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https://www.readbyqxmd.com/read/29773601/combinatorial-targeting-of-xpo1-and-flt3-exerts-synergistic-anti-leukemia-effects-through-induction-of-differentiation-and-apoptosis-in-flt3-mutated-acute-myeloid-leukemias-from-concept-to-clinical-trial
#1
Weiguo Zhang, Charlie Ly, Jo Ishizawa, Hong Mu, Vivian Ruvolo, Sharon Shacham, Naval Daver, Michael Andreeff
Targeted therapies against FLT3-mutated acute myeloid leukemia have shown limited clinical efficacy primarily because of the acquisition of secondary mutations in FLT3 and persistent activation of downstream pro-survival pathways such as MEK/ERK, PI3K/AKT, and STAT5. Activation of these additional kinases may also result in phosphorylation of tumor suppressor proteins promoting their nuclear export. Thus, co-targeting nuclear export proteins (i.e., XPO1) and FLT3 concomitantly may be therapeutically effective...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773183/cytosolic-increased-labile-zn-2-contributes-to-arrhythmogenic-action-potentials-in-left-ventricular-cardiomyocytes-through-protein-thiol-oxidation-and-cellular-atp-depletion
#2
Sinan Degirmenci, Yusuf Olgar, Aysegul Durak, Erkan Tuncay, Belma Turan
Intracellular labile (free) Zn2+ -level ([Zn2+ ]i ) is low and increases markedly under pathophysiological conditions in cardiomyocytes. High [Zn2+ ]i is associated with alterations in excitability and ionic-conductances while exact mechanisms are not clarified yet. Therefore, we examined the elevated-[Zn2+ ]i on some sarcolemmal ionic-mechanisms, which can mediate cardiomyocyte dysfunction. High-[Zn2+ ]i induced significant changes in action potential (AP) parameters, including depolarization in resting membrane-potential and prolongations in AP-repolarizing phases...
July 2018: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29772714/modulating-chemosensitivity-of-tumors-to-platinum-based-antitumor-drugs-by-transcriptional-regulation-of-copper-homeostasis
#3
REVIEW
Yu-Hsuan Lai, Chin Kuo, Macus Tien Kuo, Helen H W Chen
Platinum (Pt)-based antitumor agents have been effective in treating many human malignancies. Drug importing, intracellular shuffling, and exporting-carried out by the high-affinity copper (Cu) transporter ( hCtr1 ), Cu chaperone (Ato x1), and Cu exporters (ATP7A and ATP7B), respectively-cumulatively contribute to the chemosensitivity of Pt drugs including cisplatin and carboplatin, but not oxaliplatin. This entire system can also handle Pt drugs via interactions between Pt and the thiol-containing amino acid residues in these proteins; the interactions are strongly influenced by cellular redox regulators such as glutathione...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29772254/effect-of-interferon-alpha-and-cyclosporine-treatment-separately-and-in-combination-on-middle-east-respiratory-syndrome-coronavirus-mers-cov-replication-in-a-human-in-vitro-and-ex-vivo-culture-model
#4
H S Li, Denise I T Kuok, M C Cheung, Mandy M T Ng, K C Ng, Kenrie P Y Hui, J S Malik Peiris, Michael C W Chan, John M Nicholls
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has emerged as a coronavirus infection of humans in the past 5 years. Though confined to certain geographical regions of the world, infection has been associated with a case fatality rate of 35%, and this mortality may be higher in ventilated patients. As there are few readily available animal models that accurately mimic human disease, it has been a challenge to ethically determine what optimum treatment strategies can be used for this disease. We used in-vitro and human ex-vivo explant cultures to investigate the effect of two immunomodulatory agents, interferon alpha and cyclosporine, singly and in combination, on MERS-CoV replication...
May 14, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29772242/synthesis-molecular-modeling-and-biological-evaluation-of-potent-analogs-of-2-methoxyestradiol
#5
Nora Al-Kazaale, Phuong T Tran, Farhad Haidari, Eirik Johansson Solum, Sandra Liekens, Peter Vervaeke, Ingebrigt Sylte, Jing-Jy Cheng, Anders Vik, Trond Vidar Hansen
The endogenous steroid 2-methoxyestradiol (1) has attracted a great interest as a lead compound towards the development of new anti-cancer drugs. Herein, the synthesis, molecular modeling, anti-proliferative and anti-angiogenic effects of ten 2-ethyl and four 2-methoxy analogs of estradiol are reported. The ethyl group was introduced to the steroid A-ring using a novel Friedel-Crafts alkylation protocol. Several analogs displayed potent anti-proliferative activity with IC50 -values in the submicromolar range towards the CEM human leukemia cancer cell line...
May 14, 2018: Steroids
https://www.readbyqxmd.com/read/29770643/use-of-the-bispectral-index-to-predict-eye-position-of-children-during-general-anesthesia
#6
Koung Hoon Kook, Seung Ah Chung, Suyoun Park, Dae Hee Kim
PURPOSE: To assess the relationship between eye position and anesthesia depth using the bispectral index (BIS) value, a parameter derived from electroencephalography data. METHODS: We investigated the relationship between BIS value and eye position in 32 children who underwent surgery for epiblepharon under general anesthesia. BIS values were recorded continuously throughout the procedure (from induction to awakening). Eye positions were video-recorded and analyzed after surgery...
May 15, 2018: Korean Journal of Ophthalmology: KJO
https://www.readbyqxmd.com/read/29769077/magnetic-field-distribution-modulation-of-intrathecal-delivered-ketorolac-iron-oxide-nanoparticle-conjugates-produce-excellent-analgesia-for-chronic-inflammatory-pain
#7
Ping-Ching Wu, Dar-Bin Shieh, Hung-Tsung Hsiao, Jeffery Chi-Fei Wang, Ya-Chi Lin, Yen-Chin Liu
BACKGROUND: Nanoparticles have become one of the most promising among the potential materials used for biomedical applications. However, few researchers have focused on their effects on analgesia. Despite the fact that various nanoparticles have been evaluated for drug delivery and MRI imaging contrast enhancement in clinical settings, no reports have investigated the in vivo synergy of ketorolac iron-oxide nanoparticle conjugates to improve the analgesic effect. METHODS: Ketorolac conjugated magnetic iron oxide nanoparticles (Keto-SPIO) were synthesized via two-stage additions of protective agents and chemical co-precipitation...
May 16, 2018: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/29768894/preparation-of-a-h%C3%A2-pw-12-o-40-deposited-chitosan-coated-iron-oxide-magnetic-core-shell-nanocomposite-for-friedel-crafts-acylation
#8
Xin Wen, Huanhuan Zhang, Fei Tian, Xiaofang Liu, Libo Niu, Guoyi Bai
A novel H3PW12O40 deposited chitosan coated iron oxide magnetic core-shell nanocomposite (Fe3O4@CS@HPW) was prepared via a facile approach. Fe3O4 nanoparticles were first coated with crosslinking-agent-free chitosan, and then H3PW12O40 was loaded onto the surface of chitosan as an outer shell. The resultant nanocomposite was well characterized by Brunauer-Emmett-Teller surface area analysis (BET), inductively coupled plasma analysis (ICP), X-ray diffraction (XRD), fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and elemental mappings...
January 1, 2018: Journal of Nanoscience and Nanotechnology
https://www.readbyqxmd.com/read/29768861/construction-of-highly-efficient-fe%C3%A2-o%C3%A2-alooh-lamellar-adsorbent-for-removal-of-congo-red
#9
Yuanna Zhu, Jianrong Wang, Yingzi Wang, Xueling Song, Yanan Xu, Ping Yang
Fe3O4@AlOOH adsorbent with high efficient adsorption capacity was successfully synthesized by controlling the hydrolysis rate for aluminum isopropoxide (AIP) and introducing inductive agent thioglycolic acid (TGA). Al(OH)3-TGA clusters played a key role in the formation of Fe3O4@AlOOH adsorbent with lamellar structure. Morphology characterization revealed that magnetic Fe3O4 nanoparticles were uniformly deposited on the surface of AlOOH. The lamellar structure of AlOOH and the strong magnetic intensity of Fe3O4 were helpful for its rapid separation from solution under external magnetic field...
January 1, 2018: Journal of Nanoscience and Nanotechnology
https://www.readbyqxmd.com/read/29767250/diosmetin-suppresses-human-prostate-cancer-cell-proliferation-through-the-induction-of-apoptosis-and-cell-cycle-arrest
#10
Christine Oak, Ahmad O Khalifa, Ilaha Isali, Natarajan Bhaskaran, Ethan Walker, Sanjeev Shukla
Diosmetin, a plant flavonoid, has been shown to exert promising effects on prostate cancer cells as an anti‑proliferative and anticancer agent. In this study, using western blot analysis for protein expression and flow cytometry for cell cycle analysis, we determined that the treatment of the LNCaP and PC‑3 prostate cancer cells with diosmetin resulted in a marked decrease in cyclin D1, Cdk2 and Cdk4 expression levels (these proteins remain active in the G0‑G1 phases of the cell cycle). These changes were accompanied by a decrease in c-Myc and Bcl-2 expression, and by an increase in Bax, p27Kip1 and FOXO3a protein expression, which suggests the potential modulatory effects of diosmetin on protein transcription...
May 16, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29767237/a-novel-anti%C3%A2-proliferative-pentapeptide-ilymp-isolated-from-cyclina-sinensis-protein-hydrolysate-induces-apoptosis-of-du%C3%A2-145-prostate-cancer-cells
#11
Fangmiao Yu, Yaru Zhang, Lei Ye, Yunping Tang, Guofang Ding, Xiaojun Zhang, Zuisu Yang
Prostate cancer is the main causes of cancer associated mortality in men worldwide, cancer patients often suffer serious side effects when treated with chemotherapy or radiotherapy, therefore novel drugs are in high demand to treat prostate cancer. In the present study, a pentapeptide (Ile‑Leu‑Tyr‑Met‑Pro; ILYMP) with a molecular weight of 635.71 Da was isolated from the protein hydrolysate of Cyclina sinensis via ultrafiltration and chromatographic methods, and subsequently named Cyclina sinensis pentapeptide (CSP)...
May 14, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29765503/oleuropein-aglycone-protects-against-mao-a-induced-autophagy-impairment-and-cardiomyocyte-death-through-activation-of-tfeb
#12
Caterina Miceli, Yohan Santin, Nicola Manzella, Raffaele Coppini, Andrea Berti, Massimo Stefani, Angelo Parini, Jeanne Mialet-Perez, Chiara Nediani
Age-associated diseases such as neurodegenerative and cardiovascular disorders are characterized by increased oxidative stress associated with autophagy dysfunction. Oleuropein aglycone (OA), the main polyphenol found in olive oil, was recently characterized as an autophagy inducer and a promising agent against neurodegeneration. It is presently unknown whether OA can have beneficial effects in a model of cardiac stress characterized by autophagy dysfunction. Here, we explored the effects of OA in cardiomyocytes with overexpression of monoamine oxidase-A (MAO-A)...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29764952/samhd1-phosphorylation-coordinates-the-anti-hiv-1-response-by-diverse-interferons-and-tyrosine-kinase-inhibition
#13
Matthew A Szaniawski, Adam M Spivak, James E Cox, Jonathan L Catrow, Timothy Hanley, Elizabeth S C P Williams, Michel J Tremblay, Alberto Bosque, Vicente Planelles
Macrophages are susceptible to human immunodeficiency virus type 1 (HIV-1) infection despite abundant expression of antiviral proteins. Perhaps the most important antiviral protein is the restriction factor sterile alpha motif domain and histidine/aspartic acid domain-containing protein 1 (SAMHD1). We investigated the role of SAMHD1 and its phospho-dependent regulation in the context of HIV-1 infection in primary human monocyte-derived macrophages and the ability of various interferons (IFNs) and pharmacologic agents to modulate SAMHD1...
May 15, 2018: MBio
https://www.readbyqxmd.com/read/29762647/maternal-low-protein-diet-impairs-prostate-growth-in-young-rat-offspring-and-induces-prostate-carcinogenesis-with-aging
#14
Sergio A A Santos, Ana C Camargo, Flávia B Constantino, Ketlin T Colombelli, Fernanda Mani, Jaqueline C Rinaldi, Suelen Franco, Luiz M F Portela, Bruno O S Duran, Wellerson R Scarano, Barry T Hinton, Sergio L Felisbino, Luis A Justulin
Carcinogenesis is frequently linked to genetic background, however, exposure to environmental risk factors has gained attention as the etiologic agent for several types of cancer, including prostate. The intrauterine microenvironment has been described as a preponderant factor for offspring health; and maternal exposure to insult has been linked to chronic disease in older offspring. Using a model of maternal exposure to low protein diet (LPD; 6% protein), we demonstrated that impairment of offspring rat prostatic growth on postnatal day (PND) 21 was associated with prostate carcinogenesis in older offspring (PND 540)...
May 14, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29762523/silver-nanoparticles-two-faced-neuronal-differentiation-inducing-material-in-neuroblastoma-sh-sy5y-cells
#15
Ahmed Abdal Dayem, Soo Bin Lee, Hye Yeon Choi, Ssang-Goo Cho
We have previously demonstrated the potential of biologically synthesized silver nanoparticles (AgNP) in the induction of neuronal differentiation of human neuroblastoma, SH-SY5Y cells; we aimed herein to unveil its molecular mechanism in comparison to the well-known neuronal differentiation-inducing agent, all-trans-retinoic acid (RA). AgNP-treated SH-SY5Y cells showed significantly higher reactive oxygen species (ROS) generation, stronger mitochondrial membrane depolarization, lower dual-specificity phosphatase expression, higher extracellular-signal-regulated kinase (ERK) phosphorylation, lower AKT phosphorylation, and lower expression of the genes encoding the antioxidant enzymes than RA-treated cells...
May 15, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29761903/the-combination-of-a-sphingosine-kinase-2-inhibitor-abc294640-and-a-bcl-2-inhibitor-abt-199-displays-synergistic-anti-myeloma-effects-in-myeloma-cells-without-a-t-11-14-translocation
#16
Pasupathi Sundaramoorthy, Cristina Gasparetto, Yubin Kang
Multiple myeloma (MM) remains an incurable disease in need of the development of novel therapeutic agents and drug combinations. ABT-199 is a specific Bcl-2 inhibitor in clinical trials for MM; however, its activity as a single agent was limited to myeloma patients with the t(11;14) translocation who acquire resistance due to co-expression of Mcl-1 and Bcl-xL. These limitations preclude its use in a broader patient population. We have recently found that a sphingosine kinase 2-specific inhibitor (ABC294640) induces apoptosis in primary human CD138+ cells and MM cell lines...
May 15, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29761493/experimental-induction-of-mouthrot-in-atlantic-salmon-smolts-using-tenacibaculum-maritimum-from-western-canada
#17
K Frisch, S B Småge, C Vallestad, H Duesund, Ø J Brevik, A Klevan, R H Olsen, S T Sjaatil, D Gauthier, B Brudeseth, A Nylund
Mouthrot, or bacterial stomatitis, is a disease which mainly affects farmed Atlantic salmon, (Salmo salar, L.), smolts recently transferred into salt water in both British Columbia (BC), Canada, and Washington State, USA. It is a significant fish welfare issue which results in economic losses due to mortality and antibiotic treatments. The associated pathogen is Tenacibaculum maritimum, a bacterium which causes significant losses in many species of farmed fish worldwide. This bacterium has not been proven to be the causative agent of mouthrot in BC despite being isolated from affected Atlantic salmon...
May 14, 2018: Journal of Fish Diseases
https://www.readbyqxmd.com/read/29761248/biglycan-promotes-the-chemotherapy-resistance-of-colon-cancer-by-activating-nf-%C3%AE%C2%BAb-signal-transduction
#18
Bin Liu, Tonghong Xu, Xinning Xu, Yuzhu Cui, Xiaojing Xing
Biglycan (BGN) is overexpressed in cancer stem cells of colon cancer and induces the activation of NF-κB pathway which contributes to the chemotherapy resistance of diverse cancer types. Therefore, we hypothesized that the overexpression of BGN also promoted the development of multiple drug resistance (MDR) in colon cancer via NF-κB pathway. The expression of BGN was bilaterally modulated in colon cancer cell lines HT-29 and SW-480 and the effect of treatments on the cell proliferation and resistance to 5-FU was assessed...
May 14, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29760958/targeting-muc1-c-suppresses-bcl2a1-in-triple-negative-breast-cancer
#19
Masayuki Hiraki, Takahiro Maeda, Neha Mehrotra, Caining Jin, Maroof Alam, Audrey Bouillez, Tsuyoshi Hata, Ashujit Tagde, Amy Keating, Surender Kharbanda, Harpal Singh, Donald Kufe
B-cell lymphoma 2-related protein A1 (BCL2A1) is a member of the BCL-2 family of anti-apoptotic proteins that confers resistance to treatment with anti-cancer drugs; however, there are presently no agents that target BCL2A1. The MUC1-C oncoprotein is aberrantly expressed in triple-negative breast cancer (TNBC) cells, induces the epithelial-mesenchymal transition (EMT) and promotes anti-cancer drug resistance. The present study demonstrates that targeting MUC1-C genetically and pharmacologically in TNBC cells results in the downregulation of BCL2A1 expression...
2018: Signal Transduction and Targeted Therapy
https://www.readbyqxmd.com/read/29759562/investigational-agents-to-enhance-the-efficacy-of-chemotherapy-or-radiation-in-pancreatic-cancer
#20
REVIEW
Myrna Hurtado, Umesh T Sankpal, Amalendu Ranjan, Rajasekhar Maram, Jamboor K Vishwanatha, Ganji Purnachandra Nagaraju, Bassel F El-Rayes, Riyaz Basha
Pancreatic cancer (PC) continues to be a fatal malignancy. With standard treatments having modest impact, alternative courses of actions are being investigated such as enhancing the efficacy of standard treatment through sensitization of PC cells to chemotherapy or radiation. This review emphasizes investigational agents that increase the responses to chemotherapy or radiation in PC models. Our group has extensively investigated on Curcumin (Cur), analogs (EF31, UBS109, and L49H37), nanoparticles and a small molecule Tolfenamic acid (TA) for enhancing therapeutic efficacy in both in vitro and in vivo assays...
June 2018: Critical Reviews in Oncology/hematology
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