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https://www.readbyqxmd.com/read/28088075/development-of-a-hypoxia-triggered-and-hypoxic-radiosensitized-liposome-as-a-doxorubicin-carrier-to-promote-synergetic-chemo-radio-therapy-for-glioma
#1
Hongmei Liu, Yandong Xie, Yafei Zhang, Yifan Cai, Baiyang Li, Honglin Mao, Yingguo Liu, Jun Lu, Longzhen Zhang, Rutong Yu
The treatment of malignant primary brain tumors is challenging. Concomitant radiochemotherapy has become the standard clinical treatment for malignant glioma, but there are two critical challenges to overcome in order to increase efficacy. First, glioma is known to have increased resistant to radiation due to its intra-tumoral hypoxia. In addition, the blood-brain barrier (BBB) restricts the distribution of the chemotherapeutic agent to the brain. Therefore, we developed a hypoxic radiosensitizer-prodrug liposome (MLP), in order to deliver DOX to the tumor and to overcome the above challenges, achieving a synergistic chemo-/radiotherapy treatment of malignant glioma...
January 3, 2017: Biomaterials
https://www.readbyqxmd.com/read/28088074/anti-angiogenic-treatment-in-breast-cancer-facts-successes-failures-and-future-perspectives
#2
REVIEW
Kim C Aalders, Konstantinos Tryfonidis, Elżbieta Senkus, Fatima Cardoso
Angiogenesis is one of the hallmarks of cancer and a crucial requisite in the development of tumors. Interrupting this process by blocking the vascular endothelial growth factor (VEGF) with the monoclonal antibody bevacizumab has been considered a possible breakthrough in the treatment of various types of cancer, especially for advanced disease. However in breast cancer, studies have shown ambivalent results causing debate about the value of this drug. In this article, we review the evidence for anti-angiogenic treatment options for breast cancer, as well as discuss the possible factors limiting the effectiveness of anti-angiogenic agents and offer a recommendation regarding the future research on these therapies for the treatment of breast cancer...
January 3, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28088038/evidence-of-functional-duplicity-of-nestin-expression-in-the-adult-mouse-midbrain
#3
Parisa Farzanehfar, Shi Sheng Lu, Anupa Dey, Dharshani Musiienko, Hamzah Baagil, Malcolm K Horne, Tim D Aumann
Whether or not neurogenesis occurs in the adult substantia nigra pars compacta (SNc) is an important question relevant for developing better treatments for the motor symptoms of Parkinson's disease (PD). Although controversial, it is generally believed that dividing cells here remain undifferentiated or differentiate into glia, not neurons. However, there is a suggestion that Nestin-expressing neural precursor cells (NPCs) in the adult SNc have a propensity to differentiate into neurons, which we sought to confirm in the present study...
January 5, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28087945/innate-immune-responses-to-tuberculosis
#4
Jeffrey S Schorey, Larry S Schlesinger
Tuberculosis remains one of the greatest threats to human health. The causative bacterium, Mycobacterium tuberculosis, is acquired by the respiratory route. It is exquisitely adapted to humans and is a prototypic intracellular pathogen of macrophages, with alveolar macrophages being the primary conduit of infection and disease. However, M. tuberculosis bacilli interact with and are affected by several soluble and cellular components of the innate immune system which dictate the outcome of primary infection, most commonly a latently infected healthy human host, in whom the bacteria are held in check by the host immune response within the confines of tissue granuloma, the host histopathologic hallmark...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087910/-progress-on-anti-tumor-molecular-mechanisms-of-dihydroartemisinin
#5
Peng Cao, Dongjin Leng, Ying Li, Ziwei Zhang, Lei Liu, Xiaoyan Li
Artemisinin is an anti-malarial drug with poor water solubility and oral absorption; so a variety of derivatives based on the parent nucleus have been developed. Compared with artemisinin, dihydroartemisinin (DHA) has a stronger anti-malaria activity, and has the advantages of high metabolic rate and better water solubility. Recent studies have discovered that DHA has a good inhibitory effect on tumor cells, which is closely related to the peroxide bridge in its molecular structure. Since tumor cells need more Fe(3+) than normal cells, there are a large number of transferrin receptors on the tumor cell membrane...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28087861/jolkinolide-a-and-jolkinolide-b-inhibit-proliferation-of-a549-cells-and-activity-of-human-umbilical-vein-endothelial-cells
#6
Lei Shen, Shan-Qiang Zhang, Lei Liu, Yu Sun, Yu-Xuan Wu, Li-Ping Xie, Ji-Cheng Liu
BACKGROUND Jolkinolide A (JA) and Jolkinolide B (JB) are diterpenoids extracted from the roots of Euphorbia fischeriana Steud and have been shown to have anti-tumor activity. However, their effects on the ability of tumor cells to invade blood vessels and metastasize remain largely unknown. Investigations into the effects of JA and JB on the angiogenesis of tumor tissues may facilitate the identification of new natural drugs with anti-tumor growth and metastasis activities. MATERIAL AND METHODS We used different concentrations of JA and JB (20 μg/ml, 40 μg/ml, 60 μg/ml, 80 μg/ml, and 100 μg/ml) to stimulate A549 cells and then studied the effects on the growth and metastasis of lung cancers...
January 14, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28087810/akt1-lkb1-and-yap1-revealed-as-myc-interactors-with-nanoluc-based-protein-fragment-complementation-assay
#7
Xiu-Lei Mo, Qi Qi, Andrei A Ivanov, Qiankun Niu, Yin Luo, Jonathan Havel, Russell Goetze, Sydney Bell, Carlos S Moreno, Lee A D Cooper, Margaret A Johns, Fadlo R Khuri, Yuhong Du, Haian Fu
The c-Myc (MYC) transcription factor is a major cancer driver and a well-validated therapeutic target. However, directly targeting MYC has been challenging. Thus, identifying proteins that interact with and regulate MYC may provide alternative strategies to inhibit its oncogenic activity. Here we report the development of a NanoLuc®-based protein-fragment complementation assay (NanoPCA) and mapping of the MYC protein interaction hub in live mammalian cells. The NanoPCA system was configured to enable detection of protein-protein interactions (PPI) at the endogenous level, as shown with PRAS40 dimerization, and detection of weak interactions, such as PINCH1-NCK2...
January 13, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28087752/deficient-retinoid-driven-angiogenesis-may-contribute-to-failure-of-adult-human-lung-regeneration-in-emphysema
#8
John-Poul Ng-Blichfeldt, Joana Alçada, M Angeles Montero, Charlotte H Dean, Uta Griesenbach, Mark J Griffiths, Matthew Hind
BACKGROUND: Molecular pathways that regulate alveolar development and adult repair represent potential therapeutic targets for emphysema. Signalling via retinoic acid (RA), derived from vitamin A, is required for mammalian alveologenesis, and exogenous RA can induce alveolar regeneration in rodents. Little is known about RA signalling in the human lung and its potential role in lung disease. OBJECTIVES: To examine regulation of human alveolar epithelial and endothelial repair by RA, and characterise RA signalling in human emphysema...
January 13, 2017: Thorax
https://www.readbyqxmd.com/read/28087716/the-piggybac-transposon-derived-genes-tpb1-and-tpb6-mediate-essential-transposon-like-excision-during-the-developmental-rearrangement-of-key-genes-in-tetrahymena-thermophila
#9
Chao-Yin Cheng, Janet M Young, Chih-Yi Gabriela Lin, Ju-Lan Chao, Harmit S Malik, Meng-Chao Yao
Ciliated protozoans perform extreme forms of programmed somatic DNA rearrangement during development. The model ciliate Tetrahymena thermophila removes 34% of its germline micronuclear genome from somatic macronuclei by excising thousands of internal eliminated sequences (IESs), a process that shares features with transposon excision. Indeed, piggyBac transposon-derived genes are necessary for genome-wide IES excision in both Tetrahymena (TPB2 [Tetrahymena piggyBac-like 2] and LIA5) and Paramecium tetraurelia (PiggyMac)...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28087658/are-winter-and-summer-dormancy-symmetrical-seasonal-adaptive-strategies-the-case-of-temperate-herbaceous-perennials
#10
REVIEW
Lauren M Gillespie, Florence A Volaire
BACKGROUND: Dormancy in higher plants is an adaptive response enabling plant survival during the harshest seasons and has been more explored in woody species than in herbaceous species. Nevertheless, winter and summer shoot meristem dormancy are adaptive strategies that could play a major role in enhancing seasonal stress tolerance and resilience of widespread herbaceous plant communities. SCOPE: This review outlines the symmetrical aspects of winter and summer dormancy in order to better understand plant adaptation to severe stress, and highlight research priorities in a changing climate...
January 13, 2017: Annals of Botany
https://www.readbyqxmd.com/read/28087649/identification-of-unique-essential-proteins-from-a-m-tuberculosis-f15-lam4-kzn-phage-secretome-library
#11
Thamsanqa Emmanuel Chiliza, Manormoney Pillay, Balakrishna Pillay
Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis disease (TB), the leading cause of death from bacterial infection worldwide. Although treatable, the resurgence of multi- and extensively-drug resistance TB is a major setback for the fight against TB globally. Consequently, there is an urgent need for new Mtb derived biomarkers for use in the design of new drugs and rapid point-of-care diagnostic or prognostic tools for management of TB transmission. Therefore, the present study aimed to identify unique Mtb secreted proteins from the extensively drug resistant Mtb F15/LAM4/KZN phage secretome library...
January 12, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28087641/molecular-pathways-targeting-protein-tyrosine-phosphatases-in-cancer
#12
Lakshmi Reddy Bollu, Abhijit Mazumdar, Michelle I Savage, Powel H Brown
The aberrant activation of oncogenic signaling pathways is a universal phenomenon in cancer and drives tumorigenesis and malignant transformation. This abnormal activation of signaling pathways in cancer is due to the altered expression of protein kinases and phosphatases. In response to extra cellular signals, protein kinases activate downstream signaling pathways through a series of protein phosphorylation events, ultimately producing a signal response. Protein tyrosine phosphatases (PTPs) are a family of enzymes that hydrolytically remove phosphate groups from proteins...
January 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28087639/vegfd-modulates-both-angiogenesis-and-lymphangiogenesis-during-zebrafish-embryonic-development
#13
Neil I Bower, Adam J Vogrin, Ludovic Le Guen, Huijun Chen, Steven A Stacker, Marc G Achen, Benjamin M Hogan
Vascular endothelial growth factors (VEGFs) control angiogenesis and lymphangiogenesis during development and in pathological conditions. In the zebrafish trunk, Vegfa controls the formation of intersegmental arteries by primary angiogenesis and Vegfc is essential for secondary angiogenesis, the formation of veins and lymphatics. VEGFD has been largely thought of as dispensable for vascular development in vertebrates. Here, we generated a zebrafish vegfd mutant by genome editing. vegfd mutants display significant defects in facial lymphangiogenesis independent of vegfc function...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28087635/rb-controls-growth-survival-and-neuronal-migration-in-human-cerebral-organoids
#14
Takeshi Matsui, Vanesa Nieto-Estévez, Sergii Kyrychenko, Jay W Schneider, Jenny Hsieh
Retinoblastoma (RB) is a tumor suppressor gene which regulates cell cycle entry to S phase via E2F transcription factors. Using knockout (KO) mice, it has been described that Rb plays a role in cell migration and differentiation in developing and adult brain as well as apoptosis. In addition, the RB family is required for the self-renewal and survival of human embryonic stem cells (ESCs). However, little is known about the role of this gene in human brain development. Here, we investigated the role of RB in cerebral organoids from human ESCs deficient for RB...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28087600/sunitinib-stimulates-expression-of-vegfc-by-tumor-cells-and-promotes-lymphangiogenesis-in-clear-cell-renal-cell-carcinomas
#15
Maeva Dufies, Sandy Giuliano, Damien Ambrosetti, Audrey Claren, Papa Diogop Ndiaye, Michalis Mastri, Walid Moghrabi, Lindsay S Cooley, Marc Ettaiche, Emmanuel Chamorey, Julien Parola, Valerie Vial, Marilena Lupu-Plesu, Jean-Christophe Bernhard, Alain Ravaud, Delphine Borchiellini, Jean Marc Ferrero, Andreas Bikfalvi, John M L Ebos, Khalid S A Khabar, Renaud Grepin, Gilles Pagès
Sunitinib is an antiangiogenic therapy given as a first-line treatment for renal cell carcinoma (RCC). While treatment improves progression-free survival, most patients relapse. We hypothesized that patient relapse can stem from the development of a lymphatic network driven by the production of the main growth factor for lymphatic endothelial cells, vascular endothelial growth factor C (VEGFC). In this study, we found that sunitinib can stimulate VEGFC gene transcription and increase VEGFC mRNA half-life. Additionally, sunitinib activated p38 MAP kinase, which resulted in the upregulation/activity of HuR and inactivation of tristetraprolin, two AU-rich-element binding proteins...
January 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28087488/cathepsin-k-targeted-sub-micron-particles-for-regenerative-repair-of-vascular-elastic-matrix
#16
Brenton Jennewine, Jonathan Fox, Anand Ramamurthi
: Abdominal Aortic Aneurysms (AAA) involve slow dilation and weakening of the aortic wall due to breakdown of structural matrix components, such as elastic fibers by chronically overexpressed matrix metalloproteinases (MMPs), primarily, MMPs-2 and -9. Auto-regenerative repair of disrupted elastic fibers by smooth muscle cells (SMCs) at the AAA site is intrinsically poor and together with chronic proteolysis prevents restoration of elastin homeostasis, necessary to enable AAA growth arrest or regression to a healthy state...
January 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28087485/stepwise-targeted-drug-delivery-to-liver-cancer-cells-for-enhanced-therapeutic-efficacy-by-galactose-grafted-ultra-ph-sensitive-micelles
#17
Guoqing Yan, Jun Wang, Liefeng Hu, Xin Wang, Guanqing Yang, Shengxiang Fu, Xu Cheng, Panpan Zhang, Rupei Tang
: To promote drug accumulation and cell-killing ability at tumor tissue, we have prepared a stepwise targeted drug delivery system that can remain stealthy and long-circulating in the blood vessels, improve drug retention at extracellular stimuli, enhance cellular uptake through special targeting ligands, and then achieve rapid drug release to improve toxicity to tumor cells at intracellular stimuli. Herein, galactose-grafted, ultra-pH-sensitive drug carriers (POEAd-g-LA-DOX micelles), which could respond to both extracellular and intracellular pH, and combine with galactose-receptors in cell membrane, were constructed by a facile method, therefore achieving: (i) remaining stable at pH 7...
January 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28087484/inhibition-of-bacterial-adhesion-and-biofilm-formation-by-dual-functional-textured-and-nitric-oxide-releasing-surfaces
#18
Li-Chong Xu, Yaqi Wo, Mark E Meyerhoff, Christopher A Siedlecki
: In separate prior studies, physical topographic surface modification or nitric oxide (NO) release has been demonstrated to each be an effective approach to inhibit and control bacterial adhesion and biofilm formation on polymeric surfaces. Such approaches can prevent biomaterial-associated infection without causing the antibiotic resistance of the strain. In this work, both techniques were successfully integrated and applied to a polyurethane (PU) biomaterial surface that bears ordered pillar topographies (400/400 nm and 500/500 nm patterns) at the top surface and a S-nitroso-N-acetylpenicillamine (SNAP, NO donor) doped sub-layer in the middle, via a soft lithography two-stage replication process...
January 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28087454/an-observational-study-of-phagocytes-and-klebsiella-pneumoniae-relationships-different-behaviors
#19
Elodie Maisonneuve, Estelle Cateau, Marion Delouche, Nathalie Quellard, Marie-Helene Rodier
Klebsiella pneumoniae is a bacterium that can be in relation with free living amoebae like Acanthamoeba castellanii in natural environments such as soil and water. This pathogen, which is responsible for community-acquired pneumonia and for nosocomial infections, also has interactions with host defense mechanisms like macrophages. As it has been shown that A. castellanii shares some traits with macrophages, in particular the ability to phagocyte bacteria, we have studied the uptake and the fate of the bacteria after contact with the two phagocytic cells...
January 10, 2017: Microbes and Infection
https://www.readbyqxmd.com/read/28087332/exo-mfa-a-13c-metabolic-flux-analysis-to-dissect-tumor-microenvironment-secreted-exosome-contributions-towards-cancer-cell-metabolism
#20
Abhinav Achreja, Hongyun Zhao, Lifeng Yang, Tae Hyun Yun, Juan Marini, Deepak Nagrath
Dissecting the pleiotropic roles of tumor micro-environment (TME) on cancer progression has been brought to the foreground of research on cancer pathology. Extracellular vesicles such as exosomes, transport proteins, lipids, and nucleic acids, to mediate intercellular communication between TME components and have emerged as candidates for anti-cancer therapy. We previously reported that cancer-associated fibroblast (CAF) derived exosomes (CDEs) contain metabolites in their cargo that are utilized by cancer cells for central carbon metabolism and promote cancer growth...
January 10, 2017: Metabolic Engineering
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