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https://www.readbyqxmd.com/read/27891189/variations-in-dna-methylation-of-interferon-gamma-and-programmed-death-1-in-allograft-rejection-after-kidney-transplantation
#1
Karin Boer, L Elly A de Wit, Fleur S Peters, Dennis A Hesselink, Leo J Hofland, Michiel G H Betjes, Caspar W N Looman, Carla C Baan
BACKGROUND: The role of DNA methylation in the regulation of the anti-donor-directed immune response after organ transplantation is unknown. Here, we studied the methylation of two mediators of the immune response: the pro-inflammatory cytokine interferon γ (IFNγ) and the inhibitory receptor programmed death 1 (PD1) in naïve and memory CD8+ T cell subsets in kidney transplant recipients receiving immunosuppressive medication. Both recipients experiencing an episode of acute allograft rejection (rejectors) as well as recipients without rejection (non-rejectors) were included...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27853858/production-process-reproducibility-and-product-quality-consistency-of-transient-gene-expression-in-hek293-cells-with-anti-pd1-antibody-as-the-model-protein
#2
Kai Ding, Lei Han, Huifang Zong, Junsheng Chen, Baohong Zhang, Jianwei Zhu
Demonstration of reproducibility and consistency of process and product quality is one of the most crucial issues in using transient gene expression (TGE) technology for biopharmaceutical development. In this study, we challenged the production consistency of TGE by expressing nine batches of recombinant IgG antibody in human embryonic kidney 293 cells to evaluate reproducibility including viable cell density, viability, apoptotic status, and antibody yield in cell culture supernatant. Product quality including isoelectric point, binding affinity, secondary structure, and thermal stability was assessed as well...
November 16, 2016: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27832664/acute-interstitial-nephritis-related-to-immune-checkpoint-inhibitors
#3
Julie Belliere, Nicolas Meyer, Julien Mazieres, Sylvie Ollier, Serge Boulinguez, Audrey Delas, David Ribes, Stanislas Faguer
BACKGROUND: Immune checkpoint inhibitors (anti-PD1 or anti-CTLA-4) are increasingly used in various cancers. Immune checkpoint inhibitors (ICI)-related renal disorders are poorly described (9 cases) and were only related to Ipilimumab. METHODS: Retrospective collection of clinical charts of all the patients admitted for renal disorders following ICI in the University Hospital of Toulouse (France). RESULTS: We report on adverse renal events that occurred in three patients treated with anti-PD1 (nivolumab or pembrolizumab) or anti-CTLA-4 (ipilimumab)...
November 10, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27815440/identification-of-novel-cd4-t-cell-subsets-in-the-target-tissue-of-sj%C3%A3-gren-s-syndrome-and-their-differential-regulation-by-the-lymphotoxin-light-signaling-axis
#4
Scott Haskett, Jian Ding, Wei Zhang, Alice Thai, Patrick Cullen, Shanqin Xu, Britta Petersen, Galina Kuznetsov, Luke Jandreski, Stefan Hamann, Taylor L Reynolds, Norm Allaire, Timothy S Zheng, Michael Mingueneau
Despite being one of the most common rheumatologic diseases, there is still no disease-modifying drug for primary Sjögren's syndrome (pSS). Advancing our knowledge of the target tissue has been limited by the low dimensionality of histology techniques and the small size of human salivary gland biopsies. In this study, we took advantage of a molecularly validated mouse model of pSS to characterize tissue-infiltrating CD4(+) T cells and their regulation by the lymphotoxin/LIGHT signaling axis. Novel cell subsets were identified by combining highly dimensional flow and mass cytometry with transcriptomic analyses...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27742386/the-bad-and-the-good-news-on-cancer-immunotherapy-implications-for-organ-transplant-recipients
#5
Umberto Maggiore, Julio Pascual
Cancer immunotherapy, especially the use of checkpoint inhibitors, is expanding and can be efficacious in organ transplant recipients with malignant neoplasia. In this review, we summarize clinical findings and evolution of several patients treated with CTL4-4 or PD-1 inhibitors reported in the literature. The CTL-4 inhibitor ipilimumab has been safely used in several liver and kidney allograft recipients. PD1-inhibitors look promising for tumor shrinking, but acute rejection is the rule, so they should be avoided in recipients of life-saving organs...
September 2016: Advances in Chronic Kidney Disease
https://www.readbyqxmd.com/read/27274826/severe-acute-interstitial-nephritis-after-combination-immune-checkpoint-inhibitor-therapy-for-metastatic-melanoma
#6
Naoka Murakami, Thiago J Borges, Michifumi Yamashita, Leonardo V Riella
Immune-checkpoint inhibitors are emerging as revolutionary drugs for certain malignancies. However, blocking the co-inhibitory signals may lead to immune-related adverse events, mainly in the spectrum of autoimmune diseases including colitis, endocrinopathies and nephritis. Here, we report a case of a 75-year-old man with metastatic malignant melanoma treated with a combination of nivolumab (anti-PD1-antibody) and ipilimumab (anti-CTLA-4 antibody) who developed systemic rash along with severe acute tubulointerstitial nephritis after two doses of combination therapy...
June 2016: Clinical Kidney Journal
https://www.readbyqxmd.com/read/27079802/mechanism-driven-biomarkers-to-guide-immune-checkpoint-blockade-in-cancer-therapy
#7
Suzanne L Topalian, Janis M Taube, Robert A Anders, Drew M Pardoll
With recent approvals for multiple therapeutic antibodies that block cytotoxic T lymphocyte associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) in melanoma, non-small-cell lung cancer and kidney cancer, and additional immune checkpoints being targeted clinically, many questions still remain regarding the optimal use of drugs that block these checkpoint pathways. Defining biomarkers that predict therapeutic effects and adverse events is a crucial mandate, highlighted by recent approvals for two PDL1 diagnostic tests...
May 2016: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/26603381/cd57-cd4-t-cells-underlie-belatacept-resistant-allograft-rejection
#8
J Espinosa, F Herr, G Tharp, S Bosinger, M Song, A B Farris, R George, J Cheeseman, L Stempora, R Townsend, A Durrbach, A D Kirk
Belatacept is a B7-specific fusion protein used to prevent allograft rejection by blocking T cell costimulation. Generally efficacious, it fails to prevent acute rejection in a sizable minority of patients. In experimental models, memory T cells mediate costimulation blockade-resistant rejection (CoBRR), but this remains undefined in humans. To explore relationships between individual patients' immune cell phenotypes and CoBRR, we studied patients receiving belatacept or conventional calcineurin inhibitor-based immunosuppression...
April 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/25735315/renal-effects-of-molecular-targeted-therapies-in-oncology-a-review-by-the-cancer-and-the-kidney-international-network-c-kin
#9
REVIEW
V Launay-Vacher, M Aapro, G De Castro, E Cohen, G Deray, M Dooley, B Humphreys, S Lichtman, J Rey, F Scotté, H Wildiers, B Sprangers
A number of cancer therapy agents are cleared by the kidney and may affect renal function, including cytotoxic chemotherapy agents, molecular targeted therapies, analgesics, antibiotics, radiopharmaceuticals and radiation therapy, and bone-targeted therapies. Many of these agents can be nephrotoxic, including targeted cancer therapies. The incidence, severity, and pattern of renal toxicities may vary according to the respective target of the drug. Here, we review the renal effects associated with a selection of currenty approved targeted cancer therapies, directed to vascular endothelial growth factor or VEGF receptor(s) (VEGF/VEGFR), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor2 (HER2), BRAF, anaplastic lymphoma kinase (ALK), programmed cell death protein-1 or its ligand (PD-1/PDL-1), receptor activator of nuclear factor kappa-B ligand (RANKL), and mammalian target of rapamycin (mTOR)...
August 2015: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/24778161/anti-pd1-following-ipilimumab-for-mucosal-melanoma-durable-tumor-response-associated-with-severe-hypothyroidism-and-rhabdomyolysis
#10
Le Min, F Stephen Hodi
Treatment with fully human monoclonal antibodies against programmed death 1 (PD1) receptor has shown great promise for a number of advanced malignancies. Although inflammatory adverse events have been well described with anti-CTL antigen 4 (CTLA4) therapy, experience with the range of adverse effects of anti-PD1 remains comparatively limited. Here, we report on a patient with advanced mucosal melanoma who received four doses of MK-3475, a fully human monoclonal antibody against PD1, and experienced a durable near-complete response but developed severe hypothyroidism, rhabdomyolysis, and acute kidney injury...
January 2014: Cancer Immunology Research
https://www.readbyqxmd.com/read/24504486/potential-of-new-therapies-like-anti-pd1-in-kidney-cancer
#11
REVIEW
Anasuya Gunturi, David F McDermott
Various targeted immunotherapies have shown efficacy in metastatic renal cell carcinoma (RCC) recently. Specifically, molecules targeting the PD-1/PD-L1 pathway have shown promising results. These agents appear to provide several advantages over previous standard therapies. First, higher objective responses are attained with these agents, many of which are complete and durable. Second, these drugs are associated with less overall treatment-related toxicity. This allows for the testing of various combination therapies that may provide better clinical outcomes...
March 2014: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/23734322/re-orienting-the-immune-system-durable-tumor-regression-and-successful-re-induction-therapy-using-anti-pd1-antibodies
#12
Evan J Lipson
The blockade of immune regulatory checkpoints is emerging as a powerful anticancer strategy. We recently reported long-term results from the first-in-human clinical trial of anti-PD1 antibody-based immunotherapy, demonstrating durable tumor control off-therapy in subjects affected by colorectal and kidney cancer, as well as successful re-induction therapy in a melanoma patient.
April 1, 2013: Oncoimmunology
https://www.readbyqxmd.com/read/23730407/tumor-infiltrating-pd1-positive-lymphocytes-and-foxp3-positive-regulatory-t-cells-predict-distant-metastatic-relapse-and-survival-of-clear-cell-renal-cell-carcinoma
#13
Myoung Jae Kang, Kyoung Min Kim, Jun Sang Bae, Ho Sung Park, Ho Lee, Myoung Ja Chung, Woo Sung Moon, Dong Geun Lee, Kyu Yun Jang
BACKGROUND: Clear cell renal cell carcinoma (CRCC) is the most common malignant tumor of the kidney, and the clinical outcome of CRCC is related with the metastatic potential of CRCC. A significant proportion of metastatic CRCC remains incurable. Recently, immunotherapy against specific targets such as programmed death 1 (PD1) has been adapted for fatal cases of CRCC. MATERIALS AND METHODS: In this study, we aimed to evaluate the potential of tumor-infiltrating PD1-positive lymphocytes or FoxP3-positive regulatory T cells (Tregs) as predictors of the metastatic potential or prognosis of CRCC and investigate possible correlations with Epstein-Barr virus (EBV) infection in 199 cases of CRCC...
June 2013: Translational Oncology
https://www.readbyqxmd.com/read/23586712/intrinsic-immune-alterations-in-renal-cell-carcinoma-and-emerging-immunotherapeutic-approaches
#14
REVIEW
Bruno Bockorny, Constantin A Dasanu
INTRODUCTION: Individuals affected by kidney cancer present a variety of immune abnormalities including cellular immune dysfunction, cytokine alterations and antigen presentation defects. On the other hand, spontaneous remissions are seen in up to 4% of renal cell carcinoma (RCC) patients and they are thought to occur via immune mechanisms. AREAS COVERED: The authors comprehensively review the immune abnormalities in RCC patient and describe the kidney cancer immunotherapy candidates that are most advanced in their clinical development...
June 2013: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/23386851/omega-3-fatty-acid-derived-resolvins-and-protectins-in-inflammation-resolution-and-leukocyte-functions-targeting-novel-lipid-mediator-pathways-in-mitigation-of-acute-kidney-injury
#15
Song Hong, Yan Lu
Inflammation, in conjunction with leukocytes, plays a key role in most acute kidney injury (AKI). Non-resolving renal inflammation leads to chronic fibrosis and renal failure. Resolvin D series (RvDs) and E series (RvEs), protectins, and maresins (MaRs) are endogenous omega-3 fatty acid-derived lipid mediators (LMs) that potently promote inflammation resolution by shortening neutrophil life span and promoting macrophage (Mf) non-phelogistic phagocytosis of apoptotic cells and the subsequent exit of Mfs from inflammatory tissue...
2013: Frontiers in Immunology
https://www.readbyqxmd.com/read/21823008/relatively-increased-number-of-liver-foxp-3-regulatory-t-cells-against-hepatic-lesions-in-murine-lupus
#16
Likai Yu, Anbin Huang, Weiwei Wang, Rong Du, Lingxun Shen, Xiaohua Hou
Systemic lupus erythematosus (SLE) is a multiple organ autoimmune disorder, including the liver, but the possible reason in impairment in the liver is still unclear. Our present study assessed alterations of transcription factor Foxp3(+) regulatory T cells (Tregs) and several other immune molecules [programmed cell death 1 and its ligand (PD1 and PD-L1), and interleukin 10 (IL-10) and transform growth factor β (TGF-β)] in the liver and other major organs of lupus-prone BXSB mice by flow cytometry, real-time quantitative reverse transcription PCR, and enzyme-linked immunosorbent assay...
August 2011: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/21040746/regulation-of-the-lymphatic-endothelial-cell-cycle-by-the-prox1-homeodomain-protein
#17
Shannon A Baxter, David Y Cheung, Patricia Bocangel, Hae K Kim, Krista Herbert, Josette M Douville, Jaganmohan R Jangamreddy, Shunzhen Zhang, David D Eisenstat, Jeffrey T Wigle
The homeobox transcription factor PROX1 is essential for the development and maintenance of lymphatic vasculature. How PROX1 regulates lymphatic endothelial cell fate remains undefined. PROX1 has been shown to upregulate the expression of Cyclin E, which mediates the G(1) to S transition of the cell cycle. Here we demonstrate that PROX1 activates the mouse Cyclin E1 (Ccne1) promoter via two proximal E2F-binding sites. We have determined that the N-terminal region of PROX1 is sufficient to activate a 1-kb Ccne1 promoter, whereas the homeodomain is dispensable for activation...
January 2011: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/19616454/serum-retinol-retinol-binding-protein-and-transthyretin-in-children-receiving-dialysis
#18
Nancy Fassinger, Abubakr Imam, David M Klurfeld
OBJECTIVE: We investigated the relationships of retinol (ROH), retinol-binding protein (RBP), and transthyretin (TTR) in children with end-stage renal disease (ESRD). Our hypothesis was that levels of ROH and RBP would be elevated in children with ESRD. METHODS AND PATIENTS: We measured ROH, RBP, and TTR serum concentrations in a group of pediatric ESRD patients biannually. Children were grouped according to age and method of dialysis, i.e., hemodialysis (HD) or peritoneal dialysis (PD): HD1, aged <12 years (n = 8); PD1, aged <12 years (n = 19); HD2, aged >or=12 years (n =19); and PD2, aged >or=12 years (n = 29)...
January 2010: Journal of Renal Nutrition
https://www.readbyqxmd.com/read/19234220/acute-changes-in-dietary-omega-3-and-omega-6-polyunsaturated-fatty-acids-have-a-pronounced-impact-on-survival-following-ischemic-renal-injury-and-formation-of-renoprotective-docosahexaenoic-acid-derived-protectin-d1
#19
Iram R Hassan, Karsten Gronert
Exacerbated inflammation plays an important role in the pathogenesis of ischemic renal injury (IRI), which is the major cause of intrinsic acute renal failure. Clinical studies suggest that long-term treatment with omega-3 polyunsaturated fatty acids (PUFA) improves renal function and lowers the risk of death or end-stage renal disease. Docosahexaenoic acid, a principle omega-3 PUFA of fish oils, is of particular interest as it is found in most human tissues and is converted to protectin D1 (PD1), which exhibits antiinflammatory and proresolving bioactions...
March 1, 2009: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/19116915/genetic-immunologic-and-immunohistochemical-analysis-of-the-programmed-death-1-programmed-death-ligand-1-pathway-in-human-systemic-lupus-erythematosus
#20
George K Bertsias, Magda Nakou, Christianna Choulaki, Amalia Raptopoulou, Eva Papadimitraki, George Goulielmos, Herakles Kritikos, Prodromos Sidiropoulos, Maria Tzardi, Dimitris Kardassis, Clio Mamalaki, Dimitrios T Boumpas
OBJECTIVE: A putative regulatory intronic polymorphism (PD1.3) in the programmed death 1 (PD-1) gene, a negative regulator of T cells involved in peripheral tolerance, is associated with increased risk for systemic lupus erythematosus (SLE). We undertook this study to determine the expression and function of PD-1 in SLE patients. METHODS: We genotyped 289 SLE patients and 256 matched healthy controls for PD1.3 by polymerase chain reaction-restriction fragment length polymorphism analysis...
January 2009: Arthritis and Rheumatism
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