tbuckley/cabot-search huggingface dataset:
Surveillance for Violent Deaths — National Violent Death Reporting System, 32 States, 2016
Authors: Allison Ertl, Kameron J. Sheats, Emiko Petrosky, Carter J. Betz, Keming Yuan, Katherine A. Fowler
Journal: MMWR Surveillance Summaries (2019)

In 2016, approximately 65,000 persons died in the United States as a result of violence-related injuries. This report summarizes data from CDC's National Violent Death Reporting System (NVDRS) regarding violent deaths from 32 U.S. states for 2016. Results are reported by sex, age group, race/ethnicity, type of location where injured, method of injury, circumstances of injury, and other selected characteristics.
Does Neutrophil to Lymphocyte Ratio (NLR) Predict the Prognosis of Diffuse Large B-Cell Lymphoma?
Authors: Aya Nakaya, Shinya Fujita, Atsushi Satake, Takahisa Nakanishi, Yoshiko Azuma, Yukie Tsubokura, Ryo Saito, Akiko Konishi, Masaaki Hotta, Hideaki Yoshimura, Kazuyoshi Ishii, Tomoki Ito, Shosaku Nomura
Journal: Blood (2018)
Preliminary results of a phase I/II dose-escalation study of fractionated dose 177Lu-PSMA-617 for progressive metastatic castration resistant prostate cancer (mCRPC)
Authors: S.T. Tagawa, J.R. Osborne, A. Hackett, M.J. Niaz, V. Cooley, P. Christos, P.J. Vlachostergios, C. Thomas, L. Gracey, H. Beltran, A.M. Molina, D.M. Nanus, J. Babich, S. Vallabhajosula, O. Sartor, K. Ballman, N.H. Bander
Journal: Annals of Oncology (2019)
Triple blinded prospective study assessing the impact of genomics & artificial intelligence Watson for oncology (WFO) on MDT’s decision of adjuvant systemic therapy for hormone receptor positive early breast carcinoma
Authors: S Sampige Prasannakumar, Y. Ramya, C.K. Rohit, K. Ashwin, P. Patil, A. Rauthan
Journal: Annals of Oncology (2019)
Exploratory study on microRNA profiles from plasma-derived extracellular vesicles in Alzheimer’s disease and dementia with Lewy bodies
Authors: Ana Gámez-Valero, Jaume Campdelacreu, Dolores Vilas, Lourdes Ispierto, Ramón Reñé, Ramiro Álvarez, M. Pilar Armengol, Francesc E. Borràs, Katrin Beyer
Journal: Translational Neurodegeneration (2019)

Because of the increasing life expectancy in our society, aging-related neurodegenerative disorders are one of the main issues in global health. Most of these diseases are characterized by the deposition of misfolded proteins and a progressive cognitive decline. Among these diseases, Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the most common types of degenerative dementia. Although both show specific features, an important neuropathological and clinical overlap between them hampers their correct diagnosis. In this work, we identified molecular biomarkers aiming to improve the misdiagnosis between both diseases.Plasma extracellular vesicles (EVs) -from DLB, AD and healthy controls- were isolated using size-exclusion chromatography (SEC) and characterized by flow cytometry, Nanoparticle Tracking Analysis (NTA) and cryo-electron microscopy. Next Generation Sequencing (NGS) and related bibliographic search was performed and a selected group of EV-associated microRNAs (miRNAs) was analysed by qPCR.Results uncovered two miRNAs (hsa-miR-451a and hsa-miR-21-5p) significantly down-regulated in AD samples respect to DLB patients, and a set of four miRNAs (hsa-miR-23a-3p, hsa-miR-126-3p, hsa-let-7i-5p, and hsa-miR-151a-3p) significantly decreased in AD respect to controls. The two miRNAs showing decreased expression in AD in comparison to DLB provided area under the curve (AUC) values of 0.9 in ROC curve analysis, thus suggesting their possible use as biomarkers to discriminate between both diseases. Target gene analysis of these miRNAs using prediction online tools showed accumulation of phosphorylation enzymes, presence of proteasome-related proteins and genes involved in cell death among others.Our data suggest that plasma-EV associated miRNAs may reflect a differential profile for a given dementia-related disorder which, once validated in larger cohorts of patients, could help to improve the differential diagnosis of DLB versus AD.
Added Benefit of Noninvasive Ventilation to High-Flow Nasal Oxygen to Prevent Reintubation in Higher-Risk Patients
Authors: Irene Telias, Niall D. Ferguson
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Early postoperative PET-CT in patients with pathological stage III colon cancer may change their outcome: Results from a large single institution study
Authors: A. Moore, I. Ben-Aharon, O. Purim, G. Perl, O. Ulitsky, L. Amit, Y. Kundel, R. Lewin, N. Wasserberg, H. Kashtan, B. Brenner
Journal: Annals of Oncology (2017)
Adequate Prenatal Maternal Folate—An Additional Intervention Strategy Among Populations Affected by Prenatal Lead Exposure?
Authors: Marco Sanchez-Guerra, Andres Cardenas, Citlalli Osorio-Yáñez
Journal: JAMA Network Open (2019)

Guoying Wang, MD, PhD; Jessica DiBari, PhD; Eric Bind, MPP; Andrew M. Steffens, PhD; Jhindan Mukherjee, PhD; Romuladus E. Azuine, DrPH, RN; Gopal K. Singh, PhD; Xiumei Hong, MD, PhD; Yuelong Ji, PhD; Hongkai Ji, PhD; Colleen Pearson, BA; Barry S. Zuckerman, MD; Tina L. Cheng, MD, MPH; Xiaobin Wang, MD, MPH, ScD
Real world data on adjuvant chemotherapy for high-risk stage II colorectal cancer: The role of tumour side
Authors: C S Araujo de Carvalho, C.M.V. Moniz, G.Y. Watarai, J.A.R. Crespo, P V D S Nogueira, J.K. Martinez, P M G D Moraes, R R D C C Bonadio, M I F M Braghiroli, J. Sabbaga, P.M.G. Hoff
Journal: Annals of Oncology (2019)
Radiomic signatures for identification of tumors sensitive to nivolumab or docetaxel in squamous non-small cell lung cancer (sqNSCLC)
Authors: L. Dercle, M. Fronheiser, L. Lu, S. Du, W. Hayes, D.K. Leung, A. Roy, L.H. Schwartz, B. Zhao
Journal: Annals of Oncology (2019)
Tumor acidity activated triphenylphosphonium-based mitochondrial targeting nanocarriers for overcoming drug resistance of cancer therapy
Authors: Hui Yu, Jia-Mi Li, Kai Deng, Wei Zhou, Cai-Xia Wang, Qian Wang, Kun-Heng Li, Hong-Yang Zhao, Shi-Wen Huang
Journal: Theranostics (2019)

The drug resistance in cancer treatment with DOX is mainly related to the overexpression of drug efflux proteins, residing in the plasma and nuclear membranes. Delivering DOX into the mitochondria, lacking drug efflux proteins, is an interesting method to overcome DOX resistance. To solve the problem of positively charged triphenylphosphonium (TPP) for mitochondrial targeting in vivo, a charge reversal strategy was developed. Methods: An acidity triggered cleavable polyanion PEI-DMMA (PD) was coated on the surface of positively charged lipid-polymer hybrid nanoparticle (DOX-PLGA/CPT) to form DOX-PLGA/CPT/PD via electrostatic interaction. The mitochondrial localization and anticancer efficacy of DOX-PLGA/CPT/PD was evaluated both in vitro and in vivo. Results: The surface negative charge of DOX-PLGA/CPT/PD prevents from rapid clearance in the blood and improved the accumulation in tumor tissue through the enhanced permeability and retention (EPR) effect. The hydrolysis of amide bonds in PD in weakly acidic tumor tissue leads to the conversion of DOX-PLGA/CPT/PD to DOX-PLGA/CPT. The positive charge of DOX-PLGA/CPT enhances the interaction with tumor cells, promotes the uptake and improves DOX contents in tumor cells. Once endocytosed by tumor cells, the exposed TPP in nanomedicine results in effective mitochondrial localization of DOX-PLGA/CPT. Afterward, DOX can release from the nanomedicine in the mitochondria, target mtDNA, induce tumor cells apoptosis and overcome DOX resistance of MCF-7/ADR breast cancer. Conclusion: Tumor acidity triggered charge reversal of TPP-containing nanomedicine and activation of mitochondrial targeting is a simple and effective strategy for the delivery of DOX into the mitochondria of cancer cells and overcoming DOX resistance of MCF-7/ADR tumor both in vitro and in vivo, providing new insight in the design of nanomedicines for cancer chemotherapy.
Impact of sarcopenia in patients with metastatic melanoma treated with immunotherapy
Authors: M.G. Vitale, D. Basile, E. Bertoli, M. Giavarra, G. Pelizzari, L. Palmero, D. Zara, G. Targato, G. Pascoletti, M. Cinausero, E. Poletto, D. Iacono, F. Puglisi, G. Fasola, A.M. Minisini
Journal: Annals of Oncology (2019)
Results from TRIO030, a pre-surgical tissue-acquisition study to evaluate molecular alterations in human breast cancer tissue following short-term exposure to the androgen receptor antagonist darolutamide
Authors: H.-W. Chen, E. Von Euw, P. Millan, R. Fresco, S. Carrez, K. Afenjar, H. Fung, M. Burton, A. Santiago, R. Guzman, I. Villalobos, M. Press, W. Eiermann, D. Slamon
Journal: Annals of Oncology (2019)
FDG PET/CT As a Diagnostic and Prognostic Tool for the Evaluation of Patients with Peripheral T-Cell Lymphoma
Authors: Ronit Gurion, Hanna Bernsteine, Carmela Michelson, Liran Domachevsky, Pia Raanani, Liat Vidal, Anat Gafter-Gvili
Journal: Blood (2016)
Influence of first treatment delay on survival among breast cancer subtypes
Authors: I Zarcos Pedrinaci, D. Perez, F. Rivas-Ruiz, M. Sala, M. Padilla-Ruiz, J. Alcaide-Garcia, E. Perez-Ruiz, R. Villatoro, V. Navarro, M. Redondo
Journal: Annals of Oncology (2019)
Phase II study of olaparib (O) and durvalumab (D) (MEDIOLA): Updated results in patients (pts) with germline BRCA-mutated (gBRCAm) metastatic breast cancer (MBC)
Authors: S. Domchek, S. Postel-Vinay, S.-A. Im, Y.H. Park, J.-P. Delord, A. Italiano, J. Alexandre, B. You, S. Bastian, M.G. Krebs, D. Wang, S. Waqar, M. Lanasa, H.K. Angell, Z. Lai, C. Gresty, L.M. Opincar, P. Herbolsheimer, B. Kaufman
Journal: Annals of Oncology (2019)
Genomic characterisation of locally advanced pancreatic adenocarcinoma
Authors: S. Picardo, G.M. O’Kane, S. Fischer, A. Zhang, R. Denroche, G. Jang, A. Dodd, R.C. Grant, B. Gruenwald, S. Moura, Y. Wang, E. Elimova, R. Prince, G. Zogopoulos, F. Notta, J. Wilson, S. Gallinger, J.J. Knox
Journal: Annals of Oncology (2019)
Rare dyslipidaemias, from phenotype to genotype to management: a European Atherosclerosis Society task force consensus statement
Authors: Robert A Hegele, Jan Borén, Henry N Ginsberg, Marcello Arca, Maurizio Averna, Christoph J Binder, Laura Calabresi, M John Chapman, Marina Cuchel, Arnold von Eckardstein, Ruth Frikke-Schmidt, Daniel Gaudet, G Kees Hovingh, Florian Kronenberg, Dieter Lütjohann, Klaus G Parhofer, Frederick J Raal, Kausik K Ray, Alan T Remaley, Jane K Stock, Erik S Stroes, Lale Tokgözoğlu, Alberico L Catapano
Journal: The Lancet Diabetes & Endocrinology (2019)
Repairing Transected Peripheral Nerve Using a Biomimetic Nerve Guidance Conduit Containing Intraluminal Sponge Fillers
Authors: Yuanjing Hou, Xinyu Wang, Zongrui Zhang, Jing Luo, Zhengwei Cai, Yiyu Wang, Yi Li
Journal: Advanced Healthcare Materials (2019)

Nerve guide conduits (NGCs) with geometric design have shown significant advantages in guidance of nerve reinnervation across the defect of injured peripheral nerves. It is realized that intraluminal fillers with distinctive structure can effectively provide an inner guidance for sprouting of axons and improve the permeability of NGC. In this work, a poly(lactic-co-glycolic acid) (PLGA) NGC is prepared containing intraluminal sponge fillers (labeled as ISF-NGC) and used for reconstruction of a rat sciatic nerve with a 10 mm gap. For comparison, the same procedure is applied to a single hollow PLGA NGC (labeled as H-NGC) and an autologous nerve. As evidenced by significantly improved nerve morphology and function, the ISF-NGC achieves a superior nerve repair effect over H-NGC, which is comparable to autologous nerve grafting. It is likely that the H-NGC only provides a protected tunnel for nerve fiber regrowth and axonal extension, while ISF-NGC offers an extracellular matrix-mimetic architecture as autograft to provide contact guidance for nerve reinnervation. This newly developed ISF-NGC is a promising candidate to aid nerve reinnervation across longer gaps commonly encountered in clinical cases.
HOXA9 Is a Novel Therapeutic Target in Multiple Myeloma.
Authors: Michael A Chapman, Jean-Philippe Brunet, Jonathan J Keats, Angela Baker, Mazhar Adli, Anna C. Schinzel, Gregory Ahmann, Harview Christina, Anna Moore, Vijayalakshmi Shanmugam, Louise M. Perkins, Daniel Auclair, William C. Hahn, Bradley E. Bernstein, Leif Bergsagel, Rafael Fonseca, John Carpten, Jeffrey Trent, Todd R. Golub
Journal: Blood (2009)
Combination treatment with cobimetinib (C) and atezolizumab (A) vs pembrolizumab (P) in previously untreated patients (pts) with BRAFV600 wild type (wt) advanced melanoma: Primary analysis from the phase III IMspire170 trial
Authors: A.M. Arance, H. Gogas, B. Dreno, K.T. Flaherty, L. Demidov, D. Stroyakovskiy, Z. Eroglu, P.F. Ferrucci, J. Pigozzo, P. Rutkowski, J. Mackiewicz, I. Rooney, A. Voulgari, S. Troutman, B. Pitcher, Y. Yan, J.M.G. Larkin
Journal: Annals of Oncology (2019)
Abstract #1311: Caffeine modulates apoptosis and thymidine kinase 1 activity in several human cell lines
Authors: Breanne Loosle, Melissa Tovar, Matthew Bingham, Sara Gehen, Byron Murray, Richard Robison, Kim O'Neill
Journal: Cancer Research (2009)

Previous research has demonstrated that caffeine (3,7-dihydro-1,3,7,-trimethyl-1H-purine-6,6-dione) has strong influences on cell-cycle checkpoints which affect the cell\#8217;s progression through its cycle. Caffeine has also been shown to increase cytotoxicity in combination with other DNA damaging agents by inhibiting DNA repair. Our laboratory previously investigated the effect of caffeine on HL-60 cells by simultaneously exposing them to caffeine (concentrations ranging from 0 to 20mM), and a brief hyperthermic treatment (43° C) for one hour, followed by a recovery time of 12 hours. We discovered that approximately 50 % of the cell population receiving only the hyperthermic treatment die by apoptosis within 12 hours, whereas cells that received treatments of both caffeine and heat shock had significantly lower death rates showing an apparent suppression of apoptosis (12-48% cell death) and enhanced cell survival. In addition, we measured the effect of caffeine on thymidine incorporation levels and thymidine kinase 1 (TK1) activity. Elevated levels of TK1 in patients\#8217; serum have been demonstrated in most cancers, including breast and prostate cancer. TK1 has shown the potential to be a useful prognostic tool and early diagnostic marker of cancer. In our study, we treated three cell lines: TK6 (p53 wild type), WTK1 (p53 mutant), and Raji (Burkitt Lymphoma), with caffeine concentrations ranging from 0mM to 20mM. The cells were incubated for a twenty-four hour period after which changes in viability, cell counts, incorporation rates, and the activity of TK1 were measured. With increasing levels of caffeine, viability decreased with changes ranging from 3.4 to 42.8%. The thymidine incorporation rates showed a sharp increase (approximately 337%) from 0mM to 5mM before returning to previous levels at the 10mM concentration, followed by steady decrease to 20mM. Cell counts also showed a general trend of decreasing from the 0mM to 20mM concentration with counts dropping an average of 7 to 295%. In our p53 negative cells, TK1 activity decreased approximately 78% with increasing caffeine concentration. In the p53 positive cells, TK1 activity decreased gradually until the 20mM concentration, where it jumped to levels higher than those of our negative control. These data strongly suggest that caffeine not only suppresses heat shocked induced apoptosis, but also affects expression of TK1, a potential tumor biomarker. The significant differences observed between the p53 mutant and wild type cell lines could offer insight into why mutant p53 cancer types are so devastating.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1311.
Clinical course and therapeutic management of classical and endemic Kaposi’s Sarcoma (C/E KS)
Authors: L. Benajiba, J. Lambert, R. La Selva, D. Cochereau, B. Baroudjian, J. Roux, N. Basset-Seguin, C Pages Laurent, M. Battistella, J. Delyon, C. Lebbe
Journal: Annals of Oncology (2019)
Intracranial anti-tumour activity in melanoma brain metastases with encorafenib plus binimetinib: A multicenter, retrospective analysis
Authors: J. Lutzky, K. Holbrook, A. Amin, J.M. Davis, M.A. Davies, A. Diab, I.C. Glitza, R.N. Amaria, S. Patel, H.A. Tawbi
Journal: Annals of Oncology (2019)
Integrated data review evaluating safety, pharmacokinetics (PK) and immunogenicity of RM-1929 photoimmunotherapy (PIT) in subjects with locoregional, recurrent head and neck squamous cell carcinoma (rHNSCC)
Authors: J.M. Johnson, D.M. Cognetti, J.M. Curry, F.E. Mott, S.T. Kochuparambil, D.R. McDonald, M.J. Fidler, N.R. Vasan, M.A. Razaq, M. Tahara, M.A. Biel, M. Tello, M. Garcia-Guzman, E. Sun, A.M. Gillenwater
Journal: Annals of Oncology (2019)
Results of a Phase 2 Trial of High Dose Lenalidomide Monotherapy in Patients with Relapsed/Refractory Higher-Risk Myelodysplastic Syndromes or Acute Myeloid Leukemia with Trilineage Dysplasia
Authors: Amer M. Zeidan, B. Douglas Smith, Hetty E. Carraway, Ivana Gojo, Sarah Sakoian, Steven D. Gore, Amy E. DeZern
Journal: Blood (2015)
Comprehensive genomic profiling and clinical outcomes in patients (pts) with fibroblast growth factor receptor rearrangement-positive (FGFR2+) cholangiocarcinoma (CCA) treated with pemigatinib in the fight-202 trial
Authors: A. Hollebecque, I. Silverman, S. Owens, L. Féliz, C. Lihou, H. Zhen, R. Newton, T. Burn, D. Melisi
Journal: Annals of Oncology (2019)
Obtaining spirometric reference values when height is not available – comparison of alternative anthropometric measures
Authors: N. China, D. Vaz, C. Martins, J. Gomes, I. Ladeira, R. Lima, M. Guimarães
Journal: Pulmonology (2019)

Height is one of the variables used to derive reference values for respiratory function but it is not always available. To fulfil this need, different formulas are described in literature.To understand which method best estimate height in order to obtain Forced Vital Capacity (FVC) and Forced Expiratory Volume in 1st second (FEV1) reference values.The true stature (TS) and five alternative anthropometric measures that estimate height [arm span using a regression equation (ASR), arm span using a fix correction factor (ASF), half arm span, knee height and ulnar length] were measured for all patients. To assess the differences between the TS versus the estimated heights and the respective reference values of FVC and FEV1, T Student Test and Wilcoxon test were used. Agreement was evaluated by Intraclass Correlation Coefficient and by Bland-Altman plot.A total of 160 subjects were recruited but 14 patients were excluded due to skeletal deformities. The predicted FVC and FEV1 using all alternative anthropometric measures were statistically different from those calculated by TS, except for ASF. The limits of agreement were wide for all alternative measures. With the exception of ASF, predicted FVC and FEV1 were overestimated when using all other alternative measures.For the purpose of replacing height in order to obtain predicted values of FVC and FEV1, the ASF was shown to be the most accurate and recommendable method. However, we must be aware there is a possible degree of error.
Therapeutic Plasma Exchange for Thrombotic Microangiopathy
Authors: Osman Ilhan, Erden Atilla, Pinar Ataca Atilla, Sinem Civriz Bozdag, Meltem Kurt Yuksel, Selami Kocak Toprak, Pervin Topcuoglu, Hamdi Akan, Taner Demirer, Meral Beksac, Onder Arslan, Muhit Ozcan, Gunhan Gurman
Journal: Blood (2016)
Extending temozolomide longer than six cycles in glioblastoma: Results of the randomized GEINO-014 trial
Authors: M.A.V. Salgado, J.M. Sepulveda Sanchez, S. del barco, E. Pineda, J. Fuster, M. Navarro Martin, A. Herrero Ibañez, M. Alonso, J. Perez, C. Mesia, J. Munoz-Langa, R. de las Penas Bataller, S. Peralta, C. Olier, P. Pérez-Segura, A. Estival, C. Carrato, C. Saez, M.J. Gil, C. Balana
Journal: Annals of Oncology (2019)
Impact of Switching from Intravenous to Subcutaneous Bortezomib in Real Life. Overlapping Toxicity and Efficacy in All Settings of Myeloma Patients Balancing Schedule and Way of Bortezomib Adminisration
Authors: Silvia Mangiacavalli, Federica Cocito, Virginia Valeria Ferretti, Claudio Salvatore Cartia, Maya Ganzetti, Mario Cazzola, Alessandro Corso
Journal: Blood (2016)
Early Evidence of Anabolic Bone Activity of BHQ880, a Fully Human Anti-DKK1 Neutralizing Antibody: Results of a Phase 2 Study in Previously Untreated Patients with Smoldering Multiple Myeloma At Risk for Progression
Authors: Nikhil C. Munshi, Rafat Abonour, Joseph T. Beck, William Bensinger, Thierry Facon, Keith Stockerl-Goldstein, Rachid Baz, David S Siegel, Kai Neben, Sagar Lonial, Attaya Suvannasankha, Sanela Bilic, Sandra Chica, Subhendu Mukhopadhyay, Randi Isaacs, Sundar Jagannath
Journal: Blood (2012)
Optimizing the Pretransplant Regimen for Autologous Stem Cell Transplantation in Acute Myelogenous Leukemia : Better Outcomes with Busulfan and Melphalan Compared with Busulfan and Cyclophosphamide in High Risk Patients Autografted in First Complete Remission
Authors: Norbert Claude Gorin, Myriam Labopin, Didier Blaise, Pierre-Yves Dumas, Thomas Pabst, Silvia Maria Trisolini, William Arcese, Mohamad Mohty, Arnon Nagler
Journal: Blood (2017)
Cooperation of endogenous and exogenous reactive oxygen species induced by zinc peroxide nanoparticles to enhance oxidative stress-based cancer therapy
Authors: Li-Sen Lin, Jun-Feng Wang, Jibin Song, Yijing Liu, Guizhi Zhu, Yunlu Dai, Zheyu Shen, Rui Tian, Justin Song, Zhantong Wang, Wei Tang, Guocan Yu, Zijian Zhou, Zhen Yang, Tao Huang, Gang Niu, Huang-Hao Yang, Zhi-Yi Chen, Xiaoyuan Chen
Journal: Theranostics (2019)

Reactive oxygen species (ROS)-generating anticancer agents can act through two different mechanisms: (i) elevation of endogenous ROS production in mitochondria, or (ii) formation/delivery of exogenous ROS within cells. However, there is a lack of research on the development of ROS-generating nanosystems that combine endogenous and exogenous ROS to enhance oxidative stress-mediated cancer cell death. Methods: A ROS-generating agent based on polymer-modified zinc peroxide nanoparticles (ZnO2 NPs) was presented, which simultaneously delivered exogenous H2O2 and Zn2+ capable of amplifying endogenous ROS production for synergistic cancer therapy. Results: After internalization into tumor cells, ZnO2 NPs underwent decomposition in response to mild acidic pH, resulting in controlled release of H2O2 and Zn2+. Intriguingly, Zn2+ could increase the production of mitochondrial O2·- and H2O2 by inhibiting the electron transport chain, and thus exerted anticancer effect in a synergistic manner with the exogenously released H2O2 to promote cancer cell killing. Furthermore, ZnO2 NPs were doped with manganese via cation exchange, making them an activatable magnetic resonance imaging contrast agent. Conclusion: This study establishes a ZnO2-based theranostic nanoplatform which achieves enhanced oxidative damage to cancer cells by a two-pronged approach of combining endogenous and exogenous ROS.