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https://www.readbyqxmd.com/read/27936492/lncrna-a-versatile-regulator-of-the-nf-%C3%AE%C2%BAb-signaling-circuit
#1
REVIEW
Xiaohua Mao, Zhenyi Su, Adnan K Mookhtiar
The Nuclear Factor-κB (NF-κB) family of transcription factors play an essential role for the regulation of inflammatory responses, immune function and malignant transformation. Aberrant activity of this signaling pathway may lead to inflammation, autoimmune diseases and oncogenesis. Over the last two decades great progress has been made in the understanding of NF-κB activation and how the response is counteracted for maintaining tissue homeostasis. Therapeutic targeting of this pathway has largely remained ineffective due to the widespread role of this vital pathway and the lack of specificity of the therapies currently available...
December 9, 2016: Immunology
https://www.readbyqxmd.com/read/27936464/refractory-testicular-germ-cell-tumors-are-highly-sensitive-to-the-second-generation-dna-methylation-inhibitor-guadecitabine
#2
Costantine Albany, Mary P Hever-Jardine, Katherine M von Herrmann, Christina Y Yim, Janice Tam, Joshua M Warzecha, Leah Shin, Sarah E Bock, Brian S Curran, Aneeq S Chaudhry, Fred Kim, George E Sandusky, Pietro Taverna, Sarah J Freemantle, Brock C Christensen, Lawrence H Einhorn, Michael J Spinella
Testicular germ cell tumors (TGCTs) are the most common cancers of young males. A substantial portion of TGCT patients are refractory to cisplatin. There are no effective therapies for these patients, many of whom die from progressive disease. Embryonal carcinoma (EC) are the stem cells of TGCTs. In prior in vitro studies we found that EC cells were highly sensitive to the DNA methyltransferase inhibitor, 5-aza deoxycytidine (5-aza). Here, as an initial step in bringing demethylation therapy to the clinic for TGCT patients, we evaluated the effects of the clinically optimized, second generation demethylating agent guadecitabine (SGI-110) on EC cells in an animal model of cisplatin refractory testicular cancer...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27936442/label-free-colorimetric-detection-of-cancer-related-gene-based-on-two-step-amplification-of-molecular-machine
#3
Huo Xu, Dong Wu, Chen-Qiao Li, Zheng Lu, Xiao-Yun Liao, Jie Huang, Zai-Sheng Wu
Highly sensitive detection of K-ras gene is of great significance in biomedical research and clinical diagnosis. Here, we developed a colorimetric biosensing system for the detection of proto-oncogene K-ras based on enhanced amplification effect of DNA molecular machine, where dual isothermal circular strand-displacement amplification (D-SDA) occurs on two arms in one-to-one correspondence. Specifically, we designed a primer-locked hairpin probe (HP) and a primer-contained linear polymerization template (PPT)...
December 2, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27936277/algorithm-driven-dosage-decisions-ad3-optimizing-treatment-for-children-with-language-impairment
#4
Laura M Justice, Jessica Logan, Hui Jiang, Mary Beth Schmitt
Background: This study was designed to provide recommended amounts of treatment to achieve the optimal amount of language gain for children with language impairment. Method: The authors retrospectively analyzed treatment outcomes for 233 children for delivered dose, intensity, and cumulative intensity of therapy. The steps of the analytical process they applied to arrive at algorithms for recommended amounts of treatment were (1) multilevel modeling to predict children's language gains from the 3 intensity parameters and (2) extraction of regression weights to create a recommended amount of treatment...
December 9, 2016: American Journal of Speech-language Pathology
https://www.readbyqxmd.com/read/27936238/trehalose-6-phosphate-mediated-toxicity-determines-essentiality-of-otsb2-in-mycobacterium-tuberculosis-in-vitro-and-in-mice
#5
Jan Korte, Marina Alber, Carolina M Trujillo, Karl Syson, Hendrik Koliwer-Brandl, René Deenen, Karl Köhrer, Michael A DeJesus, Travis Hartman, William R Jacobs, Stephen Bornemann, Thomas R Ioerger, Sabine Ehrt, Rainer Kalscheuer
Trehalose biosynthesis is considered an attractive target for the development of antimicrobials against fungal, helminthic and bacterial pathogens including Mycobacterium tuberculosis. The most common biosynthetic route involves trehalose-6-phosphate (T6P) synthase OtsA and T6P phosphatase OtsB that generate trehalose from ADP/UDP-glucose and glucose-6-phosphate. In order to assess the drug target potential of T6P phosphatase, we generated a conditional mutant of M. tuberculosis allowing the regulated gene silencing of the T6P phosphatase gene otsB2...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27936237/the-immunomodulatory-small-molecule-imiquimod-induces-apoptosis-in-devil-facial-tumour-cell-lines
#6
Amanda L Patchett, Jocelyn M Darby, Cesar Tovar, A Bruce Lyons, Gregory M Woods
The survival of the Tasmanian devil (Sarcophilus harrisii) is threatened by devil facial tumour disease (DFTD). This transmissible cancer is usually fatal, and no successful treatments have been developed. In human studies, the small immunomodulatory molecule imiquimod is a successful immunotherapy, activating anti-tumour immunity via stimulation of toll-like receptor-7 (TLR7) signaling pathways. In addition, imiquimod is a potent inducer of apoptosis in human tumour cell lines via TLR7 independent mechanisms...
2016: PloS One
https://www.readbyqxmd.com/read/27935974/epigallocatechin-3-gallate-upregulates-mir-221-to-inhibit-osteopontin-dependent-hepatic-fibrosis
#7
M L Arffa, M A Zapf, A N Kothari, V Chang, G N Gupta, X Ding, M M Al-Gayyar, W Syn, N M Elsherbiny, P C Kuo, Z Mi
Osteopontin (OPN) promotes hepatic fibrosis, and developing therapies targeting OPN expression in settings of hepatic injury holds promise. The polyphenol epigallocatechin-3-gallate (EGCG), found in high concentrations in green tea, downregulates OPN expression through OPN mRNA degradation, but the mechanism is unknown. Previous work has shown that microRNAs can decrease OPN mRNA levels, and other studies have shown that EGCG modulates the expression of multiple microRNAs. In our study, we first demonstrated that OPN induces hepatic stellate cells to transform into an activated state...
2016: PloS One
https://www.readbyqxmd.com/read/27935959/crystal-structure-of-schistosoma-mansoni-adenosine-phosphorylase-5-methylthioadenosine-phosphorylase-and-its-importance-on-adenosine-salvage-pathway
#8
Juliana Roberta Torini, José Brandão-Neto, Ricardo DeMarco, Humberto D'Muniz Pereira
Schistosoma mansoni do not have de novo purine pathways and rely on purine salvage for their purine supply. It has been demonstrated that, unlike humans, the S. mansoni is able to produce adenine directly from adenosine, although the enzyme responsible for this activity was unknown. In the present work we show that S. mansoni 5´-deoxy-5´-methylthioadenosine phosphorylase (MTAP, E.C. 2.4.2.28) is capable of use adenosine as a substrate to the production of adenine. Through kinetics assays, we show that the Schistosoma mansoni MTAP (SmMTAP), unlike the mammalian MTAP, uses adenosine substrate with the same efficiency as MTA phosphorolysis, which suggests that this enzyme is part of the purine pathway salvage in S...
December 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27935952/neoadjuvant-gemcitabine-chemotherapy-followed-by-concurrent-imrt-simultaneous-boost-achieves-high-r0-resection-in-borderline-resectable-pancreatic-cancer-patients
#9
Xiaolun Huang, Jeanna L Knoble, Ming Zeng, Fernando N Aguila, Tara Patel, Lowell W Chambers, Honglin Hu, Hao Liu
BACKGROUND: To study the feasibility of down stage the borderline resectable pancreatic cancer (BRPC) to resectable disease, we reported our institutional results using an intensity-modulated radiation therapy (IMRT) simultaneous integrated boost (SIB) dose escalation approach to improve R0 resectability. METHODS: We reviewed our past 7 years of experience of using neoadjuvant induction chemotherapy with Gemcitabine followed by concurrent chemoradiaiton for BRPC...
2016: PloS One
https://www.readbyqxmd.com/read/27935867/the-bromodomain-inhibitor-otx015-mk-8628-exerts-anti-tumor-activity-in-triple-negative-breast-cancer-models-as-single-agent-and-in-combination-with-everolimus
#10
Ramiro Vázquez, María E Riveiro, Lucile Astorgues-Xerri, Elodie Odore, Keyvan Rezai, Eugenio Erba, Nicolò Panini, Andrea Rinaldi, Ivo Kwee, Luca Beltrame, Mohamed Bekradda, Esteban Cvitkovic, Francesco Bertoni, Roberta Frapolli, Maurizio D'Incalci
Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous subgroup of breast tumors clinically defined by the lack of estrogen, progesterone and HER2 receptors, limiting the use of the targeted therapies employed in other breast malignancies. Recent evidence indicates that c-MYC is a key driver of TNBC. The BET-bromodomain inhibitor OTX015 (MK-8628) has potent antiproliferative activity accompanied by c-MYC down-regulation in several tumor types, and has demonstrated synergism with the mTOR inhibitor everolimus in different models...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27935841/the-cytoplasmic-tail-domain-of-epstein-barr-virus-gh-regulates-membrane-fusion-activity-through-altering-gh-binding-to-gp42-and-epithelial-cell-attachment
#11
Jia Chen, Theodore S Jardetzky, Richard Longnecker
: Epstein-Barr virus (EBV) is associated with infectious mononucleosis and a variety of cancers as well as lymphoproliferative disorders in immunocompromised patients. EBV mediates viral entry into epithelial and B cells using fusion machinery composed of four glycoproteins: gB, the gH/gL complex, and gp42. gB and gH/gL are required for both epithelial and B cell fusion. The specific role of gH/gL in fusion has been the most elusive among the required herpesvirus entry glycoproteins. Previous mutational studies have focused on the ectodomain of EBV gH and not on the gH cytoplasmic tail domain (CTD)...
November 15, 2016: MBio
https://www.readbyqxmd.com/read/27935687/chemical-synthesis-versatile-structures-and-functions-of-tailorable-adjuvants-for-optimizing-oral-vaccination
#12
Lei Zhang, Chaohua Hu, Wendi Yang, Xiaolin Liu, Yunkun Wu
Oral vaccines have become a recent focus because of their potential significance in disease prevention and therapy. In the development of oral vaccine-based therapeutics, synthetic materials with tailorable structures and versatile functions can act as antigen conveyers with adjuvant effects, reduce the time cost for vaccine optimization, and provide high security and enhanced immunity. This review presents an overview of the current status of tailoring synthetic adjuvants for oral vaccination, modification strategies for producing effectors with specific structures and functions, enhancement of immune-associated efficiencies, including the barrier-crossing capability to protect antigens in the gastrointestinal tract, coordination of the antigens penetrating mucosa and cell barriers, targeting of concentrated antigens to immune-associated cells, and direct stimulation of immune cells...
December 9, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27935263/new-glycemic-targets-for-patients-with-diabetes-from-the-japan-diabetes-society
#13
Eiichi Araki, Masakazu Haneda, Masato Kasuga, Takeshi Nishikawa, Tatsuya Kondo, Kohjiro Ueki, Takashi Kadowaki
In the 'Evidence-based Practice Guideline for the Treatment for Diabetes in Japan 2013', a new concept of the glycemic control in patients with diabetes in Japan has been declared from the Japan Diabetes Society. The main objective value of HbA1c was set to <7% from the perspective of preventing microvascular complications. On the other hand, the objective in cases where objectives can be attained by appropriate dietary or exercise therapy, or during pharmacotherapy without the occurrence of side effects such as hypoglycemia was set to <6%, and the objective in cases where intensification of treatment was considered difficult due to side effects such as hypoglycemia or for other reasons was set to <8%...
December 9, 2016: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/27935183/metformin-in-adults-with-type-1-diabetes-design-and-methods-of-reducing-with-metformin-vascular-adverse-lesions-removal-an-international-multicentre-trial
#14
J R Petrie, N Chaturvedi, I Ford, I Hramiak, A D Hughes, A J Jenkins, B Klein, R Klein, T C Ooi, P Rossing, N Sattar, C D A Stehouwer, H M Colhoun
INTRODUCTION: Cardiovascular (CV) disease is a major cause of reduced life expectancy in type 1 diabetes (T1D). Intensive insulin therapy prevents CV complications but is constrained by hypoglycaemia and weight gain. Adjunct metformin reduces insulin dose requirement and stabilises weight but there are no data on its cardiovascular effects. AIMS: We have initiated an international double-blind, randomized, placebo-controlled trial (REMOVAL: REducing with MetfOrmin Vascular Adverse Lesions in type 1 diabetes) to examine whether metformin reduces progression of atherosclerosis in adults with T1D...
December 9, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27935117/long-noncoding-rna-malat1-affects-the-efficacy-of-radiotherapy-for-esophageal-squamous-cell-carcinoma-by-regulating-cks1-expression
#15
Zhijun Li, Yang Zhou, Bo Tu, Yu Bu, Aqiu Liu, Conghua Xie
OBJECTIVE: Long noncoding RNA MALAT1 has been well-studied in the progression of many malignancies. However, its association with the radioresistance of tumors has not been well-understood yet. This study tried to explore the role of MALAT1 in regulating the radiosensitivity of esophageal cancer (EC), especially esophageal squamous cell carcinoma (ESCC), involving its regulation on Cks1 expression. METHODS: KYSE150 cells were subcutaneously inoculated into nude mice to establish ESCC xenografts...
December 9, 2016: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/27935071/severe-murine-limb-girdle-muscular-dystrophy-type-2c-pathology-is-diminished-by-fty720-treatment
#16
Ahlke Heydemann
INTRODUCTION: Limb Girdle Muscular Dystrophy Type 2C (LGMD-2C) is caused by mutations in ɤ-sarcoglycan and is a devastating, progressive, and fully lethal human muscle wasting disease that is without effective treatment. This study examined the efficacy of the sphingosine-1-phosphate receptor modulator FTY720 in treating Sgcg-/-DBA2/J, a severe mouse model of LGMD-2C. FTY720 treatment is expected to target LGMD-2C disease progression at 2 key positions by reducing chronic inflammation and fibrosis...
December 9, 2016: Muscle & Nerve
https://www.readbyqxmd.com/read/27935058/bimodal-targeting-using-sulfonated-mannosylated-pei-for-combined-gene-delivery-and-photodynamic-therapy
#17
Upendra Chitgupi, Yi Li, Mingfu Chen, Shuai Shao, Marie Beitelshees, Myles Joshua Tan, Sriram Neelamegham, Blaine A Pfeifer, Charles Jones, Jonathan F Lovell
Photodynamic therapy (PDT) and gene delivery have both been used to target both cancer cells and tumor-associated macrophages (TAMs). Given the complex nature of tumor tissue, there could be merit in combining these strategies simultaneously. In this study, we developed a bimodal targeting approach to both cancer cells and macrophages, employing materials conducive to both gene delivery and PDT. Polymers libraries were created that consisted of cationic polyethyleneimine (PEI) conjugated to the photosensitizer pyropheophorbide-α, with sulfonation (to target selectin-expressing cells) and mannosylation (to target TAMs)...
December 9, 2016: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/27935055/sub-cellular-targeting-as-a-determinant-of-the-efficacy-of-photodynamic-therapy
#18
David Kessel
In prior studies, we have identified the ability of low-level lysosomal photodamage to potentiate the phototoxic effect of subsequent photodamage to mitochondria. The mechanism involves calpain-mediated cleavage of the autophagy-associated protein ATG5 to form a pro-apoptotic fragment (tATG5). In this report, we explore the permissible time lag between the two targeting procedures along with the effect of simultaneously targeting both lysosomes and mitochondria. This was found to be as effective as the sequential protocol with no gap between the irradiation steps...
December 9, 2016: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/27935039/the-sabotaging-role-of-myeloid-cells-in-anti-angiogenic-therapy-coordination-of-angiogenesis-and-immune-suppression-by-hypoxia
#19
REVIEW
Chunyan Li, Tao Liu, Alexandr V Bazhin, Yuhui Yang
Tumor angiogenesis has become a promising target for anti-tumor therapy. Unfortunately, the somewhat inevitable occurrence of resistance has limited the efficacy of anti-angiogenic therapy. In addition to their well-established role in immune suppression, bone marrow-derived myeloid cells actively contribute to tumor angiogenesis. More importantly, myeloid cells constitute one of the major mechanisms of resistance to angiogenesis inhibition. As the most pervasive feature in tumor microenvironment, hypoxia is able to initiate both pro-angiogenic and immunosuppressive capacities of myeloid cells...
December 9, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27935036/sentinel-node-metastasis-mitotic-rate-sn-mmr-as-a-prognostic-indicator-of-rapidly-progressing-disease-in-patients-with-sentinel-node-positive-melanomas
#20
Cornelia Baum, Christel Weiss, Christoffer Gebhardt, Jochen Utikal, Alexander Marx, Wolfgang Koenen, Cyrill Géraud
Risk stratification of sentinel lymph node biopsy (SNB)-positive patients with malignant melanoma differs among current classification systems. To improve classification of patients with rapidly progressive disease who may profit from adjuvant therapy with novel immune or targeted treatment modalities, a single-center retrospective analysis was performed including all melanoma patients diagnosed with a positive SN at a university-based skin cancer center over a 10-year period (2002-2012) (96 of 419 patients)...
December 9, 2016: International Journal of Cancer. Journal International du Cancer
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