tbuckley/cabot-search huggingface dataset:
Sustained Residual Disease Negativity Assessed By Diffusion-Weighted Whole-Body MRI (DW-MRI) Has Strong Predictive Relevance for Survival in Newly Diagnosed Multiple Myeloma Patients on Maintenance Therapy after Autologous Stem Cell Transplantation (ASCT)
Authors: Angelo Belotti, Rossella Ribolla, Alberta Villanacci, Marco Chiarini, Viviana Giustini, Giulia Vittoria Facchetti, Claudia Crippa, Valeria Cancelli, Samantha Ferrari, Annalisa Peli, Chiara Bottelli, Chiara Cattaneo, Chiara Saeli, Aldo M. Roccaro, Luigi Grazioli, Giuseppe Rossi, Alessandra Tucci
Journal: Blood (2021)
Severe Acute Complications of Sickle Cell Disease in Two Expert Referral Centers (UK and Italy): Natural History Studies Highlight Ongoing Unmet Need for Effective Disease Modifying or Curative Therapies
Authors: Raffaella Colombatti, Cynthia Sangarappillai, Muriel Soriano, Jonathan Bestwick, Will Hann, Karolina Wieczorek, Vania Munaretto, Beatrice Coppadoro, Giulia Reggiani, Laura Sainati, Anjulika Chawla, Charu Puri-Sharma, Courtney Walls, Sanjeev Kommera, Paul Telfer
Journal: Blood (2021)
ReVenG: A Phase 2 Study of Venetoclax Plus Obinutuzumab Retreatment in Patients with Relapsed Chronic Lymphocytic Leukemia
Authors: Matthew S. Davids, Kirsten Fischer, Sandra Robrecht, Can Zhang, Inhye E. Ahn, Michele Porro Lurà, Wendy Sinai, Brenda Chyla, Kavita Sail, John Pesko, Madhavi Pai, Viktor Komlosi, Michael Hallek, Jennifer R. Brown, Othman Al-Sawaf
Journal: Blood (2021)
IgA Nephropathy Needs a Diagnostic Marker of Immunologic Activity to Select the Right Patients for Immunotherapies
Authors: Marc Hilhorst, Hans-Joachim Anders
Journal: Journal of the American Society of Nephrology (2021)

In this issue of JASN , Xie et al. [1][1] report on a histopathologic marker of immunologic activity in IgA nephropathy (IgAN) that predicts treatment response to immunotherapy. IgAN is the most prevalent primary GN and progresses to ESKD in almost one-third of patients. As mesangial IgA and
Non-Invasive Liquid Biopsy to Quantify and Molecularly Characterize Circulating Multiple Myeloma Cells in the Assessment of Precursor Disease Pathology
Authors: Ankit K. Dutta, Elizabeth D. Lightbody, Ziao Lin, Jean-Baptiste Alberge, Romanos Sklavenitis-Pistofidis, Tarek H Mouhieddine, Annie Cowan, Nang K. Su, Cody J. Boehner, Hadley Barr, Steven Gross, Ornkleaw Zepp, Thai Bui, Jared Mayes, Daniel Auclair, Gad Getz, Irene M. Ghobrial
Journal: Blood (2021)
Results from a Pilot Study of ARI0002h, an Academic BCMA-Directed CAR-T Cell Therapy with Fractionated Initial Infusion and Booster Dose in Patients with Relapsed and/or Refractory Multiple Myeloma
Authors: Carlos Fernandez de Larrea, Veronica Gonzalez-Calle, Valentin Cabañas, Aina Oliver-Caldes, Marta Español-Rego, Paula Rodriguez-Otero, Juan Luis Reguera, Lucía López Corral, Susana Inogés, Beatriz Martin-Antonio, Bruno Paiva, Laura Rosinol, Ascensión López-Diaz de Cerio, Natalia Tovar, Miriam Lopez Parra, Luis Gerardo Rodríguez-Lobato, Sara Varea, Andres Sanchez Salinas, Valentín Ortiz-Maldonado, Jose A. Perez-Simon, Felipe Prósper, Manel Juan, Jose Maria Moraleda, Maria-Victoria Mateos, Mariona Pascal, Álvaro Urbano-Ispizua
Journal: Blood (2021)
Analysis of Duration of Response, Exposure-Adjusted Safety and Progression to Acute Myeloid Leukemia (AML) for Patients with Lower-Risk Myelodysplastic Syndromes (LR-MDS) Receiving Luspatercept in the MEDALIST Study
Authors: Uwe Platzbecker, Valeria Santini, Rami S. Komrokji, Amer M. Zeidan, Guillermo Garcia-Manero, Rena J. Buckstein, Shelonitda Rose, Shannon Fabre, Dimana Miteva, Jennie Zhang, Aylin Yucel, Christina Hughes, Pierre Fenaux
Journal: Blood (2021)
Total Oral Anticoagulation for Classic PNH As Primary Prophylaxis Strategy in a Complement Inhibitor Restricted Scenario: A Retrospective Analysis
Authors: Elia Apodaca Chavez, Juan Rangel-Patiño, Elena Juventina Tuna-Aguilar, Aurea Garcés-Martínez, Roberta Demichelis
Journal: Blood (2021)
Predictors of Relapse and Survival Following Autologous Stem Cell Transplant in Patients with Diffuse Large B-Cell Lymphoma
Authors: Marie Hu, Marcus P Watkins, Qing Cao, Saba Raya, David A. Russler-Germain, Veronika Bachanova, Todd A. Fehniger, Daniel J. Weisdorf
Journal: Blood (2021)
Abstract 9508: The Natural Product Zerumbone Suppresses Pressure Overload-Induced Cardiac Dysfunction by Inhibiting Cardiac Hypertrophy and Fibrosis
Authors: Mikuto Tojima, Yasufumi Katanasaka, Satoshi Shimizu, Masafumi Funamoto, Kana Shimizu, Yoichi Sunagawa, Koji Hasegawa, Tatsuya Morimoto
Journal: Circulation (2021)

Introduction: Cardiac hypertrophy and fibrosis are hallmarks of cardiac remodeling and are involved functionally in the development of heart failure (HF). Various food components effectively prevent cardiovascular diseases. However, it is unknown whether zerumbone (ZER), a major active terpene found in endemic wild ginger species, suppresses cardiac hypertrophy, fibrosis, and dysfunction. Hypothesis: We assessed the hypothesis that ZER suppresses cardiac hypertrophy and fibrosis in vitro and in vivo . Methods: The effects of ZER on phenylephrine (PE)-induced hypertrophic responses and on transforming growth factor beta (TGF-β)-induced fibrotic responses were examined in primary cultured cardiomyocytes and fibroblasts from neonatal rats. To determine whether ZER prevents the development of pressure overload-induced HF in vivo , a transverse aortic constriction mouse model was utilized (n=6-10). One day after surgery, mice were randomly divided into two groups and orally administered with ZER 20 mg / kg or vehicle for 8 weeks. Cardiac function was evaluated by echocardiography. Changes in cardiomyocyte surface area and degree of fibrosis were observed by histological analysis (HE and WGA staining). The total mRNA levels of the genes associated with hypertrophy and fibrosis were measured by qRT-PCR. Protein expression (Akt phosphorylation and α-SMA) were assessed by western blotting. Results: ZER significantly suppressed PE-induced increases in cell size, hypertrophic gene expression (ANF and BNP), and Akt phosphorylation in cardiomyocytes. TGF-β-induced increases in collagen synthesis, mRNA levels of POSTN and α-SMA, and protein expression of α-SMA were lower in the ZER-treated cultured cardiac fibroblasts. Echocardiography results showed that left ventricular fractional shortening was increased and wall thickness was reduced in the ZER group compared with the vehicle group. Histological analysis showed that pressure overload-induced cardiac hypertrophy and cardiac fibrosis were inhibited in the ZER group compared with the vehicle group. Conclusions: These results suggest that zerumbone ameliorates pressure overload-induced cardiac dysfunction, at least in part by suppressing both cardiac hypertrophy and fibrosis.
Potential Disease-Modifying Activity of Navtemadlin (KRT-232), a First-in-Class MDM2 Inhibitor, Correlates with Clinical Benefits in Relapsed/Refractory Myelofibrosis (MF)
Authors: Pankit Vachani, Andrzej Lange, Regina Garcia Delgado, Haifa Kathrin Al-Ali, Jesus Maria Hernández-Rivas, Jean-Jacques Kiladjian, Alessandro Vannucchi, Andrew Charles Perkins, Venu Valmeekam, Cecile Marie Krejsa, Anne Uyei, Jesse McGreivy, Wayne P. Rothbaum, John Mascarenhas, Srdan Verstovsek
Journal: Blood (2021)
Majic: A Phase 3 Prospective, Multicenter, Randomized, Open-Label Trial of Acalabrutinib Plus Venetoclax Versus Venetoclax Plus Obinutuzumab in Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Authors: Matthew S. Davids, Anthony R. Mato, Juliette Hum, Susana Wargo, Ugochinyere Emeribe, Mina Shahkarami, Kevin Sokolowski, Juliana M.L. Biondo, Sarang Abhyankar, Rick Hermann, Jeff P. Sharman
Journal: Blood (2021)
Abstract 13917: A Harmonized Meta-Analysis of the Associations of Steps per Day With Incident Cardiovascular Disease
Authors: Amanda E Paluch, Shivangi Bajpai, David R Bassett, Ariel Chernofsky, Mercedes Carnethon, Erin Dooley, Ulf Ekelund, Kelly R Evenson, Kelley P Pettee Gabriel, Deborah A Galuska, Barbara J Jefferis, William E Kraus, Martin Larson, I-min M Lee, charles matthews, Robert L Newton, John D Omura, Priya Palta, Carl Pieper, Erika Rees-Punia, Lisa Pompeii, Brady Rippon, Nicole L Spartano, Vasan S Ramachandran, Shengping Yang, Janet E Fulton
Journal: Circulation (2021)

Introduction: The goal of 10,000 steps/day is widely promoted. There is limited evidence, however, of the number of steps/day associated with risk of developing cardiovascular disease (CVD). Hypothesis: We hypothesize a dose-response association between higher device-measured steps/day with lower CVD incidence. Methods: The Steps for Health Collaborative conducted a meta-analysis of seven prospective studies with device-measured steps/day and followed participants for CVD events. Participants without CVD at baseline were included. CVD was defined as coronary heart disease, stroke, and/or heart failure. Data were analyzed at the study level. Study-specific associations of quartiles of steps/day with incident CVD was assessed using Cox proportional hazards regression models and summarized using random effects meta-analysis. Models were adjusted for age, race/ethnicity, sex, body mass index, device wear time, and study-specific indicators for education or income, smoking, alcohol intake, blood pressure, dysglycemia, and hyperlipidemia. Study heterogeneity was assessed using I2 statistic. Results: The meta-analysis included 16,906 adults (mean age 62 years; 51% women), with median follow-up of 6.3 years (limits 2.9-10.7 years) and 1370 (8.1%) CVD events. Medians of study-specific steps/day were 1,951 (first quartile, Q1), 3,823 (second quartile, Q2), 5,685 (third quartile, Q3), and 9,487 (fourth quartile, Q4). Compared with Q1, summary hazard ratios for CVD were 0.83 (Q2, 95% confidence interval 0.72-0.95), 0.68 (Q3, 0.58-0.80), and 0.60 (Q4, 0.47-0.78) (Figure). There was low to moderate heterogeneity; I2 values were 0% for Q2, 2% for Q3, and 37% for Q4. Conclusions: Higher steps/day were associated with progressively lower risk of CVD. Monitoring and promoting steps/day can be a simple, easy to interpret metric used for clinician-patient communication and population health to reduce the risk of CVD.
The Interim Efficacy of Epigenetic Priming Regimen with Azacytidine and Chidamide in Patients with Relapsed or Refractory Peripheral T Cell Lymphoma
Authors: Kaiyang Ding, Xiao Shi, Haiyan Yang, Lei Cao, Xiaoli Zhao, Hailing Liu, Wei Wu, Xiaoyan Zhang, Li Wang, Wei Xu, Huayuan Zhu, Jianyong Li, Lei Fan
Journal: Blood (2021)
A Clinically Validated Targeted Capture Panel to Identify Translocations, Copy Number Abnormalities, and Mutations in Multiple Myeloma
Authors: Parvathi Sudha, Aarif Ahsan, Akhil Khera, Mohammad H Kazeroun, Tasneem Kausar, Lin Wang, Mirian Angulo Salazar, Evelyn Fitzsimons, Outi Salminen, Timothy Cody Ashby, Patrick Blaney, Magdalena Czader, Gail Vance, Jon Williams, Mohammad Issam Abu Zaid, Karthik Ramasamy, Kwee Yong, Gareth J. Morgan, Frits van Rhee, Rafat Abonour, Erin Flynt, Naser Ansari-Pour, Sarah Gooding, Anjan Thakurta, Brian A Walker
Journal: Blood (2021)
Aspirin Treatment and Outcomes After Percutaneous Coronary Intervention
Authors: Katharina Mayer, Isabell Bernlochner, Siegmund Braun, Stefanie Schulz, Martin Orban, Tanja Morath, Lisena Cala, Petra Hoppmann, Heribert Schunkert, Karl-Ludwig Laugwitz, Adnan Kastrati, Dirk Sibbing
Journal: Journal of the American College of Cardiology (2014)
Non-biomedical factors affecting antibiotic use in the community: a mixed-methods systematic review and meta-analysis
Authors: Ruyu Sun, Tingting Yao, Xudong Zhou, Stephan Harbarth, Leesa Lin
Journal: Clinical Microbiology and Infection (2021)

ObjectivesIn the past two decades, human antibiotic consumption has increased globally, contributing to the emergence and spread of antimicrobial resistance and needing urgent effective actions. Our objectives were to systematically identify and collate studies exploring non-biomedical factors influencing healthcare consumers' antibiotic use globally, in order to inform future interventions to improve practices in antibiotic use.MethodsData sources were PubMed, EMBASE, PsycINFO, and Cochrane. Study eligibility criteria were original and empirical studies that identified factors for healthcare consumers' antibiotic use. Participants were healthcare consumers. Assessment of risk of bias used adapted BMJ survey appraisal tools, the Critical Appraisal Skills Programme checklist, and the Mixed Methods Appraisal Tool for quality assessment. Methods of data synthesis employed the Social Ecological Framework and Health Belief Model for data synthesis. We did random-effects meta-analyses to pool the odds ratios of risk factors for antibiotic use.ResultsWe included 71 articles for systematic review and analysis; 54 were quantitative, nine were qualitative, and eight were mixed-methods studies. Prevalent non-prescription antibiotic use and irresponsible prescriptions were reported globally, especially in low-to-middle-income countries. Barriers to healthcare—wait time, transportation, stigmatization—influenced people's practices in antibiotic use. Further, lack of oversight and regulation in the drug manufacturing and a weak supply chain have led to the use of substandard or falsified antibiotics. Knowledge had mixed effects on antibiotic use behaviours. Meta-analyses identified pro-attitudes towards self-medication with antibiotics, relatives having medical backgrounds, older age, living in rural areas, and storing antibiotics at home to be risk factors for self-medication with antibiotics.ConclusionsNon-prescription antibiotic use and irresponsible prescriptions in the community are prevalent in all WHO regions and are driven largely by a mixed collection of non-biomedical factors specific to the respective setting. Future antimicrobial resistance strategies should incorporate an implementation science approach for community-based complex interventions that address drivers of the target behaviours tailored to local contexts.
A Phase Ib Pilot Study of Itacitinib Combined with Alemtuzumab in Patients with T-Cell Prolymphocytic Leukemia (T-PLL)
Authors: Tapan M. Kadia, Farhad Ravandi, Gautam Borthakur, Musa Yilmaz, Guillermo Montalban-Bravo, Lade Adewale, Sherry A. Pierce, Nitin Jain, Alessandra Ferrajoli, William G. Wierda, Hagop Kantarjian
Journal: Blood (2021)
日本人患者における経カテーテル大動脈弁置換術の良好な臨床的転帰 K‐TAVIレジストリの承認後からの初めての報告
Authors: Takimoto Shinya, Saito Naritatsu, Minakata Kenji, Shirai Shinichi, Isotani Akihiro, Arai Yoshio, Hanyu Michiya, Komiya Tatsuhiko, Shimamoto Takeshi, Goto Tsuyoshi, Fuku Yasushi, Ehara Natsuhiko, Furukawa Yutaka, Koyama Tadaaki, Nagasawa Atsuhi, Tamura Toshihiro, Miyake Makoto, Yamanaka Kazuo, Sakaguchi Hisashi, Murata Koichiro, Onodera Tomoya, Yamazaki Fumio, Nakai Masanao, Taniguchi Tomohiko, Sakata Ryuzo, Kimura Takeshi
Journal: Circulation (2017)
Similar Survival and Genetic Features between Clonal Cytopenia of Undetermined Significance and Lower-Risk Myelodysplastic Syndrome
Authors: Eun-Ji Choi, Young-Uk Cho, Han-Seung Park, Jung-Hee Lee, Kyoo Hyung Lee, Sang-Hyun Hwang, Seongsoo Jang, Chan-jeoung Park, Je-Hwan Lee
Journal: Blood (2021)
Rejuvenated BCMA-Specific CD8 + Cytotoxic T Lymphocytes Derived from Antigen-Specific Induced Pluripotent Stem Cells : Immunotherapeutic Application in Multiple Myeloma
Authors: Jooeun Bae, Shuichi Kitayama, Laurence Daheron, Zach Herbert, Nikhil C. Munshi, Shin Kaneko, Jerome Ritz, Kenneth C. Anderson
Journal: Blood (2021)
Evaluating the Prognostic Value of Inflammatory Biomarkers and Traditional Prognostic Tools in PTCL: A National, Multicenter Retrospective Study
Authors: Sally Rose Paredes, Denisse Castro, Thanya Runciman, Yesenia M. Huerta- Collado, Brady E Beltran, Marco Antonio Zuñiga, Jorge J. Castillo, Bryan Valcarcel, Luis Malpica Castillo
Journal: Blood (2021)
Guidelines for Diagnosis of Child Physical Abuse—Let’s Get Back to Work!
Authors: Pascal Boileau
Journal: JAMA Network Open (2021)

Flora Blangis, MSc; Slimane Allali, MD, PhD; Jérémie F. Cohen, MD, PhD; Nathalie Vabres, MD; Catherine Adamsbaum, MD; Caroline Rey-Salmon, MD; Andreas Werner, MD; Yacine Refes, PhD; Pauline Adnot, MD; Christèle Gras-Le Guen, MD, PhD; Elise Launay, MD, PhD; Martin Chalumeau, MD, PhD; European Confederation of Primary Care Paediatricians (ECPCP) research group ; Daniela Karall; Per Ashorn; Andreas Werner; Thomas Fischbach; Jacob Urkin; Federica Zanetto; Patrick Theisen; Helena Porfirio; Concepción Sanchez-Pina; Paolo Ramelli
Germline GATA1s-generating mutations predispose to leukemia with acquired trisomy 21 and Down syndrome-like phenotype
Authors: Henrik Hasle, Ronald M. Kline, Eigil Kjeldsen, Nik F. Nik-Abdul-Rashid, Deepa Bhojwani, Jeffrey M. Verboon, Stephanie P. DiTroia, Katherine R. Chao, Klas Raaschou-Jensen, Josefine Palle, C. Michel Zwaan, Charlotte Guldborg Nyvold, Vijay G. Sankaran, Alan B. Cantor
Journal: Blood (2021)
Abstract 8997: TRPM7 Mediates Hypomagnesemia-Induced Mitochondrial Dysfunction, Diastolic Heart Failure, and Death
Authors: Man Liu, Hong Liu, Gyeoung-Jin Kang, Feng Feng, Jin O-uchi, Samuel C Dudley
Journal: Circulation (2021)

Introduction: Hypomagnesemia (HypoMg) induces mitochondrial dysfunction accompanied by disturbed Mg homeostasis in mouse hearts. Transient receptor potential cation channel subfamily M 7 (TRPM7) is a Mg transporter with both channel and kinase function located in the plasma membrane. Its upregulation has been observed in HypoMg. We investigated the role of TRPM7 in mitochondrial dysfunction mediated by HypoMg. Methods: Wild type (WT) C57BL/6J mice and transgenic mice with a K1646R mutation in the TRPM7 kinase domain (TRPM7 K1646R , with no kinase function) were fed with a low-Mg diet (HypoMg mice, 15-30 mg/kg Mg) or a normal Mg diet (control mice, 600 mg/kg Mg) for 6 weeks. Human cardiac RL-14 cells were cultured in a normal (with 0.81 mM MgSO 4 ) or a low-Mg medium (customized medium with 0.04 mM MgSO 4 ) for 48 h. TRPM7 knockdown was achieved by siRNA in RL-14 cells. Results: WT HypoMg mice showed significantly decreased serum Mg, diastolic dysfunction, increased mitochondrial ROS in isolated cardiomyocytes, increased TRPM7 mRNA and protein level, decreased ATP production and decreased total mitochondrial Mg content in heart tissues. TRPM7 K1646R mice on the low-Mg diet showed normal diastolic function, normal mitochondrial ROS levels in cardiomyocytes, and recovered ATP production and mitochondrial Mg content in hearts. Furthermore, TRPM7 K1646R prevent HypoMg-induced seizures and death (64.8% death in WT HypoMg mice). Hypomagnesemia in RL-14 cells resulted in increased mitochondrial ROS (1.77±0.08-fold of control, P&lt;0.0001), which was suppressed to 0.86±0.04-fold of control by TRPM7 siRNA (25-30% TRPM7 reduction confirmed by RT-PCR and Western blot). Conclusions: HypoMg induces elevation of TRPM7 protein expression, and TRPM7 is involved in mitochondrial dysfunction, diastolic dysfunction, and death associated with HypoMg.
<i>RUNX1</i> Expression Can be Complementary to <i>RUNX1</i> Mutation in MDS Prognostication
Authors: Yu-Hung Wang, Chi-Yuan Yao, Chien-Chin Lin, Chia-Lang Hsu, Hsin-An Hou, Hwei-Fang Tien, Wen-Chien Chou
Journal: Blood (2021)
Abstract 9121: Lipoprotein(a) and the Risk for Coronary Heart Disease and Ischemic Stroke Events Among Black and White Adults with Cardiovascular Disease
Authors: Lisandro D Colantonio, Vera A Bittner, Monika M Safford, Santica M Marcovina, Todd M Brown, Elizabeth A Jackson, Mei Li, J. Antonio G Lopez, Keri L Monda, Tim B Plante, Shia Kent, Paul Muntner, Robert S Rosenson
Journal: Circulation (2021)

Introduction: Lp(a) is a risk marker for incident coronary heart disease (CHD) and ischemic stroke. It is unclear if Lp(a) is associated with CHD and stroke events among adults with prevalent cardiovascular disease (CVD), particularly in non-White populations. Hypothesis: Higher Lp(a) levels are associated with an increased risk for both CHD and ischemic stroke events in Black and White adults with prevalent CVD. Methods: We conducted a case-cohort analysis including Black and White adults ≥45 years of age enrolled in the nationwide REasons for Geographic and Racial Differences in Stroke (REGARDS) study between 2003 and 2007 who had prevalent CVD at baseline. REGARDS study participants were followed for CHD and ischemic stroke events, which were expert adjudicated. Lp(a) molar concentration was measured using a particle-enhanced turbidimetric immunoassay from blood samples collected at baseline in a random subcohort of participants with prevalent CVD (n=1,948), and in all those with prevalent CVD who experienced a CHD event by December 31, 2017 (n=1,166), or an ischemic stroke by September 30, 2019 (n=492). Results: The median [25 th , 75 th percentile] Lp(a) concentration was 100 nmol/L [48, 186] among Black participants and 23 nmol/L [8, 113] among White participants (p-value &lt;0.001). Higher Lp(a) was associated with an increased risk for CHD events among both Black and White participants, but it was not associated with the risk for ischemic stroke (Table). At baseline, 49% of Black participants and 59% of White participants with prevalent CVD were taking a statin. Among Black and White participants taking a statin, the hazard ratio [95% CI] associated with 1 SD higher log-Lp(a) was 1.69 [0.98, 2.93] and 1.38 [1.03, 1.85], respectively, for CHD, and 1.29 [0.70, 2.40] and 1.18 [0.81, 1.72], respectively, for stroke. Conclusion: Higher Lp(a) is a risk marker for CHD but not for ischemic stroke events in Black and White adults with prevalent CVD, including those taking a statin.
A hydrogen peroxide economizer for on-demand oxygen production-assisted robust sonodynamic immunotherapy
Authors: Qinqin Jiang, Bin Qiao, Xiaohong Lin, Jin Cao, Nan Zhang, Huanling Guo, Weiwei Liu, Lingyu Zhu, Xue Xie, Li Wan, Rui Tang, Bing Liang, Dong Wang, Zhigang Wang, Yang Zhou, HaiTao Ran, Pan Li
Journal: Theranostics (2021)

The outcome of sonodynamic immunotherapy is significantly limited by tumor hypoxia.To overcome this obstacle, one common solution is to catalyze the conversion of endogenous H2O2 into O2.However, the effectiveness of this strategy is limited by the insufficient concentration of H2O2 in the tumor microenvironment (TME).Herein, we developed a H2O2 economizer for on-demand O2 supply and sonosensitizer-mediated reactive oxygen species production during ultrasound activation, thereby alleviating hypoxia-associated limitations and augmenting the efficacy of sonodynamic immunotherapy.Methods: The H2O2 economizer is constructed by electrostatic adsorption and π-π interactions between the Fe-doped polydiaminopyridine (Fe-PDAP) nanozyme and chlorin e6.By employing a biomimetic engineering strategy with cancer cell membranes, we addressed the premature leakage issue and increased tumor-site accumulation of nanoparticles (membrane-coated Fe-PDAP/Ce6, MFC).Results: The prepared MFC could significantly attenuate the catalytic activity of Fe-PDAP by reducing their contact with H2O2.Ultrasound irradiation promoted MFC dissociation and the exposure of Fe-PDAP for a more robust O2 supply.Moreover, the combination of MFC-enhanced sonodynamic therapy with anti-programmed cell death protein-1 antibody (aPD-1) immune checkpoint blockade induced a strong antitumor response against both primary tumors and distant tumors.Conclusion: This as-prepared H2O2 economizer significantly alleviates tumor hypoxia via reducing H2O2 expenditure and that on-demand oxygen-elevated sonodynamic immunotherapy can effectively combat tumors.