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immunosuppression minimization

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https://www.readbyqxmd.com/read/28720430/oncogenic-pathways-that-affect-antitumor-immune-response-and-immune-checkpoint-blockade-therapy
#1
REVIEW
Xianda Zhao, Subbaya Subramanian
Mechanistic insights of cancer immunology have led to the development of immune checkpoint blockade therapy (ICBT), which has elicited a remarkable clinical response in some cancer patients. Increasing evidence suggests that activation of oncogenic pathways, such as RAS/RAF/MAPK and PI3K signaling, impairs the antitumor immune response. Such oncogenic signaling, in turn, activates many inhibitory factors, including expression of immune checkpoint genes-allowing active infiltration of immunosuppressive cells into the tumor environment and inducing resistance against T-cell killing...
July 15, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28704335/mesenchymal-stromal-cell-therapy-for-solid-organ-transplantation
#2
Marlies E J Reinders, Cees van Kooten, Ton J Rabelink, Johan W de Fijter
Improvement of long term outcome of kidney transplantation has reached its limits, due to consequences of efficient, but nonspecific immunosuppressive drugs. Mesenchymal Stromal Cells (MSC) have been proposed as an alternative strategy for more refined therapy. The interest in MSCs comes from their antiinflammatory properties on the 1 hand and their propensity to ameliorate tissue damage and mediate repair on the other hand. First clinical trials have demonstrated that administration of MSCs in kidney transplant recipients is safe and feasible and follow-up studies have been initiated with the desired clinical efficacy to reduce ischemia reperfusion injury, to prevent/reverse acute transplant rejection, and to improve long-term transplant survival with minimization of immunosuppression...
July 12, 2017: Transplantation
https://www.readbyqxmd.com/read/28692442/current-issues-in-allogeneic-islet-transplantation
#3
Charles A Chang, Michael C Lawrence, Bashoo Naziruddin
PURPOSE OF REVIEW: Transplantation of allogenic pancreatic islets is a minimally invasive treatment option to control severe hypoglycemia and dependence on exogenous insulin among type 1 diabetes (T1D) patients. This overview summarizes the current issues and progress in islet transplantation outcomes and research. RECENT FINDINGS: Several clinical trials from North America and other countries have documented the safety and efficacy of clinical islet transplantation for T1D patients with impaired hypoglycemia awareness...
July 7, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28692319/low-energy-x-ray-grenz-ray-treatment-of-purified-islets-prior-to-allotransplant-markedly-decreases-passenger-leukocyte-populations
#4
Rena Pawlick, Boris Gala-Lopez, Andrew R Pepper, Nasser Abualhassan, Antonio Bruni, Kunimasa Suzuki, Gina Rayat, John F Elliott, A M James Shapiro
Grenz rays, or minimally penetrating X-rays, are known to be an effective treatment of certain recalcitrant immune-mediated skin diseases, but their use in modulating allograft rejection has not been tested. We examined the capacity of grenz ray treatment to minimize islet immunogenicity and extend allograft survival in a mouse model. In a preliminary experiment, 1 of 3 immunologically intact animals demonstrated long-term acceptance of their grenz ray treated islet allograft. Further experiments revealed that 28...
July 4, 2017: Islets
https://www.readbyqxmd.com/read/28682945/chronic-critical-illness-and-persistent-inflammation-what-can-we-learn-from-the-elderly-injured-septic-and-malnourished
#5
Vanessa Nomellini, Lewis J Kaplan, Carrie A Sims, Charles C Caldwell
Patients in the intensive care unit (ICU) who develop chronic critical illness significantly stress the clinical capacity and financial resources of healthcare systems. Although vast improvements have been made in critical care management, outcomes for this ICU subset remains poor. A hallmark for patients who progress to chronic critical illness is the development of persistent inflammation and immunosuppression. The risk factors associated with the development of chronic critical illness include increased age, medical comorbidities, severe injury, septic shock, and malnutrition...
July 4, 2017: Shock
https://www.readbyqxmd.com/read/28682561/-immunosuppression-in-kidney-transplantation-a-way-between-efficacy-and-toxicity
#6
Costanza Casati, Alberto Menegotto, Maria Luisa Querques, Federica Ravera, Giacomo Colussi
Renal transplantation is the best treatment for patients with end-stage renal disease. Over the last decades, the introduction of new immunosuppressive agents resulted into the reduction of the incidence of acute rejection and early graft loss. Despite this progress, there has been little improvement in the average life of the transplant. The main reasons of late failure are patient's death due to several complications (e.g. cancer, infectious or metabolic), and progressive deterioration of renal function caused by immunological and non-immunological factors...
April 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28663794/recent-advances-in-the-understanding-of-renal-inflammation-and-fibrosis-in-lupus-nephritis
#7
REVIEW
Susan Yung, Desmond Yh Yap, Tak Mao Chan
Lupus nephritis is a potentially reversible cause of severe acute kidney injury and is an important cause of end-stage renal failure in Asians and patients of African or Hispanic descent. It is characterized by aberrant exaggerated innate and adaptive immune responses, autoantibody production and their deposition in the kidney parenchyma, triggering complement activation, activation and proliferation of resident renal cells, and expression of pro-inflammatory and chemotactic molecules leading to the influx of inflammatory cells, all of which culminate in destruction of normal nephrons and their replacement by fibrous tissue...
2017: F1000Research
https://www.readbyqxmd.com/read/28655795/first-in-human-study-of-amg%C3%A2-820-a-monoclonal-anti-colony-stimulating-factor-1-receptor-antibody-in-patients-with-advanced-solid-tumors
#8
Kyriakos P Papadopoulos, Larry Gluck, Lainie P Martin, Anthony J Olszanski, Anthony W Tolcher, Gataree Ngarmchamnanrith, Erik Rasmussen, Benny Amore, Dirk Nagorsen, John S Hill, Joe Stephenson
Binding of colony-stimulating factor 1 (CSF1) ligand to the CSF1 receptor (CSF1R) regulates survival of tumor-associated macrophages, which generally promote an immunosuppressive tumor microenvironment. AMG 820 is an investigational, fully human CSF1R antibody that inhibits binding of the ligands CSF1 and interleukin-34 and subsequent ligand-mediated receptor activation. This first-in-human phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of AMG 820.<br /><br />Experimental Design: Adult patients with relapsed or refractory advanced solid tumors received intravenous AMG 820 0...
June 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28642375/acquired-resistance-to-corticotropin-therapy-in-nephrotic-syndrome-role-of-de-novo-neutralizing-antibody
#9
Pei Wang, Yan Zhang, Yu Wang, Andrew S Brem, Zhangsuo Liu, Rujun Gong
There is increasing evidence supporting the use of corticotropin as an alternative treatment of refractory proteinuric glomerulopathies. The efficacy of short-acting corticotropin, however, remains unknown and was tested here in an adolescent with steroid-dependent nephrotic syndrome caused by minimal change disease. After developing Cushing syndrome and recently being afflicted with severe cellulitis, the patient was weaned off all immunosuppressants, including corticosteroids. This resulted in a relapse of generalized anasarca, associated with massive proteinuria and hypoalbuminemia...
June 22, 2017: Pediatrics
https://www.readbyqxmd.com/read/28638601/the-efficacy-of-rituximab-in-adult-frequently-relapsing-minimal-change-disease
#10
Catherine King, Sarah Logan, Stuart W Smith, Peter Hewins
BACKGROUND: Corticosteroids are the basis of treatment for nephrotic syndrome due to minimal change disease (MCD), but 25% of patients have frequently relapsing nephrotic syndrome (FRNS) and 30% become steroid dependent. Prolonged use of conventional immunosuppressants causes significant toxicity. Rituximab (RTX) is now included in guidelines for childhood MCD. Evidence for use in adult MCD is limited. We describe a single-centre experience of RTX use in adult MCD. METHODS: Outcomes of all adult MCD patients treated with RTX for FRNS between 2008 and 2015 were retrospectively analysed...
February 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/28620650/graft-function-and-intermediate-term-outcomes-of-kidney-transplants-improved-in-the-last-decade-analysis-of-the-united-states-kidney-transplant-database
#11
Douglas Scott Keith, Gayle Vranic, Angie Nishio-Lucar
BACKGROUND: Previous analyses of the United States transplant database regarding long-term outcomes in kidney transplantation have shown minimal improvement in the rate of long-term graft loss. This study sought to analyze intermediate-term outcomes and graft function at 6 months in kidney transplantation in adult living and deceased donor recipients in the last decade. METHODS: Survival analysis was performed based on the year of transplant between 6 months and 3 years' posttransplant...
June 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28620390/belatacept-does-not-inhibit-follicular-t-cell-dependent-b-cell-differentiation-in-kidney-transplantation
#12
Gretchen N de Graav, Dennis A Hesselink, Marjolein Dieterich, Rens Kraaijeveld, Wenda Verschoor, Dave L Roelen, Nicolle H R Litjens, Anita S Chong, Willem Weimar, Carla C Baan
Humoral alloreactivity has been recognized as a common cause of kidney transplant dysfunction. B-cell activation, differentiation, and antibody production are dependent on IL-21(+)CXCR5(+)follicular T-helper (Tfh) cells. Here, we studied whether belatacept, an inhibitor of the costimulatory CD28-CD80/86-pathway, interrupts the crosstalk between Tfh- and B-cells more efficiently than the calcineurin inhibitor tacrolimus. The suppressive effects of belatacept and tacrolimus on donor antigen-driven Tfh-B-cell interaction were functionally studied in peripheral blood mononuclear cells from 40 kidney transplant patients randomized to a belatacept- or tacrolimus-based immunosuppressive regimen...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28619949/expansion-and-activation-of-granulocytic-myeloid-derived-suppressor-cells-in-childhood-precursor-b-cell-acute-lymphoblastic-leukemia
#13
Yu-Feng Liu, Ying-Ying Chen, Ying-Yi He, Jia-Yi Wang, Jian-Ping Yang, Shu-Ling Zhong, Nan Jiang, Pan Zhou, Hua Jiang, Jie Zhou
Precursor B cell acute lymphoblastic leukemia (B-ALL) is a B cell-derived, malignant disorder with the highest incidence among children. In addition to the genetic abnormality, a dysregulated immune system also has an important role in the pathogenesis of B-ALL. Myeloid-derived suppressor cells (MDSCs) represent one of the key drivers in immune tolerance against tumor cells, including various solid tumors and hematologic malignancies. The role of MDSCs in B-ALL remains poorly understood. Here, we showed that the granulocytic (G)-MDSC population was significantly elevated in both the peripheral blood and BM of patients with B-ALL, when compared with age-matched healthy controls...
June 15, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28615961/the-role-of-novel-biomarkers-in-childhood-idiopathic-nephrotic-syndrome-a-narrative-review-of-published-evidence
#14
REVIEW
Samuel N Uwaezuoke
Two histological subtypes of idiopathic nephrotic syndrome are commonly recognized in children, namely minimal change nephropathy and focal segmental glomerulosclerosis. Children with minimal change nephropathy (the majority of whom are steroid-sensitive) and focal segmental glomerulosclerosis (the majority of whom are steroid-resistant) require early identification in order to ensure appropriate therapeutic intervention and better outcome. Although renal biopsy and histology remain the ideal diagnostic steps to identify these histological subtypes, reports indicate that serum and urinary biomarkers are now being utilized in the investigation of childhood idiopathic nephrotic syndrome...
2017: International Journal of Nephrology and Renovascular Disease
https://www.readbyqxmd.com/read/28611638/rapid-disease-progression-of-liver-metastases-following-resection-in-a-liver-transplanted-patient-with-probable-lynch-syndrome-a-case-report-and-review-of-the-literature
#15
Noelle Suemi Wassano, Francisco Sergi, Gustavo Ferro, Tércio Genzini, Renata D'Alpino Peixoto
Solid organ transplantation provides life-saving therapy for patients with end-stage organ disease, and its outcomes have been improving dramatically over the past few decades. However, substantial morbidity results from chronic immunosuppressive therapy administered to prevent graft rejection. It predisposes patients to several life-threatening complications, such as opportunistic microbial infections and the development of different types of cancers. Here, we presented the case of a young man with probable Lynch syndrome, who developed an aggressive colon carcinoma after long-term immunosuppressive therapy due to a prior liver transplantation...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28605781/everolimus-with-cyclosporine-withdrawal-or-low-exposure-cyclosporine-in-kidney-transplantation-from-month-3-a-multicentre-randomized-trial
#16
Klemens Budde, Martin Zeier, Oliver Witzke, Wolfgang Arns, Frank Lehner, Markus Guba, Johannes Jacobi, Volker Kliem, Petra Reinke, Ingeborg A Hauser, Bruno Vogt, Rolf Stahl, Thomas Rath, Michael Duerr, Eva-Maria Paulus, Christoph May, Martina Porstner, Claudia Sommerer
Background.: Randomized trials have shown that early adoption of everolimus-based immunosuppressive regimens without a calcineurin inhibitor (CNI) improves long-term kidney graft function, but the optimal strategy for CNI minimization remains uncertain. Methods.: In a prospective, randomized, multicentre, 12-month trial, 499 de novo kidney transplant patients were randomized at Month 3 to (i) remain on standard CNI (cyclosporine) therapy with mycophenolic acid, (ii) convert to everolimus with mycophenolic acid or (iii) start everolimus with reduced CNI and no mycophenolic acid (clinical trials registry: ClinicalTrials...
June 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28602379/efficacy-and-safety-of-rituximab-in-the-management-of-pediatric-systemic-lupus-erythematosus-a-systematic-review
#17
Ines Mahmoud, Manel Jellouli, Imen Boukhris, Rim Charfi, Aicha Ben Tekaya, Olfa Saidane, Maryem Ferjani, Yousra Hammi, Sameh Trabelsi, Narjess Khalfallah, Rawdha Tekaya, Tahar Gargah, Leila Abdelmoula
OBJECTIVES: To evaluate the efficacy and safety of rituximab for treating pediatric systemic lupus erythematosus (pSLE). STUDY DESIGN: We performed a systematic review to evaluate the efficacy and safety of rituximab in children with pSLE. Data from studies performed before July 2016 were collected from MEDLINE, the Cochrane Library, Scopus, and the International Rheumatic Disease Abstracts, with no language restrictions. Study eligibility criteria included clinical trials and observational studies with a minimal sample size of 5 patients, regarding treatment with rituximab in patients with refractory pSLE (aged <18 years at the time of diagnosis)...
June 8, 2017: Journal of Pediatrics
https://www.readbyqxmd.com/read/28596584/rcan-11r-peptide-provides-immunosuppression-for-fully-mismatched-islet-allografts-in-mice
#18
Hirofumi Noguchi, Koji Sugimoto, Chika Miyagi-Shiohira, Yoshiki Nakashima, Naoya Kobayashi, Issei Saitoh, Masami Watanabe, Yasufumi Noguchi
Calcineurin inhibitors have been used for transplant therapy. However, the inhibition of calcineurin outside the immune system has a number of side effects. We previously developed a cell-permeable inhibitor of NFAT (nuclear factor of activated T cells) using the polyarginine peptide delivery system. This peptide (11R-VIVIT) selectively interferes with calcineurin-NFAT interaction without affecting the activity of calcineurin phosphatase and provides immunosuppression for fully mismatched islet allografts in mice...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28591027/necrotizing-fasciitis-a-catastrophic-complication-following-routine-tibia-fracture-surgery-a-case-report-and-literature-review
#19
REVIEW
Shuai Shang, Ruipeng Zhang, Zhiyong Hou
RATIONALE: Necrotizing fasciitis (NF) is defined as a rare, life-threatening, rapidly spreading soft tissue infection resulting from a polymicrobial origin, with a predominance of anaerobic organisms that presents with necrosis of the muscle, fascia, and surrounding soft tissue. PATIENT CONCERNS AND DIAGNOSES: A 64-year-old male who sustained tibia fracture caused by falling from a height underwent a tibia surgery with minimally invasive plate osteosynthesis technique in another institution...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28588627/comparative-investigations-of-infectious-runting-and-stunting-syndrome-in-vaccinated-breeder-chicks-by-inactivated-reovirus-and-chicks-from-non-vaccinated-breeders
#20
S P Awandkar, S D Moregaonkar, S J Manwar, B P Kamdi, M B Kulkarni
Reoviruses are important pathogens responsible for poor growth performance and silent losses in the poultry industry. They are associated with many disease and syndromes such as malabsorption (runting and stunting syndrome), respiratory diseases and immunosuppression. Broiler birds are most susceptible to viral infections during the early post hatching period. Therefore, the transfer of maternal immunity to embryonated eggs is proved to be a primary means of protection from viral infections. In the present investigation, growth performance and pathology in breeder vaccinated and non-vaccinated chicks were studied after a challenge with the homologous malabsorption strain of the reovirus...
2017: Iranian journal of veterinary research
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