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https://www.readbyqxmd.com/read/28927158/regulation-of-htra2-on-wt1-gene-expression-under-imatinib-stimulation-and-its-effects-on-the-cell-biology-of-k562-cells
#1
Lixia Zhang, Yan Li, Xiaoyan Li, Qing Zhang, Shaowei Qiu, Qi Zhang, Min Wang, Haiyan Xing, Qing Rao, Zheng Tian, Kejing Tang, Jianxiang Wang, Yingchang Mi
The aim of the present study was to investigate the regulation of Wilms Tumor 1 (WT1) by serine protease high-temperature requirement protein A2 (HtrA2), a member of the Htr family, in K562 cells. In addition, the study aimed to observe the effect of this regulation on cell biological functions and its associated mechanisms. Expression of WT1 and HtrA2 mRNA, and proteins following imatinib and the HtrA2 inhibitor 5-[5-(2-nitrophenyl) furfuryl iodine]-1, 3-diphenyl-2-thiobarbituric acid (UCF-101) treatment was detected with reverse transcription-quantitative polymerase chain reaction and western blot analysis...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927095/high-expression-of-mage-a9-is-associated-with-unfavorable-survival-in-esophageal-squamous-cell-carcinoma
#2
Yu Qi, Ke Xin Cao, Fu Chen Xing, Chun Yang Zhang, Qi Huang, Kai Wu, Feng Biao Wen, Song Zhao, Xin Li
Melanoma-associated antigens (MAGEs) are a group of well-characterized members of the cancer/testis antigen family, which are expressed in a variety of malignant tumors. MAGE-A9, a subfamily of MAGE-As, has been studied in a number of types of cancer and have been associated with unfavorable survival outcome. However, the expression of MAGE-A9 in human esophageal squamous cell carcinoma (ESCC) and association of MAGE-A9 with the clinicopathological characteristics of ESCC, particularly prognostic characteristics, remains unknown...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927072/arsenic-trioxide-potentiates-sensitivity-of-multiple-myeloma-cells-to-lenalidomide-by-upregulating-cereblon-expression-levels
#3
Yuan Jian, Wen Gao, Chuanying Geng, Huixing Zhou, Yun Leng, Yanchen Li, Wenming Chen
The mechanism of the anti-myeloma effect of the immunomodulatory drug lenalidomide relies upon the binding of lenalidomide or an analogue to cereblon (CRBN) ubiquitin ligase, which inhibits it and results in the degradation of Ikaros-family zinc finger proteins 1 and 3 (IKZF1 and IKZF3). To determine whether the traditional Chinese medicine arsenic trioxide, could potentiate sensitivity of multiple myeloma (MM) cells to lenalidomide and identify the mechanism by which this happens, the present study investigated how arsenic trioxide affected CRBN on MM cell lines and examined the anti-myeloma effect and mechanism in the combination of arsenic trioxide and lenalidomide...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926730/impact-of-evolocumab-treatment-on-low-density-lipoprotein-cholesterol-levels-in-heterozygous-familial-hypercholesterolemic-patients-withdrawing-from-regular-apheresis
#4
Masa-Aki Kawashiri, Atsushi Nohara, Toshinori Higashikata, Hayato Tada, Chiaki Nakanishi, Hirofumi Okada, Tetsuo Konno, Kenji Sakata, Kenshi Hayashi, Akihiro Inazu, Hiroshi Mabuchi, Masakazu Yamagishi
BACKGROUND AND AIMS: Low-density lipoprotein (LDL) apheresis has been used to treat refractory hyperlipidemia such as familial hypercholesterolemia (FH). Evolocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor used in clinical settings, can reduce LDL cholesterol (LDL-C) levels by >70%. Therefore, this study aimed to assess the impact of evolocumab on withdrawal from regular LDL apheresis in patients with heterozygous FH (HeFH). METHODS: Eleven patients with HeFH undergoing biweekly LDL apheresis were enrolled and were subsequently switched to a biweekly subcutaneous injection of 140 mg of evolocumab...
September 9, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28925878/genistein-induces-alterations-of-epigenetic-modulatory-signatures-in-human-cervical-cancer-cells
#5
Madhumitha Kedhari Sundaram, Mohammad Zeeshan Ansari, Abdullah Al Mutery, Maryam Ashraf, Reem Nasab, Sheethal Rai, Naushad Rais, Arif Hussain
Introduction Epidemiological studies indicate that diet rich in fruits and vegetables are associated with decreased cancer risk thereby indicating that dietary polyphenols can be potential chemo-preventive agents. The reversible nature of epigenetic modifications makes them a favorable target for cancer prevention. Polyphenols have been shown to reverse aberrant epigenetic patterns by targeting the regulatory enzymes, DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). In vitro and in silico studies of DNMTs and HDACs were planned to examine genistein's role as a natural epigenetic modifier in human cervical cancer cells, HeLa...
September 18, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28925664/preventing-falls-in-older-persons
#6
Lainie Van Voast Moncada, L Glen Mire
The American Geriatrics Society and British Geriatrics Society recommend that all adults older than 65 years be screened annually for a history of falls or balance impairment. The U.S. Preventive Services Task Force and American Academy of Family Physicians recommend exercise or physical therapy and vitamin D supplementation to prevent falls in community-dwelling older adults who are at increased risk of falls. Although the U.S. Preventive Services Task Force and American Academy of Family Physicians do not recommend routine multifactorial intervention to prevent falls in all community-dwelling older adults, they state that it may be appropriate in individual cases...
August 15, 2017: American Family Physician
https://www.readbyqxmd.com/read/28924523/the-interplay-of-genetics-and-environmental-factors-in-the-development-of-obesity
#7
REVIEW
Abu Baker Sheikh, Adeel Nasrullah, Shujaul Haq, Aisha Akhtar, Haider Ghazanfar, Amara Nasir, Rao M Afzal, Marvi M Bukhari, Ahtsham Yousaf Chaudhary, Syed W Naqvi
Obesity is a major health issue in the developed nations, and it has been increasingly clear that both genetics and environment play an important role in determining if an individual will be obese or not. We reviewed the latest researches which were carried out to identify the obesity susceptible genes and to identify the metabolic pathways having a central role in energy balance. Obesity is a heritable disorder, and some of the many obesity susceptible genes are fat mass and obesity (FTO), leptin, and Melanocortin-4 receptor (MC4R)...
July 6, 2017: Curēus
https://www.readbyqxmd.com/read/28924240/14-3-3%C3%AE-binds-the-proteasome-limits-proteolytic-function-and-enhances-sensitivity-to-proteasome-inhibitors
#8
Y Gu, K Xu, C Torre, M Samur, B G Barwick, M Rupji, J Arora, P Neri, J Kaufman, A Nooka, L Bernal-Mizrachi, P Vertino, S-Y Sun, J Chen, N Munshi, H Fu, J Kowalski, L H Boise, S Lonial
14-3-3 proteins are a family of master regulators of intracellular signaling, yet their impact on proteasome function is unknown. We demonstrate that 14-3-3ζ binds the 11S proteasome activator, limiting proteasome assembly and cellular capacity for protein degradation. To define the functional impact of 14-3-3ζ proteasomal binding in myeloma cells, silencing and overexpression experiments are performed. We find that downregulation of 14-3-3ζ impairs myeloma cell growth and confers resistance to clinically used proteasome inhibitors...
September 19, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28924147/tumor-suppression-via-inhibition-of-swi-snf-complex-dependent-nf-%C3%AE%C2%BAb-activation
#9
Kazuyoshi Kobayashi, Hiroaki Hiramatsu, Shinya Nakamura, Kyousuke Kobayashi, Takeshi Haraguchi, Hideo Iba
The transcription factor NF-κB is constitutively activated in many epithelial tumors but few NF-κB inhibitors are suitable for cancer therapy because of its broad biological effects. We previously reported that the d4-family proteins (DPF1, DPF2, DPF3a/b) function as adaptor proteins linking NF-κB with the SWI/SNF complex. Here, using epithelial tumor cell lines, A549 and HeLaS3, we demonstrate that exogenous expression of the highly-conserved N-terminal 84-amino acid region (designated "CT1") of either DPF2 or DPF3a/b has stronger inhibitory effects on anchorage-independent growth than the single knockdown of any d4-family protein...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28924146/apols-with-low-ph-dependence-can-kill-all-african-trypanosomes
#10
Frédéric Fontaine, Laurence Lecordier, Gilles Vanwalleghem, Pierrick Uzureau, Nick Van Reet, Martina Fontaine, Patricia Tebabi, Benoit Vanhollebeke, Philippe Büscher, David Pérez-Morga, Etienne Pays
The primate-specific serum protein apolipoprotein L1 (APOL1) is the only secreted member of a family of cell death promoting proteins (1-4) . APOL1 kills the bloodstream parasite Trypanosoma brucei brucei, but not the human sleeping sickness agents T.b. rhodesiense and T.b. gambiense (3) . We considered the possibility that intracellular members of the APOL1 family, against which extracellular trypanosomes could not have evolved resistance, could kill pathogenic T. brucei subspecies. Here we show that recombinant APOL3 (rAPOL3) kills all African trypanosomes, including T...
September 18, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28924009/site-specific-regulation-of-p2x7-receptor-function-in-microglia-gates-morphine-analgesic-tolerance
#11
Heather Leduc-Pessah, Nicholas L Weilinger, Churmy Y Fan, Nicole E Burma, Roger J Thompson, Tuan Trang
Tolerance to the analgesic effects of opioids is a major problem in chronic pain management. Microglia are implicated in opioid tolerance, but the core mechanisms regulating their response to opioids remain obscure. By selectively ablating microglia in the spinal cord using a saporin-conjugated antibody to Mac1, we demonstrate a causal role for microglia in the development, but not maintenance, of morphine tolerance in male rats. Increased P2X7 receptor (P2X7R) activity is a cardinal feature of microglial activation, and in this study we found that morphine potentiates P2X7R-mediated Ca(2+) responses in resident spinal microglia acutely isolated from morphine tolerant rats...
September 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28923482/the-optimal-regulation-mode-of-bcl-2-apoptotic-switch-revealed-by-bistability-analysis
#12
Zhiyong Yin, Hong Qi, Lili Liu, Zhen Jin
In most cell types, apoptosis occurs by the mitochondrial outer membrane permeability (MOMP)-mediated pathway, which is controlled by Bcl-2 family proteins (often referred to as Bcl-2 apoptotic switch). These proteins, which display a range of bioactivities, can be divided into four types: effectors, inhibitors, activators and sensitizers. Although the complex interactions among Bcl-2 family members have been studied intensively, a unifying hypothesis for the mechanism they use to regulate MOMP remains elusive...
September 15, 2017: Bio Systems
https://www.readbyqxmd.com/read/28923398/sirt1-suppresses-colorectal-cancer-metastasis-by-transcriptional-repression-of-mir-15b-5p
#13
Li-Na Sun, Zheng Zhi, Liang-Yan Chen, Qun Zhou, Xiu-Ming Li, Wen-Juan Gan, Shu Chen, Meng Yang, Yao Liu, Tong Shen, Yong Xu, Jian-Ming Li
The class III deacetylase sirtuin 1 (SIRT1), a member of the sirtuin family proteins, plays a key role in many types of cancers including colorectal cancer (CRC). Here we report that SIRT1 suppressed CRC metastasis in vitro and in vivo as a negative regulator for miR-15b-5p transcription. Mechanistically, SIRT1 impaired regulatory effects of activator protein (AP-1) on miR-15b-5p trans-activation through deacetylation of AP-1. Importantly, acyl-CoA oxidase 1 (ACOX1), a key enzyme of the fatty acid oxidation (FAO) pathway, was found as a direct target for miR-15b-5p...
September 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28923218/randomized-controlled-trials-in-soft-tissue-sarcoma-we-are-getting-there
#14
REVIEW
Andrea J MacNeill, Abha Gupta, Carol J Swallow
Soft tissue sarcoma (STS) is a family of malignancies for which individual management decisions can be complex. There is a paucity of level 1 evidence, as the rarity and heterogeneity of STS pose challenges to the design and execution of randomized controlled trials. Radiotherapy (RT) is routinely used to facilitate function-preserving surgery and to improve local control. Delivery of RT in the preoperative setting can decrease chronic toxicities at the cost of increased wound complications in the short-term...
October 2017: Surgical Oncology Clinics of North America
https://www.readbyqxmd.com/read/28923101/durable-response-rate-as-an-endpoint-in-cancer-immunotherapy-insights-from-oncolytic-virus-clinical-trials
#15
Howard L Kaufman, Robert H I Andtbacka, Frances A Collichio, Michael Wolf, Zhongyun Zhao, Mark Shilkrut, Igor Puzanov, Merrick Ross
BACKGROUND: Traditional response criteria may be insufficient to characterize full clinical benefits of anticancer immunotherapies. Consequently, endpoints such as durable response rate (DRR; a continuous response [complete or partial objective response] beginning within 12 months of treatment and lasting ≥6 months) have been employed. There has not, however, been validation that DRR correlates with other more traditional endpoints of clinical benefit such as overall survival. METHODS: We evaluated whether DRR was associated with clinically meaningful measures of benefit (eg, overall survival [OS], quality of life [QoL], or treatment-free interval [TFI]) in a phase 3 clinical trial of an oncolytic virus for melanoma treatment...
September 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28923014/scn8a-mutations-in-chinese-patients-with-early-onset-epileptic-encephalopathy-and-benign-infantile-seizures
#16
Jiaping Wang, Hua Gao, Xinhua Bao, Qingping Zhang, Jiarui Li, Liping Wei, Xiru Wu, Yan Chen, Shujie Yu
BACKGROUND: SCN8A mutations have recently been associated with epilepsy and neurodevelopmental disorders. This study aimed to broaden the phenotypic-spectrum of disease related with SCN8A mutations. METHODS: To identify the pathogenic gene of a Chinese family, in which six members suffered from epilepsy, whole-exome sequencing was performed. In addition, target next-generation sequencing (NGS) was performed on 178 sporadic patients, who had epilepsy of unknown etiology within 6 months after birth...
September 18, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28922560/betacellulin-regulates-the-proliferation-and-differentiation-of-retinal-progenitor-cells-in-vitro
#17
Dandan Zhang, Bingqiao Shen, Yi Zhang, Ni Ni, Yuyao Wang, Fan Xianqun, Hao Sun, Ping Gu
Retinal progenitor cells (RPCs) hold great potential for the treatment of retinal degenerative diseases. However, their proliferation capacity and differentiation potential towards specific retinal neurons are limited, which limit their future clinical applications. Thus, it is important to improve the RPCs' ability to proliferate and differentiate. Currently, epidermal growth factor (EGF) is commonly used to stimulate RPC growth in vitro. In this study, we find that betacellulin (BTC), a member of the EGF family, plays important roles in the proliferation and differentiation of RPCs...
September 18, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28922350/stem-cells-and-cell-based-therapies-for-cerebral-palsy-a-call-for-rigor
#18
REVIEW
Lauren L Jantzie, Joseph Scafidi, Shenandoah Robinson
Cell-based therapies hold significant promise for infants at risk for cerebral palsy (CP) from perinatal brain injury (PBI). PBI leading to CP results from multi-faceted damage to neural cells. Complex developing neural networks are injured by neural cell damage plus unique perturbations in cell signaling. Given that cell-based therapies can simultaneously repair multiple injured neural components during critical neurodevelopmental windows, these interventions potentially offer efficacy for patients with CP...
September 18, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28922007/attachment-based-family-therapy-and-individual-emotion-focused-therapy-for-unresolved-anger-qualitative-analysis-of-treatment-outcomes-and-change-processes
#19
Ravit Steinmann, Inbal Gat, Ofir Nir-Gottlieb, Ben Shahar, Gary M Diamond
Twenty-six clients who received 10 sessions of either attachment-based family therapy (ABFT) or individual emotion-focused therapy (EFT) for unresolved anger toward a parent were interviewed 6 months after completing treatment. Interviews were analyzed using the consensual qualitative research approach. Clients in both conditions reported improved relationships with parents, gaining a new perspective of their parent, increased compassion toward parent, less reactivity to anger, feeling cleaned-out, and acquiring new coping strategies...
September 2017: Psychotherapy
https://www.readbyqxmd.com/read/28921471/tlr-agonists-as-adjuvants-for-cancer-vaccines
#20
Ji-Kun Li, Jesse J Balic, Liang Yu, Brendan Jenkins
Toll-like receptors (TLRs) are one of the best characterised families of pattern recognition receptors (PRRs) and play a critical role in the host defence to infection. Accumulating evidence indicates that TLRs also participate in maintaining tissue homeostasis by controlling inflammation and tissue repair, as well as promoting antitumour effects via activation and modulation of adaptive immune responses. TLR agonists have successfully been exploited to ameliorate the efficacy of various cancer therapies. In this chapter, we will discuss the rationales of using TLR agonists as adjuvants to cancer treatments and summarise the recent findings of preclinical and clinical studies of TLR agonist-based cancer therapies...
2017: Advances in Experimental Medicine and Biology
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