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Cancer and IDO

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https://www.readbyqxmd.com/read/27913931/prognostic-value-of-tumor-infiltrating-lymphocyte-subsets-in-breast-cancer-depends-on-hormone-receptor-status
#1
Yul Ri Chung, Hyun Jeong Kim, Min Hye Jang, So Yeon Park
PURPOSE: Interaction between immune-regulatory proteins and tumor infiltrating lymphocytes (TILs) is complex, and their associations may have significant clinical implications. This study was designed to evaluate the relationships between immunomodulatory proteins and TIL subsets and their impact on prognosis in breast cancer. METHODS: 377 invasive breast cancer cases were selected, and immunohistochemistry was performed for HLA-A, HLA-ABC, and indoleamine 2,3-dioxygenase (IDO); CD4+, CD8+, and FOXP3+ T cells were counted in intratumoral and stromal areas for both absolute numbers as well as their ratios...
December 2, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27899095/effects-of-the-ayurved-siriraj-wattana-recipe-on-functional-and-phenotypic-characterization-of-cytokine-induced-killer-cells-and-dendritic-cells-in-vitro
#2
Adisak Wongkajornsilp, Nuntarak Numchaisermsuk, Khanit Sa-Ngiamsuntorn, Pravit Akarasereenont, Valla Wamanuttajinda, Kanda Kasetsinsombat, Sunisa Duangsa-Ard, Tawee Laohapan, Kittipong Maneechotesuwan
BACKGROUND: Ayurved Siriraj Wattana recipe (AVS073), has been prescribed as tonic, to increase appetite, and for pain relief. It also exhibits antioxidant, anti-inflammatory, immunomodulating and anti-cancer activities. However, the immunomodulatory effects on antigen-presenting cells and effector T cells remained elusive. We thus aimed to study the effects of AVS073 on differentiation, maturation, functions and proportions of CIK cells and monocyte-derived DCs. METHODS: CIK cells and monocyte-derived DCs were treated with AVS073, followed by the assessment of T-helper (Th) phenotypes using real-time RT-PCR and flow cytometry...
November 29, 2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27890326/the-effect-of-metabolic-comorbidities-and-commonly-used-drugs-on-the-prognosis-of-patients-with-ovarian-cancer
#3
Daniel Bar, Ofer Lavie, Nili Stein, Ido Feferkorn, Ayelet Shai
BACKGROUND: Diabetes mellitus is associated with an increased risk of recurrence in patients with ovarian cancer. Retrospective studies suggested that the use of statins, metformin and beta blockers is associated with improved prognosis in these patients. Patients with diabetes often suffer from hypertension and are usually treated concomitantly by several classes of drugs. Our aim was to assess the independent contribution of diabetes mellitus and hypertension and of the use of aspirin, statins, metformin and beta blockers on the risk of ovarian cancer recurrence and mortality...
October 14, 2016: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/27885800/sacral-neuromodulation-for-the-treatment-of-faecal-incontinence-following-proctectomy
#4
Ido Mizrahi, Sami A Chadi, Nadav Haim, Dana R Sands, Brooke Gurland, Massarat Zutshi, Steven D Wexner, Giovanna da Silva
AIM: This study assessed the effectiveness of sacral neuromodulation (SNM) for faecal incontinence (FI) following proctectomy with colorectal or coloanal anastomosis. METHODS: An IRB-approved database identified patients treated for FI following proctectomy (SNM-P) for benign or malignant disease, who were matched 1:1 by pre-operative Cleveland Clinic Florida Faecal Incontinence Scores (CCF-FIS) with patients without proctectomy (SNM-NP). Primary outcome was change in CCF-FIS...
November 25, 2016: Colorectal Disease: the Official Journal of the Association of Coloproctology of Great Britain and Ireland
https://www.readbyqxmd.com/read/27836863/checkpoint-proteins-in-pediatric-brain-and-extracranial-solid-tumors-opportunities-for-immunotherapy
#5
Eric K Ring, James M Markert, G Yancey Gillespie, Gregory K Friedman
Pediatric brain and extracranial solid tumors are a diverse group of malignancies that represent almost half of pediatric cancers. Standard therapy includes various combinations of surgery, cytotoxic chemotherapy and radiation, which can be very harmful to a developing child, and survivors carry a substantial burden of long term morbidities. While these therapies have improved survival rates for children with solid tumors, outcomes still remain extremely poor for subsets of patients. Recently, immunosuppressive checkpoint molecules that negatively regulate immune cell function have been described...
November 10, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27822771/mental-illness-is-not-associated-with-adherence-to-colorectal-cancer-screening-results-from-the-california-health-interview-survey
#6
Elizabeth Siantz, Brian Wu, Mark Shiroishi, Hita Vora, Gregory Idos
BACKGROUND: Colorectal cancer is the second leading cause of cancer-specific death in the USA. Evidence suggests people with mental illness are less likely to receive preventive health services, including cancer screening. We hypothesized that mental illness is a risk factor for non-adherence to colorectal cancer-screening guidelines. METHODS: We analyzed results of the 2007 California Health Interview Survey to test whether mental illness is a risk factor for non-adherence to colorectal cancer-screening recommendations among individuals age 50 or older (N = 15,535)...
November 7, 2016: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/27819653/an-immunostimulatory-dual-functional-nanocarrier-that-improves-cancer-immunochemotherapy
#7
Yichao Chen, Rui Xia, Yixian Huang, Wenchen Zhao, Jiang Li, Xiaolan Zhang, Pengcheng Wang, Raman Venkataramanan, Jie Fan, Wen Xie, Xiaochao Ma, Binfeng Lu, Song Li
Immunochemotherapy combines a chemotherapeutic agent with an immune-modulating agent and represents an attractive approach to improve cancer therapy. However, the success of immunochemotherapy is hampered by the lack of a strategy to effectively co-deliver the two therapeutics to the tumours. Here we report the development of a dual-functional, immunostimulatory nanomicellar carrier that is based on a prodrug conjugate of PEG with NLG919, an indoleamine 2,3-dioxygenase (IDO) inhibitor currently used for reversing tumour immune suppression...
November 7, 2016: Nature Communications
https://www.readbyqxmd.com/read/27815661/improved-radiosynthesis-and-biological-evaluations-of-l-and-d-1-18-f-fluoroethyl-tryptophan-for-pet-imaging-of-ido-mediated-kynurenine-pathway-of-tryptophan-metabolism
#8
Yangchun Xin, Hancheng Cai
PURPOSE: Tryptophan metabolism via indoleamine 2,3-dioxygenase (IDO)-mediated kynurenine pathway plays a role in immunomodulation and has been emerging as a plausible target for cancer immunotherapy. Imaging IDO-mediated kynurenine pathway of tryptophan metabolism with positron emission tomography (PET) could provide valuable information for noninvasive assessment of cancer immunotherapy response. In this work, radiotracer 1-(2-[(18)F]fluoroethyl)-L-tryptophan (1-L-[(18)F]FETrp) and its enantioisomer 1-D-[(18)F]FETrp were synthesized and evaluated for PET imaging of IDO-mediated kynurenine pathway of tryptophan metabolism...
November 4, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/27814478/haploid-human-embryonic-stem-cells-half-the-genome-double-the-value
#9
Atilgan Yilmaz, Mordecai Peretz, Ido Sagi, Nissim Benvenisty
Recent advances in the generation of haploid embryonic stem cells (ESCs), capable of self-renewal and differentiation, have laid the groundwork for numerous biomedical applications in developmental biology and reproductive medicine. When combined with the power of genetic screening, haploid human ESCs could advance cancer research, regenerative medicine, and disease modeling.
November 3, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27777979/the-head-and-neck-cancer-immune-landscape-and-its-immunotherapeutic-implications
#10
Rajarsi Mandal, Yasin Şenbabaoğlu, Alexis Desrichard, Jonathan J Havel, Martin G Dalin, Nadeem Riaz, Ken-Wing Lee, Ian Ganly, A Ari Hakimi, Timothy A Chan, Luc G T Morris
Recent clinical trials have demonstrated a clear survival advantage in advanced head and neck squamous cell carcinoma (HNSCC) patients treated with immune checkpoint blockade. These emerging results reveal that HNSCC is one of the most promising frontiers for immunotherapy research. However, further progress in head and neck immuno-oncology will require a detailed understanding of the immune infiltrative landscape found in these tumors. We leveraged transcriptome data from 280 tumors profiled by The Cancer Genome Atlas (TCGA) to comprehensively characterize the immune landscape of HNSCC in order to develop a rationale for immunotherapeutic strategies in HNSCC and guide clinical investigation...
October 20, 2016: JCI Insight
https://www.readbyqxmd.com/read/27761872/correlation-between-indoleamine-2-3-dioxygenase-mrna-and-cdkn2a-p16-mrna-a-combined-strategy-to-cervical-cancer-diagnosis
#11
Mario Cezar Saffi Junior, Ivone da Silva Duarte, Rodrigo Barbosa de Oliveira Brito, Giovana Garcia Prado, Sergio Makabe, Humberto Dellê, Cleber P Camacho
Cervical cancer (CC) is one of the most common cancers among women worldwide. The relation of the human papillomavirus (HPV) with CC and its precursor lesions was first suspected for over 40 years. The indoleamine 2,3 dioxygenase (IDO) is an immune modulator enzyme responsible for the immune system tissue protection mechanism, which may be the key to the tumoural persistence. HPV oncoprotein E7 promotes the increase in cyclin-dependent kinase inhibitor p16 (CDKN2A/p16). The isolated and combined analysis of CDKN2A/p16 mRNA to CC diagnosis was done with promising results...
November 2016: Medical Oncology
https://www.readbyqxmd.com/read/27760965/-indoleamine-2-3-dioxygenase-activity-in-intracystic-breast-tumors
#12
Kenichi Sakurai, Shigeru Fujisaki, Keita Adachi, Shuhei Suzuki, Yuki Masuo, Saki Nagashima, Yukiko Hara, Katsuhisa Enomoto, Tomohiro Hirano, Ryouichi Tomita, Kenji Gonda
We evaluated the clinical significance of indoleamine 2,3-dioxygenase(IDO)in intra-cystic tumors of the breast. IDO activitycan be measured byusing the tryptophan(Trp)/kynurenine(Kyn)ratio. Trp and Kyn were measured by high performance liquid chromatography(HPLC). We took liquid from 3 intra-cystic papilloma cases and 5 intra-cystic breast cancer cases. Then, we measured the Trp/Kyn ratio in these samples, and we evaluated the difference in the Trp/Kyn ratio between the papilloma group and the breast cancer group...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27760961/-clinical-evaluation-of-immunosuppressive-acidic-protein-in-the-serum-of-patients-with-locally-advanced-breast-cancer-during-mohs-paste-treatment
#13
Tomohiro Hirano, Kenichi Sakurai, Shigeru Fujisaki, Keita Adachi, Shuhei Suzuki, Yuki Masuo, Saki Nagashima, Yukiko Hara, Katsuhisa Enomoto, Ryouichi Tomita, Kenji Gonda
Locallyadvanced breast cancer lesions often compromise the patient's qualityof life(QOL). Mohs paste is a histopathological fixative containing zinc chloride as the main ingredient. It has been applied to perform chemosurgeryon skin tumors. In recent years, this paste has reportedlybeen veryeffective for controlling various symptoms of skin metastases in inoperable advanced cancer, such as pungent odor and hemorrhage, in the field of palliative care. We evaluated the clinical significance of immunosuppressive acidic protein(IAP)and C-reactive protein(CRP)in the serum of patients with locallyadvanced breast cancer duringMohs paste treatment...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27760945/-indoleamine-2-3-dioxygenase-activity-during-fulvestrant-therapy-for-multiple-metastatic-breast-cancer-patients
#14
Kenichi Sakurai, Shigeru Fujisaki, Keita Adachi, Shuhei Suzuki, Yuki Masuo, Saki Nagashima, Yukiko Hara, Tomohiro Hirano, Katsuhisa Enomoto, Ryouichi Tomita, Kenji Gonda
We evaluated the clinical significance of indoleamine 2,3-dioxygenase(IDO)during fulvestrant therapyfor multiple metastatic breast cancer patients. IDO activitycan be measured using the tryptophan(Trp)/kynurenine(Kyn)ratio. Trp and Kyn were measured using high-performance liquid chromatography(HPLC). The serum Trp/Kyn level in patients with multiple metastatic breast cancer was lower than in patients without metastases. IDO activityincreased after breast cancer metastases developed. IDO activitywas correlated with the number of metastatic lesions during toremifene and fulvestrant therapy...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27756892/targeting-immune-checkpoints-in-malignant-glioma
#15
Xuhao Zhang, Shan Zhu, Tete Li, Yong-Jun Liu, Wei Chen, Jingtao Chen
Malignant glioma is the most common and a highly aggressive cancer in the central nervous system (CNS). Cancer immunotherapy, strategies to boost the body's anti-cancer immune responses instead of directly targeting tumor cells, recently achieved great success in treating several human solid tumors. Although once considered "immune privileged" and devoid of normal immunological functions, CNS is now considered a promising target for cancer immunotherapy, featuring the recent progresses in neurobiology and neuroimmunology and a highly immunosuppressive state in malignant glioma...
October 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27705910/indoleamine-2-3-dioxygenase-regulates-anti-tumor-immunity-in-lung-cancer-by-metabolic-reprogramming-of-immune-cells-in-the-tumor-microenvironment
#16
Cara C Schafer, Yong Wang, Kenneth P Hough, Anandi Sawant, Stefan C Grant, Victor J Thannickal, Jaroslaw Zmijewski, Selvarangan Ponnazhagan, Jessy S Deshane
Indoleamine 2,3-dioxygenase (IDO) has been implicated in immune evasion by tumors. Upregulation of this tryptophan (Trp)-catabolizing enzyme, in tumor cells and myeloid-derived suppressor cells (MDSCs) within the tumor microenvironment (TME), leads to Trp depletion that impairs cytotoxic T cell responses and survival; however, exact mechanisms remain incompletely understood. We previously reported that a combination therapy of gemcitabine and a superoxide dismutase mimetic promotes anti-tumor immunity in a mouse model of lung cancer by inhibiting MDSCs, enhancing polyfunctional response of CD8+ memory T cells, and extending survival...
September 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27683036/proteomic-analysis-uncovers-common-effects-of-ifn-%C3%AE-and-il-27-on-the-hla-class-i-antigen-presentation-machinery-in-human-cancer-cells
#17
Andrea Petretto, Grazia Carbotti, Elvira Inglese, Chiara Lavarello, Maria Pia Pistillo, Valentina Rigo, Michela Croce, Luca Longo, Stefania Martini, Paola Vacca, Silvano Ferrini, Marina Fabbi
IL-27, a member of the IL-12-family of cytokines, has shown anti-tumor activity in several pre-clinical models due to anti-proliferative, anti-angiogenic and immune-enhancing effects. On the other hand, IL-27 demonstrated immune regulatory activities and inhibition of auto-immunity in mouse models. Also, we reported that IL-27, similar to IFN-γ, induces the expression of IL-18BP, IDO and PD-L1 immune regulatory molecules in human cancer cells. Here, a proteomic analysis reveals that IL-27 and IFN-γ display a broad overlap of functions on human ovarian cancer cells...
September 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27651314/nutritional-stress-induced-by-tryptophan-degrading-enzymes-results-in-atf4-dependent-reprogramming-of-the-amino-acid-transporter-profile-in-tumor-cells
#18
Elina Timosenko, Hemza Ghadbane, Jonathan D Silk, Dawn Shepherd, Uzi Gileadi, Lauren J Howson, Robert Laynes, Qi Zhao, Robert L Strausberg, Lars R Olsen, Stephen Taylor, Francesca M Buffa, Richard Boyd, Vincenzo Cerundolo
Tryptophan degradation is an immune escape strategy shared by many tumors. However, cancer cells' compensatory mechanisms remain unclear. We demonstrate here that a shortage of tryptophan caused by expression of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) resulted in ATF4-dependent upregulation of several amino acid transporters, including SLC1A5 and its truncated isoforms, which in turn enhanced tryptophan and glutamine uptake. Importantly, SLC1A5 failed to be upregulated in resting human T cells kept under low tryptophan conditions but was enhanced upon cognate antigen T-cell receptor engagement...
November 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27643646/metformin-increases-e-cadherin-in-tumors-of-diabetic-patients-with-endometrial-cancer-and-suppresses-epithelial-mesenchymal-transition-in-endometrial-cancer-cell-lines
#19
Ido Laskov, Paul Abou-Nader, Oreekha Amin, Charles-Andre Philip, Marie-Claude Beauchamp, Amber Yasmeen, Walter H Gotlieb
PURPOSE: Epithelial-mesenchymal transition (EMT) is a critical process for cancer metastasis and recurrence. Metformin, an effective oral antidiabetic drug, has been associated with decreased cancer risk and mortality. In this pilot study, we started to evaluate the effect of metformin on EMT in vivo and in vitro in endometrial cancer (EC). METHODS: Endometrial cancer cell lines and freshly isolated EC tumor specimens were used to assess EMT after metformin treatment...
September 2016: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/27622052/peg-ril-10-treatment-decreases-foxp3-tregs-despite-upregulation-of-intratumoral-ido
#20
Ivan H Chan, Victoria Wu, Melissa Bilardello, Brett Jorgenson, Harminder Bal, Scott McCauley, Peter Van Vlasselaer, John B Mumm
IL-10 has been classically defined as a broad-spectrum immunosuppressant and is thought to facilitate the development of regulatory CD4(+) T cells. IL-10 is believed to represent one of the major suppressive factors secreted by IDO(+)FoxP3(+)CD4(+) Tregs. Contrary to this view, we have previously reported that PEGylated recombinant IL-10 (PEG-rIL-10) treatment of mice induces potent IFNγ and CD8(+) T-cell-dependent antitumor immunity. This hypothesis is currently being tested in clinical trials and we have reported that treatment of cancer patients with PEG-rHuIL-10 results in inhibition and regression of tumor growth as well as increased serum IFNγ...
July 2016: Oncoimmunology
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