tbuckley/cabot-search huggingface dataset:
Reversal of Chemoresistance via Staged Liberation of Chemodrug and siRNA in Hierarchical Response to ROS Gradient
Authors: Juanjuan Dang, Yongjuan Li, Jing Yan, Jianhua Wu, Kaimin Cai, Lichen Yin, Zhuchao Zhou
Journal: Advanced Healthcare Materials (2024)

Abstract P‐glycoprotein (P‐gp)‐mediated multidrug resistance (MDR) often leads to the failure of antitumor chemotherapy, and codelivery of chemodrug with P‐gp siRNA (siP‐gp) represents a promising approach for treating chemoresistant tumors. To maximize the antitumor efficacy, it is desired that the chemodrug be latently released upon completion of siP‐gp‐mediated gene silencing, which however, largely remains an unmet demand. Herein, core–shell nanocomplexes (NCs) are developed to overcome MDR via staged liberation of siP‐gp and chemodrug (doxorubicin, Dox) in hierarchical response to reactive oxygen species (ROS) concentration gradients. The NCs are constructed from mesoporous silica nanoparticles (MSNs) surface‐decorated with cRGD‐modified, PEGylated, ditellurium‐crosslinked polyethylenimine (RPPT), wherein thioketal‐linked dimeric doxorubicin (TK‐Dox 2 ) and photosensitizer are coencapsulated inside MSNs while siP‐gp is embedded in the RPPT polymeric layer. RPPT with ultrahigh ROS‐sensitivity can be efficiently degraded by the low‐concentration ROS inside cancer cells to trigger siP‐gp release. Upon siP‐gp‐mediated gene silencing and MDR reversal, light irradiation is performed to generate high‐concentration, lethal amount of ROS, which cleaves thioketal with low ROS‐sensitivity to liberate the monomeric Dox. Such a latent release profile greatly enhances Dox accumulation in Dox‐resistant cancer cells (MCF‐7/ADR) in vitro and in vivo, which cooperates with the generated ROS to efficiently eradicate MCF‐7/ADR xenograft tumors.
Dissecting the biology of feeding and eating disorders
Authors: Laura M. Huckins, Kristen Brennand, Cynthia M. Bulik
Journal: Trends in Molecular Medicine (2024)

Feeding and eating disorders (FEDs) are heterogenous and characterized by varying patterns of dysregulated eating and weight. Genome-wide association studies (GWASs) are clarifying their underlying biology and their genetic relationship to other psychiatric and metabolic/anthropometric traits. Genetic research on anorexia nervosa (AN) has identified eight significant loci and uncovered genetic correlations implicating both psychiatric and metabolic/anthropometric risk factors. Careful explication of these metabolic contributors may be key to developing effective and enduring treatments for devastating, life-altering, and frequently lethal illnesses. We discuss clinical phenomenology, genomics, phenomics, intestinal microbiota, and functional genomics and propose a path that translates variants to genes, genes to pathways, and pathways to metabolic outcomes to advance the science and eventually treatment of FEDs.
An orientation to the US National Cancer plan for the research community
Authors: Ann M Geiger, Elizabeth M Jaffee, Mitchel S Berger, Carol L Brown, W Kimryn Rathmell, Monica M Bertagnolli
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract The US National Cancer Act of 1971 designated the director of the National Cancer Institute as responsible for coordinating federal agencies and nonfederal organizations to make progress against cancer. As part of her role, the immediate past director of the National Cancer Institute (MMB) led the development of a National Cancer Plan that was formally released on April 3, 2023. The plan includes 8 aspirational goals “to achieve a society where every person with cancer lives a full and active life and to prevent most cancers so that few people need to face this diagnosis.” Research findings provide a foundation for each goal, and research gaps are included in the strategies for meeting each goal. The President’s Cancer Panel, also created by the National Cancer Act, conducted an initial assessment of progress toward the plan goals by hearing from 12 organizations at a virtual public meeting on September 7, 2023. The purpose of this commentary is to orient the scientific community to the plan and call attention to related knowledge gaps that could benefit from research.
CD155/PVR determines acute myeloid leukemia targeting by Delta One T cells
Authors: Sofia Mensurado, Carolina Condeço, Diego Sánchez-Martínez, Sara Shirley, Rui M. L. Coelho, Néstor Tirado, Meritxell Vinyoles, Rafael Blanco-Domínguez, Leandro Barros, Beatriz Galvão, Noélia Custódio, Maria Gomes da Silva, Pablo Menéndez, Bruno Silva-Santos
Journal: Blood (2024)

Relapsed or refractory acute myeloid leukemia (AML) remains a major therapeutic challenge. We have recently developed a Vδ1+ γδ T cell-based product for adoptive immunotherapy, named Delta One T (DOT) cells, and demonstrated their cytolytic capacity to eliminate AML cell lines and primary blasts in vitro and in vivo. However, the molecular mechanisms responsible for the broad DOT-cell recognition of AML cells remain poorly understood. Here, we dissected the role of natural killer (NK) cell receptor ligands in AML cell recognition by DOT cells. Screening of multiple AML cell lines highlighted a strong upregulation of the DNAM-1 ligands, CD155/pulmonary vascular resistance (PVR), CD112/nectin-2, as well as the NKp30 ligand, B7-H6, in contrast with NKG2D ligands. CRISPR-mediated ablation revealed key nonredundant and synergistic contributions of PVR and B7-H6 but not nectin-2 to DOT-cell targeting of AML cells. We further demonstrate that PVR and B7-H6 are critical for the formation of robust immunological synapses between AML and DOT cells. Importantly, PVR but not B7-H6 expression in primary AML samples predicted their elimination by DOT cells. These data provide new mechanistic insight into tumor targeting by DOT cells and suggest that assessing PVR expression levels may be highly relevant to DOT cell-based clinical trials.
BRG1/BRM inhibitor targets AML stem cells and exerts superior preclinical efficacy combined with BET or menin inhibitor
Authors: Warren Fiskus, Jessica Piel, Mike Collins, Murphy Hentemann, Branko Cuglievan, Christopher P. Mill, Christine E. Birdwell, Kaberi Das, John A. Davis, Hanxi Hou, Antrix Jain, Anna Malovannaya, Tapan M. Kadia, Naval Daver, Koji Sasaki, Koichi Takahashi, Danielle Hammond, Patrick K. Reville, Jian Wang, Sanam Loghavi, Rwik Sen, Xinjia Ruan, Xiaoping Su, Lauren B. Flores, Courtney D. DiNardo, Kapil N. Bhalla
Journal: Blood (2024)
Altered Oxidative Phosphorylation Confers Vulnerability on <i>IDH1</i>-Mutant Leukemia Cells: Is This Therapeutically Tractable?
Authors: David P. Steensma
Journal: Blood Cancer Discovery (2024)

Isocitrate dehydrogenase (IDH)-mutant acute myeloid leukemia (AML) is treatable with inhibitors of mutant IDH and also responds well to combination therapies including venetoclax, but most patients with IDH-mutant AML either never achieve complete remission or relapse because mutant hematopoietic stem cells persist despite treatment. An interesting new study in Blood Cancer Discovery characterizes a specific vulnerability in the mitochondrial oxidative phosphorylation system in preleukemic hematopoietic stem cells from patients with IDH1 mutations that is not present in those with IDH2 mutations; will this susceptibility prove amenable to therapy? See related article by Landberg et al., p. 114 (10).
The Siren Song of Synergy
Authors: Patrick D. Bhola, Anthony Letai
Journal: Blood Cancer Discovery (2024)

Summary: In ancient Greek mythology, sirens were creatures of stunning beauty whose mystical songs led sailors to sail their boats onto hidden rocks and into total destruction. In this issue, Mason-Osann and colleagues present data in the context of acute myelogenous leukemia to suggest that while synergy may show initial attractions in drug combinations, it may carry with it hazards previously unforeseen. See related article by Mason-Osann et al., p. 95 (1).
Antibiotic Exposure and Risk of New-Onset Inflammatory Bowel Disease: A Systematic Review and Dose-Response Meta-Analysis
Authors: Ruqiao Duan, Cunzheng Zhang, Gaonan Li, Jun Li, Liping Duan
Journal: Clinical Gastroenterology and Hepatology (2024)

Background & AimsThe association between antibiotic exposure and inflammatory bowel disease (IBD) remains controversial, especially whether there is a dose-response relationship. We aimed to conduct a systematic review and meta-analysis to thoroughly evaluate the risk of new-onset IBD associated with antibiotic exposure.MethodsFour databases were searched from their inception to September 30, 2023 for all relevant studies. The risk estimates were pooled together using random-effects models, and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, stratified by IBD subtype, age, exposure period, study type, and antibiotic classes. Dose-response relationship between the number of antibiotic prescriptions and IBD risk was assessed using generalized least squares regression analysis.ResultsTwenty-eight studies involving 153,027 patients with IBD were included. Antibiotic exposure was significantly associated with an increased risk of new-onset IBD for prescription-based studies (pooled OR, 1.41; 95% CI, 1.29–1.53) and for questionnaire-based studies (pooled OR, 1.35; 95% CI, 1.08–1.68). This association existed for both Crohn's disease and ulcerative colitis, as well as in children and adults for prescription-based studies. The majority of antibiotic classes were associated with an increased IBD risk, with metronidazole (OR, 1.70; 95% CI, 1.38–2.10) and quinolones (OR, 1.56; 95% CI, 1.37–1.77) having relatively higher risk estimates. A positive nonlinear dose-response association was observed between the number of antibiotic prescriptions and IBD risk.ConclusionsAntibiotic exposure was significantly associated with an increased risk of new-onset IBD, and a positive nonlinear dose-response relationship was observed. Antibiotic stewardship may be important for reducing IBD risk.
Prognostic and predictive value of angiogenesis-associated serum proteins for immunotherapy in esophageal cancer
Authors: Mengting Gao, Xueying Wu, Xi Jiao, Ying Hu, Yanni Wang, Na Zhuo, Fengxiao Dong, Yujiao Wang, Fengyuan Wang, Yanshuo Cao, Chang Liu, Jian Li, Lin Shen, Henghui Zhang, Zhihao Lu
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Immune checkpoint inhibitors (ICIs) have significantly improved patient survival in multiple cancers. However, therapy response in esophageal cancer is limited to subgroups of patients and clinically useful predictive biomarkers are lacking. Methods We collected a series of plasma samples from 91 patients with esophageal cancer before and after ICI treatment. The Olink Immuno-Oncology panel (92 proteins) with proximity extension assays was used to detect the dynamic changes in plasma and potential biomarkers associated with treatment outcomes. We screened all survival-related proteins and established a risk score model to better predict the prognosis and treatment response in patients with esophageal cancer immunotherapy. Results We found that 47 out of 92 quantified proteins had significant changes in plasma levels during ICI treatment (p&lt;0.050), and these changed proteins were involved in immune-related reactions, such as intercellular adhesion and T-cell activation. Notably, the baseline levels of three angiogenesis-related proteins (IL-8, TIE2, and HGF) were significantly associated with the survival outcomes of patients treated with ICIs (p&lt;0.050). According to these prognostic proteins, we established an angiogenesis-related risk score, which could be a superior biomarker for ICI response prediction. In addition, antiangiogenic therapy combined with ICIs significantly improved overall survival compared with ICI monotherapy (p=0.044). Conclusions An angiogenesis-related risk score based on three proteins (IL-8, TIE2, and HGF) could predict ICI response and prognosis in patients with esophageal cancer, which warrants verification in the future. Our study highlights the potential application of combining ICIs and antiangiogenic therapy and supports Olink plasma protein sequencing as a liquid biopsy method for biomarker exploration.
Phosphatidylethanol Detects Occult Heavy Alcohol Use in Patients With Acute and Chronic Pancreatitis
Authors: Nicole Wong, Cihang Gu, Dhiraj Yadav, Gregory A. Cote, Emily Jonica, Saad Jazrawi, Melissa Saul, Kaveh Sharzehi, Jessica Yu
Journal: Clinical Gastroenterology and Hepatology (2024)
Chronic hepatitis B baseline viral load and on-treatment liver cancer risk: A multinational cohort study of HBeAg-positive patients
Authors: Won-Mook Choi, Terry Cheuk-Fung Yip, W. Ray Kim, Leland J. Yee, Craig Brooks-Rooney, Tristan Curteis, Laura J. Clark, Zarena Jafry, Chien-Hung Chen, Chi-Yi Chen, Yi-Hsiang Huang, Young-Joo Jin, Dae Won Jun, Jin-Wook Kim, Neung Hwa Park, Cheng-Yuan Peng, Hyun Phil Shin, Jung Woo Shin, Yao-Hsu Yang, Grace Lai-Hung Wong, Young-Suk Lim
Journal: Hepatology (2024)

Background and Aims: A single-nation study reported that pretreatment HBV viral load is associated with on-treatment risk of HCC in patients who are HBeAg-positive without cirrhosis and with chronic hepatitis B initiating antiviral treatment. We aimed to validate the association between baseline HBV viral load and on-treatment HCC risk in a larger, multinational cohort. Approach and Results: Using a multinational cohort from Korea, Hong Kong, and Taiwan involving 7545 adult patients with HBeAg-positive, without cirrhosis and with chronic hepatitis B who started entecavir or tenofovir treatment with baseline HBV viral load ≥5.00 log 10 IU/mL, HCC risk was estimated by baseline viral load. HBV viral load was analyzed as a categorical variable. During continuous antiviral treatment (median, 4.28 y), HCC developed in 200 patients (incidence rate, 0.61 per 100 person-years). Baseline HBV DNA level was independently associated with on-treatment HCC risk in a nonlinear pattern. HCC risk was lowest with the highest baseline viral load (≥8.00 log 10 IU/mL; incidence rate, 0.10 per 100 person-years), but increased sharply as baseline viral load decreased. The adjusted HCC risk was 8.05 times higher (95% CI, 3.34–19.35) with baseline viral load ≥6.00 and &lt;7.00 log 10 IU/mL (incidence rate, 1.38 per 100 person-years) compared with high (≥8.00 log 10 IU/mL) baseline viral load ( p &lt;0.001). Conclusions: In a multinational cohort of adult patients with HBeAg-positive without cirrhosis and with chronic hepatitis B, baseline HBV viral load was significantly associated with HCC risk despite antiviral treatment. Patients with the highest viral load who initiated treatment had the lowest long-term risk of HCC development.
Core Outcome Set for <scp>IgE</scp>‐mediated food allergy clinical trials and observational studies of interventions: International Delphi consensus study ‘<scp>COMFA</scp>’
Authors: Anastasia Demidova, Karl Philipp Drewitz, Parisut Kimkool, Nikolina Banjanin, Vladyslava Barzylovich, Erna Botjes, India Capper, Mary Anne R. Castor, Pasquale Comberiati, Emma E. Cook, Joana Costa, Derek K. Chu, Michelle M. Epstein, Audrey Dunn Galvin, Mattia Giovannini, Frédéric Girard, Michael A. Golding, Matthew Greenhawt, Despo Ierodiakonou, Christina J. Jones, Ekaterina Khaleva, Rebecca C. Knibb, Melahat Sedanur Macit‐Çelebi, Douglas P. Mack, Isabel Mafra, Mary Jane Marchisotto, Dragan Mijakoski, Nikita Nekliudov, Cevdet Özdemir, Nandinee Patel, Ekaterina Pazukhina, Jennifer L. P. Protudjer, Pablo Rodríguez del Rio, Jelena Roomet, Patrick Sammut, Ann‐Marie Malby Schoos, Anita Fossaluzza Schopfer, Fallon Schultz, Nina Seylanova, Isabel Skypala, Martin Sørensen, Sasho Stoleski, Eva Stylianou, Julia Upton, Willem van de Veen, Jon Genuneit, Robert J. Boyle, Christian Apfelbacher, Daniel Munblit
Journal: Allergy (2024)

Abstract Background IgE‐mediated food allergy (FA) is a global health concern with substantial individual and societal implications. While diverse intervention strategies have been researched, inconsistencies in reported outcomes limit evaluations of FA treatments. To streamline evaluations and promote consistent reporting, the Core Outcome Measures for Food Allergy (COMFA) initiative aimed to establish a Core Outcome Set (COS) for FA clinical trials and observational studies of interventions. Methods The project involved a review of published clinical trials, trial protocols and qualitative literature. Outcomes found as a result of review were categorized and classified, informing a two‐round online‐modified Delphi process followed by hybrid consensus meeting to finalize the COS. Results The literature review, taxonomy mapping and iterative discussions with diverse COMFA group yielded an initial list of 39 outcomes. The iterative online and in‐person meetings reduced the list to 13 outcomes for voting in the formal Delphi process. One more outcome was added based on participant suggestions after the first Delphi round. A total of 778 participants from 52 countries participated, with 442 participating in both Delphi rounds. No outcome met a priori criteria for inclusion, and one was excluded as a result of the Delphi. Thirteen outcomes were brought to the hybrid consensus meeting as a result of Delphi and two outcomes, ‘allergic symptoms’ and ‘quality of life’ achieved consensus for inclusion as ‘core’ outcomes. Conclusion In addition to the mandatory reporting of adverse events for FA clinical trials or observational studies of interventions, allergic symptoms and quality of life should be measured as core outcomes. Future work by COMFA will define how best to measure these core outcomes.
Celebrating the 30th Anniversary of the European Association of Neuro-Oncology (EANO)
Authors: Matthias Preusser, Michael Platten, Susan C Short
Journal: Neuro-Oncology (2024)

Journal Article Accepted manuscript Celebrating the 30th Anniversary of the European Association of Neuro-Oncology (EANO) Get access Matthias Preusser, Matthias Preusser Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria https://orcid.org/0000-0003-3541-2315 Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael Platten, Michael Platten Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neurosciences (MCTN), University of Heidelberg, Mannheim, Germany; Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany https://orcid.org/0000-0002-4746-887X Search for other works by this author on: Oxford Academic PubMed Google Scholar Susan C Short Susan C Short Leeds Institute of Medical Research at St James's, The University of Leeds, Leeds UK Corresponding author: Susan C. Short, MD, Leeds Institute of Medical Research at St James's, The University of Leeds, Leeds UK, Wellcome Trust Brenner Building, St James's University Hospital, Leeds LS9 7TF, Email: s.c.short@leeds.ac.uk Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, noae039, https://doi.org/10.1093/neuonc/noae039 Published: 02 March 2024 Article history Received: 10 February 2024 Published: 02 March 2024
Dietary interventions in cancer: a systematic review of all randomized controlled trials
Authors: Nosakhare Paul Ilerhunmwuwa, Abul Hasan Shadali Abdul Khader, Calvin Smith, Edward R Scheffer Cliff, Christopher M Booth, Evevanne Hottel, Muhammad Aziz, Wade Lee-Smith, Aaron Goodman, Rajshekhar Chakraborty, Ghulam Rehman Mohyuddin
Journal: JNCI Journal of the National Cancer Institute (2024)

Prior systematic reviews addressing the impact of diet on cancer outcomes have focused on specific dietary interventions. In this systematic review, we assessed all randomized controlled trials (RCTs) investigating dietary interventions for cancer patients, examining the range of interventions, endpoints, patient populations, and results.
The Lebanese Geitawi Hospital-University Medical Center Heart Failure Registry
Authors: El Murr Tony, Youssef Boutros, Abi Rached Nagi, Bassil George, Ward Ricardo, Faddoul Joelle
Journal: Clinical Cardiology and Cardiovascular Interventions (2020)

Heart Failure (HF) has become a major cause of death and hospitalization among people older than 60 year. Lack of available data and registries from different countries that may aid in understanding the burden of the disease does exist. The aim of the lebanese Geitawi Hospital-University Medical Center (LGH-UMC) heart failure registry is to point toward the incidence of heart failure, in patients with suspected dyspnea, during a 7 months period in a single university medical center based on Trans-thoracic echocardiography (TTE) findings with emphasis on its etiology. Study population The LGH-HFR includes inpatients and outpatients (≥18 years) presenting for further evaluation of possible HF by performing a TTE after suspicious clinical findings. Patients with clinical impression of possible heart failure were reported to LGH-HFR by their doctors. The final decision to register a patient in the LGH-HFR is made by a single cardiologist to ensure the validity of the clinical suspicion. Approximately 1422 patients with clinically suspicion HF were registered in the LGH-HFR between 1.1.2018 and 31.7.2018. Main variables and descriptive data Our study will be a retrospective cohort analysis of data collected from the LGH-HFR between 1.1.2018 and 31.7.2018. Our number of studied patients is about 1422. The main variables recorded in the LGH-HFR are related to the TTE findings: LVEDV, LVEF, presence of LVH, the presence of diastolic dysfunction, documentation of any valvulopathies, measurements of PAPs. Furthermore, pro-BNP level and basic patient characteristics (age and sex) will be recorded. The findings then will be pooled according to the documentation of heart failure, either systolic or diastolic. Furthermore, specific TTE findings will be mentioned in each case after correlation with the HF type pointing toward the possible etiology of the cardiac function degradation. Results of our study will be reported back to clinicians to promote awareness for HF and communicated with the HFRs of different hospitals and LSC in order to optimize the standards of care regarding HF and discussing the cost effectiveness issue if possible. Conclusion The LGH-HFR is a valuable tool for continuous improvement of quality of care in patients and awareness regarding HF in Lebanon. Furthermore, it will be an important resource for the Lebanese registry-based HF research once available.