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Hiroyuki Sumi, Masakazu Inazuka, Megumi Morimoto, Ryosuke Hibino, Kentaro Hashimoto, Tomoyasu Ishikawa, Keisuke Kuida, Peter G Smith, Sei Yoshida, Masato Yabuki
Inhibitors of apoptosis proteins (IAPs) are antiapoptotic regulators that block cell death, and are frequently overexpressed in several human cancers, where they facilitate evasion of apoptosis and promote cell survival. IAP antagonists are also known as second mitochondria-derived activator of caspase (SMAC)-mimetics, and have recently been considered as novel therapeutic agents for inducing apoptosis, alone and in combination with other anticancer drugs. In this study, we showed that T-3256336, the orally available IAP antagonist has synergistically enhances the antiproliferative effects of the NEDD8-activating enzyme (NAE) inhibitor pevonedistat (TAK-924/MLN4924), and these effects were attenuated by a TNFα-neutralizing antibody...
October 19, 2016: Biochemical and Biophysical Research Communications
S Zappavigna, M Scuotto, A M Cossu, D Ingrosso, M De Rosa, C Schiraldi, R Filosa, M Caraglia
BACKGROUND: Embelin is a potent dual inhibitor of 5-lipoxigenase (5-LOX) and microsomal prostaglandin E2 synthase (mPGES)-1 that suppresses proliferation of human glioma cells and induces apoptosis by inhibiting XIAP and NF-κB signaling pathway. Synthetic structural modification yielded the derivative 3-((decahydronaphthalen-6-yl)methyl)-2,5-dihydroxycyclohexa-2,5-diene-1,4-dione (RF-Id), an embelin constrained analogue, with improved efficiency against 5-LOX in human neutrophils and anti-inflammatory activity in vivo...
October 22, 2016: Journal of Experimental & Clinical Cancer Research: CR
Tomohiro Hirano, Kenichi Sakurai, Shigeru Fujisaki, Keita Adachi, Shuhei Suzuki, Yuki Masuo, Saki Nagashima, Yukiko Hara, Katsuhisa Enomoto, Ryouichi Tomita, Kenji Gonda
Locallyadvanced breast cancer lesions often compromise the patient's qualityof life(QOL). Mohs paste is a histopathological fixative containing zinc chloride as the main ingredient. It has been applied to perform chemosurgeryon skin tumors. In recent years, this paste has reportedlybeen veryeffective for controlling various symptoms of skin metastases in inoperable advanced cancer, such as pungent odor and hemorrhage, in the field of palliative care. We evaluated the clinical significance of immunosuppressive acidic protein(IAP)and C-reactive protein(CRP)in the serum of patients with locallyadvanced breast cancer duringMohs paste treatment...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Tomohiro Hirano, Kenichi Sakurai, Shigeru Fujisaki, Keita Adachi, Shuhei Suzuki, Yuki Masuo, Saki Nagashima, Yukiko Hara, Katsuhisa Enomoto, Ryouichi Tomita, Kenji Gonda
To determine the role of immunosuppressive acidic protein(IAP)in the host defense of surgical patients, we investigated the kinetics of the post-operative elevation of IAP, as well as factors influencing the increase in serum IAP concentration, in 17 patients who underwent breast surgery. IAP was not increased in the pre-operation phase, post-operation phase, or 2 weeks after surgery, byvarious breast surgerymethods. In contrast, IL-6 was increased in the post-operation phase byall breast surgerymethods. IL-6 correlated with anesthesia time...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Lorenz Kadletz, Elisabeth Enzenhofer, Ulana Kotowski, Gabriela Altorjai, Gregor Heiduschka
CONCLUSION: On the one hand, AZD5582, an inhibitor of inhibitor of apoptosis family proteins (IAP), leads to cellular growth arrest and induction of apoptosis in head and neck squamous cell carcinoma (HNSCC) cell lines. On the other hand, it is a viable candidate for combination therapy with irradiation. OBJECTIVES: The aim and purpose of this study was to evaluate the effects of AZD5582 on HNSCC cell lines. METHODS: HNSCC cell lines SCC25, Cal27, and FaDu were used for all cell culture experiments...
October 14, 2016: Acta Oto-laryngologica
Chengcheng Yang, Huangzhen Wang, Boxiang Zhang, Yimeng Chen, Yamin Zhang, Xin Sun, Guodong Xiao, Kejun Nan, Hong Ren, Sida Qin
BACKGROUND: LCL161, a novel Smac mimetic, is known to have anti-tumor activity and improve chemosensitivity in various cancers. However, the function and mechanisms of the combination of LCL161 and paclitaxel in non-small cell lung cancer (NSCLC) remain unknown. METHODS: Cellular inhibitor of apoptotic protein 1 and 2 (cIAP1&2) expression in NSCLC tissues and adjacent non-tumor tissues were assessed by immunohistochemistry. The correlations between cIAP1&2 expression and clinicopathological characteristics, prognosis were analyzed...
September 30, 2016: Journal of Experimental & Clinical Cancer Research: CR
Simone Wicki, Ursina Gurzeler, W Wei-Lynn Wong, Philipp J Jost, Daniel Bachmann, Thomas Kaufmann
Neutrophils are essential players in the first-line defense against invading bacteria and fungi. Besides its antiapoptotic role, the inhibitor of apoptosis protein (IAP) family member X-linked IAP (XIAP) has been shown to regulate innate immune signaling. Whereas the role of XIAP in innate signaling pathways is derived mostly from work in macrophages and dendritic cells, it is not known if and how XIAP contributes to these pathways in neutrophils. Here we show that in response to bacterial lipopolysaccharides (LPS), mouse neutrophils secreted considerable amounts of tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) and, in accordance with earlier reports, XIAP prevented LPS-induced hypersecretion of IL-1β also in neutrophils...
October 13, 2016: Cell Death & Disease
Jing Zhou, Lu Ke, Dongliang Yang, Yizhe Chen, Gang Li, Zhihui Tong, Weiqin Li, Jieshou Li
BACKGROUND: Splanchnic venous thrombosis (SVT) is a relatively rare but important complication of necrotizing acute pancreatitis (NAP). Clinical manifestations and severity of this complication in different patients vary greatly, ranging from mild abdominal discomfort even asymptomatic to lethal gastrorrhagia or hepatic failure. The aim of the present study was to develop a model to predict the clinical manifestations of SVT in NAP patients. METHODS: This retrospective cohort study was conducted in the surgical intensive care unit (SICU) of Jinling Hospital...
October 3, 2016: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
Marije Smit, Maureen J M Werner, Annemieke Oude Lansink-Hartgring, Willem Dieperink, Jan G Zijlstra, Matijs van Meurs
BACKGROUND: Intra-abdominal hypertension (IAH) is frequently present in critically ill patients and is an independent predictor for mortality. Better recognition of clinically important thresholds is necessary. Increased intra-abdominal pressure (IAP) is associated with renal dysfunction, and renal failure is one of the most consistently described organ dysfunctions associated with IAH. Obesity is also associated with kidney injury. The underlying mechanisms are not yet fully understood...
December 2016: Annals of Intensive Care
Yuko Yoshikawa, Yoshitsugu Ochiai, Mariko Mochizuki, Osamu Fujita, Takashi Takano, Ryo Hondo, Fukiko Ueda
Pulse field gel electrophoresis (PFGE) is widely used for listeriosis surveillance. Although this technique is effective for epidemiology, the data among laboratories are inconsistent. We previously reported a method for L. monocytogenes subtyping combined with sequence analysis of partial iap and whole genome restriction fragment length polymorphism (RFLP) using XbaI, ClaI (BanIII) and PstI. However, distinguishing subtypes was challenging, because the output comprised complicated fragment patterns. In this study, we aimed to establish a simple genotyping method that does not depend on visual observation, rather it focuses on multi-locus sequence typing (MLST) using three genes, iap, sigB and actA...
October 1, 2016: Journal of Veterinary Medical Science
Liang Zhu, Huanming Xia, Zhenfeng Wang, Eliza Li Shan Fong, Junjun Fan, Wen Hao Tong, Yen Peng Daphne Seah, Weian Zhang, Qiushi Li, Hanry Yu
Although hepatocytes in vivo experience intra-abdominal pressure (IAP), pressure is typically not incorporated in hepatocyte culture systems. The cuboidal cell shape and extent of intercellular contact between cultured hepatocytes are critical parameters that influence the differentiated hepatic phenotype. Using a microfluidic device, the application of pressure to artificially compact cells and forge cell-cell interactions was previously demonstrated to be effective in accelerating hepatic repolarization. In seeking to implement this approach to higher throughput culture platforms for potential drug screening applications, we specifically designed a vertical-flow compaction bioreactor array (VCBA) that compacts hepatocytes within the range of IAP and portal pressure in vivo in a multi-well setup...
October 5, 2016: Lab on a Chip
Prashant P Kadam, Nithya Jaideep Gogtay, Sunil Karande, V Shah, Urmila M Thatte
OBJECTIVES: Studies on antimalarial kinetics in children or adults who are undernourished or malnourished are both limited and have yielded conflicting results. The present study was carried out with the objectives of evaluating the pharmacokinetics of single dose chloroquine and its metabolite desethylchloroquine in children who were undernourished and compare them with children who were normally nourished. METHODS: Children of either gender between the ages of 5 and 12 years, smear positive for P...
September 2016: Indian Journal of Pharmacology
Mohamed Salah I Abaza, Mohammad Afzal, Raja'a J Al-Attiyah, Radhika Guleri
BACKGROUND: Natural products are valuable sources for anticancer agents. In the present study, methylferulate (MF) was identified for the first time from Tamarix aucheriana. Spectral data were used for identification of MF. The potential of MF to control cell growth, cell cycle, apoptosis, generation of reactive oxygen species (ROS), cancer cell invasion, nuclear factor kappa B (NFkB) DNA-binding activity and proteasomal activities, as well as the enhancement of chemosensitivity in human colorectal cancer cells, were evaluated...
October 1, 2016: BMC Complementary and Alternative Medicine
Eva Martini, Evelyn Schneider, Clemens Neufert, Markus F Neurath, Christoph Becker
As an inhibitor of apoptosis (IAP) family member, Survivin is known for its role during regulation of apoptosis. More recently its function as a cell cycle regulator has become evident. Survivin was shown to play a pivotal role during embryonic development and is highly expressed in regenerative tissue as well as in many cancer types. We examined the function of Survivin during mouse intestinal organogenesis and in gut pathophysiology. We found high expression of Survivin in experimentally induced colon cancer in mice but also in colon tumors of humans...
October 7, 2016: Cell Cycle
Sachin Sharma, Thomas Kaufmann, Subhrajit Biswas
The routes leading to programmed cell death are as tightly regulated as those of cellular growth and proliferation, and a finely synchronized balance between the life and death of cells ensures proper organ size and function. Inhibitors of apoptosis (IAPs) proteins were initially characterized by their ability to directly bind and inhibit apoptotic caspases. However, recent studies have clarified that IAPs are much more functionally versatile, modulating a vast range of signaling pathways that have an impact on antimicrobial responses, tumorigenesis, metastasis and cellular migration...
October 7, 2016: Immunology and Cell Biology
Sanam Arami, Majid Mahdavi, Mohammad Reza Rashidi, Marziyeh Fathi, Mohammad-Saeid Hejazi, Nasser Samadi
As a gene delivery method in breast cancer therapy, knocking down the undesired genes in the cancerous cells would be promising. Inhibitors of Apoptosis Protein (IAP) family genes are some of the genes whose responsibility is inhibition of apoptosis in cells. Silencing these genes seems to be helpful directing the tumor cells to death. siRNA sequence designed against survivin anti-apoptotic gene can play this role if carried to the cytoplasm. Here we prepared a positive charged biocompatible nano-sized particle made up of a Fe3O4 core covered respectively by polyacrylate (PA) and polyethyleneimine (PEI) layer, which could successfully deliver the siRNA into the MCF-7 cells...
October 3, 2016: Biologicals: Journal of the International Association of Biological Standardization
Selma J Lekkerkerker, Marc G Besselink, Olivier R Busch, Joanne Verheij, Marc R Engelbrecht, Erik A Rauws, Paul Fockens, Jeanin E van Hooft
BACKGROUND AND AIMS: Currently, 3 guidelines are available for the management of pancreatic cysts. These guidelines vary in their indication for resection of high-risk cysts. We retrospectively compared the final pathological outcome of surgically removed pancreatic cysts with the indications for resection according to 3 different guidelines. METHODS: Patients who underwent pancreatic resection were extracted from our prospective pancreatic cyst database (2006-present)...
September 29, 2016: Gastrointestinal Endoscopy
June-Sun Yoon, Jayendra Nath Shukla, Zhong Jun Gong, Kanakachari Mogilicherla, Subba Reddy Palli
RNA interference (RNAi) is a useful reverse genetics tool for investigation of gene function as well as for practical applications in many fields including medicine and agriculture. RNAi works very well in coleopteran insects including the Colorado potato beetle (CPB), Leptinotarsa decemlineata. We used a cell line (Lepd-SL1) developed from CPB to identify genes that play key roles in RNAi. We screened 50 genes with potential functions in RNAi by exposing Lepd-SL1 cells to dsRNA targeting one of the potential RNAi pathway genes followed by incubation with dsRNA targeting inhibitor of apoptosis (IAP, silencing of this gene induces apoptosis)...
September 26, 2016: Insect Biochemistry and Molecular Biology
Javier Barrio, Carlos L Errando, Guillermo San Miguel, Boris I Salas, Juan Raga, José L Carrión, Jaime García-Ramón, Juan Gallego
STUDY OBJECTIVE: To evaluate the effect of neuromuscular blockade (NMB) upon the abdominal space during pneumoperitoneum establishment in laparoscopic surgery, comparing moderate NMB and deep NMB. DESIGN: Prospective, randomized, crossover clinical trial. SETTING: Operating room. PATIENTS: Seventy-six American Society of Anesthesiologists 1 to 2 patients scheduled for elective laparoscopic surgery. INTERVENTIONS: Two independent evaluations were performed at the establishment of pneumoperitoneum for a preset intraabdominal pressures (IAPs) of 8 and 12 mm Hg, both during moderate NMB (train-of-four count, 1-3) and deep NMB (posttetanic count, <5)...
November 2016: Journal of Clinical Anesthesia
Stephen M Condon
No abstract text is available yet for this article.
2016: Cell Death & Disease
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