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https://www.readbyqxmd.com/read/29352003/gene-expression-signatures-characterized-by-longitudinal-stability-and-interindividual-variability-delineate-baseline-phenotypic-groups-with-distinct-responses-to-immune-stimulation
#1
Adam D Scheid, Virginia P Van Keulen, Sara J Felts, Steven C Neier, Sumit Middha, Asha A Nair, Robert W Techentin, Barry K Gilbert, Jin Jen, Claudia Neuhauser, Yuji Zhang, Larry R Pease
Human immunity exhibits remarkable heterogeneity among individuals, which engenders variable responses to immune perturbations in human populations. Population studies reveal that, in addition to interindividual heterogeneity, systemic immune signatures display longitudinal stability within individuals, and these signatures may reliably dictate how given individuals respond to immune perturbations. We hypothesize that analyzing relationships among these signatures at the population level may uncover baseline immune phenotypes that correspond with response outcomes to immune stimuli...
January 19, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29351372/a-preclinical-population-pharmacokinetic-model-for-anti-cd20-cd3-t-cell-dependent-bispecific-antibodies
#2
Gregory Z Ferl, Arthur Reyes, Liping L Sun, Melissa Cheu, Amy Oldendorp, Saroja Ramanujan, Eric G Stefanich
CD20 is a cell-surface receptor expressed by healthy and neoplastic B cells and is a well-established target for biologics used to treat B-cell malignancies. Pharmacokinetic (PK) and pharmacodynamic (PD) data for the anti-CD20/CD3 T-cell-dependent bispecific antibody BTCT4465A were collected in transgenic mouse and nonhuman primate (NHP) studies. Pronounced nonlinearity in drug elimination was observed in the murine studies, and time-varying, nonlinear PK was observed in NHPs, where three empirical drug elimination terms were identified using a mixed-effects modeling approach: i) a constant nonsaturable linear clearance term (7 mL/day/kg); ii) a rapidly decaying time-varying, linear clearance term (t½  = 1...
January 19, 2018: Clinical and Translational Science
https://www.readbyqxmd.com/read/29349612/dexamethasone-induced-leukocytosis-is-associated-with-poor-survival-in-newly-diagnosed-glioblastoma
#3
Daniel Dubinski, Sae-Yeon Won, Florian Gessler, Johanna Quick-Weller, Bedjan Behmanesh, Simon Bernatz, Marie-Therese Forster, Kea Franz, Karl-Heinz Plate, Volker Seifert, Patrick N Harter, Christian Senft
Despite its well-characterized side effects, dexamethasone is widely used in the pre-, peri- and postoperative neurosurgical setting due to its effective relief of tumor-induced symptoms through the reduction of tumor-associated edema. However, some patients show laboratory-defined dexamethasone induced elevation of white blood cell count, and its impact on glioblastoma progression is unknown. We retrospectively analyzed 113 patients with newly diagnosed glioblastoma to describe the incidence, risk factors and clinical features of dexamethasone-induced leukocytosis in primary glioblastoma patients...
January 18, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29348660/generation-and-characterization-of-alloantigen-specific-regulatory-t-cells-for-clinical-transplant-tolerance
#4
James M Mathew, Jessica H Voss, Scott T McEwen, Iwona Konieczna, Arjun Chakraborty, Xuemei Huang, Jie He, Lorenzo Gallon, Richard S Kornbluth, Joseph R Leventhal
Donor-specific CD4+CD127-CD25+FOXP3+ regulatory T cells (AgTregs) have the potential to induce clinical transplant tolerance; however, their expansion ex vivo remains challenging. We optimized a novel expansion protocol to stimulate donor-specific Tregs using soluble 4-trimer CD40 ligand (CD40L)-activated donor B cells that expressed mature antigen-presenting cell markers. This avoided the use of CD40L-expressing stimulator cells that might otherwise result in potential cellular contamination. Purified allogeneic "recipient" CD4+CD25+ Tregs were stimulated on days 0 and 7 with expanded "donor" B cells in the presence of IL-2, TGFβ and sirolimus (SRL)...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29345340/berberine-demonstrates-anti-inflammatory-properties-in-helicobacter-pylori-infected-mice-with-chronic-gastritis-by-attenuating-the-th17-response-triggered-by-the-b-cell-activating-factor
#5
Xiuxia Wu, Xian Li, Zhongqin Dang, Yunfei Jia
Berberine (BBR) is an isoquinoline alkaloid derived from various medicinal herbs. Previous studies have suggested that BBR exerts antimicrobial, antitumor, and antidiabetic effects and can be used to treat Helicobacter pylori-induced chronic gastritis. However, the exact mechanism by which BBR inhibits H. pylori infection is not fully understood. We investigated the anti-inflammatory properties and potential mechanism of BBR in H. pylori-infected mice with chronic gastritis. We found that BBR can suppress the expression of pro-inflammatory genes IL-6, TGF-β, and IL-1β and upregulate anti-inflammatory gene IL-10 expression in the mucosa and RAW 264...
January 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29345064/tlr8-ligation-induces-apoptosis-of-monocytic-myeloid-derived-suppressor-cells
#6
Yushe Dang, Zina J Rutnam, Gregory Dietsch, Hailing Lu, Yi Yang, Robert Hershberg, Mary L Disis
Myeloid-derived suppressor cells (MDSCs) accumulate in tumors and the peripheral blood of cancer patients and demonstrate cancer-promoting activity across multiple tumor types. A limited number of agents are known to impact MDSC activity. TLR8 is expressed in myeloid cells. We investigated expression of TLR8 on MDSC and the effect of a TLR8 agonist, motolimod, on MDSC survival and function. TLR8 was highly expressed in monocytic MDSC (mMDSC) but absent in granulocytic MDSC (gMDSC). Treatment of human PBMC with motolimod reduced the levels of mMDSC in volunteers and cancer donors versus control (P < 0...
January 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345017/effects-of-nutritional-support-on-short-term-clinical-outcomes-and-immune-response-in-unresectable-locally-advanced-oesophageal-squamous-cell-carcinoma
#7
F Chen, J Fang, H Wang, T Song, W Zhu, M Wu, Y Wu
This retrospective study investigated the efficiency of nutritional support in unresectable locally advanced oesophageal squamous cell carcinoma (LAOSCC) patients who received concurrent chemoradiotherapy (CCRT) based on 5-fluorouracil and cisplatin. In the routine care group, 63 patients served as historical controls and received nutrition support in a reactive manner. In addition, 57 patients in the nutritional support group received timely diet counselling, oral nutritional supplements, enteral nutrition and/or parenteral nutrition during CCRT...
January 18, 2018: European Journal of Cancer Care
https://www.readbyqxmd.com/read/29344283/antigen-presentation-of-the-oct4-and-sox2-peptides-by-cd154-activated-b-lymphocytes-enhances-the-killing-effect-of-cytotoxic-t-lymphocytes-on-tumor-stem-like-cells-derived-from-cisplatin-resistant-lung-cancer-cells
#8
Xueyan Zhang, Yanwei Zhang, Jianlin Xu, Huimin Wang, Xiaoxuan Zheng, Yuqing Lou, Baohui Han
The present study investigated whether antigen presentation of the Oct4 and Sox2 peptides by CD154-activated B lymphocytes can enhance the killing effect of CD8+ cytotoxic T lymphocytes (CTLs) on lung stem-like cancer cells (SLCCs). The CTLs were generated using an accelerated co-cultured dendritic cells (DC) (acDC) assay by incubating human peripheral blood mononuclear cells (PBMCs) from non-small-cell lung cancer patients with antigen peptides of Oct4 and Sox2 in the presence of several DC-activating agents...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29343525/lack-of-remuscularization-following-transplantation-of-human-embryonic-stem-cell-derived-cardiovascular-progenitor-cells-in-infarcted-nonhuman-primates
#9
Keyang Zhu, Qiang Wu, Cheng Ni, Peng Zhang, Zhiwei Zhong, Yan Wu, Yingchao Wang, Yinchuan Xu, Minjian Kong, Haifeng Cheng, Zhihua Tao, Qian Yang, He Liang, Yun Jiang, Qingju Li, Jing Zhao, Jijun Huang, Fengjiang Zhang, Qi Chen, Yi Li, Jinghai Chen, Wei Zhu, Hong Yu, Jianyi Zhang, Huang-Tian Yang, Xinyang Hu, Jian'an Wang
Rationale: Human pluripotent stem cell-derived cardiovascular progenitor cells (hPSC-CVPCs) should be thoroughly investigated in large animal studies before testing in clinical trials. Objective: To clarify if hPSC-CVPCs can engraft for long time in the heart of primates after myo-cardial infarction (MI) and compare the effectiveness and safety of immunosuppression with cy-closporine alone or multiple-drug regimen (MDR) containing cyclosporine, methylprednisolone, and Simulect in cynomolgous monkeys that had received intramyocardial injections of 1×107 EGFP-expressing hPSC-CVPCs after MI...
January 17, 2018: Circulation Research
https://www.readbyqxmd.com/read/29343197/coexpression-of-cd3-and-cd20-in-canine-enteropathy-associated-t-cell-lymphoma
#10
Erica L Noland, Matti Kiupel
The majority of primary intestinal lymphomas in dogs are T-cell lymphomas, with enteropathy-associated T-cell lymphoma (EATL) large cell type (type 1) being the most common. While most T-cell lymphomas express the T-cell marker CD3, there is increasing evidence that some human and canine T-cell lymphomas coexpress the B-cell marker CD20. We describe 3 cases of CD3+, CD20+, Pax5- EATL type 1 in dogs. All 3 cases had clonal rearrangement of T-cell receptor gamma. Initial clinical signs included weight loss, inappetence, diarrhea, and/or vomiting...
January 1, 2018: Veterinary Pathology
https://www.readbyqxmd.com/read/29340095/tumoral-immune-infiltrate-if-pd-l1-expression-and-role-of-cd8-tia-1-lymphocytes-in-localized-osteosarcoma-patients-treated-within-protocol-isg-os1
#11
Emanuela Palmerini, Claudio Agostinelli, Piero Picci, Stefano Pileri, Teresa Marafioti, Pier-Luigi Lollini, Katia Scotlandi, Alessandra Longhi, Maria Serena Benassi, Stefano Ferrari
Background: We hypothesized that immune-infiltrates were associated with superior survival, and examined a primary osteosarcoma tissue microarrays (TMAs) to test this hypothesis. Methods: 129 patients (pts) with localized osteosarcoma treated within protocol ISG-OS1 were included in the study. Clinical characteristics, expression of CD8, CD3, FOXP3, CD20, CD68/CD163 (tumor associated macrophage, TAM), Tia-1 (cytotoxic T cell), CD303 (plasmacytoid dendritic cells: pDC), Arginase-1 (myeloid derived suppressor cells: MDSC), PD-1 on immune-cells (IC), and PD-L1 on tumoral cells (TC) and IC were analysed and correlated with outcome...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339550/relative-target-affinities-of-t-cell-dependent-bispecific-antibodies-determine-biodistribution-in-a-solid-tumor-mouse-model
#12
Danielle Mandikian, Nene Takahashi, Amy A Lo, Ji Li, Jeffrey Eastham-Anderson, Dionysos Slaga, Jason Ho, Maria Hristopoulos, Robyn Clark, Klara Totpal, Kedan Lin, Sean B Joseph, Mark S Dennis, Saileta Prabhu, Teemu T Junttila, C Andrew Boswell
Anti-HER2/CD3, a T cell-dependent bispecific antibody (TDB) construct, induces T cell-mediated cell death in cancer cells expressing HER2 by cross-linking tumor HER2 with CD3 on cytotoxic T cells, thereby creating a functional cytolytic synapse. TDB design is a very challenging process that requires consideration of multiple parameters. While therapeutic antibody design strategy is commonly driven by striving for the highest attainable antigen binding affinity, little is known about how the affinity of each TDB arm can affect the targeting ability of the other arm and the consequent distribution and efficacy...
January 16, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29339496/thymic-stromal-lymphopoietin-drives-the-development-of-il-13-th2-cells
#13
Sotaro Ochiai, Ferdinand Jagot, Ryan L Kyle, Evelyn Hyde, Ruby F White, Melanie Prout, Alfonso J Schmidt, Hidehiro Yamane, Olivier Lamiable, Graham Le Gros, Franca Ronchese
T helper 2 (Th2) cells are pivotal in the development of allergy. Allergen exposure primes IL-4+ Th2 cells in lymph node, but production of effector cytokines including IL-5 and IL-13 is thought to require additional signals from antigen and the environment. Here we report that a substantial proportion of naive CD4+ T cells in spleen and lymph node express receptors for the epithelium-derived inflammatory cytokine thymic stromal lymphopoietin (TSLP). Culture of naive CD4+ T cells in anti-(a)CD3, aCD28, and TSLP-supplemented Th2 conditions enabled the development of a unique population of IL-13-single positive (IL-13-SP) CD4+ T cells; TSLP and Th2 conditions were both required for their development...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29337962/the-relationship-between-right-sided-tumour-location-tumour-microenvironment-systemic-inflammation-adjuvant-therapy-and-survival-in-patients-undergoing-surgery-for-colon-and-rectal-cancer
#14
Meera Patel, Stephen T McSorley, James H Park, Campbell S D Roxburgh, Joann Edwards, Paul G Horgan, Donald C McMillan
BACKGROUND: There has been an increasing interest in the role of tumour location in the treatment and prognosis of patients with colorectal cancer (CRC), specifically in the adjuvant setting. Together with genomic data, this has led to the proposal that right-sided and left-sided tumours should be considered as distinct biological and clinical entities. The aim of the present study was to examine the relationship between tumour location, tumour microenvironment, systemic inflammatory response (SIR), adjuvant chemotherapy and survival in patients undergoing potentially curative surgery for stage I-III colon and rectal cancer...
January 16, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29336230/alterations-of-global-dna-methylation-and-dnmt-expression-in-t-and-b-lymphocytes-from-patients-with-newly-diagnosed-aitd-after-treatment-a-follow-up-study
#15
Qingling Guo, Dan Wu, Huixin Yu, Jiandong Bao, Shiqiao Peng, Zhongyan Shan, Haixia Guan, Weiping Teng
BACKGROUND: Dysregulated DNA methylation in lymphocytes has been linked to autoimmune disorders. The aims of this study were to identify global DNA methylation patterns in patients with autoimmune thyroid diseases (AITDs) and to observe methylation changes after treatment for these conditions. METHODS: We conducted a cross-sectional study design including the following patients: 51 with newly diagnosed Graves' disease (GD), 28 with autoimmune hypothyroidism (AIT), 29 with positive thyroid autoantibodies (pTAb) and 39 matched healthy volunteers...
January 16, 2018: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/29335838/effect-of-immunonutrition-on-colorectal-cancer-patients-undergoing-surgery-a-meta-analysis
#16
Jing Xu, Xian Sun, Qianqian Xin, Ying Cheng, Zhen Zhan, Junfeng Zhang, Juan Wu
PURPOSE: Immunonutrition has been used to prevent the complications after colorectal elective surgery. This systematic review aimed to analyze and assess the effect of immunonutrition on colorectal cancer patients who received elective surgery. METHODS: Three electronic databases (Medline, Embase, Cochrane) were used to search the latent studies which investigated the effects of enteral immunonutrition (EIN) compared with standard enteral nutrition (EN) or parenteral immunonutrition (PIN) compared with standard parenteral nutrition (PN) on colorectal cancer patients who are undergoing surgery until 21st of April, 2017...
January 15, 2018: International Journal of Colorectal Disease
https://www.readbyqxmd.com/read/29334915/monitoring-the-responsiveness-of-t-and-antigen-presenting-cell-compartments-in-breast-cancer-patients-is-useful-to-predict-clinical-tumor-response-to-neoadjuvant-chemotherapy
#17
David A Bernal-Estévez, Oscar García, Ramiro Sánchez, Carlos A Parra-López
BACKGROUND: Vaccination of mice with tumors treated with Doxorubicin promotes a T cell immunity that relies on dendritic cell (DC) activation and is responsible for tumor control in vaccinated animals. Despite Doxorubicin in combination with Cyclophosphamide (A/C) is widely used to treat breast cancer patients, the stimulating effect of A/C on T and APC compartments and its correlation with patient's clinical response remains to be proved. METHODS: In this prospective study, we designed an in vitro system to monitor various immunological readouts in PBMCs obtained from a total of 17 breast cancer patients before, and after neoadjuvant anti-tumor therapy with A/C...
January 15, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29334370/scaffolds-that-mimic-antigen-presenting-cells-enable-ex-vivo-expansion-of-primary-t-cells
#18
Alexander S Cheung, David K Y Zhang, Sandeep T Koshy, David J Mooney
Therapeutic ex vivo T-cell expansion is limited by low rates and T-cell products of limited functionality. Here we describe a system that mimics natural antigen-presenting cells (APCs) and consists of a fluid lipid bilayer supported by mesoporous silica micro-rods. The lipid bilayer presents membrane-bound cues for T-cell receptor stimulation and costimulation, while the micro-rods enable sustained release of soluble paracrine cues. Using anti-CD3, anti-CD28, and interleukin-2, we show that the APC-mimetic scaffolds (APC-ms) promote two- to tenfold greater polyclonal expansion of primary mouse and human T cells compared with commercial expansion beads (Dynabeads)...
January 15, 2018: Nature Biotechnology
https://www.readbyqxmd.com/read/29333888/primary-diffuse-large-b-cell-lymphoma-of-the-ciliary-body
#19
Hayyam Kiratli, Abdullah Ağın, Berrin Büyükeren, Figen Söylemezoğlu
PURPOSE: To report an unusual case of an eye with primary ciliary body lymphoma which came to enucleation allowing detailed histopathological examination. METHODS: A 50-year-old man presented with a painful loss of vision in the left eye. The clinical, imaging, and immunohistopathological features of this case were reviewed. RESULTS: The vision in the left eye was light perception. There were keratic precipitates, an irregular and thickened iris with neovascularization...
January 15, 2018: Ocular Immunology and Inflammation
https://www.readbyqxmd.com/read/29332332/a-study-on-cellular-immune-function-of-patients-treated-with-radical-resection-of-pulmonary-carcinoma-with-two-different-methods-of-anesthesia-and-analgesia
#20
Jie Chen, Feng Luo, Min Lei, Zhoumiao Chen
PURPOSE: To compare the influence on the immune system of two different methods of anesthesia and analgesia in patients treated with radical resection of pulmonary carcinoma. METHODS: Thirty-four patients treated with radical resection of pulmonary carcinoma were randomly divided into two groups (group A and group B, 17 cases in each group). Patients in group A were administered total intravenous anesthesia (TIVA) without inhaled hypnotics and intravenous analgesia while patients in group B were administered TIVA combined with epidural anesthesia and epidural analgesia...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
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