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https://www.readbyqxmd.com/read/28214929/myeloid-cells-as-a-target-for-oligonucleotide-therapeutics-turning-obstacles-into-opportunities
#1
REVIEW
Marcin Kortylewski, Dayson Moreira
Immunotherapies emerged as an alternative for cancer treatment, yet their clinical efficacies are still limited, especially in case of solid tumors. Myeloid immune cells, such as macrophages and myeloid-derived suppressor cells (MDSCs), are often hijacked by tumors and become pivotal inhibitors of antitumor immunity. Immunosuppressive functions of tumor-associated myeloid cells result from the activity of Signal Transducer and Activator of Transcription 3 (STAT3), a transcription factor with well-defined tumorigenic and tolerogenic roles in human cancers...
February 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28214675/directional-delivery-of-rspo1-by-mesenchymal-stem-cells-ameliorates-radiation-induced-intestinal-injury
#2
Wei Chen, Songwen Ju, Ting Lu, Yongfang Xu, Xiaocui Zheng, Haiyan Wang, Yan Ge, Songguang Ju
Radiation-induced intestinal injury (RIII) commonly occurs in patients who received radiotherapy for pelvic or abdominal cancer, or who suffered from whole-body irradiation during a nuclear accident. RIII can lead to intestinal disorders and even death given its integrity damage that results from intestinal stem cell (ISC) loss. Recovery from RIII relies on the intensity of supportive treatment, which can attenuate lethal infection and give surviving stem cells an opportunity to regenerate. It has been reported that RSPO1 is a cytokine with potent and specific proliferative effects on intestinal crypt cells...
February 16, 2017: Cytokine
https://www.readbyqxmd.com/read/28213818/acceptability-of-an-internet-cognitive-behavioural-therapy-program-for-people-with-early-stage-cancer-and-cancer-survivors-with-depression-and-or-anxiety-thematic-findings-from-focus-groups
#3
A Karageorge, M J Murphy, J M Newby, L Kirsten, G Andrews, K Allison, S Loughnan, M Price, J Shaw, H Shepherd, J Smith, P Butow
PURPOSE: We developed an eight-lesson internet-delivered CBT (iCBT) program targeting anxiety and depression in early-stage cancer and cancer survivors. To explore the acceptability of the program, we showed volunteers the first two lessons and asked for their views. METHODS: Focus groups (n = 3) and individual interviews (n = 5) were undertaken with 15 participants (11 survivors) with mainly breast (11 of the 15) cancer, who had reviewed intervention materials...
February 18, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28213729/alpha-tocopherol-transfer-protein-%C3%AE-ttp-is-expressed-in-endometrial-carcinoma-and-is-correlated-with-figo-stage-and-5-year-survival
#4
Sabine Heublein, Thomas Vrekoussis, Ronny Etzl, Daisy Rotzoll, Christina Kuhn, Gesine Faigle, Iordanis Navrozoglou, Theodore Stefos, Antonis Makrigiannakis, Udo Jeschke
BACKGROUND: Increased oxidative stress plays an important role in cancer development. Vitamin E is considered a potent anti-oxidant and its transfer protein αTTP facilitates its cellular delivery. We hypothesize that αTTP could be present in and have an impact on endometrial cancer. MATERIALS AND METHODS: Ishikawa endometrial cancer cells were treated with BSO and AAPH to mimick oxidative stress conditions. αTTP was detected by immunocytochemistry and western blot...
February 17, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28213334/reactive-oxygen-a-novel-antimicrobial-mechanism-for-targeting-biofilm-associated-infection
#5
REVIEW
Matthew S Dryden, Jonathan Cooke, Rami J Salib, Rebecca E Holding, Timothy Biggs, Ali A Salamat, Raymond N Allan, Rachel S Newby, Fenella Halstead, Beryl Oppenheim, Thomas Hall, Sophie C Cox, Liam M Grover, Zain Al-Hindi, Lilyann Novak-Frazer, Malcolm D Richardson
Reactive oxygen species (ROS) is a novel therapeutic strategy for topical or local application to wounds, mucosa or internal structures where there may be heavy bacterial bioburden with biofilm and chronic inflammation. Bacterial biofilms are a significant problem in clinical settings owing to their increased tolerance towards conventionally prescribed antibiotics and their propensity for selection of further antibacterial resistance. There is therefore a pressing need for the development of alternative therapeutic strategies that can improve antibiotic efficacy towards biofilms...
February 14, 2017: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/28213274/differentially-cleaving-peptides-as-a-strategy-for-controlled-drug-release-in-human-retinal-pigment-epithelial-cells
#6
Madhushree Bhattacharya, Sanjay Sarkhel, Jonne Peltoniemi, Robert Broadbridge, Marjo Tuomainen, Seppo Auriola, Arto Urtti
Currently, drug delivery to the posterior eye segment relies on intravitreal injections of therapeutics. This approach requires frequent injections and does not guarantee drug delivery to intracellular targets. Controlled release systems and nanoparticles are being investigated to mitigate these challenges but most of these approaches lack translational success to the clinics. In our present study, we report a peptide based delivery system that utilizes enzyme assisted cleavable linkers to release conjugated cargo within the retinal pigment epithelial (RPE) cells...
February 14, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28212891/sulforaphane-inhibits-platelet-derived-growth-factor-induced-vascular-smooth-muscle-cell-proliferation-by-targeting-mtor-p70s6kinase-signaling-independent-of-nrf2-activation
#7
Noha M Shawky, Lakshman Segar
Activation of nuclear factor erythroid 2-related factor 2 (Nrf2, a transcription factor) and/or inhibition of mammalian target of rapamycin (mTOR) are implicated in the suppression of vascular smooth muscle cell (VSMC) proliferation. The present study has examined the likely regulatory effects of sulforaphane (SFN, an antioxidant) on Nrf2 activation and platelet-derived growth factor (PDGF)-induced mTOR signaling in VSMCs. Using human aortic VSMCs, nuclear extraction and siRNA-mediated downregulation studies were performed to determine the role of Nrf2 on SFN regulation of PDGF-induced proliferative signaling...
February 14, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28212798/protein-kinase-c-as-regulator-of-vascular-smooth-muscle-function-and-potential-target-in-vascular-disorders
#8
H C Ringvold, R A Khalil
Vascular smooth muscle (VSM) plays an important role in maintaining vascular tone. In addition to Ca(2+)-dependent myosin light chain (MLC) phosphorylation, protein kinase C (PKC) is a major regulator of VSM function. PKC is a family of conventional Ca(2+)-dependent α, β, and γ, novel Ca(2+)-independent δ, ɛ, θ, and η, and atypical ξ, and ι/λ isoforms. Inactive PKC is mainly cytosolic, and upon activation it undergoes phosphorylation, maturation, and translocation to the surface membrane, the nucleus, endoplasmic reticulum, and other cell organelles; a process facilitated by scaffold proteins such as RACKs...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28212737/gene-delivery-of-apoptin-derived-peptide-using-an-adeno-associated-virus-vector-inhibits-glioma-and-prolongs-animal-survival
#9
Xiuli Zhong, Hengyu Zhao, Songhe Liang, DanYang Zhou, Wenjia Zhang, Lijie Yuan
Glioblastoma (GBM) is the most common malignant brain tumor in adults. We designed an adeno-associated virus (AAV) vector for intracranial delivery of the secreted HSP70-targeted peptide APOPTIN derived from Apoptin to GBM tumors. We applied this therapy to GBM models using human U87MG glioma cells and GBM xenograft models in mice. In U87MG and U251MG cells, conditioned medium from AAV2-apoptin-derived peptide (ADP)-expressing cells induced 83% and 78% cell death. In mice bearing intracranial U87MG tumors treated with AAV2-ADP, treatment resulted in a significant decrease in tumor growth and longer survival in mice bearing orthotopic invasive GBM brain tumors...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28212621/feasibility-of-an-implementation-strategy-for-the-integration-of-health-promotion-in-routine-primary-care-a-quantitative-process-evaluation
#10
Alvaro Sanchez, Gonzalo Grandes, Josep M Cortada, Haizea Pombo, Catalina Martinez, Mary Helen Corrales, Enrique de la Peña, Justo Mugica, Esther Gorostiza
BACKGROUND: Process evaluation is recommended to improve the understanding of underlying mechanisms related to clinicians, patients, context and intervention delivery that may impact on trial or program results, feasibility and transferability to practice. The aim of this study was to assess the feasibility of the Prescribe Healthy Life (PVS from the Spanish "Prescribe Vida Saludable") implementation strategy for enhancing the adoption and implementation of an evidence-based health promotion intervention in primary health care...
February 17, 2017: BMC Family Practice
https://www.readbyqxmd.com/read/28212584/hyaluronic-acid-serum-albumin-conjugate-based-nanoparticles-for-targeted-cancer-therapy
#11
Ravit Edelman, Yehuda G Assaraf, Inna Levitzky, Tal Shahar, Yoav D Livney
Multiple carcinomas including breast, ovarian, colon, lung and stomach cancer, overexpress the hyaluronic acid (HA) receptor, CD44. Overexpression of CD44 contributes to key cancer processes including tumor invasion, metastasis, recurrence, and chemoresistance. Herein, we devised novel targeted nanoparticles (NPs) for delivery of anticancer chemotherapeutics, comprised of self-assembling Maillard reaction-based conjugates of HA and bovine serum albumin (BSA). HA served as the hydrophilic block, and as the ligand for actively targeting cancer cells overexpressing CD44...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212490/vitamin-e-succinate-grafted-chitosan-oligosaccharide-rgd-conjugated-tpgs-mixed-micelles-loaded-with-paclitaxel-for-u87mg-tumor-therapy
#12
Yanzuo Chen, Shu Feng, Wenchao Liu, Zeting Yuan, Peihao Yin, Feng Gao
The poor therapeutic efficacy of hydrophobic chemotherapeutic drugs is an intrinsic limitation to successful chemotherapy. In the present study, a multi-task delivery system based on arginine-glycine-aspartic acid peptide (RGD) decorated vitamin E succinate (VES)-grafted-chitosan oligosaccharide (CSO)/RGD-conjugated D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS-RGD) mixed micelles (VeC/T-RGD MM) was first prepared for targeted delivery of paclitaxel (PTX), a hydrophobic anticancer drug, to improve the efficacy of U87MG tumor therapy...
February 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28212425/job-satisfaction-and-determinant-factors-among-midwives-working-at-health-facilities-in-addis-ababa-city-ethiopia
#13
Eyasu Tamru Bekru, Amsale Cherie, Antehun Alemayehu Anjulo
BACKGROUND: Midwives are the primary source of care and support for mothers and newborns at the most vulnerable time in their lives.The Ethiopian National Reproductive Health Strategy targeted reduction of Maternal Mortality rate to 267/100,000 live births in the years 2006-2015. Midwives play a crucial role in the care of pregnant women, from the first antenatal visit right through to the delivery and the postpartum period. METHODOLOGY: Institution based cross-sectional study was carried out from March 2015 to April 2015 in Addis Ababa city, Ethiopia to assess job satisfaction and its determinants among midwives working at government health facilities...
2017: PloS One
https://www.readbyqxmd.com/read/28212339/adamantane-in-drug-delivery-systems-and-surface-recognition
#14
REVIEW
Adela Štimac, Marina Šekutor, Kata Mlinarić-Majerski, Leo Frkanec, Ruža Frkanec
The adamantane moiety is widely applied in design and synthesis of new drug delivery systems and in surface recognition studies. This review focuses on liposomes, cyclodextrins, and dendrimers based on or incorporating adamantane derivatives. Our recent concept of adamantane as an anchor in the lipid bilayer of liposomes has promising applications in the field of targeted drug delivery and surface recognition. The results reported here encourage the development of novel adamantane-based structures and self-assembled supramolecular systems for basic chemical investigations as well as for biomedical application...
February 16, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28212183/cxcl12-cxcr4-signaling-contributes-to-the-pathogenesis-of-opioid-tolerance-a-translational-study
#15
Chih-Peng Lin, Kai-Hsiang Kang, Huang-Ju Tu, Ming-Yueh Wu, Tzu-Hung Lin, Houng-Chi Liou, Wei-Zen Sun, Wen-Mei Fu
BACKGROUND: Long-term opioid therapy for chronic pain may lead to analgesic tolerance, especially when administered intrathecally, thus preventing adequate pain relief. Discovering drug targets to treat opioid tolerance using a mechanism-based approach targeting opioid-induced neuroinflammation provides new therapeutic opportunities. In this study, we provide translational evidence that CXCL12/CXCR4 signaling contributes to the pathogenesis of opioid tolerance. METHODS: The CXCL12 levels in the cerebrospinal fluid of opioid-tolerant patients were compared with those of opioid-naive subjects...
March 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28212092/modeling-contrast-imaging-assisted-optimal-targeted-drug-delivery-a-touchable-communication-channel-estimation-and-waveform-design-perspective
#16
Yifan Chen, Yu Zhou, Ross Murch, Panagiotis Kosmas
To maximize the effect of treatment and minimize the adverse effect on patients, we propose to optimize nanorobotsassisted targeted drug delivery (TDD) for locoregional treatment of tumor from the perspective of touchable communication channel estimation and waveform design. The drug particles are the information molecules; the loading/injection and unloading of the drug correspond to the transmitting and receiving processes; the concentration-time profile of the drug particles administered corresponds to the signalling pulse...
February 15, 2017: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/28210967/core-shell-drug-carrier-from-folate-conjugated-chitosan-obtained-from-prawn-shell-for-targeted-doxorubicin-delivery
#17
Md Sazedul Islam, Papia Haque, Taslim U Rashid, M Nuruzzaman Khan, Abul K Mallik, M Nazrul I Khan, Mala Khan, Mohammed Mizanur Rahman
A multifunctional drug carrier with dual targeting (magnetic and folate-receptor) and pH sensitive core-shell hybrid nanomaterial has been developed to carry an anticancer drug doxorubicin.Superparamagnetic iron oxide nanoparticles (IONPs) were used as core of the carrier and cross-linked folate conjugated chitosan (FA-CS) was acted as shell in which doxorubicin was physically entrapped. Transmission electron microscopy (TEM) analysis confirmed the average particle size of IONPs and FA-CS coated IONPs 8.2 and 15...
April 2017: Journal of Materials Science. Materials in Medicine
https://www.readbyqxmd.com/read/28210939/deep-phenotyping-of-systemic-arterial-hemodynamics-in-hfpef-part-1-physiologic-and-technical-considerations
#18
REVIEW
Julio A Chirinos
A better understanding of the pathophysiology of heart failure with a preserved left ventricular ejection fraction (HFpEF) is important. Detailed phenotyping of pulsatile hemodynamics has provided important insights into the pathophysiology of left ventricular remodeling and fibrosis, diastolic dysfunction, microvascular disease, and impaired oxygen delivery to peripheral skeletal muscle, all of which contribute to exercise intolerance, the cardinal feature of HFpEF. Furthermore, arterial pulsatile hemodynamic mechanisms likely contribute to the frequent presence of comorbidities, such as renal failure and dementia, in this population...
February 16, 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28209991/microrna-therapeutics-towards-a-new-era-for-the-management-of-cancer-and-other-diseases
#19
REVIEW
Rajesha Rupaimoole, Frank J Slack
In just over two decades since the discovery of the first microRNA (miRNA), the field of miRNA biology has expanded considerably. Insights into the roles of miRNAs in development and disease, particularly in cancer, have made miRNAs attractive tools and targets for novel therapeutic approaches. Functional studies have confirmed that miRNA dysregulation is causal in many cases of cancer, with miRNAs acting as tumour suppressors or oncogenes (oncomiRs), and miRNA mimics and molecules targeted at miRNAs (antimiRs) have shown promise in preclinical development...
February 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28209587/genome-surgery-using-cas9-ribonucleoproteins-for-the-treatment-of-age-related-macular-degeneration
#20
Kyoungmi Kim, Sung Wook Park, Jin Hyoung Kim, Seung Hwan Lee, Daesik Kim, Taeyoung Koo, Kwang-Eun Kim, Jeong Hun Kim, Jin-Soo Kim
RNA-guided genome surgery using CRISPR-Cas9 nucleases has shown promise for the treatment of diverse genetic diseases. Yet, the potential of such nucleases for therapeutic applications in nongenetic diseases is largely unexplored. Here, we focus on age-related macular degeneration (AMD), a leading cause of blindness in adults, which is associated with retinal overexpression of, rather than mutations in, the VEGFA gene. Subretinal injection of preassembled, Vegfa gene-specific Cas9 ribonucleoproteins (RNPs) into the adult mouse eye gave rise to mutagenesis at the target site in the retinal pigment epithelium...
February 16, 2017: Genome Research
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