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https://www.readbyqxmd.com/read/29342325/the-neuromuscular-complications-of-immune-checkpoint-inhibitor-therapy
#1
REVIEW
Noah A Kolb, Christopher R Trevino, Waqar Waheed, Fatemeh Sobhani, Kara K Landry, Alissa A Thomas, Mike Hehir
Immune checkpoint inhibitor (ICPI) therapy unleashes the body's natural immune system to fight cancer. ICPIs improve overall cancer survival, however the unbridling of the immune system may induce a variety of immune related adverse events. Neuromuscular immune complications are rare but they can be severe. Myasthenia gravis and inflammatory neuropathy are the most common neuromuscular adverse events but a variety of others including inflammatory myopathy are reported. The pathophysiologic mechanism of these autoimmune disorders may differ from that of non-ICPI related immune diseases...
January 17, 2018: Muscle & Nerve
https://www.readbyqxmd.com/read/29342309/prognostic-power-of-a-tumor-differentiation-gene-signature-for-bladder-urothelial-carcinomas
#2
Qianxing Mo, Fotis Nikolos, Fengju Chen, Zoe Tramel, Yu-Cheng Lee, Kazukuni Hayashi, Jing Xiao, Jianjun Shen, Keith Syson Chan
Background: Muscle-invasive bladder cancers (MIBCs) cause approximately 150 000 deaths per year worldwide. Survival for MIBC patients is heterogeneous, with no clinically validated molecular markers that predict clinical outcome. Non-MIBCs (NMIBCs) generally have favorable outcome; however, a portion progress to MIBC. Hence, development of a prognostic tool that can guide decision-making is crucial for improving clinical management of bladder urothelial carcinomas. Methods: Tumor grade is defined by pathologic evaluation of tumor cell differentiation, and it often associates with clinical outcome...
January 12, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29341936/rheumatic-manifestations-among-cancer-patients-treated-with-immune-checkpoint-inhibitors
#3
REVIEW
Merav Lidar, Eitan Giat, Daniela Garelick, Yuval Horowitz, Howard Amital, Yael Steinberg-Silman, Jacob Shachter, Ronnie Shapira-Frommer, Gal Markel
BACKGROUND: The use of immune checkpoint inhibitors (ICI) has grown incessantly since they were first approved in 2014. These monoclonal antibodies inhibit T cell activation, yielding a dramatic tumor response with improved survival. However, immunotherapy is frequently hampered by immune adverse events (iAE) such as hypophysitis, colitis, hepatitis, pneumonitis and rash. Until recently, rheumatic side effects were only infrequently reported. Aim To describe the rheumatic manifestations encountered among patients treated with ICIs in a large tertiary cancer center in Israel METHODS: The cancer center's patient registry was screened for patients who had ever been treated with ipilimumab, pembrolizumab and/or nivolumab with relevant data gathered from clinical charts...
January 13, 2018: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29341162/impact-of-genomics-on-the-surgical-management-of-melanoma
#4
REVIEW
P M Ferguson, G V Long, R A Scolyer, J F Thompson
BACKGROUND: Although surgery for early-stage melanoma offers the best chance of cure, recent advances in molecular medicine have revolutionized the management of late-stage melanoma, leading to significant improvements in clinical outcomes. Research into the genomic drivers of disease and cancer immunology has not only ushered in a new era of targeted and immune-based therapies for patients with metastatic melanoma, but has also provided new tools for monitoring disease recurrence and selecting therapeutic strategies...
January 2018: British Journal of Surgery
https://www.readbyqxmd.com/read/29340907/harnessing-a-different-dependency-how-to-identify-and-target-androgen-receptor-positive-versus-quadruple-negative-breast-cancer
#5
REVIEW
Jessica L Christenson, Jane B Trepel, Haythem Y Ali, Sunmin Lee, Joel R Eisner, Edwina S Baskin-Bey, Anthony D Elias, Jennifer K Richer
The androgen receptor (AR) is a promising therapeutic target for a subset of triple-negative breast cancers (TNBCs) in which AR is expressed. However, the mechanistic action of AR and the degree to which primary and metastatic tumors depend on AR, both before and after conventional treatment, remain to be defined. We discuss preclinical and clinical data for AR+ TNBC, the difficulties in monitoring AR protein levels, new methods for determining AR status, the influence of AR on "stemness" in the context of TNBC, the role of combined inhibition of sex steroid production and AR, and the role of AR in regulation of the immune system...
January 16, 2018: Hormones & Cancer
https://www.readbyqxmd.com/read/29340837/exacerbation-of-autoimmune-hemolytic-anemia-induced-by-the-first-dose-of-programmed-death-1-inhibitor-pembrolizumab-a-case-report
#6
Kenta Ogawa, Jiro Ito, Daichi Fujimoto, Mari Morita, Yuko Yoshizumi, Koichi Ariyoshi, Keisuke Tomii, Nobuyuki Katakami
Immune checkpoint inhibitors (ICIs) have demonstrated efficacy against various types of cancers. In addition to immune-related adverse events (irAEs) induced by ICIs, exacerbation of baseline autoimmune disease has been occasionally reported. This is the first report of autoimmune hemolytic anemia (AIHA) exacerbated by pembrolizumab. An 82-year-old Japanese male was diagnosed with lung adenocarcinoma 2 years ago. The patient had chronic anemia with positive direct and indirect Coombs test prior to initiating pembrolizumab therapy at a nearby hospital...
January 16, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29340102/the-impact-of-antibiotic-usage-on-the-efficacy-of-chemoimmunotherapy-is-contingent-on-the-source-of-tumor-reactive-t-cells
#7
Michal P Kuczma, Zhi-Chun Ding, Tao Li, Tsadik Habtetsion, Tingting Chen, Zhonglin Hao, Locke Bryan, Nagendra Singh, James N Kochenderfer, Gang Zhou
In recent years the combined use of chemotherapy and immunotherapy, collectively termed chemoimmunotherapy, has emerged as a promising treatment option for patients with cancer. Antibiotics are commonly used to reduce infection-related complications in patients undergoing chemotherapy. Intriguingly, accumulating evidence has implicated gut microbiota as a critical determinant of host antitumor immune responses, raising the question as to whether the use of broad-spectrum antibiotics would invariably diminish tumor response to chemoimmunotherapies...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339738/dna-methyltransferase-inhibition-upregulates-mhc-i-to-potentiate-cytotoxic-t-lymphocyte-responses-in-breast-cancer
#8
Na Luo, Mellissa J Nixon, Paula I Gonzalez-Ericsson, Violeta Sanchez, Susan R Opalenik, Huili Li, Cynthia A Zahnow, Michael L Nickels, Fei Liu, Mohammed N Tantawy, Melinda E Sanders, H Charles Manning, Justin M Balko
Potentiating anti-tumor immunity by inducing tumor inflammation and T cell-mediated responses are a promising area of cancer therapy. Immunomodulatory agents that promote these effects function via a wide variety of mechanisms, including upregulation of antigen presentation pathways. Here, we show that major histocompatibility class-I (MHC-I) genes are methylated in human breast cancers, suppressing their expression. Treatment of breast cancer cell lines with a next-generation hypomethylating agent, guadecitabine, upregulates MHC-I expression in response to interferon-γ...
January 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29339567/erythrocyte-membrane-coated-gold-nanocages-for-targeted-photothermal-and-chemical-cancer-therapy
#9
Dao-Ming Zhu, Wei Xie, Yu-Sha Xiao, Meng Suo, Ming-Hui Zan, Qing-Quan Liao, Xue-Jia Hu, Li-Ben Chen, Bei Chen, Wen-Tao Wu, Li-Wei Ji, Hui-Ming Huang, Shi-Shang Guo, Xing-Zhong Zhao, Quan-Yan Liu, Wei Liu
Recently, red blood cell (RBC) membrane-coated nanoparticles have attracted much attention because of their excellent immune escapability; meanwhile, gold nanocages (AuNs) have been extensively used for cancer therapy due to their photothermal effect and drug delivery capability. The combination of the RBC membrane coating and AuNs may provide an effective approach for targeted cancer therapy. However, few reports have shown the utilization of combining these two technologies. Here, we design erythrocyte membrane-coated gold nanocages for targeted photothermal and chemical cancer therapy...
January 17, 2018: Nanotechnology
https://www.readbyqxmd.com/read/29339449/targeting-irf3-as-a-yap-agonist-therapy-against-gastric-cancer
#10
Shi Jiao, Jingmin Guan, Min Chen, Wenjia Wang, Chuanchuan Li, Yugong Wang, Yunfeng Cheng, Zhaocai Zhou
The Hippo pathway plays a vital role in tissue homeostasis and tumorigenesis. The transcription factor IRF3 is essential for innate antiviral immunity. In this study, we discovered IRF3 as an agonist of Yes-associated protein (YAP). The expression of IRF3 is positively correlated with that of YAP and its target genes in gastric cancer; the expression of both IRF3 and YAP is up-regulated and prognosticates patient survival. IRF3 interacts with both YAP and TEAD4 in the nucleus to enhance their interaction, promoting nuclear translocation and activation of YAP...
January 16, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29339440/repurposing-tin-mesoporphyrin-as-an-immune-checkpoint-inhibitor-shows-therapeutic-efficacy-in-preclinical-models-of-cancer
#11
Tamara Muliaditan, James W Opzoomer, Jonathan Caron, Mary Okesola, Paris Kosti, Sharanpreet Lall, Mieke Van Hemelrijck, Francesco Dazzi, Andrew Tutt, Anita Grigoriadis, Cheryl Gillett, Stephen F Madden, Joy M Burchell, Shahram Kordasti, Sandra S Diebold, James Spicer, James N Arnold
PURPOSE: Unprecedented clinical outcomes have been achieved in a variety of cancers by targeting immune checkpoint molecules. This preclinical study investigates heme oxygenase-1 (HO-1), an immune suppressive enzyme that is expressed in a wide variety of cancers, as a potential immune checkpoint target in the context of a chemotherapy-elicited anti-tumor immune response. We evaluate repurposing tin mesoporphyrin (SnMP), which has demonstrated safety and efficacy targeting hepatic HO in the clinic for the treatment of hyperbilirubinaemia, as an immune checkpoint blockade therapy for the treatment of cancer...
January 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29339377/robust-antitumor-responses-result-from-local-chemotherapy-and-ctla-4-blockade
#12
Charlotte E Ariyan, Mary Sue Brady, Robert H Siegelbaum, Jian Hu, Danielle M Bello, Jamie Green, Charles Fisher, Robert A Lefkowitz, Katherine S Panageas, Melissa Pulitzer, Marissa Vignali, Ryan Emerson, Christopher Tipton, Harlan Robins, Taha Merghoub, Jianda Yuan, Achim Jungbluth, Jorge Blando, Padmanee Sharma, Alexander Y Rudensky, Jedd D Wolchok, James P Allison
Clinical responses to immunotherapy have been associated with augmentation of preexisting immune responses, manifested by heightened inflammation in the tumor microenvironment. However, many tumors have a non-inflamed microenvironment, and response rates to immunotherapy in melanoma have been <50%. We approached this problem by utilizing immunotherapy (CTLA-4 blockade) combined with chemotherapy to induce local inflammation. In murine models of melanoma and prostate cancer, the combination of chemotherapy and CTLA-4 blockade induced a shift in the cellular composition of the tumor microenvironment, with infiltrating CD8+ and CD4+ T cells increasing the CD8/Foxp3 T-cell ratio...
January 16, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29339375/tusc2-immunogene-synergizes-with-anti-pd1-through-enhanced-proliferation-and-infiltration-of-natural-killer-cells-in-syngeneic-kras-mutant-mouse-lung-cancer-models
#13
Ismail M Meraz, Mourad Majidi, Xiaobo Cao, Heather Lin, Lerong Li, Jing Wang, Veerabhadran Baladandayuthapani, David Rice, Boris Sepesi, Lin Ji, Jack A Roth
Expression of the multikinase inhibitor encoded by tumor suppressor gene TUSC2 (also known as FUS1) is lost or decreased in non-small cell lung carcinoma (NSCLC). TUSC2 delivered systemically by nanovesicles has mediated tumor regression in clinical trials. Because of the role of TUSC2 in regulating immune cells, we assessed TUSC2 efficacy on antitumor immune responses alone and in combination with anti-PD-1 in two Kras-mutant syngeneic mouse lung cancer models. TUSC2 alone significantly reduced tumor growth and prolonged survival compared with anti-PD-1...
January 16, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29339144/addressing-barriers-to-effective-cancer-immunotherapy-with-nanotechnology-achievements-challenges-and-roadmap-to-the-next-generation-of-nanoimmunotherapeutics
#14
Enping Hong, Marina A Dobrovolskaia
Cancer is a complex systemic disorder that affects many organs and tissues and arises from the altered function of multiple cellular and molecular mechanisms. One of the systems malfunctioning in cancer is the immune system. Restoring and improving the ability of the immune system to effectively recognize and eradicate cancer is the main focus of immunotherapy, a topic which has garnered recent and significant interest. The initial excitement about immunotherapy, however, has been challenged by its limited efficacy in certain patient populations and the development of adverse effects such as therapeutic resistance and autoimmunity...
January 12, 2018: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29338610/cns-side-effects-of-immune-checkpoint-inhibitors-preclinical-models-genetics-and-multimodality-therapy
#15
Gwendolyn J McGinnis, Jacob Raber
Following cancer treatment, patients often report behavioral and cognitive changes. Novel cancer immunotherapeutics have the potential to produce sustained cancer survivorship, meaning patients will live longer with the side effects of treatment. Given the role of inflammatory pathways in mediating behavioral and cognitive impairments seen in cancer, we aim in this review to discuss emerging evidence for the contribution of immune checkpoint blockade to exacerbate these CNS effects. We discuss ongoing studies regarding the ability of immune checkpoint inhibitors to reach the brain and how treatment responses to checkpoint inhibitors may be modulated by genetic factors...
September 2017: Immunotherapy
https://www.readbyqxmd.com/read/29337640/molecular-determinants-of-response-to-anti-programmed-cell-death-pd-1-and-anti-programmed-death-ligand-pd-l-ligand-1-blockade-in-patients-with-non-small-cell-lung-cancer-profiled-with-targeted-next-generation-sequencing
#16
Hira Rizvi, Francisco Sanchez-Vega, Konnor La, Walid Chatila, Philip Jonsson, Darragh Halpenny, Andrew Plodkowski, Niamh Long, Jennifer L Sauter, Natasha Rekhtman, Travis Hollmann, Kurt A Schalper, Justin F Gainor, Ronglai Shen, Ai Ni, Kathryn C Arbour, Taha Merghoub, Jedd Wolchok, Alexandra Snyder, Jamie E Chaft, Mark G Kris, Charles M Rudin, Nicholas D Socci, Michael F Berger, Barry S Taylor, Ahmet Zehir, David B Solit, Maria E Arcila, Marc Ladanyi, Gregory J Riely, Nikolaus Schultz, Matthew D Hellmann
Purpose Treatment of advanced non-small-cell lung cancer with immune checkpoint inhibitors (ICIs) is characterized by durable responses and improved survival in a subset of patients. Clinically available tools to optimize use of ICIs and understand the molecular determinants of response are needed. Targeted next-generation sequencing (NGS) is increasingly routine, but its role in identifying predictors of response to ICIs is not known. Methods Detailed clinical annotation and response data were collected for patients with advanced non-small-cell lung cancer treated with anti-programmed death-1 or anti-programmed death-ligand 1 [anti-programmed cell death (PD)-1] therapy and profiled by targeted NGS (MSK-IMPACT; n = 240)...
January 16, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29337566/cationic-polymeric-nanoparticle-delivering-ccr2-sirna-to-inflammatory-monocytes-for-tumor-microenvironment-modification-and-cancer-therapy
#17
Song Shen, Yue Zhang, Kai-Ge Chen, Ying-Li Luo, Jun Wang
Accumulating evidence has confirmed that malignant tumors have a complex microenvironment, which consists of a heterogeneous collection of tumor cells and other cell subsets (including the full gamut of immune cells). Tumor-associated macrophages (TAMs), derived from circulating Ly6Chi monocytes, constitute the most substantial fraction of tumor-infiltrating immune cells in nearly all cancer types and contribute to tumor progression, vascularization, metastasis, immunosuppression and therapeutic resistance...
January 16, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29337457/-pharmacovigilance-update
#18
Françoise Livio
The main pharmacovigilance updates in 2017 are reviewed. Denosumab : rebound-associated multiple vertebral fractures after discontinuation. Canagliflozine: increased risk of foot/leg amputations. Biologic and targeted cancer therapies, direct-acting antivirals for chronic hepatitis C: risk of hepatitis B reactivation. Checkpoint inhibitors : immune-related adverse events and graft rejection. Fingolimod : rebound-associated reactivation of MS following withdrawal. Daclizumab: risk of severe liver injury leading to restricted use in MS patients...
January 10, 2018: Revue Médicale Suisse
https://www.readbyqxmd.com/read/29337311/dinaciclib-induces-immunogenic-cell-death-and-enhances-anti-pd-1-mediated-tumor-suppression
#19
Dewan Md Sakib Hossain, Sarah Javaid, Mingmei Cai, Chunsheng Zhang, Anandi Sawant, Marlene Hinton, Manjiri Sathe, Jeff Grein, Wendy Blumenschein, Elaine M Pinheiro, Alissa Chackerian
Blockade of the checkpoint inhibitor programmed death 1 (PD1) has demonstrated remarkable success in the clinic for the treatment of cancer; however, a majority of tumors are resistant to anti-PD1 monotherapy. Numerous ongoing clinical combination therapy studies will likely reveal additional therapeutics that complement anti-PD1 blockade. Recent studies found that immunogenic cell death (ICD) improves T cell responses against different tumors, thus indicating that ICD may further augment antitumor immunity elicited by anti-PD1...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29337259/mathematical-modeling-of-tumor-induced-immunosuppression-by-myeloid-derived-suppressor-cells-implications-for-therapeutic-targeting-strategies
#20
Seyed Peyman Shariatpanahi, Seyed Pooya Shariatpanahi, Keivan Madjidzadeh, Moustapha Hassan, Manuchehr Abedi-Valugerdi
Myeloid-derived suppressor cells (MDSCs) belong to immature myeloid cells that are generated and accumulated during the tumor development. MDSCs strongly suppress the anti-tumor immunity and provide conditions for tumor progression and metastasis. In this study, we present a mathematical model based on ordinary differential equations (ODE) to describe tumor-induced immunosuppression caused by MDSCs. The model consists of four equations and incorporates tumor cells, cytotoxic T cells (CTLs), natural killer (NK) cells and MDSCs...
January 11, 2018: Journal of Theoretical Biology
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