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https://www.readbyqxmd.com/read/29334667/lithium-a-classic-drug-in-psychiatry-improves-nilotinib-mediated-antileukemic-effects
#1
Janaína Peixoto-da-Silva, Andrana K Calgarotto, Katiucha R Rocha, Caroline Palmeira-Dos-Santos, Soraya S Smaili, Gustavo J S Pereira, Fernando V Pericole, Adriana da Silva S Duarte, Sara T O Saad, Claudia Bincoletto
Although Tyrosine kinase inhibitors (TKIs) that target Bcr-Abl play a key role in Chronic Myeloid Leukemia (CML) therapy, they do not eradicate CML-initiating cells, which lead to the emergence of drug resistance. Here we used the lithium, a GSK-3 inhibitor, to attempt to potentiate the effects of nilotinib against leukemia cells. For this purpose, a K562 leukemia cell line and bone marrow cells from untreated Chronic Myeloid Leukemia (CML) patients, prior to any exposure to TKIs, were used as a model. Our results demonstrated that the combination of lithium + nilotinib (L + N) induced K562-cell death and cleaved caspase-3 when compared to lithium or nilotinib alone, accompanied by GSK-3β phosphorylation and Bcr-Abl oncoprotein levels reduction...
January 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29334665/i-7ab-inhibited-the-growth-of-tnbc-cells-via-targeting-hdac3-and-promoting-the-acetylation-of-p53
#2
Mei Yang, Xuefei Dang, Yue Tan, Meixing Wang, Xiaojing Li, Gang Li
Triple negative breast cancer (TNBC) is a heterogenous disease with high aggressive and poor outcome. The lack of biomarkers and targeted therapies makes it a challenge for the treatment of TNBC. Histone deacetylase inhibitors (HDACis) are emerging as novel anti-tumor agents in many types of human cancers. In this study, we found that I-7ab, a novel HDACi, inhibited the cell viability of TNBC cells and induced the cell apoptosis. Mechanistically, I-7ab specifically decreased the expression of HDAC3 and promoted the acetylation of p53 at both Lys373 and Lys382 amino acids...
January 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29334641/do-clinically-anxious-children-cluster-according-to-their-expression-of-factors-that-maintain-child-anxiety
#3
Samantha Pearcey, Anna Alkozei, Bhismadev Chakrabarti, Helen Dodd, Kou Murayama, Suzannah Stuijfzand, Cathy Creswell
BACKGROUND: Cognitive Behaviour Therapy (CBT) is an effective treatment for childhood anxiety disorders, yet a significant proportion of children do not benefit from it. CBT for child anxiety disorders typically includes a range of strategies that may not all be applicable for all affected children. This study explored whether there are distinct subgroups of children with anxiety disorders who are characterized by their responses to measures of the key mechanisms that are targeted in CBT (i...
January 3, 2018: Journal of Affective Disorders
https://www.readbyqxmd.com/read/29334522/themes-in-literature-related-to-incidence-risk-and-prevention-of-cancer-in-solid-organ-transplantation-recipients-on-immunosuppressive-therapy
#4
Stefanie L Rashti
BACKGROUND: Solid-organ transplants provide a second chance to thousands of critically ill patients with end-organ failure each year. Immunosuppressants are administered to patients to prevent graft rejection of a transplanted organ, such as a heart, kidney, or liver, while placing the recipient at greater risk for infection and cancer. OBJECTIVE: The literature provides evidence of various cancers that have been found to develop in patients' posttransplantation...
January 12, 2018: Cancer Nursing
https://www.readbyqxmd.com/read/29334492/anti-il-10-mediated-enhancement-of-antitumor-efficacy-of-a-dendritic-cell-targeting-mip3%C3%AE-gp100-vaccine-in-the-b16f10-mouse-melanoma-model-is-dependent-on-type-i-interferons
#5
James T Gordy, Kun Luo, Brian Francica, Charles Drake, Richard B Markham
The chemokine MIP3α (CCL20) binds to CCR6 on immature dendritic cells. Vaccines fusing MIP3α to gp100 have been shown to be effective in therapeutically reducing melanoma tumor burden and prolonging survival in a mouse model. Other studies have provided evidence that interleukin-10 (IL-10) neutralizing antibodies (αIL-10) enhance immunologic melanoma therapies by modulating the tolerogenic tumor microenvironment. In the current study, we have utilized the B16F10 syngeneic mouse melanoma model to demonstrate for the first time that a therapy neutralizing IL-10 enhances the antitumor efficacy of a MIP3α-gp100 DNA vaccine, leading to significantly smaller tumors, slower growing tumors, and overall increases in mouse survival...
January 12, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29334376/positively-selected-enhancer-elements-endow-osteosarcoma-cells-with-metastatic-competence
#6
James J Morrow, Ian Bayles, Alister P W Funnell, Tyler E Miller, Alina Saiakhova, Michael M Lizardo, Cynthia F Bartels, Maaike Y Kapteijn, Stevephen Hung, Arnulfo Mendoza, Gursimran Dhillon, Daniel R Chee, Jay T Myers, Frederick Allen, Marco Gambarotti, Alberto Righi, Analisa DiFeo, Brian P Rubin, Alex Y Huang, Paul S Meltzer, Lee J Helman, Piero Picci, Henri Versteeg, John Stamatoyannopolus, Chand Khanna, Peter C Scacheri
Metastasis results from a complex set of traits acquired by tumor cells, distinct from those necessary for tumorigenesis. Here, we investigate the contribution of enhancer elements to the metastatic phenotype of osteosarcoma. Through epigenomic profiling, we identify substantial differences in enhancer activity between primary and metastatic human tumors and between near isogenic pairs of highly lung metastatic and nonmetastatic osteosarcoma cell lines. We term these regions metastatic variant enhancer loci (Met-VELs)...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29334372/pharmacological-blockade-of-asct2-dependent-glutamine-transport-leads-to-antitumor-efficacy-in-preclinical-models
#7
Michael L Schulte, Allie Fu, Ping Zhao, Jun Li, Ling Geng, Shannon T Smith, Jumpei Kondo, Robert J Coffey, Marc O Johnson, Jeffrey C Rathmell, Joe T Sharick, Melissa C Skala, Jarrod A Smith, Jordan Berlin, M Kay Washington, Michael L Nickels, H Charles Manning
The unique metabolic demands of cancer cells underscore potentially fruitful opportunities for drug discovery in the era of precision medicine. However, therapeutic targeting of cancer metabolism has led to surprisingly few new drugs to date. The neutral amino acid glutamine serves as a key intermediate in numerous metabolic processes leveraged by cancer cells, including biosynthesis, cell signaling, and oxidative protection. Herein we report the preclinical development of V-9302, a competitive small molecule antagonist of transmembrane glutamine flux that selectively and potently targets the amino acid transporter ASCT2...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29334371/cooperative-targeting-of-melanoma-heterogeneity-with-an-axl-antibody-drug-conjugate-and-braf-mek-inhibitors
#8
Julia Boshuizen, Louise A Koopman, Oscar Krijgsman, Aida Shahrabi, Elke Gresnigt- van den Heuvel, Maarten A Ligtenberg, David W Vredevoogd, Kristel Kemper, Thomas Kuilman, Ji-Ying Song, Nora Pencheva, Jens Thing Mortensen, Marnix Geukes Foppen, Elisa A Rozeman, Christian U Blank, Maarten L Janmaat, David Satijn, Esther C W Breij, Daniel S Peeper, Paul W H I Parren
Intratumor heterogeneity is a key factor contributing to therapeutic failure and, hence, cancer lethality. Heterogeneous tumors show partial therapy responses, allowing for the emergence of drug-resistant clones that often express high levels of the receptor tyrosine kinase AXL. In melanoma, AXL-high cells are resistant to MAPK pathway inhibitors, whereas AXL-low cells are sensitive to these inhibitors, rationalizing a differential therapeutic approach. We developed an antibody-drug conjugate, AXL-107-MMAE, comprising a human AXL antibody linked to the microtubule-disrupting agent monomethyl auristatin E...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29334363/macrophage-membrane-coated-iron-oxide-nanoparticles-for-enhanced-photothermal-tumor-therapy
#9
Qian-Fang Meng, Lang Rao, Minghui Zan, Ming Chen, Guang-Tao Yu, Xiaoyun Wei, Zhuhao Wu, Yue Sun, Shi Shang Guo, Xing-Zhong Zhao, Fu-Bing Wang, Wei Liu
Nanotechnology possesses the potential to revolutionize the diagnosis and treatment of tumors. The ideal nanoparticles used for in vivo cancer therapy should own long blood circulation and active cancer targeting. Additionally, they should be innoxious and invisible to the immune system. Here, we developed a biomimetic nanoplatform with the above properties for cancer therapy. Macrophage membranes were reconstructed into vesicles and then coated onto magnetic iron oxide nanoparticles (Fe3O4 NPs). Inherited from the Fe3O4 core and the macrophage membrane shell, the resulting Fe3O4@MM NPs exhibited good biocompatibility, immune evasion, cancer targeting, and light-to-heat conversion capabilities...
January 15, 2018: Nanotechnology
https://www.readbyqxmd.com/read/29334312/targeting-of-phospho-eif4e-by-homoharringtonine-eradicates-a-distinct-subset-of-human-acute-myeloid-leukemia
#10
Hong Zhou, Rong Zhen Xu, Ying Gu, Peng Fei Shi, Shenxian Qian
More than half of the patients with acute myeloid leukemia (AML) fail to achieve long-term disease-free survival with current therapies and novel therapeutic strategies are urgently needed. The effects of homoharringtonine (HHT) on the growth of AML cell lines and primary leukemia cells were examined using MTT, colony formation assay. The effects of HHT on both eukaryotic translation initiation factor 4E (eIF4E) and phospho-eIF4E(p-eIF4E) were examined through western blot and immunofluorescence staining. HHT selectively reduced levels of p-eIF4E and its downstream oncoprotein Mcl-1, and potently inhibited in vitro and in vivo the growth of a distinct subset of AML cells and primary leukemia cells expressing high level of p-eIF4E through apoptosis...
January 15, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29334288/targeted-anti-il-13-therapies-in-asthma-current-data-and-future-perspectives
#11
Polyxeni Ntontsi, Evgenia Papathanassiou, Stelios Loukides, Petros Bakakos, Georgios Hillas
Introduction The identification of patients with severe asthma who will benefit from a personalized management approach remains an unmet need. Interleukin-13 (IL-13) is a cytokine possessing a significant role in asthma pathogenesis and progression of disease. Humanised monoclonal antibodies against IL-13 and IL-13 and IL-4 receptors are mainly proposed as add-on therapy in patients with TH2-high inflammation with uncontrolled asthma despite maximum therapy. Areas covered The role of IL-13 in airway inflammation in severe asthma, the targeted anti-IL-13 therapies and biomarkers that predict response to anti-IL-13 treatment are discussed...
January 15, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29334216/lysosome-independent-intracellular-drug-gene-co-delivery-by-lipoprotein-derived-nanovector-for-synergistic-apoptosis-inducing-cancer-targeted-therapy
#12
Wei Wang, Kerong Chen, Yujie Su, Jielei Zhang, Min Li, Jianping Zhou
In this paper, reconstituted high-density lipoprotein (rHDL), a lipoprotein-derived nanovector, were constructed for co-delivery of paclitaxel (PTX) and wild type p53 gene (p53). The particle size and the zeta potential of PTX-DODAB/p53-rHDL nanoparticles were 177.2 nm and -20.06 mV, respectively. Meanwhile, they exhibited great serum stability and satisfactory sustained release characteristics in vitro. PTX-DODAB/pDNA-rHDL nanoparticles simultaneously improved the cellular uptake of PTX and pDNA via scavenger receptor B type I (SR-BI) mediated lysosome-independent internalization and promoted the transfection of pDNA in MCF-7 cells, which were revealed by flow cytometry and confocal laser scanning microscopy analyses...
January 15, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29334189/a-multifunctional-micellar-nanoplatform-with-ph-triggered-cell-penetration-and-nuclear-targeting-for-effective-cancer-therapy-and-inhibition-to-lung-metastasis
#13
Yuting Jing, Xiang Xiong, Yang Ming, Jingya Zhao, Xing Guo, Guang Yang, Shaobing Zhou
The enhancement of cellular internalization and subsequent achievement of a nuclear targeting of nanocarriers play an important role in maximizing the therapeutic potency and minimizing the side effects of encapsulated drugs. Herein, a multifunctional micellar nanoplatform simultaneously with high cell penetration and nuclear targeting through pH-triggered surface charge reversal is presented. The miscellar system is constructed from poly(ethylene glycol)-poly(ε-caprolactone) with 2,3-dimethylmaleic anhydride-Tat decoration (PECL/DA-Tat)...
January 15, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29334184/ph-responsive-peg-doxorubicin-encapsulated-aza-bodipy-nanotheranostic-agent-for-imaging-guided-synergistic-cancer-therapy
#14
Dapeng Chen, Qianyun Tang, Jianhua Zou, Xiaoyan Yang, Wei Huang, Qi Zhang, Jinjun Shao, Xiaochen Dong
Synergistic cancer therapy is of great interest for multiple advantages, such as excellent targeting accuracy, low side effects, and enhanced therapeutic efficiency. Herein, a near-infrared photosensitizer aza-BODIPY (AB) with high singlet oxygen quantum yield (ΦΔ = 82%) is designed and synthesized. With Schiff's base obtained from condensation reaction between doxorubicin (DOX) and polyethylene glycol-benzaldehyde (PEG-CHO) as the polymer matrix, aza-BODIPY is encapsulated to afford hydrophilic nanoparticles (DAB NPs)...
January 15, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29334123/cancer-associated-fibroblasts-tailored-tumor-microenvironment-of-therapy-resistance-in-gastrointestinal-cancers
#15
REVIEW
Yeqi Sun, Ruifen Wang, Meng Qiao, Yanchun Xu, Wenbin Guan, Lifeng Wang
Gastrointestinal cancers (GI) are a group of highly aggressive malignancies with heavy cancer-related mortalities. Even if continued development of therapy methods, therapy resistance has been a great obstruction for cancer treatment and thereby inevitably leads to depressed final mortality. Peritumoral cancer associated fibroblasts (CAFs), a versatile population assisting cancer cells to build a facilitated tumor microenvironment (TME), has been demonstrated exerting a promotion influence on cancer proliferation, migration, invasion, metastasis and also therapy resistance...
January 15, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29333945/remarkable-response-with-pembrolizumab-plus-albumin-bound-paclitaxel-in-2-cases-of-her2-positive-metastatic-breast-cancer-who-have-failed-to-multi-anti-her2-targeted-therapy
#16
Bian Li, Wang Tao, Zhang Shao-Hua, Q U Ze-Rui, Jin Fu-Quan, L I Fan, Jiang Ze-Fei
In clinical practice, one subgroup patients of breast cancer might have developed resistance to multi-anti-HER2 targeted drugs(trastuzumab,lapatinib and/or T-DM1) and can not benefit from the anti-HER2 targeted therapy continuously. We attempt to change the next therapic way for these patients.Two patients with metastatic breast cancer who have failed to multi-anti-HER2 targeted therapy were treated with pembrolizumab(2mg/Kg, day1) plus albumin-bound paclitaxel(125mg/m2, day1,8) every 3 weeks.CT evaluation and HER2 ECD test were performed every 2 cycles...
January 15, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29333926/engrailed-1-overexpression-as-a-potential-prognostic-marker-in-quintuple-negative-breast-cancer
#17
Yu Jin Kim, Minjung Sung, Ensel Oh, Michael Van Vrancken, Ji-Young Song, Kyungsoo Jung, Yoon-La Choi
Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by poor patient prognosis and for which no targeted therapies are currently available. TNBC can be further categorized as either basal-like (BLBC) or quintuple-negative breast cancer (QNBC). In the present study, we aimed to identify novel molecular therapeutic targets for TNBC by analyzing the mRNA expression of TNBC-related genes in publicly available microarray data sets. We found that Engrailed 1 (EN1) was significantly overexpressed in TNBC...
January 15, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29333925/androgen-receptor-independent-prostate-cancer-an-emerging-clinical-entity
#18
Ilyas Sahin, Anthony E Mega, Benedito A Carneiro
Androgen deprivation therapy remains the backbone of prostate cancer treatment given its pivotal role in the pathogenesis of prostate cancer. The growing knowledge of androgen receptor-independent (i.e. AR-null) prostate cancer cells, however, might advance the treatment paradigm of prostate cancer particularly in castration resistance stage by targeting these pathways. Here, we examined the results of two recent studies, published in Cancer Cell by Bluemn and Shukla et al., and possible clinical impact of these studies in the near future in castration resistance prostate cancer...
January 15, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29333921/targeting-brd4-proteins-suppresses-the-growth-of-nsclc-through-downregulation-of-eif4e-expression
#19
Zhongyuan Gao, Ting Yuan, Xiao Zhou, Ping Ni, Geng Sun, Ping Li, Zhixiang Cheng, Xuerong Wang
Lung cancer is the leading cause of cancer-related death worldwide. Bromodomain and extraterminal domain (BET) proteins act as epigenome readers for gene transcriptional regulation. Among BET family members, BRD4 was well studied, but for its mechanism in non-small cell lung carcinoma has not been elucidated. eIF4E regulates gene translation and has been proved to play an important role in the progression of lung cancer. In this study, we first confirmed that BET inhibitors JQ1 and I-BET151 suppressed the growth of NSCLCs, in parallel with downregulated eIF4E expression...
January 15, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29333658/in-situ-shrna-synthesis-on-dna-polylactide-nanoparticles-to-treat-multidrug-resistant-breast-cancer
#20
Qianqian Ni, Fuwu Zhang, Yunlei Zhang, Guizhi Zhu, Zhe Wang, Zhaogang Teng, Chunyan Wang, Bryant C Yung, Gang Niu, Guangming Lu, Longjiang Zhang, Xiaoyuan Chen
Nanomedicine has shown unprecedented potential for cancer theranostics. Nucleic acid (e.g., DNA and RNA) nanomedicines are of particular interest for combination therapy with chemotherapeutics. However, current nanotechnologies to construct such nucleic acid nanomedicines, which rely on chemical conjugation or physical complexation of nucleic acids with chemotherapeutics, have restrained their clinical translation due to limitations such as low drug loading efficiency and poor biostability. Herein, in situ rolling circle transcription (RCT) is applied to synthesize short hairpin RNA (shRNA) on amphiphilic DNA-polylactide (PLA) micelles...
January 15, 2018: Advanced Materials
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