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https://www.readbyqxmd.com/read/28436946/essential-role-for-bim-in-mediating-the-apoptotic-and-antitumor-activities-of-immunotoxins
#1
A Antignani, D Segal, N Simon, R J Kreitman, D Huang, D J FitzGerald
Protein synthesis is crucial for regulating cell homeostasis and, when unrestricted, it can lead to tumorigenesis. Immunotoxins derived from Pseudomonas exotoxin are antibody-toxin fusion proteins that inhibit protein synthesis of mammalian cells via ADP-ribosylation of the eukaryotic elongation factor-2. Here we investigate the role of the Bcl-2 family proteins in the response of cancer cells to immunotoxin challenge. Besides the well-known reduction of the prosurvival Bcl-2 family member, Mcl-1, following inhibition of protein synthesis, we show for the first time that immunotoxins also reduce the levels of selected proapoptotic BH-3-only proteins...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28432551/partial-p53-dependence-of-anisomycin-induced-apoptosis-in-pc12-cells
#2
R Schipp, J Varga, J Bátor, M Vecsernyés, Z Árvai, M Pap, József Szeberényi
The bacterial antibiotic anisomycin is known to induce apoptosis by activating several mitogen-activated protein kinases and by inhibiting protein synthesis. In this study, the influence of p53 protein on the apoptosis-inducing effect of anisomycin was investigated. The effect of protein synthesis-inhibiting concentration of anisomycin on apoptotic events was analyzed using Western blot, DNA fragmentation, and cell viability assays in wild-type PC12 and in mutant p53 protein expressing p143p53PC12 cells. Anisomycin stimulated the main apoptotic pathways in both cell lines, but p143p53PC12 cells showed lower sensitivity to the drug than their wild-type counterparts...
April 21, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28428545/beclin-1-mediated-autophagy-protects-against-cadmium-activated-apoptosis-via-the-fas-fasl-pathway-in-primary-rat-proximal-tubular-cell-culture
#3
Gang Liu, Yan Yuan, Mengfei Long, Tongwang Luo, Jianchun Bian, Xuezhong Liu, Jianhong Gu, Hui Zou, Ruilong Song, Yi Wang, Lin Wang, Zongping Liu
The Fas/FasL signaling pathway is one of the primary apoptosis pathways, but the involvement and regulatory mechanism of this pathway by autophagy remain unclear. Here we demonstrated that cadmium (Cd) activated the Fas/FasL apoptosis pathway in rat proximal tubular (rPT) cells; this was accompanied by simultaneous activation of autophagy resulted in reduced apoptosis. In this model, we induced autophagy through RAPA and further demonstrated that autophagy protects against activation of Fas/FasL signaling and apoptosis...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424891/a-phase-i-dose-escalation-study-of-selumetinib-in-combination-with-erlotinib-or-temsirolimus-in-patients-with-advanced-solid-tumors
#4
Jeffrey R Infante, Roger B Cohen, Kevin B Kim, Howard A Burris, Gregory Curt, Ugochi Emeribe, Delyth Clemett, Helen K Tomkinson, Patricia M LoRusso
Background Combinations of molecularly targeted agents may provide optimal anti-tumor activity and improve clinical outcomes for patients with advanced cancers. Selumetinib (AZD6244, ARRY-142886) is an oral, potent and highly selective, allosteric inhibitor of MEK1/2, a component of the RAS/RAF/MEK/ERK pathway which is constitutively activated in many cancers. We investigated the safety, tolerability, and pharmacokinetics (PK) of selumetinib in combination with molecularly targeted drugs erlotinib or temsirolimus in patients with advanced solid tumors...
April 19, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28424818/dose-requirements-for-idarucizumab-reversal-of-dabigatran-in-a-lethal-porcine-trauma-model-with-continuous-bleeding
#5
Markus Honickel, Henri M Spronk, Rolf Rossaint, Christian Stoppe, Joanne van Ryn, Hugo Ten Cate, Oliver Grottke
Idarucizumab is licensed for emergency reversal of dabigatran. A single 5 g dose is usually sufficient, but higher doses may sometimes be required and optimum dosing has not been defined. It was the aim of this study to investigate the effect of idarucizumab, given once or as a split dose, after double trauma in pigs anticoagulated with dabigatran. Dabigatran etexilate (30 mg/kg bid) was given to 18 male pigs orally for 3 days. On day 4, animals were randomised 1:1:1 to receive idarucizumab 60+0, 60+60 or 120+0 mg/kg...
April 20, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28423919/joint-attention-difficulties-in-autistic-adults-an-interactive-eye-tracking-study
#6
Nathan Caruana, Heidi Stieglitz Ham, Jon Brock, Alexandra Woolgar, Nadine Kloth, Romina Palermo, Genevieve McArthur
Joint attention - the ability to coordinate attention with a social partner - is critical for social communication, learning and the regulation of interpersonal relationships. Infants and young children with autism demonstrate impairments in both initiating and responding to joint attention bids in naturalistic settings. However, little is known about joint attention abilities in adults with autism. Here, we tested 17 autistic adults and 17 age- and nonverbal intelligence quotient-matched controls using an interactive eye-tracking paradigm in which participants initiated and responded to joint attention bids with an on-screen avatar...
April 1, 2017: Autism: the International Journal of Research and Practice
https://www.readbyqxmd.com/read/28420720/a-phase-i-study-of-abc294640-a-first-in-class-sphingosine-kinase-2-inhibitor-in-patients-with-advanced-solid-tumors
#7
Carolyn D Britten, Melanie B Thomas, Elizabeth Garrett-Mayer, Steven H Chin, Keisuke Shirai, Besim Ogretmen, Tricia A Bentz, Alan Brisendine, Kate Anderton, Susan L Cusack, Lynn W Maines, Yan Zhuang, Charles D Smith
Purpose:  Sphingosine kinases (SK1 and SK2) regulate tumor growth by generating the mitogenic and pro-inflammatory lipid sphingosine 1-phosphate (S1P). This phase I study investigated the safety, pharmacokinetics, pharmacodynamics and anti-tumor activity of ABC294640, a first-in-class orally-available inhibitor of SK2.  <p>Experimental Design:  Escalating doses of ABC294640 were administered orally to patients with advanced solid tumors in sequential cohorts at the following dose levels: 250 mg qd, 250 mg bid, 500 mg bid and 750 mg bid, continuously in cycles of 28 days...
April 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28419648/the-role-of-body-image-dissatisfaction-in-the-association-between-treatment-related-scarring-or-disfigurement-and-psychological-distress-in-adult-survivors-of-childhood-cancer
#8
Stefanie C Vuotto, Rohit P Ojha, Chenghong Li, Cara Kimberg, James L Klosky, Kevin R Krull, Deo Kumar Srivastava, Leslie L Robison, Melissa M Hudson, Tara M Brinkman
PURPOSE: To examine the potential mediating role of body image dissatisfaction on the association between treatment-related scarring/disfigurement and psychological distress in adult survivors of childhood cancer. METHODS: Participants included 1,714 adult survivors of childhood cancer (mean[SD] age at evaluation = 32.4[8.0] years, time since diagnosis = 24.1[8.1] years) enrolled in the St. Jude Lifetime Cohort Study. Survivors completed measures of body image, emotional distress and posttraumatic stress symptoms (PTSS)...
April 18, 2017: Psycho-oncology
https://www.readbyqxmd.com/read/28418370/-current-study-aimed-to-highlight-extent-of-clot-resolution-in-deep-veins-and-its-association-with-anticoagulation-pattern-in-vte-patients
#9
E A Shcheglov, N N Alontzeva
MATERIAL AND METHODS: Data of 70 patients with acute VTE of lower extremities (iliofemoral level) was analyzed. There were 42 patients in the study group which were treated with rivaroxaban (15 mg BID for 21 days, 20 mg od from day 22); 28 patients were in control group treated with conventional therapy (LMWH/VKA). Extent of clot resolution was assessed on ultrasound. Data was collected at a day of VTE diagnosis and further at 1, 3, 6 month. RESULTS: The results of the study demonstrated, that patients treated with rivaroxaban had earlier recanalization and extent of clot resolution was higher than in patients treated with conventional therapy...
2017: Khirurgiia
https://www.readbyqxmd.com/read/28417284/a-phase-i-dose-escalation-study-of-the-safety-and-pharmacokinetics-of-a-tablet-formulation-of-voxtalisib-a-phosphoinositide-3-kinase-inhibitor-in-patients-with-solid-tumors
#10
Janice M Mehnert, Gerald Edelman, Mark Stein, Heather Camisa, Joanne Lager, Jean-François Dedieu, Anne-Frédérique Ghuysen, Jyoti Sharma, Li Liu, Patricia M LoRusso
Background Voxtalisib, a PI3K/mTOR inhibitor, has shown antitumor activity in capsule formulation in patients with solid tumors. This Phase I study assessed safety and pharmacokinetics of voxtalisib administered as immediate-release tablets in patients with solid tumors (NCT01596270). Methods A "3 + 3" dose escalation design was used. Adverse events (AEs), pharmacokinetics (PK), food effect and tumor response were evaluated. Results Thirty-two patients received voxtalisib doses ranging from 50 mg to 70 mg once daily (QD) and 17 patients received voxtalisib doses ranging from 30 mg to 50 mg twice daily (BID), for two 28-day cycles...
April 17, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28416970/dna-methylation-profiling-in-peripheral-lung-tissues-of-smokers-and-patients-with-copd
#11
Isaac K Sundar, Qiangzong Yin, Brian S Baier, Li Yan, Witold Mazur, Dongmei Li, Martha Susiarjo, Irfan Rahman
BACKGROUND: Epigenetics changes have been shown to be affected by cigarette smoking. Cigarette smoke (CS)-mediated DNA methylation can potentially affect several cellular and pathophysiological processes, acute exacerbations, and comorbidity in the lungs of patients with chronic obstructive pulmonary disease (COPD). We sought to determine whether genome-wide lung DNA methylation profiles of smokers and patients with COPD were significantly different from non-smokers. We isolated DNA from parenchymal lung tissues of patients including eight lifelong non-smokers, eight current smokers, and eight patients with COPD and analyzed the samples using Illumina's Infinium HumanMethylation450 BeadChip...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28414160/paraquat-induces-extrinsic-pathway-of-apoptosis-in-a549-cells-by-induction-of-dr5-and-repression-of-anti-apoptotic-proteins-ddx3-and-gsk3-expression
#12
Sasiphen Hathaichoti, Daranee Visitnonthachai, Pronrumpa Ngamsiri, Apichaya Niyomchan, Oyu Tsogtbayar, Churaibhon Wisessaowapak, Piyajit Watcharasit, Jutamaad Satayavivad
Paraquat (PQ) is a bipyridyl derivative herbicide known to cause lung toxicity partly through induction of apoptosis. Here we demonstrated that PQ caused apoptosis in A549 cells. PQ increased cleavage of caspase-8 and Bid, indicating caspase-8 activation and truncated Bid, the two key mediators of extrinsic apoptosis. Additionally, PQ treatment caused an increase in DR5 (death receptor-5) and caspase-8 interaction, indicating formation of DISC (death-inducing signaling complex). These results indicate that PQ induces apoptosis through extrinsic pathway in A549 cells...
April 14, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28410209/mir-106b-inhibitors-sensitize-trail-induced-apoptosis-in-hepatocellular-carcinoma-through-increase-of-death-receptor-4
#13
Changlong Xu, Liang Shi, Weilai Chen, Peipei Fang, Jie Li, Lingxiang Jin, Zhenzhen Pan, Chenwei Pan
TNF-related apoptosis-inducing ligand (TRAIL), which is a member of the TNF superfamily, can induce tumor cell apoptosis. However, multiple types of tumor, including hepatocellular carcinoma, show tolerance to TRAIL. Previous studies have demonstrated that tumor cells usually change their expression profile of microRNA (miRNA) to obtain the ability of tolerance to drugs. However, whether such change of miRNA on TRAIL sensitivity is seen in hepatocellular carcinoma still needs to be explored. In this study, we observed overexpression of miR-106b in both HCC patients' tumor tissues and cell lines...
March 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408716/sex-specific-comparative-effectiveness-of-oral-anticoagulants-in-elderly-patients-with-newly-diagnosed-atrial-fibrillation
#14
Ghanshyam Palamaner Subash Shantha, Prashant D Bhave, Saket Girotra, Denice Hodgson-Zingman, Alexander Mazur, Michael Giudici, Elizabeth Chrischilles, Mary S Vaughan Sarrazin
BACKGROUND: Sex-specific comparative effectiveness of direct oral anticoagulants among patients with nonvalvular atrial fibrillation is not known. Via this retrospective cohort study, we assessed the sex-specific, comparative effectiveness of direct oral anticoagulants (rivaroxaban and dabigatran), compared to each other and to warfarin among patients with atrial fibrillation. METHODS AND RESULTS: Elderly (aged ≥66 years) Medicare beneficiaries enrolled in Medicare Part D benefit plan from November 2011 to October 2013 with newly diagnosed atrial fibrillation formed the study cohort (65 734 [44...
April 2017: Circulation. Cardiovascular Quality and Outcomes
https://www.readbyqxmd.com/read/28407303/rifampicin-reverses-nicardipine-effect-inducing-uncontrolled-essential-hypertension
#15
Elena-Mihaela Cordeanu, Sébastien Gaertner, Alix Faller, Corina Mirea, Jean-Marc Lessinger, Veronique Kemmel, Dominique Stephan
Dihydropyridine calcium-channel blockers are a known substrate for the cytochrome P450 isoform 3A4. Rifampicin, an antitubercular agent, is one of the most potent inducers of hepatic and intestinal CYP3A4 thus increasing dihydropyridine metabolism. We report a case of a 67-year-old hypertensive female treated with a 4-drug antihypertensive regimen including a dihydropyridine (nicardipine 50mg bid), who was admitted for septic arthritis of the knee requiring antibiotic treatment with teicoplanin 400mg od and rifampicin 600mg bid...
April 13, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28397263/protective-effect-of-cirsimaritin-against-streptozotocin-induced-apoptosis-in-pancreatic-beta-cells
#16
Dahae Lee, Ki Hyun Kim, Jaemin Lee, Gwi Seo Hwang, Hye Lim Lee, Dae-Hyun Hahm, Chang Ki Huh, Sang Cheon Lee, Sanghyun Lee, Ki Sung Kang
OBJECTIVES: Maintaining glucose homoeostasis is essential for the survival of cells. Despite the various health benefits of Korean thistle (Cirsium japonicum var. maackii), their effects on pancreatic β-cell apoptosis in type 1 diabetes mellitus and the underlying mechanisms remain unclear, and experimentally investigated in this study. METHODS: The effects of C. japonicum var. maackii and its active component cirsimaritin against streptozotocin (STZ)-induced cytotoxicity were assessed in INS-1 cells...
April 11, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28397098/persian-shallot-allium-hirtifolium-boiss-induced-apoptosis-in-human-hepatocellular-carcinoma-cells
#17
Farzaneh Sadat Hosseini, Soudeh Khanamani Falahati-Pour, Mohammad Reza Hajizadeh, Alireza Khoshdel, Mohammad Reza Mirzaei, Hadis Ahmadirad, Reza Behroozi, Nesa Jafari, Mehdi Mahmoodi
This study investigated the potential of Persian shallot extract as an anticancer agent in HepG2 tumor cell line, an in vitro human hepatoma cancer model system. The inhibitory effect of Persian shallot on the growth of HepG2 cells was measured by MTT assay. To explore the underlying mechanism of cell growth inhibition of Persian shallot, the activity of Persian shallot in inducing apoptosis was investigated through the detection of annexin V signal by flow cytometry and expression of some apoptosis related genes such p21, p53, puma, caspase-8 family-Bcl-2 proteins like bid, bim, bcl-2 and bax were measured by real-time PCR in HepG2 cells...
April 10, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28395687/perceptions-of-healthcare-professionals-regarding-their-own-body-weight-in-selected-public-hospitals-in-mpumalanga-province-south-africa
#18
M C Phetla, L Skaal
BACKGROUND: Obesity has been cited as a public health problem in both developing and developed countries. There is evidence that rates of obesity have increased among healthcare workers (HCWs) in South Africa (SA), especially those who do night shifts, with a negative effect on health. Perceptions of body weight contribute significantly to the desire to lose weight or not to do so. OBJECTIVE: To determine perceptions of HCWs regarding their own body weight in selected public hospitals in Mpumalanga Province, SA...
March 29, 2017: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
https://www.readbyqxmd.com/read/28395529/mother-child-interactions-in-young-children-with-excessive-physical-aggression-and-in-typically-developing-young-children
#19
Nadine Urbain-Gauthier, Jaqueline Wendland
BACKGROUND: Among the multiple risk factors, the emergence of conduct problems in young children may be linked to harsh parenting and child's temperamental difficulties, leading to a reciprocal early discordant relationship. Little is known about the characteristics of early parent-child interactions in young children with physical aggression. OBJECTIVE: The purpose of the current study was to evaluate the characteristics of mother-child interactions in dyads referred for excessive physical aggression in young children under 5 years of age compared to mother-child interactions in typically developing young children...
April 1, 2017: Clinical Child Psychology and Psychiatry
https://www.readbyqxmd.com/read/28394459/ergogenic-properties-of-metformin-in-simulated-high-altitude
#20
Rebecca L Scalzo, Hunter L Paris, Scott E Binns, Janelle L Davis, Joseph W Beals, Christopher L Melby, Gary J Luckasen, Matthew S Hickey, Benjamin F Miller, Karyn L Hamilton, Christopher Bell
Metformin augments glucose/glycogen regulation and may acutely promote fatigue resistance during high-intensity exercise. In hypobaric environments, such as high altitude, the important contribution of carbohydrates to physiological function is accentuated as glucose/glycogen dependence is increased. Because hypoxia/hypobaria decreases insulin sensitivity, replenishing skeletal muscle glycogen in high altitude becomes challenging and subsequent physical performance may be compromised. We hypothesized that in conditions where glycogen repletion was critical to physical outcomes, metformin would attenuate hypoxia-mediated decrements in exercise performance...
April 10, 2017: Clinical and Experimental Pharmacology & Physiology
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