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https://www.readbyqxmd.com/read/28646772/prevalence-of-immune-related-systemic-adverse-events-in%C3%A2-patients-treated-with-anti-programmed-cell-death-1-anti-programmed-cell-death-ligand-1-agents-a-single-centre-pharmacovigilance-database-analysis
#1
Sébastien Le Burel, Stéphane Champiat, Christine Mateus, Aurélien Marabelle, Jean-Marie Michot, Caroline Robert, Rakiba Belkhir, Jean-Charles Soria, Salim Laghouati, Anne-Laure Voisin, Olivier Fain, Arsène Mékinian, Laetitia Coutte, Tali-Anne Szwebel, Laetitia Dunogeant, Bertrand Lioger, Cécile Luxembourger, Xavier Mariette, Olivier Lambotte
AIM: The growing use of immune checkpoint inhibitors (ICIs) is associated with the occurrence of immune-related adverse events (irAEs). Few data are published on systemic, immunohaematological and rheumatic irAEs. In a pharmacovigilance database analysis, we screened for these irAEs and calculated their prevalence. PATIENTS AND METHODS: Participants were recruited via Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie (REISAMIC)(1) a French registry of grade ≥2 irAEs occurring in ICI-treated patients...
June 21, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28646771/efficacy-of-alectinib-in-central-nervous-system-metastases-in-crizotinib-resistant-alk-positive-non-small-cell-lung-cancer-comparison-of-recist-1-1-and-rano-hgg-criteria
#2
Leena Gandhi, Sai-Hong Ignatius Ou, Alice T Shaw, Fabrice Barlesi, Anne-Marie C Dingemans, Dong-Wan Kim, D Ross Camidge, Brett G M Hughes, James C-H Yang, Javier de Castro, Lucio Crino, Hervé Léna, Pascal Do, Sophie Golding, Walter Bordogna, Ali Zeaiter, Ahmed Kotb, Shirish Gadgeel
BACKGROUND: Central nervous system (CNS) progression is common in patients with anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer (NSCLC) receiving crizotinib. Next-generation ALK inhibitors have shown activity against CNS metastases, but accurate assessment of response and progression is vital. Data from two phase II studies in crizotinib-refractory ALK+ NSCLC were pooled to examine the CNS efficacy of alectinib, a CNS-active ALK inhibitor, using Response Evaluation Criteria in Solid Tumours (RECIST version 1...
June 21, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28646664/wogonin-attenuates-inflammation-by-activating-ppar-%C3%AE-in-alcoholic-liver-disease
#3
Hai-Di Li, Xin Chen, Yang Yang, Hui-Min Huang, Ling Zhang, Xin Zhang, Lei Zhang, Cheng Huang, Xiao-Ming Meng, Jun Li
Alcoholic liver disease (ALD) is one of the predominant causes of liver-related morbidity and mortality worldwide. However, effective therapy for ALD is still lacking. Wogonin, a major flavonoid compound, is found in Scutellaria baicalensis Georgi. Accumulating studies have revealed that wogonin possesses anti-inflammatory and anti-tumour activities in various models. However, the hepatoprotective activity of wogonin in ALD is still obscure. In this study, we found that wogonin significantly attenuated inflammatory response in EtOH-fed mice, and reduced the expression of inflammatory cytokines such as TNF-α and IL-6 in EtOH-induced RAW264...
June 21, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28646646/antileukemic-activity-and-cellular-effects-of-the-antimalarial-agent-artesunate-in-acute-myeloid-leukemia
#4
Bijender Kumar, Arjun Kalvala, Su Chu, Steven Rosen, Stephen J Forman, Guido Marcucci, Ching-Cheng Chen, Vinod Pullarkat
The artimisinins are a class of antimalarial compounds whose antiparasitic activity is mediated by induction of reactive oxygen species (ROS). Herein, we report that among the artimisinins, artesunate (ARTS), an orally bioavailable compound has the most potent antileukemic activity in AML models and primary patients' blasts. ARTS was most cytotoxic to the FLT3-ITD+ AML MV4-11 and MOLM-13 cells (IC50 values of 1.1 and 0.82μM respectively), inhibited colony formation in primary AML and MDS cells and augmented cytotoxicity of chemotherapeutics...
May 10, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28646616/curcumin-alleviates-macrophage-activation-and-lung-inflammation-induced-by-influenza-virus-infection-through-inhibiting-the-nf-%C3%AE%C2%BAb-signaling-pathway
#5
Yiming Xu, Ling Liu
BACKGROUND: Influenza A viruses (IAV) result in severe public health problems with worldwide each year. Over-response of immune system to IAV infection leads to complications, and ultimately causing morbidity and mortality. OBJECTIVE: Curcumin has been reported to have anti-inflammatory ability. However, its molecular mechanism in immune responses remains unclear. METHODS: We detected the pro-inflammatory cytokine secretion and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) related protein expression in human macrophages or mice infected by IAV with or without curcumin treatment...
June 24, 2017: Influenza and Other Respiratory Viruses
https://www.readbyqxmd.com/read/28646606/vismodegib-for-recurrent-locally-destructive-basal-cell-carcinoma-in-a-renal-transplant-patient
#6
P Koelblinger, R Dummer, M Laimer, S Hecht, J W Bauer, A Gaggl, A Kugler
Solid organ transplant patients are at an increased risk of developing cutaneous malignancies owing to long-lasting immunosuppression. The strongest increase in incidence (35-fold) has been reported for cutaneous squamous cell carcinoma [1]. Basal cell carcinoma (BCC) may occur even more frequently, especially during the first years after transplantation [2]. The hedgehog-inhibitor vismodegib has been safely used for the treatment of locally advanced or metastatic BCC in immunocompetent patients since 2012 [3]...
June 24, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28646585/prognostic-value-of-cell-cycle-arrest-biomarkers-in-patients-at-high-risk-for-acute-kidney-injury-a-systematic-review-and-meta-analysis
#7
REVIEW
Hui-Miao Jia, Li-Feng Huang, Yue Zheng, Wen-Xiong Li
AIM: Urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) are G1 cell cycle arrest biomarkers. This systematic review aimed to evaluate the prognostic value of urinary [TIMP-2]·[IGFBP7] in patients at high risk for AKI. METHODS: The MEDLINE (via PubMed), Ovid, EMBASE and Cochrane Library databases were systematically searched from inception to December 25, 2016. Original clinical studies which met the eligibility criteria were included in this study...
June 24, 2017: Nephrology
https://www.readbyqxmd.com/read/28646565/complete-molecular-remission-in-relapsed-and-refractory-acute-myeloid-leukaemia-with-mll-af9-treated-with-chidamide-based-chemotherapy
#8
Y Lun, J-J Yang, Y Wu
WHAT IS KNOWN AND OBJECTIVE: The mixed lineage leukaemia (MLL) gene translocations are found in approximately 10% of adults with acute myeloid leukaemia (AML) and are markers of poor prognosis. As the best reported response in relapsed and refractory MLL-rearranged AML is around 40%, reinduction treatment is very challenging for those patients. CASE DESCRIPTION: We report a case of relapsed and refractory AML with MLL-AF9, who did not respond to FLAG (fludarabine, cytarabine, granulocyte colony stimulating factor) regimen reinduction treatment, but achieved complete response and molecular remission after chidamide-based chemotherapy...
June 23, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28646552/targeting-histone-deacetylase-4-ubc9-impairs-dna-repair-for-radiosensitization-of-hepatocellular-carcinoma-cells
#9
Chiao-Ling Tsai, Wei-Lin Liu, Feng-Ming Hsu, Po-Sheng Yang, Ruoh-Fang Yen, Kai-Yuan Tzen, Ann-Lii Cheng, Pei-Jer Chen, Jason Chia-, Hsien Cheng
Several strategies to improve the efficacy of radiation therapy against hepatocellular carcinoma (HCC) have been investigated. One approach was to develop radiosensitizing compounds. Because histone deacetylase 4 (HDAC4) is highly expressed in liver cancer and known to regulate oncogenesis through chromatin structure remodeling and controlling protein access to DNA, we postulated that HDAC4 inhibition might enhance radiation's effect on HCC cells. HCC cell lines (Huh7 and PLC5) and an ectopic xenograft were pretreated with HDAC inhibitor or shRNA to knock down expression of HDAC4, and then irradiated (2...
June 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28646535/targeting-stat3-by-ho3867-induces-apoptosis-in-ovarian-clear-cell-carcinoma
#10
Kristin Bixel, Uksha Saini, Hemant Kumar Bid, John Fowler, Maria Riley, Ross Wanner, Kalpana Deepa Priya Dorayappan, Sneha Rajendran, Ikuo Konishi, Noriomi Matsumura, David E Cohn, Karuppaiyah Selvendiran
Advanced ovarian clear cell carcinoma (OCCC) carries a very poor prognosis in large part secondary to the extremely high rate of resistance to standard platinum and taxane chemotherapy. STAT3 expression and activation has been shown to regulate tumor progression in various human cancers, though has not been well studied in OCCC. Preliminary work in our lab has demonstrated constitutive activation of STAT3 (pSTAT3Tyr705 or pSTAT3727) in OCCC cell lines as well as human OCCC tumor tissue samples. Significantly, pSTAT3 is expressed in the absence of other forms of activated STAT (pSTAT1, 2, 6)...
June 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28646512/wmj-8-b-a-novel-hydroxamate-derivative-induces-mda-mb-231-breast-cancer-cell-death-via-shp-1-stat3-survivin-cascade
#11
Yu-Fan Chuang, Shiu-Wen Huang, Ya-Fen Hsu, Meng-Chieh Yu, George Ou, Wei-Jan Huang, Ming-Jen Hsu
BACKGROUND AND PURPOSE: Histone deacetylase (HDAC) inhibitors with broad-spectrum anti-tumor properties has been described and attracted lots of attention in the field of drug discovery. However, the underlying anti-tumor mechanisms of HDAC inhibitors remain incompletely understood. In this study, we aimed to characterize the underlying mechanisms of a novel hydroxamate-based HDAC inhibitor, WMJ-8-B, in inducing MDA-MB-231 breast cancer cell death. EXPERIMENTAL APPROACH: WMJ-8-B's effects on cell viability, cell cycle distribution, apoptosis, as well as signaling molecules modification and activation were analyzed by MTT assay, flowcytometric analysis, immunoblotting, reporter assay, ChIP analysis and siRNA strategy...
June 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28646493/src-family-kinase-phosphorylation-of-the-motor-domain-of-the-human-kinesin-5-eg5
#12
Kathleen G Bickel, Barbara J Mann, Joshua S Waitzman, Taylor A Poor, Sarah E Rice, Patricia Wadsworth
Spindle formation in mammalian cells requires precise spatial and temporal regulation of the kinesin-5, Eg5, which generates outward force to establish spindle bipolarity. Our results demonstrate that Eg5 is phosphorylated in cultured cells by Src family kinases (SFKs) at three sites in the motor head: Y125, Y211, and Y231. Mutation of these sites diminishes motor activity in vitro, and replacement of endogenous Eg5 with phosphomimetic Y211 in LLC-Pk1 cells results in monopolar spindles, consistent with loss of Eg5 activity...
June 23, 2017: Cytoskeleton
https://www.readbyqxmd.com/read/28646488/mutation-in-the-fgfr1-tyrosine-kinase-domain-or-inactivation-of-pten-is-associated-with-acquired-resistance-to-fgfr-inhibitors-in-fgfr1-driven-leukemia-lymphomas
#13
John K Cowell, Haiyan Qin, Tianxiang Hu, Qing Wu, Aaron Bhole, Mingqiang Ren
Stem cell leukemia/lymphoma syndrome (SCLL) is driven by constitutive activation of chimeric FGFR1 kinases generated by chromosome translocations. We have shown that FGFR inhibitors significantly suppress leukemia and lymphoma development in vivo, and cell viability in vitro. Since resistance to targeted therapies is a major reason for relapse, we developed FGFR1-overexpressing mouse and human cell lines that are resistant to the specific FGFR inhibitors AZD4547 and BGJ398, as well as non-specific inhibitors, such as ponatinib, TKI258 and E3810...
June 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28646304/ndrg2-knockdown-promotes-fibrosis-in-renal-tubular-epithelial-cells-through-tgf-%C3%AE-1-smad3-pathway
#14
Zhibo Jin, Chaohui Gu, Fengyan Tian, Zhankui Jia, Jinjian Yang
Renal fibrosis is a common pathological pathway of various chronic kidney diseases progressing to end-stage renal disease and is characterized by tubular atrophy, fibroblast/myofibroblast activation and excessive deposition of extracellular matrix (ECM). N-Myc downstream-regulated gene-2 (NDRG2) is reported to be associated with liver fibrosis in rats. However, the biological function of NDRG2 in renal fibrosis remains unclear. Therefore, we investigate the effect of NDRG2 on renal fibrosis and the underlying mechanism of NDRG2 in TGF-β1-induced renal tubular epithelial cells (HK-2)...
June 23, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28646226/a-microrna-signature-of-response-to-erlotinib-is-descriptive-of-tgf%C3%AE-behaviour-in-nsclc
#15
Madeline Krentz Gober, James P Collard, Katherine Thompson, Esther P Black
Our previous work identified a 13-gene miRNA signature predictive of response to the epidermal growth factor receptor (EGFR) inhibitor, erlotinib, in Non-Small Cell Lung Cancer cell lines. Bioinformatic analysis of the signature showed a functional convergence on TGFβ canonical signalling. We hypothesized that TGFβ signalling controls expression of the miRNA genes comprising an erlotinib response signature in NSCLC. Western analysis revealed that TGFβ signalling via Smad2/3/4 occurred differently between erlotinib-resistant A549 and erlotinib- sensitive PC9 cells...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646172/dacomitinib-a-pan-inhibitor-of-erbb-receptors-suppresses-growth-and-invasive-capacity-of-chemoresistant-ovarian-carcinoma-cells
#16
Majid Momeny, Ghazaleh Zarrinrad, Farima Moghaddaskho, Arash Poursheikhani, Ghazaleh Sankanian, Azam Zaghal, Shahab Mirshahvaladi, Fatemeh Esmaeili, Haniyeh Eyvani, Farinaz Barghi, Zahra Sabourinejad, Zivar Alishahi, Hassan Yousefi, Reza Ghasemi, Leila Dardaei, Davood Bashash, Bahram Chahardouli, Ahmad R Dehpour, Javad Tavakkoly-Bazzaz, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy worldwide. Development of chemoresistance and peritoneal dissemination of EOC cells are the major reasons for low survival rate. Targeting signal transduction pathways which promote therapy resistance and metastatic dissemination is the key to successful treatment. Members of the ErbB family of receptors are over-expressed in EOC and play key roles in chemoresistance and invasiveness. Despite this, single-targeted ErbB inhibitors have demonstrated limited activity in chemoresistant EOC...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646158/metabolic-recovery-of-lipodystrophy-liver-steatosis-and-pancreatic-%C3%AE-cell-proliferation-after-the-withdrawal-of-osi-906
#17
Kazuki Tajima, Jun Shirakawa, Yu Togashi, Shunsuke Yamazaki, Tomoko Okuyama, Mayu Kyohara, Hiromi Konishi, Yasuo Terauchi
Growth factor signaling via insulin receptor (IR) and IGF-1 receptor (IGF1R) plays several important roles in the pathogenesis of metabolic syndrome and diabetes. OSI-906 (linsitinib), an anti-tumor drug, is an orally bioavailable dual inhibitor of IR and IGF1R. To investigate the recovery from metabolic changes induced by the acute inhibition of IR and IGF1R in adult mice, mice were treated with OSI-906 or a vehicle for 7 days and the results were analyzed on the last day of injection (Day 7) or after 7 or 21 days of withdrawal (Day 14 or Day 28)...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646117/cyclin-dependent-kinase-9-is-a-novel-specific-molecular-target-in-adult-t-cell-leukemia-lymphoma
#18
Tomoko Narita, Takashi Ishida, Asahi Ito, Ayako Masaki, Shiori Kinoshita, Susumu Suzuki, Hisashi Takino, Takashi Yoshida, Masaki Ri, Shigeru Kusumoto, Hirokazu Komatsu, Kazunori Imada, Yuetsu Tanaka, Takaori-Kondo Akifumi, Hiroshi Inagaki, Arne Scholz, Philip Lienau, Taruho Kuroda, Ryuzo Ueda, Shinsuke Iida
Cyclin-dependent kinase 9 (CDK9), a subunit of the positive transcription elongation factor b (P-TEFb) complex, regulates gene transcription elongation by phosphorylating the carboxy-terminal domain (CTD) of RNA polymerase II (RNAPII).  The deregulation of CDK9/P-TEFb has important implications for many cancer types.  BAY 1143572 is a novel and highly selective CDK9/P-TEFb inhibitor currently being investigated in phase I studies. We evaluated the therapeutic potential of BAY 1143572 in adult T-cell leukemia/lymphoma (ATL)...
June 23, 2017: Blood
https://www.readbyqxmd.com/read/28646039/monocyte-adhesion-migration-and-extracellular-matrix-breakdown-is-regulated-by-integrin-%C3%AE-v%C3%AE-3-in-mycobacterium-tuberculosis-infection
#19
Sara Brilha, Riccardo Wysoczanski, Ashley M Whittington, Jon S Friedland, Joanna C Porter
In tuberculosis (TB), the innate inflammatory immune response drives tissue destruction, morbidity, and mortality. Monocytes secrete matrix metalloproteinases (MMPs), which have key roles in local tissue destruction and cavitation. We hypothesized that integrin signaling might regulate monocyte MMP secretion in pulmonary TB during cell adhesion to the extracellular matrix (ECM). Adhesion to type I collagen and fibronectin by Mycobacterium tuberculosis-stimulated monocytes increased MMP-1 gene expression by 2...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28646031/metabolism-and-acetylation-contribute-to-leucine-mediated-inhibition-of-cardiac-glucose-uptake
#20
Edith Renguet, Audrey Ginion, Roselle Gélinas, Laurent Bultot, Julien Auquier, Isabelle Robillard Frayne, Caroline Daneault, Jean-Louis Vanoverschelde, Christine Des Rosiers, Louis Hue, Sandrine Horman, Christophe Beauloye, Luc Bertrand
High plasma leucine levels strongly correlate with type 2 diabetes. Studies of muscle cells suggest that leucine alters the insulin response for glucose transport by activating an insulin-negative feedback loop driven by the mammalian target of rapamycin/p70 ribosomal S6 kinase (mTOR/p70S6K) pathway. Here, we examined the molecular mechanism involved in leucine's action on cardiac glucose uptake. Leucine was indeed able to curb glucose uptake after insulin stimulation in both cultured cardiomyocytes and perfused hearts...
June 23, 2017: American Journal of Physiology. Heart and Circulatory Physiology
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