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Cancer and IDO

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https://www.readbyqxmd.com/read/29355622/an-indoleamine-2-3-dioxygenase-sirna-nanoparticle-coated-and-trp2-displayed-recombinant-yeast-vaccine-inhibits-melanoma-tumor-growth-in-mice
#1
Dong-Qun Liu, Shuai Lu, Ling-Xiao Zhang, Mei Ji, Shu-Ying Liu, Shao-Wei Wang, Rui-Tian Liu
Therapeutic vaccine is a promising approach in cancer therapy. But tumor-associated antigen peptides have weak immunogenicity and cancer patients are often characterized by immunosuppression and tolerance, leading to less efficiency of immunotherapy. We here successfully developed indoleamine 2, 3-dioxygenase (IDO) siRNA nanoparticle-coated and tyrosinase-related protein 2 (Trp2)-displayed recombinant Saccharomyces cerevisiae (YCP). YCPs had positive charges with a diameter of approximately 5μm, resulting in selective phagocytosis by APC cells...
January 17, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29355614/head-and-neck-squamous-cell-carcinoma-genomics-and-emerging-biomarkers-for-immunomodulatory-cancer-treatments
#2
REVIEW
Benjamin Solomon, Richard J Young, Danny Rischin
Head and neck squamous cell carcinoma (HNSCC) comprises a heterogeneous group of tumors that arise from the squamous epithelium of the oral cavity, oropharynx, larynx and hypopharynx. While many HNSCCs are related to classical etiologic factors of smoking and alcohol, a clinically, genomically, and immunologically distinct subgroup of tumors arise from the epithelium of the tonsil and the base of tongue as a result of infection with Human Papilloma Virus (HPV). In this review we describe the genomic and immunologic landscape of HNSCC, highlighting differences between HPV-positive and HPV-negative HNSCC...
January 17, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29344159/p38-predicts-depression-and-poor-outcome-in-esophageal-cancer
#3
Yao Cheng, Zhe Qiao, Chengxue Dang, Bin Zhou, Shaomin Li, Wei Zhang, Jiantao Jiang, Yongchun Song, Jin Zhang, Dongmei Diao
p38 mitogen-activated protein kinase (MAPK) signaling has been implicated in the cancer development and progression. However, the precise mechanism of this association remains unknown. The aim of the present study was to evaluate the association between p38 and cancer progression, including investigations into the effects on cell proliferation, resistance to thalidomide, indoleamine 2,3-dioxygenase (IDO) expression and prognosis in patients with esophageal cancer. The present retrospective study included patients with stage I-III esophageal cancer...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343435/paracrine-wnt5a-%C3%AE-catenin-signaling-triggers-a-metabolic-program-that-drives-dendritic-cell-tolerization
#4
Fei Zhao, Christine Xiao, Kathy S Evans, Tbalamayooran Theivanthiran, Nicholas DeVito, Alisha Holtzhausen, Juan Liu, Xiaojing Liu, David Boczkowski, Smita Nair, Jason W Locasale, Brent A Hanks
Despite recent advances, many cancers remain refractory to available immunotherapeutic strategies. Emerging evidence indicates that the tolerization of local dendritic cells (DCs) within the tumor microenvironment promotes immune evasion. Here, we have described a mechanism by which melanomas establish a site of immune privilege via a paracrine Wnt5a-β-catenin-peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling pathway that drives fatty acid oxidation (FAO) in DCs by upregulating the expression of the carnitine palmitoyltransferase-1A (CPT1A) fatty acid transporter...
January 16, 2018: Immunity
https://www.readbyqxmd.com/read/29331741/extracellular-acidification-induces-ros-and-mptp-mediated-death-in-hek293-cells
#5
José Teixeira, Farhan Basit, Herman G Swarts, Marleen Forkink, Paulo J Oliveira, Peter H G M Willems, Werner J H Koopman
The extracellular pH (pHe) is a key determinant of the cellular (micro)environment and needs to be maintained within strict boundaries to allow normal cell function. Here we used HEK293 cells to study the effects of pHe acidification (24h), induced by mitochondrial inhibitors (rotenone, antimycin A) and/or extracellular HCl addition. Lowering pHe from 7.2 to 5.8 reduced cell viability by 70% and was paralleled by a decrease in cytosolic pH (pHc), hyperpolarization of the mitochondrial membrane potential (Δψ), increased levels of hydroethidine-oxidizing ROS and stimulation of protein carbonylation...
December 30, 2017: Redox Biology
https://www.readbyqxmd.com/read/29321667/the-management-of-retinoblastoma
#6
REVIEW
Ido D Fabian, Zerrin Onadim, Esin Karaa, Catriona Duncan, Tanzina Chowdhury, Irene Scheimberg, Shin-Ichi Ohnuma, M Ashwin Reddy, Mandeep S Sagoo
Retinoblastoma (Rb) is the most common primary intraocular malignancy of childhood, but an uncommon paediatric cancer, with a constant incidence worldwide of 1:15,000-1:20,000 live births. Despite its rarity, Rb has served as a cornerstone in the field of oncology in many of the aspects that comprise cancer management, including classification schemes, treatment modalities, genetic testing and screening. Until just over half a century ago, the major treatment for Rb was eye removal, and prognosis was poor with outcome fatal for most children...
January 11, 2018: Oncogene
https://www.readbyqxmd.com/read/29316566/double-anterior-stereotactic-cingulotomy-for-intractable-oncological-pain
#7
Ido Strauss, Assaf Berger, Shlomit Ben Moshe, Michal Arad, Uri Hochberg, Tal Gonen, Rotem Tellem
BACKGROUND: Stereotactic anterior cingulotomy has been used in the treatment of patients suffering from refractory oncological pain due to its effects on pain perception. However, the optimal targets as well as suitable candidates and outcome measures have not been well defined. We report our initial experience in the ablation of 2 cingulotomy targets on each side and the use of the Brief Pain Inventory (BPI) as a perioperative assessment tool. METHODS: A retrospective review of all patients who underwent stereotactic anterior cingulotomy in our Department between November 2015 and February 2017 was performed...
January 10, 2018: Stereotactic and Functional Neurosurgery
https://www.readbyqxmd.com/read/29308328/b-cell-lymphoma-progression-promotes-the-accumulation-of-circulating-ly6clo-monocytes-with-immunosuppressive-activity
#8
Sara J McKee, Zewen K Tuong, Takumi Kobayashi, Brianna L Doff, Megan Sf Soon, Michael Nissen, Pui Yeng Lam, Colm Keane, Frank Vari, Davide Moi, Roberta Mazzieri, Graham Leggatt, Maher K Gandhi, Stephen R Mattarollo
Monocytosis is considered a poor prognostic factor for many cancers, including B cell lymphomas. The mechanisms by which different monocyte subsets support the growth of lymphoma is poorly understood. Using a pre-clinical mouse model of B cell non-Hodgkin's lymphoma (B-NHL), we investigated the impact of tumor progression on circulating monocyte levels, subset distribution and their activity, with a focus on immune suppression. B-NHL development corresponded with significant expansion initially of classical (Ly6Chi) and non-classical (Ly6Clo) monocytes, with accumulation and eventual predominance of Ly6Clo cells...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29305519/antigen-specific-antitumor-responses-induced-by-ox40-agonist-are-enhanced-by-ido-inhibitor-indoximod
#9
Zuzana Berrong, Mikayel Mkrtichyan, Shamim Ahmad, Mason Webb, Eslam Mohamed, Grigori Okoev, Adelaida Matevosyan, Rajeev Shrimali, Rasha Abu Eid, Scott Hammond, John E Janik, Samir N Khleif
Although an immune response to tumors may be generated using vaccines, so far, this approach has only shown minimal clinical success. This is attributed to the tendency of cancer to escape immune surveillance via multiple immune suppressive mechanisms. Successful cancer immunotherapy requires targeting these inhibitory mechanisms along with enhancement of antigen-specific immune responses to promote sustained tumor-specific immunity. Here we evaluated the effect of indoximod, an inhibitor of the immunosuppressive indoleamine-(2,3)-dioxygenase (IDO) pathway, on antitumor efficacy of anti-OX40 agonist in the context of vaccine in the IDO- TC-1 tumor model...
January 5, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29302770/modulating-tumor-immunology-by-inhibiting-indoleamine-2-3-dioxygenase-ido-recent-developments-and-first-clinical-experiences
#10
Diwakar Davar, Nathan Bahary
Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) catalyze the first rate-limiting step in the oxidative metabolism of compounds containing indole rings, including the transformation of the essential amino acid L-tryptophan to N-formyl-L-kynurenine. Through direct and indirect means, IDO exerts both tolerogenic and pro-inflammatory effects and has a profound immunoregulatory role in the tumor microenvironment. Although the role of IDO in mediating peripheral acquired immunologic tolerance has been known for some time, its role in tumorigenesis and the subversion of anti-tumor immunity have only recently been appreciated...
January 4, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29296206/indoleamine-2-3-dioxygenase-and-interleukin-6-associated-with-tumor-response-to-neoadjuvant-chemotherapy-in-breast-cancer
#11
Fangxuan Li, Lijuan Wei, Shixia Li, Juntian Liu
Purpose: Indoleamine-2,3-dioxygenase (IDO) and Interleukin-6 (IL-6) contribute to poor therapeutic effects, tumor relapse and aggressive tumor growth. IDO and IL-6 incorporate a positive feedback signal loop to maintain IDO and IL-6 constitutive expression and facilitate tumor progression. Results: IDO expression was associated with IL-6 expression and plasma IL-6 level (P<0.05). Concentrating on clinicopathological features prior neoadjuvant chemotherapy, both IDO expression and plasma IL-6 level were associated with clinical T stage and N stage (P<0...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29275469/tryptophan-catabolism-and-cancer-immunotherapy-targeting-ido-mediated-immune-suppression
#12
Adaobi Amobi, Feng Qian, Amit A Lugade, Kunle Odunsi
Over the last decade, tryptophan catabolism has been firmly established as a powerful mechanism of innate and adaptive immune tolerance. The catabolism of tryptophan is a central pathway maintaining homeostasis by preventing autoimmunity or immunopathology that would result from uncontrolled and overreacting immune responses. This is driven by the key and rate-limiting enzymes indoleamine-2,3-dioxygenase 1 (IDO1) and tryptophan-2,3-dioxygenase 2 (TDO), resulting in local depletion of tryptophan, while tryptophan catabolites accumulate, including kynurenine and its derivatives, depending on the presence of downstream enzymes in the kynurenine pathway...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29275462/cancer-immunotherapy-targets-based-on-understanding-the-t-cell-inflamed-versus-non-t-cell-inflamed-tumor-microenvironment
#13
Thomas F Gajewski, Leticia Corrales, Jason Williams, Brendan Horton, Ayelet Sivan, Stefani Spranger
Most cancers express tumor antigens that can be recognized by T cells of the host. The fact that cancers become clinically evident nonetheless implies that immune escape must occur. Two major subsets of human melanoma metastases have been identified based on gene expression profiling. One subgroup has a T cell-inflamed phenotype that includes expression of chemokines, T cell markers, and a type I IFN signature. In contrast, the other major subset lacks this phenotype and has been designated as non-T cell-inflamed...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29247038/discovery-of-ido1-inhibitors-from-bench-to-bedside
#14
REVIEW
George C Prendergast, William P Malachowski, James B DuHadaway, Alexander J Muller
Small-molecule inhibitors of indoleamine 2,3-dioxygenase-1 (IDO1) are emerging at the vanguard of experimental agents in oncology. Here, pioneers of this new drug class provide a bench-to-bedside review on preclinical validation of IDO1 as a cancer therapeutic target and on the discovery and development of a set of mechanistically distinct compounds, indoximod, epacadostat, and navoximod, that were first to be evaluated as IDO inhibitors in clinical trials. As immunometabolic adjuvants to widen therapeutic windows, IDO inhibitors may leverage not only immuno-oncology modalities but also chemotherapy and radiotherapy as standards of care in the oncology clinic...
December 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/29240291/novel-4-amino-1-2-3-triazole-inhibitors-of-indoleamine-2-3-dioxygenase-form-a-long-lived-complex-with-the-enzyme-and-display-exquisite-cellular-potency
#15
Julie Alexandre, Michael Swan, Mike Latchem, Dean Boyall, John Pollard, Stuart Hughes, James Westcott
Indoleamine-2,3 dioxygenase (IDO) has emerged as a central regulator of immune responses in both normal and disease biology. Due to its established role in promoting tumour immune escape, IDO has become an attractive target for cancer treatment. We have identified a novel series of highly cell potent IDO inhibitors based on a 4-amino-1,2,3-triazole core. Comprehensive kinetic, biochemical and structural studies demonstrate that compounds from this series have a non-competitive kinetic mechanism-of-action with respect to the tryptophan substrate...
December 14, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29203865/albumin-vaccine-nanocomplexes-that-assemble-in-vivo-for-combination-cancer-immunotherapy
#16
Guizhi Zhu, Geoffrey M Lynn, Orit Jacobson, Kai Chen, Yi Liu, Huimin Zhang, Ying Ma, Fuwu Zhang, Rui Tian, Qianqian Ni, Siyuan Cheng, Zhantong Wang, Nan Lu, Bryant C Yung, Zhe Wang, Lixin Lang, Xiao Fu, Albert Jin, Ido D Weiss, Harshad Vishwasrao, Gang Niu, Hari Shroff, Dennis M Klinman, Robert A Seder, Xiaoyuan Chen
Subunit vaccines have been investigated in over 1000 clinical trials of cancer immunotherapy, but have shown limited efficacy. Nanovaccines may improve efficacy but have rarely been clinically translated. By conjugating molecular vaccines with Evans blue (EB) into albumin-binding vaccines (AlbiVax), here we develop clinically promising albumin/AlbiVax nanocomplexes that self-assemble in vivo from AlbiVax and endogenous albumin for efficient vaccine delivery and potent cancer immunotherapy. PET pharmacoimaging, super-resolution microscopies, and flow cytometry reveal almost 100-fold more efficient co-delivery of CpG and antigens (Ags) to lymph nodes (LNs) by albumin/AlbiVax than benchmark incomplete Freund's adjuvant (IFA)...
December 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/29195503/recent-development-in-clinical-applications-of-pd-1-and-pd-l1-antibodies-for-cancer-immunotherapy
#17
REVIEW
Bingshan Liu, Yongping Song, Delong Liu
Antibodies against programmed death (PD) pathway are revolutionizing cancer immunotherapy. Currently five antibodies against PD-1/PD-L1 have been approved. The clinical use of these antibodies is rapidly expanding. Incorporation of PD antibodies into chemotherapy regimens is in active clinical investigations. The combination of pembrolizumab with carboplatin and pemetrexed has been approved for the first line therapy of metastatic non-squamous non-small cell lung cancer. Combination of PD-1/PD-L1 antibodies with small molecule inhibitors such as tyrosine kinase inhibitors and IDO inhibitors are in active clinical trials...
December 1, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29190885/the-ido-inhibitor-1-methyl-tryptophan-activates-the-aryl-hydrocarbon-receptor-response-in-mesenchymal-stromal-cells
#18
Holly C Lewis, Raghavan Chinnadurai, Steven E Bosinger, Jacques Galipeau
The catabolism of tryptophan (Trp) by indoleamine 2,3-dioxygenase (IDO) is a key step in tolerance effected by a variety of cell types, including mesenchymal stromal cells (MSCs). Trp catabolism generates molecules known as kynurenines, whose tolerance mechanisms involve activation of the Aryl Hydrocarbon Receptor (AHR). A synthetic analog of Trp, 1-methyl tryptophan (1MT), is a selective inhibitor of IDO enzymatic activity being utilized in cancer immunotherapy trials. We hypothesized 1MT might activate AHR independently of its effects on IDO...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29180759/nano-enabled-pancreas-cancer-immunotherapy-using-immunogenic-cell-death-and-reversing-immunosuppression
#19
Jianqin Lu, Xiangsheng Liu, Yu-Pei Liao, Felix Salazar, Bingbing Sun, Wen Jiang, Chong Hyun Chang, Jinhong Jiang, Xiang Wang, Anna M Wu, Huan Meng, Andre E Nel
While chemotherapy delivery by nanocarriers has modestly improved the survival prospects of pancreatic ductal adenocarcinoma (PDAC), additional engagement of the immune response could be game changing. We demonstrate a nano-enabled approach for accomplishing robust anti-PDAC immunity in syngeneic mice through the induction of immunogenic cell death (ICD) as well as interfering in the immunosuppressive indoleamine 2,3-dioxygenase (IDO) pathway. This is accomplished by conjugating the IDO inhibitor, indoximod (IND), to a phospholipid that allows prodrug self-assembly into nanovesicles or incorporation into a lipid bilayer that encapsulates mesoporous silica nanoparticles (MSNP)...
November 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/29176007/between-biology-and-medicine-perspectives-on-the-use-of-dendritic-cells-in-anticancer-therapy
#20
Agnieszka Szczygieł, Elżbieta Pajtasz-Piasecka
Dendritic cells (DCs), as a link between innate and adaptive immunity, play a pivotal role in maintaining homeostasis of the immune system. The DC population is characterized by heterogeneity; it consists of many subpopulations which, despite their phenotypic and localization differences, play an essential function - they are professional antigen presenting cells. Due to their role, DCs can be utilized in a new cancer treatment strategy. Their main purpose is to generate an anticancer response leading to the elimination of cancer cells...
November 19, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
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