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Laura Juárez-Chávez, Socorro Pina-Canseco, Delia Soto-Castro, Rosa Santillan, Nancy E Magaña-Vergara, Paz María Salazar-Schettino, Margarita Cabrera-Bravo, Eduardo Pérez-Campos
The increasing use of dendrimers shows promise for the treatment of inflammatory diseases, Chagas disease and other conditions such as cancer. In this study, the activity of 1st and 2nd generation dendrimers over T. cruzi in the epimastigote stage was tested. Dendrimers were derived from α-ethynylestradiol (EE) modified with PAMAM-type dendrons through a triazole ring. The activity of each compound was evaluated in five doses (from 1.3 to 20 µmol/mL) by flow cytometry, including benznidazole (Bz) as positive control...
January 28, 2019: Bioorganic Chemistry
Gang Wang, Yu-Zhu Wang, Yang Yu, Jun-Jie Wang
ETHNOPHARMACOLOGICAL RELEVANCE: Studies have shown that the etiology and pathogenesis of colorectal cancer are closely related to the tumor microenvironment, and the cancer tissue is still in the state of "energy deficit" and has to promote energy generation through high glycolysis. Rhus chinensis Mill is a Chinese herbal medicine used to treat various types of solid tumors in China. Colorectal cancer (CRC) is a heterogeneous disease group caused by abnormal changes in glucose metabolism resulted in lactic acid production, which remodels acidosis...
February 14, 2019: Journal of Ethnopharmacology
Reina Mizuno, Takumi Maruhashi, Daisuke Sugiura, Kenji Shimizu, Mizuki Watada, Il-Mi Okazaki, Taku Okazaki
Cancer immunotherapies targeting programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 revolutionized cancer treatment and instigated various trials to develop new cancer immunotherapies with higher therapeutic efficacy. Agonistic Abs against tumor necrosis factor receptor super family (TNFRSF) molecules are highly expected due to their high potential to enhance survival, proliferation, and effector function of T cells. To date, agonistic antibodies (Abs) against CD27, GITR, OX40, and 4-1BB have been reported to increase the efficacy of anti-PD-1 therapy in animal models and clinical trials of these combinatorial therapies are underway...
February 13, 2019: Biochemical and Biophysical Research Communications
Turki Turki, Jason T L Wang
Predicting the response, or sensitivity, of a clinical drug to a specific cancer type is an important research problem. By predicting the clinical drug response correctly, clinicians are able to understand patient-to-patient differences in drug sensitivity outcomes, which in turn results in lesser time spent and lower cost associated with identifying effective drug candidates. Although technological advances in high-throughput drug screening in cells led to the generation of a substantial amount of relevant data, the analysis of such data would be a challenging task...
January 3, 2019: Computers in Biology and Medicine
James Nyagwange, Elias Awino, Edwin Tijhaar, Nicholas Svitek, Roger Pelle, Vishvanath Nene
Chemotherapy of East Coast fever, a lymphoproliferative cancer-like disease of cattle causing significant economic losses in Africa, is largely dependent on the use of buparvaquone, a drug that was developed in the late 1980's. The disease is caused by the tick-borne protozoan pathogen Theileria parva. Buparvaquone can be used prophylactically and it is also active against tropical theileriosis, caused by the related parasite Theileria annulata. Recently, drug resistance was reported in T. annulata, and could occur in T...
January 25, 2019: International Journal for Parasitology, Drugs and Drug Resistance
David G Leach, Simon Young, Jeffrey D Hartgerink
Macroscale biomaterials, such as preformed implantable scaffolds and injectable soft materials, possess powerful synergies with anti-cancer immunotherapies. Immunotherapies on their own typically have poor delivery properties, and often require repeated high-dose injections that result in serious off-tumor effects and/or limited efficacy. Rationally designed biomaterials allow for discrete localization and controlled release of immunotherapeutic agents, and have been shown in a large number of applications to improve outcomes in the treatment of cancers via immunotherapy...
February 13, 2019: Acta Biomaterialia
Jong Woo Lee, Yu Zhang, Kyung Jin Eoh, Roshan Sharma, Miguel F Sanmamed, Jenny Wu, Justin Choi, Hee Sun Park, Akiko Iwasaki, Edward Kaftan, Lieping Chen, Vali Papadimitrakopoulou, Roy S Herbst, Ja Seok Koo
PURPOSE: To characterize the tumor-infiltrating immune cells population in Kras/p53-driven lung tumors and to evaluate the combinatorial anti-tumor effect with MEK inhibitor (MEKi), trametinib, and immunomodulatory monoclonal antibodies (mAbs) targeting either programmed cell death protein-1 (PD-1) or programmed cell death protein ligand 1 (PD-L1) in vivo. EXPERIMENTAL DESIGN: Trp53FloxFlox ;KrasG12D/+ ;Rosa26LSL-Luciferase/LSL-Luciferase (PKL) genetically engineered mice were utilized to develop autochthonous lung tumors with intratracheal delivery of adenoviral Cre recombinase...
February 13, 2019: Journal of Thoracic Oncology
Bárbara Paranhos Coelho, Mariana Maier Gaelzer, Fernanda Dos Santos Petry, Juliana Bender Hoppe, Vera Maria Treis Trindade, Christianne G Salbego, Fátima T C R Guma
Several studies have demonstrated the antitumor effect of doxazosin, an α1-adrenergic blocker, against glioma and breast, bladder and prostate cancers. Doxazosin is also being evaluated as a treatment for posttraumatic stress disorder and alcoholism, and α1-adrenergic blockers have been linked to neuroprotection in neurodegenerative disorders, such as Alzheimer's Disease (AD). Cancer and AD have an inverse relationship in many aspects, with several factors that contribute to apoptosis inhibition and proliferation being increased in cancers but decreased in AD...
February 13, 2019: Neuroscience
Kangkang Liu, Erlin Sun, Mingde Lei, Limin Li, Jingda Gao, Xuewu Nian, Lining Wang
Bacillus Calmette-Guerin (BCG) is one of the most effective treatments for bladder cancer. Little attention has been paid to the possible role of neutrophils in BCG immunotherapy. In this study, we examined neutrophil extracellular traps (NETs) formation induced by BCG stimulation, and found that BCG-induced NETs exerted cytotoxicity, induced apoptosis and cell-cycle arrest, and inhibited migration in bladder tumor cells. BCG-activated tumor cells but not non-activated ones elicited NETs formation, in which IL-8 and TNF-α from activated tumor cells both took effect...
February 13, 2019: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Jian Zhang, Huali Zhang, Yongli Luo
BACKGROUND The aim of this study was to investigate the clinical correlation between sPD-1 (soluble programmed cell death-1) and PD-1 (programmed cell death-1) expression and cancer pain. MATERIAL AND METHODS sPD-1 content in peripheral blood was determined by enzyme-linked immunosorbent assay (ELISA). T cell surface-positive rate was determined by flow cytometry, and the correlation of clinical characteristics of patients with cancer pain was analyzed. RESULTS The positive expression rate of PD-1 in sPD-1 and T cells of patients with cancer pain was higher than that in normal patients...
February 16, 2019: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Martin Sebastian, Andreas Schröder, Birgit Scheel, Henoch S Hong, Anke Muth, Lotta von Boehmer, Alfred Zippelius, Frank Mayer, Martin Reck, Djordje Atanackovic, Michael Thomas, Folker Schneller, Jan Stöhlmacher, Helga Bernhard, Andreas Gröschel, Thomas Lander, Jochen Probst, Tanja Strack, Volker Wiegand, Ulrike Gnad-Vogt, Karl-Josef Kallen, Ingmar Hoerr, Florian von der Muelbe, Mariola Fotin-Mleczek, Alexander Knuth, Sven D Koch
CV9201 is an RNActive® -based cancer immunotherapy encoding five non-small cell lung cancer-antigens: New York esophageal squamous cell carcinoma-1, melanoma antigen family C1/C2, survivin, and trophoblast glycoprotein. In a phase I/IIa dose-escalation trial, 46 patients with locally advanced (n = 7) or metastatic (n = 39) NSCLC and at least stable disease after first-line treatment received five intradermal CV9201 injections (400-1600 µg of mRNA). The primary objective of the trial was to assess safety...
February 15, 2019: Cancer Immunology, Immunotherapy: CII
Karin H Simons, Alwin de Jong, J Wouter Jukema, Margreet R de Vries, Ramon Arens, Paul H A Quax
The role of inflammation in cardiovascular disease (CVD) is now widely accepted. Immune cells, including T cells, are influenced by inflammatory signals and contribute to the onset and progression of CVD. T cell activation is modulated by T cell co-stimulation and co-inhibition pathways. Immune checkpoint inhibitors (ICIs) targeting T cell inhibition pathways have revolutionized cancer treatment and improved survival in patients with cancer. However, ICIs might induce cardiovascular toxicity via T cell re-invigoration...
February 15, 2019: Nature Reviews. Cardiology
D Merino, T S Weber, A Serrano, F Vaillant, K Liu, B Pal, L Di Stefano, J Schreuder, D Lin, Y Chen, M L Asselin-Labat, T N Schumacher, D Cameron, G K Smyth, A T Papenfuss, G J Lindeman, J E Visvader, S H Naik
Primary triple negative breast cancers (TNBC) are prone to dissemination but sub-clonal relationships between tumors and resulting metastases are poorly understood. Here we use cellular barcoding of two treatment-naïve TNBC patient-derived xenografts (PDXs) to track the spatio-temporal fate of thousands of barcoded clones in primary tumors, and their metastases. Tumor resection had a major impact on reducing clonal diversity in secondary sites, indicating that most disseminated tumor cells lacked the capacity to 'seed', hence originated from 'shedders' that did not persist...
February 15, 2019: Nature Communications
Mingshui Chen, Aditi Sharma, Yanling Lin, Yanheng Wu, Qi He, Yushu Gu, Zhi Ping Xu, Michael Monteiro, Wenyi Gu
BACKGROUND: Programmed cell death ligand 1 (PD-L1) is an important immune-inhibitory protein expressed on cancer cells to mediate cancer escape through interaction with PD-1 expressed on activated T lymphocytes (T cells). Previously, we reported that colon and breast cancer stem cells (CSCs) expressed much higher levels of PD-L1 than their parental cells, suggesting they will be more resistant to immune attack. METHODS: We investigated the underlining mechanism of PD-L1 increase in colon CSCs, with a special focus on the effect of insulin and epithelial growth factor (EGF), the two fundamental components to sustain the metabolism and stemness in the culture of CSCs...
February 15, 2019: BMC Cancer
Cecilia Roux, Soode Moghadas Jafari, Rahul Shinde, Gordon Duncan, David W Cescon, Jennifer Silvester, Mandy F Chu, Kelsey Hodgson, Thorsten Berger, Andrew Wakeham, Luis Palomero, Mar Garcia-Valero, Miguel A Pujana, Tak W Mak, Tracy L McGaha, Paola Cappello, Chiara Gorrini
The combination of immune checkpoint blockade with chemotherapy is currently under investigation as a promising strategy for the treatment of triple negative breast cancer (TNBC). Tumor-associated macrophages (TAMs) are the most prominent component of the breast cancer microenvironment because they influence tumor progression and the response to therapies. Here we show that macrophages acquire an immunosuppressive phenotype and increase the expression of programmed death ligand-1 (PD-L1) when treated with reactive oxygen species (ROS) inducers such as the glutathione synthesis inhibitor, buthionine sulphoximine (BSO), and paclitaxel...
February 15, 2019: Proceedings of the National Academy of Sciences of the United States of America
(no author information available yet)
Mutant p53-specific T cells were isolated from patients with metastatic epithelial cancers.
February 15, 2019: Cancer Discovery
(no author information available yet)
Researchers have isolated a mix of 11 strains of bacteria that increase the effectiveness of checkpoint inhibitors in mice. The bacteria boosted IFNγ+ CD8+ T-cell counts and enhanced anti-PD-1 and anti-CTLA4 treatments in mice implanted with colon cancer or melanoma cells, findings that could have implications for patient care.
February 15, 2019: Cancer Discovery
Hampartsoum B Barsoumian, Lalit Batra, Pradeep Shrestha, William S Bowen, Hong Zhao, Nejat K Egilmez, Jorge G Gomez-Gutierrez, Esma S Yolcu, Haval Shirwan
: Costimulation through 4-1BB (CD137) receptor generates robust CD8+ T-effector and memory responses. The only known ligand, 4-1BBL, is a trimeric transmembrane protein that has no costimulatory activity as a soluble molecule. Thus, agonistic antibodies to the receptor have been used for cancer immunotherapy in preclinical models and are currently being evaluated in the clinic. Here, we report that treatment with an oligomeric form of the ligand, SA-4-1BBL, as a single agent is able to protect mice against subsequent tumor challenge irrespective of the tumor type...
February 15, 2019: Cancer Research
Duncan Murray, Jack Luke McMurray, Suzy Eldershaw, Hayden Pearce, Nathaniel Davies, Julia J Scarisbrick, Paul Moss
Immunotherapy is a valuable treatment for many cancer patients, and there is considerable interest in understanding the mechanisms of immune evasion to guide appropriate management. Mycosis fungoides (MF) is a malignant disorder of skin-homing CD4+ T cells, and it exhibits a highly variable clinical course during which the tumor-specific immune response may be an important determinant. An unusual feature of MF is that tumor-infiltrating lymphocytes (TILs) must attempt to control a malignant cell from within their own lineage...
February 26, 2019: Blood Advances
Kyung Hae Jung, Patricia M LoRusso, Howard A Burris, Michael S Gordon, Yung-Jue Bang, Matthew D Hellmann, Andres Cervantes, Maria Ochoa de Olza, Aurélien Marabelle, F Stephen Hodi, Myung-Ju Ahn, Leisha A Emens, Fabrice Barlesi, Omid Hamid, Emiliano Calvo, David F McDermott, Hatem Soliman, Ina Rhee, Ray Lin, Tony Pourmohamad, Julia Suchomel, Amy Tsuhako, Kari M Morrissey, Sami Mahrus, Roland Morley, Andrea Pirzkall, S Lindsey Davis
PURPOSE: IDO1 induces immune suppression in T cells through L-tryptophan (Trp) depletion and kyneurinine (Kyn) accumulation in the local tumor microenvironment, suppressing effector T-cells and hyperactivating Tregs. Navoximod is an investigational small molecule inhibitor of IDO1. This Phase I study evaluated safety, tolerability, PK and PD of navoximod in combination with atezolizumab, a PD-L1 inhibitor, in patients with advanced cancer. EXPERIMENTAL DESIGN: The study consisted of a 3+3 dose-escalation stage (n=66) and a tumor-specific expansion stage (n=92)...
February 15, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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