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Anti-tumor response

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https://www.readbyqxmd.com/read/28227912/a-hybrid-discrete-continuous-model-of-in-vitro-spheroid-tumor-growth-and-drug-response
#1
Giorgos Tzedakis, Evangelos Liapis, Eleftheria Tzamali, Giannis Zacharakis, Vangelis Sakkalis, Giorgos Tzedakis, Evangelos Liapis, Eleftheria Tzamali, Giannis Zacharakis, Vangelis Sakkalis, Giannis Zacharakis, Vangelis Sakkalis, Evangelos Liapis, Giorgos Tzedakis, Eleftheria Tzamali
Anti-cancer therapy efficacy in solid tumors mainly depends on drug transportation through the vasculature system and the extracellular matrix, on diffusion gradients and clonal heterogeneity within the tumor mass, as well as on the responses of the individual tumor cells to drugs and their interactions with each other and their local microenvironment. In this work, we develop a mathematical predictive model for tumor growth and drug response based on 3D spheroids experiments that possess several in vivo features of tumors and are considered better for drug screening...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28227433/microprinted-tumor-spheroids-enable-anti-cancer-drug-screening
#2
Pradip S Thakuri, Stephanie L Ham, Hossein Tavana, Pradip S Thakuri, Stephanie L Ham, Hossein Tavana, Stephanie L Ham, Hossein Tavana
Spheroids present a biologically relevant model of avascular tumors and a unique tool for discovery of anti-cancer drugs. Despite being used in research laboratories for several decades, spheroids are not routinely used for drug discovery primarily due to the difficulty of mass-producing uniformly-sized spheroids and intense labor involved in handling, drug treatment, and analyzing them. We overcome this barrier using a novel technology to robotically microprint spheroids in standard 384-well plates. An aqueous drop containing cancer cells is dispensed into a bath of a second, immiscible aqueous phase...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28225051/low-muscle-mass-at-initiation-of-anti-tnf-therapy-for-inflammatory-bowel-disease-is-associated-with-early-treatment-failure-a-retrospective-analysis
#3
D Q Holt, P Varma, B J G Strauss, A S Rajadurai, G T Moore
BACKGROUND/OBJECTIVES: Delayed treatment failure occurs in a significant proportion of inflammatory bowel disease (IBD) patients treated with tumor necrosis factor-alpha (TNF) antagonists. Identification of predictors of loss of response (LOR) may help to optimize therapy. We sought to determine whether body composition parameters at the commencement of anti-TNF therapy were associated with earlier treatment failure. SUBJECTS/METHODS: A retrospective cohort study was performed on 68 patients who had undergone cross-sectional abdominal imaging coincident with the commencement of anti-TNF drugs...
February 22, 2017: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28224333/anti-neuroinflammatory-effects-of-grossamide-from-hemp-seed-via-suppression-of-tlr-4-mediated-nf-%C3%AE%C2%BAb-signaling-pathways-in-lipopolysaccharide-stimulated-bv2-microglia-cells
#4
Qian Luo, Xiaoli Yan, Larisa Bobrovskaya, Mei Ji, Huiqing Yuan, Hongxiang Lou, Peihong Fan
Grossamide, a representative lignanamide in hemp seed, has been reported to possess potential anti-inflammatory effects. However, the potential anti-neuroinflammatory effects and underlying mechanisms of action of grossamide are still unclear. Therefore, the present study investigated the possible effects and underlying mechanisms of grossamide against lipopolysaccharide (LPS)-induced inflammatory response in BV2 microglia cells. BV2 microglia cells were pre-treated with various concentrations of grossamide before being stimulated with LPS to induce inflammation...
February 21, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28224210/tumor-specific-regulatory-t-cells-in-the-bone-marrow-of-breast-cancer-patients-selectively-upregulate-the-emigration-receptor-s1p1
#5
Anchana Rathinasamy, Christoph Domschke, Yingzi Ge, Hans-Henning Böhm, Steffen Dettling, David Jansen, Felix Lasitschka, Ludmila Umansky, Markus H Gräler, Jennifer Hartmann, Christel Herold-Mende, Florian Schuetz, Philipp Beckhove
Regulatory T cells (Treg) hamper anti-tumor T-cell responses resulting in reduced survival and failure of cancer immunotherapy. Among lymphoid organs, the bone marrow (BM) is a major site of Treg residence and recirculation. However, the process governing the emigration of Treg from BM into the circulation remains elusive. We here show that breast cancer patients harbour reduced Treg frequencies in the BM as compared to healthy individuals or the blood. This was particularly the case for tumor antigen-specific Treg which were quantified by MHCII tumor peptide loaded tetramers...
February 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28223726/dendritic-cells-engineered-to-secrete-anti-dcr3-antibody-augment-cytotoxic-t-lymphocyte-response-against-pancreatic-cancer-in-vitro
#6
Jiang Chen, Xiao-Zhong Guo, Hong-Yu Li, Jia-Jun Zhao, Wen-Da Xu
AIM: To investigate the enhanced cytotoxic T lymphocyte responses against pancreatic cancer (PC) in vitro induced by dendritic cells (DCs) engineered to secrete anti-DcR3 monoclonal antibody (mAb). METHODS: DCs, T lymphocytes and primary PC cells were obtained from PC patients. DCs were transfected with a designed humanized anti-DcR3 monoclonal antibody heavy and light chain mRNA and/or total tumor RNA (DC-tumor-anti-DcR3 RNA or DC-total tumor RNA) by using electroporation technology...
February 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28223539/thymol-mitigates-lipopolysaccharide-induced-endometritis-by-regulating-the-tlr4-and-ros-mediated-nf-%C3%AE%C2%BAb-signaling-pathways
#7
Haichong Wu, Kangfeng Jiang, Nannan Yin, Xiaofei Ma, Gan Zhao, Changwei Qiu, Ganzhen Deng
The purpose of this study was to investigate the effects of thymol on lipopolysaccharide (LPS)-induced inflammatory responses and to clarify the potential mechanism of these effects. LPS-induced mouse endometritis was used to confirm the anti-inflammatory action of thymol in vivo. RAW264.7 cells were used to examine the molecular mechanism and targets of thymol in vitro. In vivo, thymol markedly alleviated LPS-induced pathological injury, myeloperoxidase (MPO) activity, and the production of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in mice...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28223426/resistance-mechanism-against-trastuzumab-in-her2-positive-cancer-cells-and-its-negation-by-src-inhibition
#8
Mei Hua Jin, Ah-Rong Nam, Ji Eun Park, Ju-Hee Bang, Yung-Jue Bang, Do-Youn Oh
Trastuzumab in combination with chemotherapy is the standard of care for patients with human epidermal growth factor receptor 2 (HER2)-positive breast and gastric cancers. Several resistance mechanisms against anti-HER2 therapy have been proposed. Src activation has been suggested to be responsible for the resistance of HER2-positive breast cancer. In our study, we generated four trastuzumab-resistant (HR) cancer cell lines from HER2-amplified gastric and biliary tract cancer cell lines (SNU-216, NCI-N87, SNU-2670, and SNU-2773)...
February 21, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28223062/nivolumab-for-previously-treated-unresectable-metastatic-anal-cancer-nci9673-a-multicentre-single-arm-phase-2-study
#9
Van K Morris, Mohamed E Salem, Halla Nimeiri, Syma Iqbal, Preet Singh, Kristen Ciombor, Blase Polite, Dustin Deming, Emily Chan, James L Wade, Lianchun Xiao, Tanios Bekaii-Saab, Luis Vence, Jorge Blando, Armeen Mahvash, Wai Chin Foo, Chimela Ohaji, Manolo Pasia, Gail Bland, Aki Ohinata, Jane Rogers, Amir Mehdizadeh, Kimberly Banks, Richard Lanman, Robert A Wolff, Howard Streicher, James Allison, Padmanee Sharma, Cathy Eng
BACKGROUND: Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy associated with infection by human papillomavirus (HPV). No consensus treatment approach exists for the treatment of metastatic disease. Because intratumoral HPV oncoproteins upregulate immune checkpoint proteins such as PD-1 to evade immune-mediated cytotoxicity, we did a trial of the anti-PD-1 antibody nivolumab for patients with metastatic SCCA. METHODS: We did this single-arm, multicentre, phase 2 trial at ten academic centres in the USA...
February 17, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28222333/immunoprofiling-as-a-predictor-of-patient-s-response-to-cancer-therapy-promises-and-challenges
#10
REVIEW
Daniel Bethmann, Zipei Feng, Bernard A Fox
Immune cell infiltration is common to many tumors and has been recognized by pathologists for more than 100 years. The application of digital imaging and objective assessment software allowed a concise determination of the type and quantity of immune cells and their location relative to the tumor and, in the case of colon cancer, characterized overall survival better than AJCC TNM staging. Subsequently, expression of PD-L1, by 50% or more tumor cells, identified NSCLC patients with double the response rate to anti-PD-1...
February 18, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28220199/-novel-pharmaceutical-treatment-approaches-for-gastric-cancer
#11
F Lordick
This review article delineates novel approaches for the pharmaceutical treatment of gastric cancer. A newly developed molecular classification of gastric cancer based on histology, genetic, epigenetic and proteomic characteristics has evolved. It provides a road map for development of new drugs and combinations as well as for patient stratification in clinical research and it is expected to be introduced into clinical practice in the near future. Anti-HER2 targeted treatment is a validated strategy for treatment of metastatic gastric cancer and is now also being studied in the perioperative setting to increase response rates and ultimately survival in patients undergoing curative surgery; however, the resistance mechanisms of HER2-targeted treatment are poorly understood and optimal patient selection remains challenging...
February 20, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28219722/regulation-and-control-of-nitric-oxide-no-in-macrophages-protecting-the-professional-killer-cell-from-its-own-cytotoxic-arsenal-via-mrp1-and-gstp1
#12
REVIEW
Z Kovacevic, S Sahni, H Lok, M J Davies, D A Wink, D R Richardson
We recently demonstrated that a novel storage and transport mechanism for nitric oxide (NO) mediated by glutathione-S-transferase P1 (GSTP1) and multidrug resistance protein 1 (MRP1/ABCC1), protects M1-macrophage (M1-MØ) models from large quantities of endogenous NO. This system stores and transports NO as dinitrosyl-dithiol-iron complexes (DNICs) composed of iron, NO and glutathione (GSH). Hence, this gas with contrasting anti- and pro-tumor effects, which has been assumed to be a freely diffusible, is a tightly-regulated species in M1-MØs...
February 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28219421/regulation-of-voltage-gated-potassium-channels-attenuates-resistance-of-side-population-cells-to-gefitinib-in-the-human-lung-cancer-cell-line-nci-h460
#13
Seon Young Choi, Hang-Rae Kim, Pan Dong Ryu, So Yeong Lee
BACKGROUND: Side-population (SP) cells that exclude anti-cancer drugs have been found in various tumor cell lines. Moreover, SP cells have a higher proliferative potential and drug resistance than main population cells (Non-SP cells). Also, several ion channels are responsible for the drug resistance and proliferation of SP cells in cancer. METHODS: To confirm the expression and function of voltage-gated potassium (Kv) channels of SP cells, these cells, as well as highly expressed ATP-binding cassette (ABC) transporters and stemness genes, were isolated from a gefitinib-resistant human lung adenocarcinoma cell line (NCI-H460), using Hoechst 33342 efflux...
February 21, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28219202/-precision-treatment-after-resistance-to-first-generation-egfr-tki-in-patients-with-non-small-cell-lung-cancer
#14
C Pi, Y C Zhang, C R Xu, Q Zhou
Recently, with the research progress in molecular classification, the treatment of advanced non-small cell lung cancer (NSCLC) has been established as a model of anti-tumor treatment of precision medicine. The discovery of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) has transformed the treatment of NSCLC from platinum based doublet chemotherapy into era of target therapy. EGFR-TKI, such as erlotinib and gefitinib, have been recommended as standard first-line treatment of patients with EGFR mutation...
February 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28218903/macrophage-migration-inhibitory-factor-downregulation-a-novel-mechanism-of-resistance-to-anti-angiogenic-therapy
#15
B A Castro, P Flanigan, A Jahangiri, D Hoffman, W Chen, R Kuang, M De Lay, G Yagnik, J R Wagner, S Mascharak, M Sidorov, S Shrivastav, G Kohanbash, H Okada, M K Aghi
Anti-angiogenic therapies for cancer such as VEGF neutralizing antibody bevacizumab have limited durability. While mechanisms of resistance remain undefined, it is likely that acquired resistance to anti-angiogenic therapy will involve alterations of the tumor microenvironment. We confirmed increased tumor-associated macrophages in bevacizumab-resistant glioblastoma patient specimens and two novel glioblastoma xenograft models of bevacizumab resistance. Microarray analysis suggested downregulated macrophage migration inhibitory factor (MIF) to be the most pertinent mediator of increased macrophages...
February 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28218497/chemotherapy-induces-tumor-immune-evasion-by-upregulation-of-programmed-cell-death-ligand%C3%A2-1-expression-in-bone-marrow-stromal-cells
#16
Mengqi Yang, Panpan Liu, Kefeng Wang, Christophe Glorieux, Yumin Hu, Shijun Wen, Wenqi Jiang, Peng Huang
Programmed cell death ligand 1 (PD-L1) is a negative regulator of the immune response that enables tumor cells to escape T-cell immunity. Although PD-L1 expression in cancer cells has been extensively studied, the expression of PD-L1 in stromal cells and its clinical significance remain largely unknown. Here, we show that bone marrow stromal cells express a low level of PD-L1 and that this molecule is significantly upregulated by key drugs used in the treatment of lymphoma at clinically relevant concentrations...
December 28, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28218039/demethylation-and-alterations-in-the-expression-level-of-the-cell-cycle-related-genes-as-possible-mechanisms-in-arsenic-trioxide-induced-cell-cycle-arrest-in-human-breast-cancer-cells
#17
Farima Moghaddaskho, Haniyeh Eyvani, Mohsen Ghadami, Javad Tavakkoly-Bazzaz, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
Arsenic trioxide (As2O3) has been used clinically as an anti-tumor agent. Its mechanisms are mostly considered to be the induction of apoptosis and cell cycle arrest. However, the detailed molecular mechanisms of its anti-cancer action through cell cycle arrest are poorly known. Furthermore, As2O3 has been shown to be a potential DNA methylation inhibitor, inducing DNA hypomethylation. We hypothesize that As2O3 may affect the expression of cell cycle regulatory genes by interfering with DNA methylation patterns...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28217371/pathogenic-mechanisms-of-pancreatitis
#18
REVIEW
Murli Manohar, Alok Kumar Verma, Sathisha Upparahalli Venkateshaiah, Nathan L Sanders, Anil Mishra
Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pancreatitis characterized by marked stroma formation with a high number of infiltrating granulocytes (such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells (PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i...
February 6, 2017: World Journal of Gastrointestinal Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28216876/wheatgrass-extract-ameliorates-hypoxia-induced-mucin-gene-expression-in-a549-cells
#19
Ju Hwan Sim, Moon-Hee Choi, Hyun-Jae Shin, Ji-Eun Lee
BACKGROUND: Wheatgrass is known to have antioxidant, antiaging, and anti-inflammatory effect. However, its protective effect against hypoxia is not yet evaluated. OBJECTIVE: In this study, we evaluated the protective and anti-inflammatory effect of wheatgrass against the hypoxia in airway epithelial cells. MATERIALS AND METHODS: A549 human lung adenocarcinoma cells were incubated in a hypoxic condition (CO2 5%/O2 1%) for 24 hr in the presence of different concentration of wheatgrass 50, 75, 100, and 150 μg/mL, and the magnitude of each immunologic response produced by the A549 cells was compared...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28216579/a-plant-proteinase-inhibitor-from-enterolobium-contortisiliquum-attenuates-pulmonary-mechanics-inflammation-and-remodeling-induced-by-elastase-in-mice
#20
Osmar Aparecido Theodoro-Júnior, Renato Fraga Righetti, Rafael Almeida-Reis, Bruno Tadeu Martins-Oliveira, Leandro Vilela Oliva, Carla Máximo Prado, Beatriz Mangueira Saraiva-Romanholo, Edna Aparecida Leick, Nathalia Montouro Pinheiro, Yara Aparecida Lobo, Mílton de Arruda Martins, Maria Luiza Vilela Oliva, Iolanda de Fátima Lopes Calvo Tibério
Proteinase inhibitors have been associated with anti-inflammatory and antioxidant activities and may represent a potential therapeutic treatment for emphysema. Our aim was to evaluate the effects of a plant Kunitz proteinase inhibitor, Enterolobium contortisiliquum trypsin inhibitor (EcTI), on several aspects of experimental elastase-induced pulmonary inflammation in mice. C57/Bl6 mice were intratracheally administered elastase (ELA) or saline (SAL) and were treated intraperitoneally with EcTI (ELA-EcTI, SAL-EcTI) on days 1, 14 and 21...
February 14, 2017: International Journal of Molecular Sciences
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