of TET2 (related to Fig 1, Fig S1)
Supplementary Table S11 from Botensilimab, an Fc-Enhanced Anti–CTLA-4 Antibody, Is Effective against Tumors Poorly Responsive to Conventional Immunotherapy
Authors: Chand Dhan , Savitsky David A. , Krishnan Shanmugarajan , Mednick Gabriel , Delepine Chloe , Garcia-Broncano Pilar , Soh Kah Teong , Wu Wei , Wilkens Margaret K. , Udartseva Olga , Vincent Sylvia , Joshi Bishnu , Keith Justin G. , Manrique Mariana , Marques Marilyn , Tanne Antoine , Levey Daniel L. , Han Haiyong , Ng Serina , Ridpath Jackson , Huber Olivia , Morin Benjamin , Galand Claire , Bourdelais Sean , Gombos Randi B. , Ward Rebecca , Qin Yu , Waight Jeremy D. , Costa Matthew R. , Sebastian-Yague Alvaro , Rudqvist Nils-Petter , Pupecka-Swider Malgorzata , Venkatraman Vignesh , Slee Andrew , Patel Jaymin M. , Grossman Joseph E. , Wilson Nicholas S. , Von Hoff Daniel D. , Stebbing Justin , Curiel Tyler J. , Buell Jennifer S. , O’Day Steven J. , Stein Robert B.
Published: December 2024

This table provides technical information about the multiplex immunofluorescence studies performed using the Akoya Biosciences CODEX platform. This is crucial for the reproducibility and interpretation of the multiplex immunofluorescence results.