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Immune cancer

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https://www.readbyqxmd.com/read/29786888/injectable-bioresponsive-gel-depot-for-enhanced-immune-checkpoint-blockade
#1
Shuangjiang Yu, Chao Wang, Jicheng Yu, Jinqiang Wang, Yue Lu, Yuqi Zhang, Xudong Zhang, Quanyin Hu, Wujin Sun, Chaoliang He, Xuesi Chen, Zhen Gu
Although cancer immunotherapy based on immune checkpoint inhibitors holds great promise toward many types of cancers, several challenges still remain, associated with low objective response of patient rate as well as systemic side effects. Here, a combination immunotherapy strategy is developed based on a thermogelling reactive oxygen species (ROS)-responsive polypeptide gel for sustained release of anti-programmed cell death-ligand 1 antibody and dextro-1-methyl tryptophan, inhibitor of indoleamine-2,3-dioxygenase with leveraging the ROS level in the tumor microenvironment...
May 22, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29786788/transplantable-animal-studies-and-whole-body-optical-imaging-in-prostate-carcinoma
#2
Geertje van der Horst, Maaike van der Mark, Henry Cheung, Gabri van der Pluijm
Current treatments of advanced prostate cancer only marginally increase overall survival and can be regarded as predominantly palliative. Hence, there is an urgent need for novel therapeutic strategies for the treatment of primary tumors and, more importantly perhaps, for the prevention of tumor progression and metastasis formation. Clinically relevant preclinical models are therefore urgently needed. An ideal, clinically relevant preclinical model would mimic the genetic and phenotypic changes that occur at the different stages of human prostate cancer progression and subsequent metastasis...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29786170/immunopeptidomic-profiling-of-hla-a2-positive-triple-negative-breast-cancer-identifies-potential-immunotherapy-target-antigens
#3
Nicola Ternette, Marloes J M Olde Nordkamp, Julius Muller, Amanda P Anderson, Annalisa Nicastri, Adrian V S Hill, Benedikt M Kessler, Demin Li
The recent development in immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cells in the treatment of cancer has not only demonstrated the potency of utilising T-cell reactivity for cancer therapy, but has also highlighted the need for developing new approaches to discover targets suitable for such novel therapeutics. Here we analysed the immunopeptidomes of 6 HLA-A2-positive triple negative breast cancer (TNBC) samples by nano-ultra performance liquid chromatography tandem mass spectrometry (nUPLC-MS2 )...
May 22, 2018: Proteomics
https://www.readbyqxmd.com/read/29786075/tp53-gain-of-function-mutation-promotes-inflammation-in-glioblastoma
#4
Seok Won Ham, Hee-Young Jeon, Xiong Jin, Eun-Jung Kim, Jun-Kyum Kim, Yong Jae Shin, Yeri Lee, Se Hoon Kim, Seon Yong Lee, Sunyoung Seo, Min Gi Park, Hye-Mi Kim, Do-Hyun Nam, Hyunggee Kim
Glioblastoma (GBM), the most severe and common brain tumor in adults, is characterized by multiple somatic mutations and aberrant activation of inflammatory responses. Immune cell infiltration and subsequent inflammation cause tumor growth and resistance to therapy. Somatic loss-of-function mutations in the gene encoding tumor suppressor protein p53 (TP53) are frequently observed in various cancers. However, numerous studies suggest that TP53 regulates malignant phenotypes by gain-of-function (GOF) mutations...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29786070/selective-elimination-of-senescent-cells-by-mitochondrial-targeting-is-regulated-by-ant2
#5
Sona Hubackova, Eliska Davidova, Katerina Rohlenova, Jan Stursa, Lukas Werner, Ladislav Andera, LanFeng Dong, Mikkel G Terp, Zdenek Hodny, Henrik J Ditzel, Jakub Rohlena, Jiri Neuzil
Cellular senescence is a form of cell cycle arrest that limits the proliferative potential of cells, including tumour cells. However, inability of immune cells to subsequently eliminate senescent cells from the organism may lead to tissue damage, inflammation, enhanced carcinogenesis and development of age-related diseases. We found that the anticancer agent mitochondria-targeted tamoxifen (MitoTam), unlike conventional anticancer agents, kills cancer cells without inducing senescence in vitro and in vivo. Surprisingly, it also selectively eliminates both malignant and non-cancerous senescent cells...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29785657/novel-non-invasive-early-detection-of-lung-cancer-using-liquid-immunobiopsy-metabolic-activity-profiles
#6
Yochai Adir, Shoval Tirman, Shirley Abramovitch, Cynthia Botbol, Aviv Lutaty, Tali Scheinmann, Eyal Davidovits, Irit Arbel, Giora Davidovits, Sonia Schneer, Michal Shteinberg, Hagit Peretz Soroka, Ruven Tirosh, Fernando Patolsky
Lung cancer is the leading cause of cancer death worldwide. Survival is largely dependent on the stage of diagnosis: the localized disease has a 5-year survival greater than 55%, whereas, for spread tumors, this rate is only 4%. Therefore, the early detection of lung cancer is key for improving prognosis. In this study, we present an innovative, non-invasive, cancer detection approach based on measurements of the metabolic activity profiles of immune system cells. For each Liquid ImmunoBiopsy test, a 384 multi-well plate is loaded with freshly separated PBMCs, and each well contains 1 of the 16 selected stimulants in several increasing concentrations...
May 21, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29785577/atezolizumab-a-review-in-previously-treated-advanced-non-small-cell-lung-cancer
#7
REVIEW
Hannah A Blair
Atezolizumab (TECENTRIQ™), an immune checkpoint inhibitor, is an immunoglobulin G1 monoclonal antibody that binds to programmed death ligand 1 (PD-L1) and blocks its interactions with programmed death 1 and B7.1 receptors. Atezolizumab is approved as monotherapy in several countries worldwide for the treatment of patients with advanced non-small cell lung cancer (NSCLC) who have previously received chemotherapy. Approval was based on its clinical benefit in this setting in the phase II POPLAR and phase III OAK trials...
May 21, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29785404/enhanced-suppressive-activity-of-regulatory-t-cells-in-the-microenvironment-of-malignant-pleural-effusions
#8
Joanna Budna, Mariusz Kaczmarek, Agata Kolecka-Bednarczyk, Łukasz Spychalski, Piotr Zawierucha, Joanna Goździk-Spychalska, Michał Nowicki, Halina Batura-Gabryel, Jan Sikora
Cancer metastatic spread to serous cavity causes malignant pleural effusions (MPEs), indicating dismal prognosis. Tumor microenvironment can implement suppressive activity on host immune responses. Thus, we investigated the prevalence of Tregs and the relationship between them and TGF- β and IL-10 concentrations and measured expression of FOXP3 , CTLA-4 , CD28 , and GITR genes, as well as protein expression of selected genes in benign effusions and MPEs. The percentage of Tregs was determined by means of multicolor flow cytometry system...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29785403/immunotherapy-for-hepatocellular-carcinoma-current-advances-and-future-expectations
#9
REVIEW
Yingjun Xie, Yien Xiang, Jiyao Sheng, Dan Zhang, Xiaoxiao Yao, Yongsheng Yang, Xuewen Zhang
Primary liver cancer is a common kind of digestive cancers with high malignancy, causing 745,500 deaths each year. Hepatocellular carcinoma is the major pathological type of primary liver cancer. Traditional treatment methods for patients with hepatocellular carcinoma have shown poor efficacy in killing residual cancer cells for a long time. In recent years, tumor immunotherapy has emerged as a promising method owing to its safety and efficacy with respect to delaying the progression of advanced tumors and protecting postoperative patients against tumor relapse and metastasis...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29785173/phytochemicals-that-influence-gut-microbiota-as-prophylactics-and-for-the-treatment-of-obesity-and-inflammatory-diseases
#10
REVIEW
Lucrecia Carrera-Quintanar, Rocío I López Roa, Saray Quintero-Fabián, Marina A Sánchez-Sánchez, Barbara Vizmanos, Daniel Ortuño-Sahagún
Gut microbiota (GM) plays several crucial roles in host physiology and influences several relevant functions. In more than one respect, it can be said that you "feed your microbiota and are fed by it." GM diversity is affected by diet and influences metabolic and immune functions of the host's physiology. Consequently, an imbalance of GM, or dysbiosis, may be the cause or at least may lead to the progression of various pathologies such as infectious diseases, gastrointestinal cancers, inflammatory bowel disease, and even obesity and diabetes...
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29785121/association-between-angiogenesis-and-cytotoxic-signatures-in-the-tumor-microenvironment-of-gastric-cancer
#11
Yi Feng, Ying Dai, Zhihua Gong, Jia-Nan Cheng, Longhui Zhang, Chengdu Sun, Xianghua Zeng, Qingzhu Jia, Bo Zhu
Background: A suppressive immune microenvironment and pathological angiogenesis are hallmarks of gastric cancer. Theoretically, immune checkpoint inhibitors (ICIs) stimulate pre-primed neoantigen-specific T cells, and antiangiogenic agents then facilitate their infiltration into the tumor niche by promoting vascular normalization. Currently, the interconnections of these two phenotypes and their relevance to the tumor microenvironment (TME) have not been fully characterized in gastric cancer...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29785006/the-era-of-immunogenomics-immunopharmacogenomics
#12
REVIEW
Makda Zewde, Kazuma Kiyotani, Jae-Hyun Park, Hua Fang, Kai Lee Yap, Poh Yin Yew, Houda Alachkar, Taigo Kato, Tu H Mai, Yuji Ikeda, Tatsuo Matsuda, Xiao Liu, Lili Ren, Boya Deng, Makiko Harada, Yusuke Nakamura
Although germline alterations and somatic mutations in disease cells have been extensively analyzed, molecular changes in immune cells associated with disease conditions have not been characterized in depth. It is clear that our immune system has a critical role in various biological and pathological conditions, such as infectious diseases, autoimmune diseases, drug-induced skin and liver toxicity, food allergy, and rejection of transplanted organs. The recent development of cancer immunotherapies, particularly drugs modulating the immune checkpoint molecules, has clearly demonstrated the importance of host immune cells in cancer treatments...
May 21, 2018: Journal of Human Genetics
https://www.readbyqxmd.com/read/29784935/a-causal-mechanism-for-childhood-acute-lymphoblastic-leukaemia
#13
REVIEW
Mel Greaves
In this Review, I present evidence supporting a multifactorial causation of childhood acute lymphoblastic leukaemia (ALL), a major subtype of paediatric cancer. ALL evolves in two discrete steps. First, in utero initiation by fusion gene formation or hyperdiploidy generates a covert, pre-leukaemic clone. Second, in a small fraction of these cases, the postnatal acquisition of secondary genetic changes (primarily V(D)J recombination-activating protein (RAG) and activation-induced cytidine deaminase (AID)-driven copy number alterations in the case of ETS translocation variant 6 (ETV6)-runt-related transcription factor 1 (RUNX1)+ ALL) drives conversion to overt leukaemia...
May 21, 2018: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29784888/identification-of-brain-metastasis-genes-and-therapeutic-evaluation-of-histone-deacetylase-inhibitors-in-a-clinically-relevant-model-of-breast-cancer-brain-metastasis
#14
Soo-Hyun Kim, Richard P Redvers, Lap Hing Chi, Xiawei Ling, Andrew J Lucke, Robert C Reid, David P Fairlie, Ana Carolina Baptista Moreno Martin, Robin L Anderson, Delphine Denoyer, Normand Pouliot
Breast cancer brain metastasis remains largely incurable. While several mouse models have been developed to investigate the genes and mechanisms regulating breast cancer brain metastasis, these models often lack clinical relevance since they require the use of immune-compromised mice and/or are poorly metastatic to brain from the mammary gland. We describe the development and characterisation of an aggressive brain metastatic variant of the 4T1 syngeneic model (4T1Br4) that spontaneously metastasises to multiple organs, but is selectively more metastatic to the brain from the mammary gland than parental 4T1 tumours...
May 21, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29784854/molecular-subtype-specific-immunocompetent-models-of-high-grade-urothelial-carcinoma-reveal-differential-neoantigen-expression-and-response-to-immunotherapy
#15
Ryoichi Saito, Christof C Smith, Takanobu Utsumi, Lisa M Bixby, Jordan Kardos, Sara E Wobker, Kyle G Stewart, Shengjie Chai, Ujjawal Manocha, Kevin Matthew Byrd, Jeffrey S Damrauer, Scott E Williams, Benjamin G Vincent, William Y Kim
High-grade urothelial cancer contains intrinsic molecular subtypes that exhibit differences in underlying tumor biology and can be divided into luminal-like and basal-like subtypes. We describe here the first subtype-specific murine models of bladder cancer and show that Upk3a-CreERT2; Trp53L/L; PtenL/L; Rosa26LSL-Luc (UPPL: luminal-like) and BBN (basal-like) tumors are more faithful to human bladder cancer than the widely-used MB49 cells. Following engraftment into immunocompetent C57BL/6 mice, BBN tumors were more responsive to PD-1 inhibition than UPPL tumors...
May 21, 2018: Cancer Research
https://www.readbyqxmd.com/read/29784788/mistimed-food-intake-and-sleep-alters-24-hour-time-of-day-patterns-of-the-human-plasma-proteome
#16
Christopher M Depner, Edward L Melanson, Andrew W McHill, Kenneth P Wright
Proteomics holds great promise for understanding human physiology, developing health biomarkers, and precision medicine. However, how much the plasma proteome varies with time of day and is regulated by the master circadian suprachiasmatic nucleus brain clock, assessed here by the melatonin rhythm, is largely unknown. Here, we assessed 24-h time-of-day patterns of human plasma proteins in six healthy men during daytime food intake and nighttime sleep in phase with the endogenous circadian clock (i.e., circadian alignment) versus daytime sleep and nighttime food intake out of phase with the endogenous circadian clock (i...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29784734/new-nccn-guidelines-recognition-and-management-of-immunotherapy-related-toxicity
#17
John A Thompson
Immune checkpoint inhibitors (ICIs) are now FDA-approved for the treatment of 8 different cancers, and more approvals are likely, including use of these drugs in combinations. Although ICIs represent a true advance in cancer care, they can cause a range of immune-related adverse events. As more experience with ICIs is gained, more information is becoming available on immunotoxicity and optimal management. Physicians and patients need to be educated about potential adverse events and management of ICI-associated toxicity...
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29784675/radiation-followed-by-ox40-stimulation-drives-local-and-abscopal-antitumor-effects-in-an-anti-pd1-resistant-lung-tumor-model
#18
Sharareh Niknam, Hampartsoum B Barsoumian, Jonathan E Schoenhals, Heather Jackson, Niranjan Yanamandra, Mauricio S Caetano, Ailin Li, Ahmed I Younes, Alexandra P Cadena, Taylor R Cushman, Joe Y Chang, Quynh Nguyen, Daniel R Gomez, Adi Diab, John V Heymach, Patrick Hwu, Maria Angelica Cortez, James W Welsh
PURPOSE: Radiation is used extensively to treat localized cancer, but improved understanding of its effects on the immune system have increased interest in its potential systemic (abscopal) effects, particularly in combination with checkpoint inhibitors such as anti-PD1. The majority of patients either do not respond or develop resistance to monotherapy over time. Here, we investigated the efficacy of OX40 (CD134) stimulation as an alternative immunotherapeutic approach in combination with radiotherapy (XRT) in a murine model of anti-PD1-resistant lung tumors...
May 21, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29784649/small-molecular-inhibitors-targeting-protein-sumoylation-as-novel-anticancer-compounds
#19
Yanfang Yang, Zijing Xia, Xixi Wang, Xinyu Zhao, Zenghua Sheng, Yang Ye, Gu He, Liangxue Zhou, Hongxia Zhu, Ningzhi Xu, Shufang Liang
SUMOylation, one of post-translational modifications, is covalently modified on lysine residues of a target protein through an enzymatic cascade reaction similar to protein ubiquitination. Along with identification of many SUMOylated proteins, protein SUMOylation has been proven to regulate multiple biological activities including transcription, cell cycle, DNA repair and innate immunity. The dysregulation of protein SUMOylation and deSUMOylation modification is linked with carcinogenesis and tumor progression...
May 21, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29784646/latest-developments-in-muc1-immunotherapy
#20
REVIEW
Joyce Taylor-Papadimitriou, Joy M Burchell, Rosalind Graham, Richard Beatson
Currently, there is renewed interest in attempting to recruit the host immune system to eliminate cancers, and within this renewed activity, MUC1 continues to arouse interest. MUC1 has been considered a possible therapeutic target for the past 30 years as it is up-regulated, aberrantly glycosylated and its polarization is lost in many adenocarcinomas. Moreover, MUC1 is expressed by some haematopoietic cancers, including acute myeloid leukaemia and myeloma. Although multiple clinical trials have been initiated and immune responses have been documented, effective clinical benefit worthy of approval for general application has not as yet been achieved...
May 21, 2018: Biochemical Society Transactions
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