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Targeting therapy

Kevin Isgrig, Wade W Chien
Inner ear gene therapy offers great promise as a potential treatment for hearing loss and dizziness. One of the critical determinants of the success of inner ear gene therapy is to find a delivery method which results in consistent transduction efficiency of targeted cell types while minimizing hearing loss. In this study, we describe the posterior semicircular canal approach as a viable method for inner ear gene delivery in neonatal mice. We show that gene delivery through the posterior semicircular canal is able to perfuse the entire inner ear...
March 2, 2018: Journal of Visualized Experiments: JoVE
Patrick J Atkinson, Yaodong Dong, Shuping Gu, Wenwen Liu, Elvis Huarcaya Najarro, Tomokatsu Udagawa, Alan G Cheng
During development, Sox2 is indispensable for cell division and differentiation, yet its roles in regenerating tissues are less clear. Here, we used combinations of transgenic mouse models to reveal that Sox2 haploinsufficiency (Sox2haplo) increases rather than impairs cochlear regeneration in vivo. Sox2haplo cochleae had delayed terminal mitosis and ectopic sensory cells, yet normal auditory function. Sox2haplo amplified and expanded domains of damage-induced Atoh1+ transitional cell formation in neonatal cochlea...
March 19, 2018: Journal of Clinical Investigation
Carlo Alberto Scirè, Cristina Rossi, Leonardo Punzi, Augusto Genderini, Claudio Borghi, Walter Grassi
Despite being regarded as an easily-treatable disease, gout diagnosis and management can be challenging. We discuss here current issues in gout management and propose some potential solutions. Gout diagnosis should be reached as early as possible and often requires specific tests, such as synovial fluid analysis or imaging techniques that are not available in most centers, leaving health care professionals to rely only on clinical presentations and their experience. In addition, gout management requires the evaluation of multiple aspects, such as monitoring of serum uric acid (sUA) level (which should be reduced to <6 mg/dL) to ensure adherence and efficacy of treatment, evaluation of patient's risk profile and comorbidities, and continuous assessments to manage clinical manifestations...
March 19, 2018: Current Medical Research and Opinion
Amit A Vernekar, Gilles Berger, Anna E Czapar, Frank A Veliz, David I Wang, Nicole F Steinmetz, Stephen J Lippard
Efficient loading of drugs in novel delivery agents has the potential to substantially improve therapy by targeting the diseased tissue while avoiding unwanted side effects. Here we report the first systematic study of the loading mechanism of phenanthriplatin and its analogs into tobacco mosaic virus (TMV), previously used by our group as an efficient carrier for anticancer drug delivery. A detailed investigation of the preferential uptake of phenanthriplatin in its aquated form (∼2000 molecules per TMV particle versus ∼1000 for the chlorido form) is provided...
March 19, 2018: Journal of the American Chemical Society
Adriely Goes, Gregor Fuhrmann
Biogenic and biomimetic therapeutics are a relatively new class of systems that are of physiological origin and/or take advantage of natural pathways, or aim at mimicking these to improve selective interaction with target tissue. The number of biogenic and bioengineered avenues for drug therapy and diagnostics has multiplied over the past years for many applications, indicating the high expectations associated with this biological route. Nevertheless, the use of "bio"-related approaches for treating or diagnosing infectious diseases is still rare...
March 19, 2018: ACS Infectious Diseases
Lan Huang, Huaxi Xu, Guangyong Peng
Cellular energy metabolism not only promotes tumor cell growth and metastasis but also directs immune cell survival, proliferation and the ability to perform specific and functional immune responses within the tumor microenvironment. A better understanding of the molecular regulation of metabolism in different cell components in the tumor-suppressive microenvironment is critical for the development of effective strategies for human cancer treatments. Toll-like receptors (TLRs) have recently been recognized as critical factors involved in tumor pathogenesis, regulating both tumor cells and tumor-infiltrating innate and adaptive immune cells...
March 19, 2018: Cellular & Molecular Immunology
Yukio Fujiwara, Yoichi Saito, Takuya Shiota, Pan Cheng, Tsuyoshi Ikeda, Koji Ohnishi, Motohiro Takeya, Yoshihiro Komohara
Recent progress in anti-tumor therapy has revealed the significance of anti-tumor immune responses in tumor progression and clinical course in several kinds of malignant tumors. The draining lymph node is an important immune system component that contains a number of antigen-presenting cells, which induce rapid immune responses to foreign antigens. Current studies have shown that higher expression of CD169 on lymph node sinus macrophages is associated with the induction of anti-tumor immunity. In the present study, we searched for natural compounds that regulate the CD169-positive phenotype in macrophages to identify potential new anti-cancer agents targeting macrophage activation...
2018: Journal of Clinical and Experimental Hematopathology: JCEH
Tanya B Dorff, Neeraj Agarwal
Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including (1) bisphosphonates such as zoledronic acid, which directly target osteoclasts, (2) denosumab, a receptor activator of nuclear factor-kappa B (RANK) ligand inhibitor, which targets a key component of bone stromal interaction, and (3) radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA...
March 16, 2018: Asian Journal of Andrology
Frans Moll, Iris Baumgartner, Michael Jaff, Chuke Nwachuku, Marco Tangelder, Gary Ansel, George Adams, Thomas Zeller, John Rundback, Michael Grosso, Min Lin, Michele F Mercur, Erich Minar
PURPOSE: To report a randomized study that investigated the safety (risk of major bleeds) and potential efficacy of edoxaban, an oral anticoagulant that targets the major components of arterial thrombi, to prevent loss of patency following endovascular treatment (EVT). METHODS: Between February 2012 and June 2014, 203 patients who underwent femoropopliteal EVT were randomized to receive aspirin plus edoxaban or aspirin plus clopidogrel for 3 months in the Edoxaban in Peripheral Arterial Disease (ePAD) study ( ClinicalTrials...
April 2018: Journal of Endovascular Therapy
László Márk, Mária Nagy, Győző Dani, Csaba Baranyai, Marianna Borbély, András Katona, Zoltán Jambrik
INTRODUCTION: The actual guidelines of cardiovascular prevention lay special emphasis on the lipid-lowering therapy of patients suffering from acute coronary syndrome (ACS). AIM: To evaluate the occurrence of high-intensity statin therapy, recommended by guidelines, at discharge in a Hungarian county hospital with hemodynamic laboratory in patients who underwent percutaneous intervention, furthermore the LDL-cholesterol (LDL-C) levels and goal attainment rate in the first year...
March 2018: Orvosi Hetilap
Alajos Pár, Gabriella Pár
More than 25 years after the discovery of hepatitis C virus, the development of the direct acting antivirals can lead to the regional or long-term global elimination of the virus with over 90% efficacy. This is the success of basic and clinical translational research. Yet, some unsolved challanges remain, such as the great number of unidentified patients who are not aware of their condition, the limited access to the therapy due to the high prices of the drugs, and the treatment of resistance-associated variants...
March 2018: Orvosi Hetilap
Chengfei Hao, Xibo Zhang, Hongtao Zhang, Haitao Shang, Jianheng Bao, Haibo Wang, Zhonglian Li
PURPOSE: Plants produce a diversity of molecular scaffolds with tremendous pharmacological potential. In the present study we evaluated the anticancer activity of the plant-derived natural product sugiol. We also evaluated its effects on apoptosis-related key proteins, cell cycle phase distribution, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP). METHODS: Cell viability was evaluated by MTT assay while clonogenic assay was done to determine the effects of sugiol on the cancer cell colony formation...
January 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Enzo Emanuelli, Andrea Ciorba, Daniele Borsetto, Diego Cazzador, Samantha Sarcognato, Filippo Marino, Stefano Fusetti, Chiara Bianchini, Francesco Stomeo, Stefano Pelucchi
PURPOSE: Most primary tumors spreading metastasis to the parotid gland are usually located in the head and neck region, nonetheless, rarely, parotid gland can also be the target of metastatic localization site of distant primary tumors. The purpose of this study was to describe a clinical series of metastasis to the parotid gland from distant primary tumors (non Head & Neck). METHODS: The clinical databases of parotid tumors in two academic centers have been analyzed and 11 cases of parotid metastatic cancers from distant primary tumors were found...
January 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Aziza Alrafiah, Evangelia Karyka, Ian Coldicott, Kayleigh Iremonger, Katherin E Lewis, Ke Ning, Mimoun Azzouz
Spinal muscular atrophy (SMA) is a devastating childhood motor neuron disease. SMA is caused by mutations in the survival motor neuron gene ( SMN1 ), leading to reduced levels of SMN protein in the CNS. The actin-binding protein plastin 3 (PLS3) has been reported as a modifier for SMA, making it a potential therapeutic target. Here, we show reduced levels of PLS3 protein in the brain and spinal cord of a mouse model of SMA. Our study also revealed that lentiviral-mediated PLS3 expression restored axonal length in cultured Smn-deficient motor neurons...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
Zhongzhen Yi, Brooke L Prinzing, Felicia Cao, Stephen Gottschalk, Giedre Krenciute
Glioblastoma is the most aggressive primary brain tumor in humans and is virtually incurable with conventional therapies. Chimeric antigen receptor (CAR) T cell therapy targeting the glioblastoma antigen EphA2 is an attractive approach to improve outcomes because EphA2 is expressed highly in glioblastoma but only at low levels in normal brain tissue. Building upon our previous findings in this area, we generated and evaluated a panel of EphA2-specific CARs. We demonstrate here that T cells expressing CD28...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
Harrison C Brown, Philip M Zakas, Stephan N George, Ernest T Parker, H Trent Spencer, Christopher B Doering
Potency is a key optimization parameter for hemophilia A gene therapy product candidates. Optimization strategies include promoter engineering to increase transcription, codon optimization of mRNA to improve translation, and amino-acid substitution to promote secretion. Herein, we describe both rational and empirical design approaches to the development of a minimally sized, highly potent AAV-fVIII vector that incorporates three unique elements: a liver-directed 146-nt transcription regulatory module, a target-cell-specific codon optimization algorithm, and a high-expression bioengineered fVIII variant...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
Seung Won Jun, Junyoung Kwon, Soo Kyung Chun, Hyun Ah Lee, Jaebeom Lee, Dae Youn Hwang, Chen-Yuan Dong, Chang-Seok Kim
Owing to its near infrared (NIR) absorption, graphene oxide (GO) is promising for both photothermal (PT) therapy and multiphoton (MP) imaging. Novel therapy/imaging modality switching is proposed here based on the selected excitation wavelength of femtosecond (FS) laser. GO-based destruction of cancer cells is demonstrated when the laser power of 800-nm-wavelength FS laser is increased above 7 mW. However, GO-based imaging is mainly monitored without damaging the sample when using 1200-nm wavelength FS laser in the same laser power range...
February 1, 2018: Biomedical Optics Express
Derrick S Haslem, Ingo Chakravarty, Gail Fulde, Heather Gilbert, Brian P Tudor, Karen Lin, James M Ford, Lincoln D Nadauld
The impact of precision oncology on guiding treatment decisions of late-stage cancer patients was previously studied in a retrospective analysis. However, the overall survival and costs were not previously evaluated. We report the overall survival and healthcare costs associated with precision oncology in these patients with advanced cancer. Building on a matched cohort study of 44 patients with metastatic cancer who received all of their care within a single institution, we evaluated the overall survival and healthcare costs for each patient...
February 23, 2018: Oncotarget
Xuzhi He, Jazmina L Cruz, Shannon Joseph, Nicola Pett, Hui Yi Chew, Zewen K Tuong, Satomi Okano, Gabrielle Kelly, Margaret Veitch, Fiona Simpson, James W Wells
The Epidermal Growth Factor Receptor (EGFR) is selectively expressed on the surface of numerous tumours, such as non-small cell lung, ovarian, colorectal and head and neck carcinomas. EGFR has therefore become a target for cancer therapy. Cetuximab is a chimeric human/mouse monoclonal antibody (mAb) that binds to EGFR, where it both inhibits signaling and induces cell death by antibody-dependent cell mediated cytotoxicity (ADCC). Cetuximab has been approved for clinical use in patients with head and neck squamous cell carcinoma (HNSCC) and colorectal cancer...
February 23, 2018: Oncotarget
Qiang Wang, Yiwan Teng, Rong Wang, Danni Deng, Yijie You, Ya Peng, Naiyuan Shao, Feng Zhi
Malignant glioma is one of the most common types of primary brain tumours. Long non-coding RNAs (lncRNAs) have recently emerged as a new class of therapeutic targets for many cancers. In this study, we aimed to explore the functional involvement of small nucleolar RNA host gene 14 (SNHG14) and its potential regulatory mechanism in glioma progression. SNHG14 was found to be downregulated in human glioma tissues and cell lines. SNHG14 significantly inhibited cell viability, reduced cell invasion, and induced apoptosis in glioma cell lines...
February 23, 2018: Oncotarget
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