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https://www.readbyqxmd.com/read/28515361/lupus-and-proliferative-nephritis-are-pad4-independent-in-murine-models
#1
Rachael A Gordon, Jan M Herter, Florencia Rosetti, Allison M Campbell, Hiroshi Nishi, Michael Kashgarian, Sheldon I Bastacky, Anthony Marinov, Kevin M Nickerson, Tanya N Mayadas, Mark J Shlomchik
Though recent reports suggest that neutrophil extracellular traps (NETs) are a source of antigenic nucleic acids in systemic lupus erythematosus (SLE), we recently showed that inhibition of NETs by targeting the NADPH oxidase complex via cytochrome b-245, β polypeptide (cybb) deletion exacerbated disease in the MRL.Faslpr lupus mouse model. While these data challenge the paradigm that NETs promote lupus, it is conceivable that global regulatory properties of cybb and cybb-independent NETs confound these findings...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28515156/anti-glomerular-basement-membrane-disease
#2
Stephen P McAdoo, Charles D Pusey
Anti-glomerular basement membrane (anti-GBM) disease is a rare small vessel vasculitis that affects the capillary beds of the kidneys and lungs. It is an archetypic autoimmune disease, caused by the development of directly pathogenic autoantibodies targeting a well characterized autoantigen expressed in the basement membranes of these organs, although the inciting events that induce the autoimmune response are not fully understood. The recent confirmation of spatial and temporal clustering of cases suggests that environmental factors, including infection, may trigger disease in genetically susceptible individuals...
May 17, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28509135/renal-limited-vasculitis-with-elevated-levels-of-multiple-antibodies
#3
Noriaki Sato, Hideki Yokoi, Hirotaka Imamaki, Eiichiro Uchino, Kaoru Sakai, Takeshi Matsubara, Tatsuo Tsukamoto, Sachiko Minamiguchi, Motoko Yanagita
Renal-limited vasculitis (RLV) is a type of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis that presents with crescentic glomerulonephritis with no other organ involvement. Although several studies reported patients with crescentic glomerulonephritis who were dual positive for proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA or ANCA and anti-glomerular basement membrane (GBM) antibody, patients positive for all three antibodies, i.e., triple-positive patients, were rarely reported. We herein report the case of a male with pauci-immune type crescentic glomerulonephritis positive for MPO-ANCA, PR3-ANCA, and anti-GBM antibody...
May 2017: CEN Case Reports
https://www.readbyqxmd.com/read/28509125/a-case-of-pr3-anca-positive-anti-gbm-disease-associated-with-intrarenal-arteritis-and-thrombotic-microangiopathy
#4
Shun Manabe, Mayuko Banno, Marie Nakano, Teruhiro Fujii, Yukio Kakuta, Kosaku Nitta, Michiyasu Hatano
Coexistence of anti-glomerular basement membrane (anti-GBM) disease with anti-neutrophil cytoplasmic antibody (ANCA) is occasionally reported and termed "double positive" disease. Interestingly, the majority of "double positive" ANCA is myeloperoxidase (MPO)-ANCA, and some of the MPO-ANCA-positive cases reveal intrarenal arteritis indicating an ANCA-associated renal lesion. In contrast, proteinase 3 (PR3)-ANCA-positive "double positive" disease had rarely been reported, and as far as we know, none of the cases showed intrarenal arteritis...
May 2017: CEN Case Reports
https://www.readbyqxmd.com/read/28509118/anti-glomerular-basement-membrane-disease-accompanied-by-systemic-lupus-erythematosus-presenting-central-nervous-system-involvement
#5
Hirohito Sugawara, Hideki Takizawa, Yoshinosuke Shimamura, Norihito Moniwa, Koichi Hasegawa, Yayoi Ogawa
We report a case of rapidly progressive glomerulonephritis caused by anti-glomerular basement membrane (GBM) disease accompanied by systemic lupus erythematosus (SLE) presenting central nervous system involvement in a 32-year-old Japanese male. He was admitted to our hospital because of a 3-week history of fever and rapidly failing renal function requiring hemodialysis (HD). Laboratory tests showed anti-GBM antibody elevation with a value of 16,385 units/ml. On day 85, he had generalized tonic-clonic seizure...
May 2017: CEN Case Reports
https://www.readbyqxmd.com/read/28507806/preclinical-efficacy-of-immune-checkpoint-monotherapy-does-not-recapitulate-corresponding-biomarkers-based-clinical-predictions-in-glioblastoma
#6
Abhishek D Garg, Lien Vandenberk, Matthias Van Woensel, Jochen Belmans, Marco Schaaf, Louis Boon, Steven De Vleeschouwer, Patrizia Agostinis
Glioblastoma (GBM) is resistant to most multimodal therapies. Clinical success of immune-checkpoint inhibitors (ICIs) has spurred interest in applying ICIs targeting CTLA4, PD1 or IDO1 against GBM. This amplifies the need to ascertain GBM's intrinsic susceptibility (or resistance) toward these ICIs, through clinical biomarkers that may also "guide and prioritize" preclinical testing. Here, we interrogated the TCGA and/or REMBRANDT human patient-cohorts to predict GBM's predisposition toward ICIs. We exploited various broad clinical biomarkers, including mutational or predicted-neoantigen burden, pre-existing or basal levels of tumor-infiltrating T lymphocytes (TILs), differential expression of immune-checkpoints within the tumor and their correlation with particular TILs/Treg-associated functional signature and prognostic impact of differential immune-checkpoint expression...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28506760/patients-double-seropositive-for-anca-and-anti-gbm-antibodies-have-varied-renal-survival-frequency-of-relapse-and-outcomes-compared-to-single-seropositive-patients
#7
Stephen P McAdoo, Anisha Tanna, Zdenka Hrušková, Lisa Holm, Maria Weiner, Nishkantha Arulkumaran, Amy Kang, Veronika Satrapová, Jeremy Levy, Sophie Ohlsson, Vladimir Tesar, Mårten Segelmark, Charles D Pusey
Co-presentation with both ANCA and anti-GBM antibodies is thought to be relatively rare. Current studies of such 'double-positive' cases report small numbers and variable outcomes. To study this further we retrospectively analyzed clinical features and long-term outcomes of a large cohort of 568 contemporary patients with ANCA-associated vasculitis, 41 patients with anti-GBM disease, and 37 double-positive patients with ANCA and anti-GBM disease from four European centers. Double-positive patients shared characteristics of ANCA-associated vasculitis (AAV), such as older age distribution and longer symptom duration before diagnosis, and features of anti-GBM disease, such as severe renal disease and high frequency of lung hemorrhage at presentation...
May 12, 2017: Kidney International
https://www.readbyqxmd.com/read/28504686/ndga-p21-a-novel-derivative-of-nordihydroguaiaretic-acid-inhibits-glioma-cell-proliferation-and-stemness
#8
Qi-Wen Zhao, Yong Lin, Chang-Rong Xu, Yue-Liang Yao, You-Hong Cui, Xia Zhang, Xiu-Wu Bian
Nordihydroguaiaretic acid (NDGA) and its synthetic chiral analog dl-nordihydroguaiaretic acid (Nordy) show collective benefits in anti-tumor, and defending against viral and bacterial infections. Here, we synthetized a new derivative-NDGA-P21 based on NDGA structure. Regardless of the structural similarity, NDGA-P21 exhibited stronger capability in suppression of glioblastoma (GBM) cell growth as compared to Nordy. Mechanically, NDGA-P21 is able to arrest cell cycle of GBM cells in G0/G1 phase, and to block cell proliferation sequentially...
May 15, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28498803/differentially-expressed-proteins-in-glioblastoma-multiforme-identified-with-a-nanobody-based-anti-proteome-approach-and-confirmed-by-oncofinder-as-possible-tumor-class-predictive-biomarker-candidates
#9
Ivana Jovčevska, Neja Zupanec, Žiga Urlep, Andrej Vranič, Boštjan Matos, Clara Limbaeck Stokin, Serge Muyldermans, Michael P Myers, Anton A Buzdin, Ivan Petrov, Radovan Komel
Glioblastoma multiforme is the most frequent primary malignancy of the central nervous system. Despite remarkable progress towards an understanding of tumor biology, there is no efficient treatment and patient outcome remains poor. Here, we present a unique anti-proteomic approach for selection of nanobodies specific for overexpressed glioblastoma proteins. A phage-displayed nanobody library was enriched in protein extracts from NCH644 and NCH421K glioblastoma cell lines. Differential ELISA screenings revealed seven nanobodies that target the following antigens: the ACTB/NUCL complex, VIM, NAP1L1, TUFM, DPYSL2, CRMP1, and ALYREF...
April 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28497778/pten-regulates-glioblastoma-oncogenesis-through-chromatin-associated-complexes-of-daxx-and-histone-h3-3
#10
Jorge A Benitez, Jianhui Ma, Matteo D'Antonio, Antonia Boyer, Maria Fernanda Camargo, Ciro Zanca, Stephen Kelly, Alireza Khodadadi-Jamayran, Nathan M Jameson, Michael Andersen, Hrvoje Miletic, Shahram Saberi, Kelly A Frazer, Webster K Cavenee, Frank B Furnari
Glioblastoma (GBM) is the most lethal type of human brain cancer, where deletions and mutations in the tumour suppressor gene PTEN (phosphatase and tensin homolog) are frequent events and are associated with therapeutic resistance. Herein, we report a novel chromatin-associated function of PTEN in complex with the histone chaperone DAXX and the histone variant H3.3. We show that PTEN interacts with DAXX and, in turn PTEN directly regulates oncogene expression by modulating DAXX-H3.3 association on the chromatin, independently of PTEN enzymatic activity...
May 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28494176/comparative-analysis-of-the-effects-of-a-sphingosine-kinase-inhibitor-to-temozolomide-and-radiation-treatment-on-glioblastoma-cell-lines
#11
Liliana R Oancea-Castillo, Carmen Klein, Amir Abdollahi, Klaus-Josef Weber, Anne Régnier-Vigouroux, Ivana Dokic
Glioblastoma multiforme (GBM) exhibits high resistance to the standard treatment of temozolomide (TMZ) combined with radiotherapy, due to its remarkable cell heterogeneity. Accordingly, there is a need to target alternative molecules enhancing specific GBM autocrine or paracrine mechanisms and amplifying the effect of standard treatment. Sphingosine 1-phosphate (S1P) is such a lipid target molecule with an important role in cell invasion and proliferation. Sphingosine kinase inhibitors (SKI) prevent S1P formation and induce increased production of reactive oxygen species (ROS), which may potentiate radiation cytotoxicity...
May 11, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28487072/isocostunolide-inhibited-glioma-stem-cell-by-suppression-proliferation-and-inducing-caspase-dependent-apoptosis
#12
Zhi Dai, Shi-Rong Li, Pei-Feng Zhu, Lu Liu, Bei Wang, Ya-Ping Liu, Xiao-Dong Luo, Xu-Dong Zhao
Glioblastoma multiform (GBM) is a highly aggressive brain tumor with poor life expectancy, and glioma stem cells (GSCs) are a small population of tumor cells existed in GBM, in which GSCs response to drive GBM recurrence, invasion and contribute to the anti-cancer resistance. GSCs have been identified and developed as a therapeutic target for GBM and can be used in drugs screening. Isocostunolide is a natural sesquiterpenoid and contained abundant resource in medicinal plants, but the anti-cancer efficacies of it against GSCs are still unexplored...
April 26, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28477008/combination-therapy-with-micellarized-cyclopamine-and-temozolomide-attenuate-glioblastoma-growth-through-gli1-down-regulation
#13
Yu-Jie Liu, Ying-Cong Ma, Wen-Jie Zhang, Zhen-Zhen Yang, De-Sheng Liang, Zhi-Fu Wu, Xian-Rong Qi
Glioblastoma multiforme (GBM) is the most common and deadly brain cancer, characterized by its aggressive proliferation to adjacent tissue and high recurrence rate. We studied the efficacy and related mechanisms of the combination of cyclopamine (Cyp, a Sonic-hedgehog pathway (Shh) inhibitor) and temozolomide (TMZ, the clinically most used chemotherapeutic agent) in anti-GBM treatment. The micellarized Cyp (MCyp) showed better performance than Cyp solution in inhibiting GBM cells proliferation (3.77-fold against U87 MG cells and 3...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28476618/identification-of-repaglinide-as-a-therapeutic-drug-for-glioblastoma-multiforme
#14
Zui Xuan Xiao, Ruo Qiao Chen, Dian Xing Hu, Xiao Qiang Xie, Shang Bin Yu, Xiao Qian Chen
Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a median survival time of only 14 months after treatment. It is urgent to find new therapeutic drugs that increase survival time of GBM patients. To achieve this goal, we screened differentially expressed genes between long-term and short-term survived GBM patients from Gene Expression Omnibus database and found gene expression signature for the long-term survived GBM patients. The signaling networks of all those differentially expressed genes converged to protein binding, extracellular matrix and tissue development as revealed in BiNGO and Cytoscape...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28469165/the-regulatory-t-cell-transcription-factor-foxp3-protects-against-crescentic-glomerulonephritis
#15
Chen Yang, Xiao-Ru Huang, Erik Fung, Hua-Feng Liu, Hui-Yao Lan
Regulatory T cells (Tregs) have been shown to play a protective role in glomerulonephritis (GN) and Foxp3 is a master transcription factor in Treg development. In this study, we examined the functional role and mechanisms of Foxp3 in a mouse model of accelerated anti-glomerular basement membrane (anti-GBM) GN induced in antigen-primed Foxp3 transgenic (Tg) mice. Compared with littermate of wildtype (WT) mice in which induced severe crescentic GN developed with progressive renal dysfunction, Foxp3 Tg mice had reduced crescent formation, urinary protein excretion, plasma creatinine and decline in creatinine clearance...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28459999/diagnostic-and-management-challenges-in-goodpasture-s-anti-glomerular-basement-membrane-disease
#16
Scott R Henderson, Alan D Salama
Goodpasture's or anti-glomerular basement membrane (GBM) disease is classically characterized by the presence of circulating autoantibodies directed against the non-collagenous domain of the α3 chain of type IV collagen, targeting glomerular and alveolar basement membranes, and associated with rapidly progressive crescentic glomerulonephritis, with alveolar haemorrhage in over half the patients. However, there are increasing examples of variants or atypical presentations of this disease, and novel therapeutic options have been proposed, which nephrologists should be aware of...
April 28, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28459147/synergistic-effects-of-arsenic-trioxide-and-radiation-triggering-of-intrinsic-pathway-of-apoptosis
#17
Kave Moloudi, Ali Neshasteriz, Arshad Hosseini, Nazila Eyvazzadeh, Mehdi Shomali, Samira Eynali, Elahe Mirzaei, Asaad Azarnezhad
Background: Arsenic trioxide (ATO) has been reported as an effective anti-cancer and a US Food and Drug Administration (FDA) approved drug for treatment of some cancers. The aim of this study is to determine the underlying apoptosis molecular and cellular mechanisms of ATO in the presence or absence of ionizing radiation (IR) in vitro in the glioblastoma multiforme (GBM) cell line, U87MG. Methods: Cells were treated by different concentrations of ATO either in presence or absence of IR...
May 1, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28457424/what-can-we-do-when-all-collapses-fatal-outcome-of-collapsing-glomerulopathy-and-systemic-lupus-erythematosus-with-diffuse-alveolar-hemorrhage-case-report
#18
H Pinto, R Leal, L Rodrigues, L Santos, C Romãozinho, F Macário, R Alves, J Pratas, V Sousa, C Marinho, L Prado E Castro, F Costa, M Campos, A Mota, A Figueiredo
INTRODUCTION: Collapsing glomerulopathy (CG) is a rare form of glomerular injury. Although commonly associated with human immunodeficiency virus (HIV) infection, it can occur in association with systemic lupus erythematosus (SLE). CASE REPORT: We present the case of a 50-year-old man, with chronic kidney disease secondary to focal and segmental glomerulosclerosis, who received a cadaveric kidney transplant in 2007. There were no relevant intercurrences until May 2015, when he presented with nephrotic range proteinuria (± 4 g/d)...
May 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28454354/pt93-a-novel-caffeic-acid-amide-derivative-suppresses-glioblastoma-cells-migration-proliferation-and-mmp-2-9-expression
#19
Kaishu Li, Yalin Tu, Qingyu Liu, Ying Ouyang, Mingliang He, Ming Luo, Jingkao Chen, Rongbiao Pi, Anmin Liu
Glioblastoma multiforme (GBM) is the most malignant type of primary brain tumor in adults and can diffusely infiltrate adjacent normal tissue. GBM is therefore rarely cured by surgery or radiation therapy. Matrix metalloproteinases (MMPs) are involved in tissue remodeling and numerous other physiological progresses. The MMPs MMP-2 and MMP-9 are associated with the invasion ability of GBM. PT93 is a novel caffeic acid amide derivative that was first synthesized in 2013. In the present study, the human GBM T98G, U87 and U251 cell lines and the normal mouse neuron HT22 cell line were used to investigate the anticancer and cytotoxic effects of PT93 in vitro...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28453552/specific-blockade-of-rictor-mtor-association-inhibits-mtorc2-activity-and-is-cytotoxic-in-glioblastoma
#20
Angelica Benavides-Serrato, Jihye Lee, Brent Holmes, Kenna A Landon, Tariq Bashir, Michael E Jung, Alan Lichtenstein, Joseph Gera
A small molecule which specifically blocks the interaction of Rictor and mTOR was identified utilizing a high-throughput yeast two-hybrid screen and evaluated as a potential inhibitor of mTORC2 activity in glioblastoma multiforme (GBM). In vitro, CID613034 inhibited mTORC2 kinase activity at submicromolar concentrations and in cellular assays specifically inhibited phosphorylation of mTORC2 substrates, including AKT (Ser-473), NDRG1 (Thr-346) and PKCα (Ser-657), while having no appreciable effects on the phosphorylation status of the mTORC1 substrate S6K (Thr-389) or mTORC1-dependent negative feedback loops...
2017: PloS One
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