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https://www.readbyqxmd.com/read/28095907/the-targeted-smac-mimetic-sw-iv-134-is-a-strong-enhancer-of-standard-chemotherapy-in-pancreatic-cancer
#1
Yassar M Hashim, Suwanna Vangveravong, Narendra V Sankpal, Pratibha S Binder, Jingxia Liu, S Peter Goedegebuure, Robert H Mach, Dirk Spitzer, William G Hawkins
BACKGROUND: Pancreatic cancer is a lethal malignancy that frequently acquires resistance to conventional chemotherapies often associated with overexpression of inhibitors of apoptosis proteins (IAPs). We have recently described a novel means to deliver second mitochondria-derived activator of caspases (SMAC) mimetics selectively to cancer cells employing the sigma-2 ligand/receptor interaction. The intrinsic death pathway agonist SMAC offers an excellent opportunity to counteract the anti-apoptotic activity of IAPs...
January 17, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28077494/practice-guideline-summary-use-of-fmri-in-the-presurgical-evaluation-of-patients-with-epilepsy-report-of-the-guideline-development-dissemination-and-implementation-subcommittee-of-the-american-academy-of-neurology
#2
Jerzy P Szaflarski, David Gloss, Jeffrey R Binder, William D Gaillard, Alexandra J Golby, Scott K Holland, Jeffrey Ojemann, David C Spencer, Sara J Swanson, Jacqueline A French, William H Theodore
OBJECTIVE: To assess the diagnostic accuracy and prognostic value of functional MRI (fMRI) in determining lateralization and predicting postsurgical language and memory outcomes. METHODS: An 11-member panel evaluated and rated available evidence according to the 2004 American Academy of Neurology process. At least 2 panelists reviewed the full text of 172 articles and selected 37 for data extraction. Case reports, reports with <15 cases, meta-analyses, and editorials were excluded...
January 11, 2017: Neurology
https://www.readbyqxmd.com/read/28061770/viscumtt-induces-apoptosis-and-alters-iap-expression-in-osteosarcoma-in-vitro-and-has-synergistic-action-when-combined-with-different-chemotherapeutic-drugs
#3
Susann Kleinsimon, Gwenda Kauczor, Sebastian Jaeger, Angelika Eggert, Georg Seifert, Catharina Delebinski
BACKGROUND: Osteosarcoma is the most common bone tumor and is associated with a poor prognosis. Conventional therapies, surgery and chemotherapy, are still the standard but soon reach their limits. New therapeutic approaches are therefore needed. Conventional aqueous mistletoe extracts from the European mistletoe (Viscum album L.) are used in complementary cancer treatment. These commercial extracts are water-based and do not include water-insoluble compounds such as triterpenic acids...
January 7, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28057023/xiap-bir-domain-suppresses-mir-200a-expression-and-subsequently-promotes-egfr-protein-translation-and-anchorage-independent-growth-of-bladder-cancer-cell
#4
Chao Huang, Xingruo Zeng, Guosong Jiang, Xin Liao, Claire Liu, Jingxia Li, Honglei Jin, Junlan Zhu, Hong Sun, Xue-Ru Wu, Chuanshu Huang
BACKGROUND: The X-linked inhibitor of apoptosis protein (XIAP) is a well-known potent apoptosis suppressor and also participates in cancer cell biological behaviors, therefore attracting great attentions as a potential antineoplastic therapeutic target for past years. Anti-IAP therapy is reported to be closely related to epidermal growth factor receptor (EGFR) expression level. However, whether and how XIAP modulates EGFR expression remains largely unknown. METHODS: Human XIAP was knockdown with short-hairpin RNA in two different bladder cancer cell lines, T24T and UMUC3...
January 5, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28050781/the-role-of-ciap1-and-xiap-in-apoptosis-induced-by-tumor-necrosis-factor-alpha-in-esophageal-squamous-cell-carcinoma-cells
#5
Shoichiro Hikami, Atsushi Shiozaki, Maki Kitagawa-Juge, Daisuke Ichikawa, Toshiyuki Kosuga, Hirotaka Konishi, Shuhei Komatsu, Hitoshi Fujiwara, Kazuma Okamoto, Eigo Otsuji
BACKGROUND: The inhibitor of apoptosis protein (IAP) family are reported to play important roles in cancer cells evading apoptosis. However, the significance of their expression in human esophageal squamous cell carcinoma (ESCC) cells remains uncertain. AIMS: The present study aimed to investigate the role of the IAP family members in tumor necrosis factor-α (TNF-α)-induced apoptosis of human ESCC cells. METHODS: Five human ESCC cell lines were pretreated with TNF-α, cycloheximide (CHX, protein synthesis inhibitor), epoxomicin (proteasome inhibitor)...
January 3, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28039474/preclinical-assesement-of-survivin-and-xiap-as-prognostic-biomarkers-and-therapeutic-targets-in-gastroenteropancreatic-neuroendocrine-neoplasia
#6
Levent Dizdar, Kira A Oesterwind, Jasmin C Riemer, Thomas A Werner, Sabrina Mersch, Birte Möhlendick, Sina C Schütte, Pablo E Verde, Katharina Raba, Stefan A Topp, Nikolas H Stoecklein, Irene Esposito, Wolfram T Knoefel, Andreas Krieg
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) represent a rare and heterogenous tumor entity. Importantly, the highly proliferative subgroup of neuroendocrine carcinoma (GEP-NEC) is characterized by high resistance to conventional chemotherapy. Consequently, there is an urgent need to identify novel therapeutic targets, especially for GEP-NEC. Thus, we focused on Inhibitor of apoptosis protein (IAP) family members survivin and XIAP that orchestrate inhibition of apoptosis, induce resistance against chemotherapeutics and facilitate tumor metastasis...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28039309/tissue-nonspecific-alkaline-phosphatase-expression-is-needed-for-the-full-stimulation-of-t-cells-and-t-cell-dependent-colitis
#7
Cristina Hernández-Chirlaque, Reyes Gámez-Belmonte, Borja Ocón, Patricia Martínez-Moya, Stefan Wirtz, Fermín Sánchez de Medina, Olga Martínez-Augustin
BACKGROUND AND AIMS: Two alkaline phosphatase isoforms, intestinal (IAP) and tissue non-specific alkaline phosphatase (TNAP), are coexpressed in mouse colon, with the latter predominating in colitis. We aimed to examine the role of TNAP in T lymphocytes using heterozygous TNAP(+/-) mice (as TNAP(-/-) mice are nonviable). METHODS: In vitro primary cultures and in vivo T cell models using TNAP(+/-) mice were used. RESULTS: Stimulated splenocytes (lipopolysaccharide and concanavalin A) and T lymphocytes (concanavalin A and a-CD3/a-CD28) showed a decreased cytokine production and expression when compared with WT cells...
December 30, 2016: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28039268/therapeutic-small-molecules-target-inhibitor-of-apoptosis-proteins-in-cancers-with-deregulation-of-extrinsic-and-intrinsic-cell-death-pathways
#8
Adeeb Derakhshan, Zhong Chen, Carter Van Waes
The Cancer Genome Atlas (TCGA) has unveiled genomic deregulation of various components of the extrinsic and intrinsic apoptotic pathways in different types of cancers. Such alterations are particularly common in head and neck squamous cell carcinomas (HNSCC), which frequently display amplification and overexpression of the Fas-associated via death domain (FADD) and inhibitor of apoptosis proteins (IAPs), that complex with members of the tumor necrosis factor (TNF) receptor family. SMAC mimetics, modeled after the endogenous IAP antagonist second mitochondria-derived activator of caspases (SMAC), and IAP inhibitors, represent important classes of novel small-molecules currently in phase I/II clinical trials...
December 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28038379/high-density-lipoprotein-hdl-associated-sphingosine-1-phosphate-s1p-inhibits-macrophage-apoptosis-by-stimulating-stat3-activity-and-survivin-expression
#9
Renata Feuerborn, Susen Becker, Francesco Potì, Petra Nagel, Martin Brodde, Harmut Schmidt, Christina Christoffersen, Uta Ceglarek, Ralph Burkhardt, Jerzy-Roch Nofer
BACKGROUND AND AIMS: Macrophage apoptosis is critically involved in atherosclerosis. We here examined the effect of anti-atherogenic high density lipoprotein (HDL) and its component sphingosine-1-phosphate (S1P) on apoptosis in RAW264.7 murine macrophages. METHODS: Mitochondrial or endoplasmic reticulum-dependent apoptosis was induced by exposure of macrophages to etoposide or thapsigargin/fukoidan, respectively. RESULTS: Cell death induced by these compounds was inhibited by S1P as inferred from reduced annexin V binding, TUNEL staining, and caspase 3, 9 and 12 activities...
December 9, 2016: Atherosclerosis
https://www.readbyqxmd.com/read/28036295/identification-of-mtor-as-a-primary-resistance-factor-of-the-iap-antagonist-at406-in-hepatocellular-carcinoma-cells
#10
Mao-Chuan Zhen, Fu-Qiang Wang, Shao-Feng Wu, Yi-Lin Zhao, Ping-Guo Liu, Zhen-Yu Yin
Dysregulation of inhibitor of apoptosis (IAP) proteins (IAPs) in hepatocellular carcinoma (HCC) is often associated with poor prognosis. Here we showed that AT406, an IAP antagonist, was cytotoxic and pro-apoptotic to both established (HepG2, SMMC-7721 lines) and primary HCC cells. Activation of mTOR could be a key resistance factor of AT406 in HCC cells. mTOR inhibition (by OSI-027), kinase-dead mutation or knockdown remarkably enhanced AT406-induced lethality in HCC cells. Reversely, forced-activation of mTOR by adding SC79 or exogenous expressing a constitutively active S6K1 (T389E) attenuated AT406-induced cytotoxicity against HCC cells...
December 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/28029353/intra-abdominal-hypertension-increases-spatial-qrs-t-angle-and-elevates-st-segment-j-point-in-healthy-women-undergoing-laparoscopic-surgery
#11
Wojciech Dabrowski, Andrzej Jaroszynski, Anna Jaroszynska, Ziemowit Rzecki, Todd T Schlegel, Manu Lng Malbrain
BACKGROUND: Intra-abdominal hypertension (IAH) impairs cardiovascular function, however an effect of IAH on cardiac electrophysiology has been poorly documented. The aim of this study was to evaluate the effect of IAH following pneumoperitoneum on vectorcardiographic variables reflecting cardiac repolarisation and depolarisation. METHODS: Otherwise healthy women undergoing elective gynaecological laparoscopy were studied. Intra-abdominal pressure (IAP), spatial QRS-T angle and ST-segment J-point (STJ) were observed during surgery and the early postoperative period...
October 13, 2016: Journal of Electrocardiology
https://www.readbyqxmd.com/read/28027920/examining-the-short-term-effects-of-emotion-under-an-adaptation-level-theory-model-of-tinnitus-perception
#12
Mithila Durai, Mary G O'Keeffe, Grant D Searchfield
OBJECTIVES: Existing evidence suggests a strong relationship between tinnitus and emotion. The objective of this study was to examine the effects of short-term emotional changes along valence and arousal dimensions on tinnitus outcomes. Emotional stimuli were presented in two different modalities: auditory and visual. The authors hypothesized that (1) negative valence (unpleasant) stimuli and/or high arousal stimuli will lead to greater tinnitus loudness and annoyance than positive valence and/or low arousal stimuli, and (2) auditory emotional stimuli, which are in the same modality as the tinnitus, will exhibit a greater effect on tinnitus outcome measures than visual stimuli...
December 24, 2016: Hearing Research
https://www.readbyqxmd.com/read/28027896/international-consensus-for-the-treatment-of-autoimmune-pancreatitis
#13
Kazuichi Okazaki, Suresh T Chari, Luca Frulloni, Markus M Lerch, Terumi Kamisawa, Shigeyuki Kawa, Myung-Hwan Kim, Philippe Lévy, Atsushi Masamune, George Webster, Tooru Shimosegawa
BACKGROUND AND AIMS: The International Consensus Diagnostic Criteria (ICDC) for AIP has proposed two distinctive type of AIP, type 1 and type 2, and enabled us first to differentiate two types of AIP each other. By initial steroid treatment for induction of remission, remission can be successfully induced in almost all subjects with type 1 and type 2 AIP. As relapse rate in type 1 AIP is significantly higher than in type 2 AIP, there has been ongoing debate on how to treat effectively relapse of type 1 AIP...
December 12, 2016: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28017431/who-consultation-on-group-b-streptococcus-vaccine-development-report-from-a-meeting-held-on-27-28-april-2016
#14
Miwako Kobayashi, Stephanie J Schrag, Mark R Alderson, Shabir A Madhi, Carol J Baker, Ajoke Sobanjo-Ter Meulen, David C Kaslow, Peter G Smith, Vasee S Moorthy, Johan Vekemans
Globally, group B Streptococcus (GBS) remains a leading cause of sepsis and meningitis in infants in the first 90days of life. Intrapartum antibiotic prophylaxis (IAP) for women at increased risk of transmitting GBS to their newborns has been effective in reducing part, but not all, of the GBS disease burden in many high income countries (HICs). In low- and middle-income countries (LMICs), IAP use is low. Immunization of pregnant women with a GBS vaccine represents an alternative strategy to protecting newborns and young infants, through transplacental antibody transfer and potentially by reducing new vaginal colonization...
December 22, 2016: Vaccine
https://www.readbyqxmd.com/read/28010158/abnormalities-of-language-pathways-in-schizophrenia-patients-with-and-without-a-lifetime-history-of-auditory-verbal-hallucinations-a-dti-based-tractography-study
#15
Elise Leroux, Nicolas Delcroix, Sonia Dollfus
OBJECTIVES: Auditory verbal hallucinations (AVHs) are frequently observed in patients with schizophrenia and could be the result of white matter (WM) fibre abnormalities involved in speech production/comprehension and perception. We evaluated WM integrity changes in schizophrenia with (SZ+) and without (SZ-) lifetime AVHs compared to healthy controls, using diffusion tensor imaging-based tractography, with a novel focus on the structural connectivity within both intra- and interhemispheric fasciculi...
December 23, 2016: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/28006677/the-alienation-of-affection-toward-parents-and-influential-factors-in-chinese-left-behind-children
#16
Q Dai, G Yang, C Hu, L Wang, K Liu, Y Guang, R Zhang, S Xu, B Liu, Y Yang, Z Feng
OBJECTIVE: Although alienation toward parents is important for children (for current mental health status or later interpersonal relationships in adulthood), it is undervalued and even lacks a standardized tool of assessment. Moreover, the large number of left-behind children in China is a cause of public concern. However, their experienced alienation toward their parents remains unclear, which may be important for early detection or intervention for behavioral problems in this population...
December 19, 2016: European Psychiatry: the Journal of the Association of European Psychiatrists
https://www.readbyqxmd.com/read/28004187/erratum-to-abstracts-xxxi-international-congress-of-the-iap-and-28th-congress-of-the-esp
#17
Bianca Machado, Catarina Meireles, Ana Pires-Luís, Manuel Jácome
No abstract text is available yet for this article.
December 22, 2016: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28003471/pirna-associated-proteins-and-retrotransposons-are-differentially-expressed-in-murine-testis-and-ovary-of-aryl-hydrocarbon-receptor-deficient-mice
#18
Eva M Rico-Leo, Nuria Moreno-Marín, Francisco J González-Rico, Eva Barrasa, Cristina Ortega-Ferrusola, Patricia Martín-Muñoz, Luis O Sánchez-Guardado, Elena Llano, Alberto Alvarez-Barrientos, Ascensión Infante-Campos, Inmaculada Catalina-Fernández, Matías Hidalgo-Sánchez, Dirk G de Rooij, Alberto M Pendás, Fernando J Peña, Jaime M Merino, Pedro M Fernández-Salguero
Previous studies suggested that the aryl hydrocarbon receptor (AhR) contributes to mice reproduction and fertility. However, the mechanisms involved remain mostly unknown. Retrotransposon silencing by Piwi-interacting RNAs (piRNAs) is essential for germ cell maturation and, remarkably, AhR has been identified as a regulator of murine B1-SINE retrotransposons. Here, using littermate AhR(+/+) and AhR(-/-) mice, we report that AhR regulates the general course of spermatogenesis and oogenesis by a mechanism likely to be associated with piRNA-associated proteins, piRNAs and retrotransposons...
December 2016: Open Biology
https://www.readbyqxmd.com/read/27997218/inhibition-of-the-gut-enzyme-intestinal-alkaline-phosphatase-may-explain-how-aspartame-promotes-glucose-intolerance-and-obesity-in-mice
#19
Sarah S Gul, A Rebecca L Hamilton, Alexander R Munoz, Tanit Phupitakphol, Wei Liu, Sanjiv K Hyoju, Konstantinos P Economopoulos, Sara Morrison, Dong Hu, Weifeng Zhang, Mohammad Hadi Gharedaghi, Haizhong Huo, Sulaiman R Hamarneh, Richard A Hodin
Diet soda consumption has not been associated with tangible weight loss. Aspartame (ASP) commonly substitutes sugar and one of its breakdown products is phenylalanine (PHE), a known inhibitor of intestinal alkaline phosphatase (IAP), a gut enzyme shown to prevent metabolic syndrome in mice. We hypothesized that ASP consumption might contribute to the development of metabolic syndrome based on PHE's inhibition of endogenous IAP. The design of the study was such that for the in vitro model, IAP was added to diet and regular soda, and IAP activity was measured...
January 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/27993220/intestinal-alkaline-phosphatase-decreases-intraperitoneal-adhesion-formation
#20
Sanjiv K Hyoju, Sara Morrison, Sarah Gul, Mohammad Hadi Gharedaghi, Mohamed Mussa, Mehran Najibi, Konstantinos P Economopoulos, Sulaiman R Hamarneh, Richard A Hodin
BACKGROUND: Damage to the peritoneum initiates an inflammatory response leading to the formation of adhesions, which subsequently cause significant morbidity in some patients. Intestinal alkaline phosphatase (IAP) is a gut enzyme capable of detoxifying various inflammatory mediators such as lipopolysaccharide, lipoteichoic acid, CpG DNA, and adenosine triphosphate. In this study, we aimed to examine the anti-inflammatory effects of IAP on postoperative adhesions in mice. METHODS: C57BL/6 mice were subjected to a midline laparotomy and then six musculoperitoneal buttons (MPBs) were created by pinching and ligating the peritoneum and underlying muscle...
February 2017: Journal of Surgical Research
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