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https://www.readbyqxmd.com/read/29458203/precision-pharmacology-for-alzheimer-s-disease
#1
REVIEW
Harald Hampel, Andrea Vergallo, Lisi Flores Aguilar, Norbert Benda, Karl Broich, A Claudio Cuello, Jeffrey Cummings, Bruno Dubois, Howard J Federoff, Massimo Fiandaca, Remy Genthon, Marion Haberkamp, Eric Karran, Mark Mapstone, George Perry, Lon S Schneider, Lindsay A Welikovitch, Janet Woodcock, Filippo Baldacci, Simone Lista
The complex multifactorial nature of polygenic Alzheimer's disease (AD) presents significant challenges for drug development. AD pathophysiology is progressing in a non-linear dynamic fashion across multiple systems levels - from molecules to organ systems - and through adaptation, to compensation, and decompensation to systems failure. Adaptation and compensation maintain homeostasis: a dynamic equilibrium resulting from the dynamic non-linear interaction between genome, epigenome, and environment. An individual vulnerability to stressors exists on the basis of individual triggers, drivers, and thresholds accounting for the initiation and failure of adaptive and compensatory responses...
February 16, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29457385/-current-status-and-expectations-in-the-surgical-treatment-of-recurrent-lateral-patellar-dislocation
#2
Zhi-Dong Zhao, Peng-Cui Li, Xiao-Chun Wei
Up to now, surgical treatment of recurrent lateral patellar dislocation mainly includes: medial patellofemoral ligament reconstruction, tibial tubercle osteotomy, trochleoplasty, lateral retinacular release, derotation osteotomy and so on . Clinical reports show that: the use of a single or combined with several methods have achieved ideal short to mid-term clinical outcomes. However, there is no consolidate criterion concerning the choices of different kinds of surgical ways for the treatment of individual recurrent lateral patellar dislocation...
November 25, 2017: Zhongguo Gu Shang, China Journal of Orthopaedics and Traumatology
https://www.readbyqxmd.com/read/29457382/an-international-multi-specialty-validation-study-of-the-igg4-related-disease-responder-index
#3
Zachary S Wallace, Arezou Khosroshahi, Mollie D Carruthers, Cory A Perugino, Hyon Choi, Corrado Campochiaro, Emma L Culver, Frank Cortazar, Emanuel Dellatorre, Mikael Ebbo, Ana Fernandes, Luca Frulloni, Philip Hart, Omer Karadag, Shigeyuki Kawa, Mitsuhiro Kawano, Myung-Hwan Kim, Marco Lanzillotta, Shoko Matsui, Kazuichi Okazaki, Jay H Ryu, Takako Saeki, Nicolas Schleinitz, Paula Tanasa, Hisanori Umehara, George Webster, Wen Zhang, John H Stone
OBJECTIVE: IgG4-related disease (IgG4-RD) can cause fibro-inflammatory lesions in nearly any organ, leading to organ dysfunction and failure. The IgG4-RD Responder Index (RI) was developed to help investigators assess the efficacy of treatment in a structured manner. We sought to validate the RI in a multi-national investigation. METHODS: The RI guides investigators through assessments of disease activity and damage in 25 domains, incorporating higher weights for disease manifestations that require treatment urgently or that worsen despite treatment...
February 18, 2018: Arthritis Care & Research
https://www.readbyqxmd.com/read/29456735/metadherin-contributes-to-epithelial-mesenchymal-transition-and-paclitaxel-resistance-induced-by-acidic-extracellular-ph-in-nasopharyngeal-carcinoma
#4
Changyun Yu, Yong Liu, Zhaobing Qin
Paclitaxel resistance is a challenge to the treatment of nasopharyngeal carcinoma (NPC). An acidic extracellular pH (pHe ), a hallmark of solid tumors, is demonstrated to decrease the efficacy of chemotherapy. However, the precise function of acidic pHe in mediating chemotherapy in NPC remains unknown. In the present study, acidic pHe significantly decreased the cytotoxicity of paclitaxel in NPC cells. In addition, epithelial-mesenchymal transition (EMT)-like changes were observed in NPC cells cultured at acidic pHe ...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29455777/palliative-treatment-of-coronary-atherosclerotic-cancer-by-drug-eluting-or-bare-metal-stents-from-oculo-stenotic-reflex-period-to-age-of-precision-medicine
#5
Elif Hande Ozcan Cetin, Ozcan Ozeke, Erdogan Ilkay, Dursun Aras, Serkan Topaloglu, Zehra Golbasi, Sinan Aydogdu, Can Ozer
Medications and treatments are said to have a palliative effect if they relieve symptoms without having a curative effect on the underlying disease such as atherosclerosis or cancer. Some authors speculated that atherosclerotic coronary artery disease (CAD) could be considered a "cancer of the coronary arterial wall". Although the percutaneous coronary intervention (PCI) has proven to be effective in decreasing mortality rates among patients with acute coronary syndromes, the previous meta-analyses of PCI versus optimal medical therapy for stable CAD have not been able to demonstrate a reduction in major adverse cardiac outcomes...
January 2018: Indian Heart Journal
https://www.readbyqxmd.com/read/29455650/management-of-acquired-resistance-to-egfr-tki-targeted-therapy-in-advanced-non-small-cell-lung-cancer
#6
REVIEW
Shang-Gin Wu, Jin-Yuan Shih
Recent advances in diagnosis and treatment are enabling a more targeted approach to treating lung cancers. Therapy targeting the specific oncogenic driver mutation could inhibit tumor progression and provide a favorable prognosis in clinical practice. Activating mutations of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) are a favorable predictive factor for EGFR tyrosine kinase inhibitors (TKIs) treatment. For lung cancer patients with EGFR-exon 19 deletions or an exon 21 Leu858Arg mutation, the standard first-line treatment is first-generation (gefitinib, erlotinib), or second-generation (afatinib) TKIs...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455084/nherf1-between-promises-and-hopes-overview-on-cancer-and-prospective-openings
#7
REVIEW
Matteo Centonze, Concetta Saponaro, Anita Mangia
Na+ /H+ exchanger regulatory factor 1 (NHERF1) is a scaffold protein, with two tandem PDZ domains and a carboxyl-terminal ezrin-binding (EB) region. This particular sticky structure is responsible for its interaction with different molecules to form multi-complexes that have a pivotal role in a lot of diseases. In particular, its involvement during carcinogenesis and cancer progression has been deeply analyzed in different tumors. The role of NHERF1 is not unique in cancer; its activity is connected to its subcellular localization...
February 15, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29454916/mitochondria-targeting-indolizino-3-2-c-quinolines-as-novel-class-of-photosensitizers-for-photodynamic-anticancer-activity
#8
Soonbum Kwon, Yeongcheol Lee, Youngeun Jung, Ju Hee Kim, Byungyeob Baek, Bumhee Lim, Jungeun Lee, Ikyon Kim, Jeeyeon Lee
To achieve efficient photodynamic activity, substantial effort has been dedicated to precise control of the intracellular localization of current photosensitizers (PSs). Given the extremely small radius of action of singlet oxygen, the direct targeting of PSs to the mitochondria is expected to greatly enhance the photodynamic therapy (PDT) activity. Here, we report mitochondria-targeting 6-(furan-2-yl)- and 6-(thiophen-2-yl) indolizino[3,2-c]quinolines (IQs) as novel PSs. IQ derivatives containing 5-membered heterocyclic aromatic rings were synthesized, and their photophysical properties as PSs were characterized...
February 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29453278/molecular-signatures-of-circulating-melanoma-cells-for-monitoring-early-response-to-immune-checkpoint-therapy
#9
Xin Hong, Ryan J Sullivan, Mark Kalinich, Tanya Todorova Kwan, Anita Giobbie-Hurder, Shiwei Pan, Joseph A LiCausi, John D Milner, Linda T Nieman, Ben S Wittner, Uyen Ho, Tianqi Chen, Ravi Kapur, Donald P Lawrence, Keith T Flaherty, Lecia V Sequist, Sridhar Ramaswamy, David T Miyamoto, Michael Lawrence, Mehmet Toner, Kurt J Isselbacher, Shyamala Maheswaran, Daniel A Haber
A subset of patients with metastatic melanoma have sustained remissions following treatment with immune checkpoint inhibitors. However, analyses of pretreatment tumor biopsies for markers predictive of response, including PD-1 ligand (PD-L1) expression and mutational burden, are insufficiently precise to guide treatment selection, and clinical radiographic evidence of response on therapy may be delayed, leading to some patients receiving potentially ineffective but toxic therapy. Here, we developed a molecular signature of melanoma circulating tumor cells (CTCs) to quantify early tumor response using blood-based monitoring...
February 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29452948/photo-tearable-tape-close-wrapped-upconversion-nanocapsules-for-near-infrared-modulated-efficient-sirna-delivery-and-therapy
#10
Yue Zhang, Kewei Ren, Xiaobo Zhang, Zhicong Chao, Yuqin Yang, Deju Ye, Zhihui Dai, Ying Liu, Huangxian Ju
RNA interference (RNAi) has become an appealing therapeutic approach for cancer and other diseases. One key challenge is the effective protection of these small fragile biomolecules against complicated physiological environments as well as efficient on-demand release. Here we design a photo-tearable polymer tape close-wrapped nanocapsule for efficient NIR modulated siRNA delivery. The photo-tearable nanocapsules comprise core-shell upconversion nanoparticles (UCNPs) coated with mesoporous silica layer for loading of photosensitizer hypocrellin A (HA) and small interfering RNA (siRNA) against polo-like kinase 1 (PLK1), and covalently bound thin membranes of polyethylene glycol (PEG) via a synthesized photocleavable linker (PhL)...
February 9, 2018: Biomaterials
https://www.readbyqxmd.com/read/29451575/functionalized-cu-3-bis-3-nanoparticles-for-dual-modal-imaging-and-targeted-photothermal-photodynamic-therapy
#11
Yanke Wang, Dongdong Cai, Huixia Wu, Yu Fu, Yang Cao, Yingjian Zhang, Dongmei Wu, Qiwei Tian, Shiping Yang
Multifunctional nano-biomaterials with the integration of diagnostic and therapeutic functions have shown great promise in improving the efficacy of cancer therapy. Herein, a new nanoplatform based on functionalized Cu 3 BiS 3 nanoparticles (NPs) is fabricated for tumour-targeted combination phototherapy. The as-synthesized hydrophobic Cu 3 BiS 3 NPs are modified with DSPE-PEG/DSPE-PEG-NH 2 , followed by the conjugation of the photosensitizer chlorin e6 (Ce6) and the target ligand folic acid (FA). The introduced Ce6 can further form a chelate complex with Gd 3+ ...
February 16, 2018: Nanoscale
https://www.readbyqxmd.com/read/29449955/prospects-for-precision-medicine-in-glomerulonephritis-treatment
#12
REVIEW
Yulu Cherry Liu, Justin Chun
Background: Glomerulonephritis (GN) consists of a group of kidney diseases that are categorized based on shared histopathological features. The current classifications for GN make it difficult to distinguish the individual variability in presentation, disease progression, and response to treatment. GN is a significant cause of end-stage renal disease (ESRD), and improved therapies are desperately needed because current immunosuppressive therapies sometimes lack efficacy and can lead to significant toxicities...
2018: Canadian Journal of Kidney Health and Disease
https://www.readbyqxmd.com/read/29449770/adverse-events-following-cervical-manipulative-therapy-consensus-on-classification-among-dutch-medical-specialists-manual-therapists-and-patients
#13
Hendrikus A Kranenburg, Sandra E Lakke, Maarten A Schmitt, Cees P Van der Schans
Objectives: To obtain consensus-based agreement on a classification system of adverse events (AE) following cervical spinal manipulation. The classification system should be comprised of clear definitions, include patients' and clinicians' perspectives, and have an acceptable number of categories. Methods: Design : A three-round Delphi study. Participants : Thirty Dutch participants (medical specialists, manual therapists, and patients) participated in an online survey...
December 2017: Journal of Manual & Manipulative Therapy
https://www.readbyqxmd.com/read/29449656/ultrasound-beam-steering-of-oxygen-nanobubbles-for-enhanced-bladder-cancer-therapy
#14
Pushpak Bhandari, Gloriia Novikova, Craig J Goergen, Joseph Irudayaraj
New intravesical treatment approaches for bladder cancer are needed as currently approved treatments show several side effects and high tumor recurrence rate. Our study used MB49 murine urothelial carcinoma model to evaluate oxygen encapsulated cellulosic nanobubbles as a novel agent for imaging and ultrasound guided drug delivery. In this study, we show that oxygen nanobubbles (ONB) can be propelled (up to 40 mm/s) and precisely guided in vivo to the tumor by an ultrasound beam. Nanobubble velocity can be controlled by altering the power of the ultrasound Doppler beam, while nanobubble direction can be adjusted to different desired angles by altering the angle of the beam...
February 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29449555/intravenous-injections-of-the-oncolytic-virus-m1-as-a-novel-therapy-for-muscle-invasive-bladder-cancer
#15
Cheng Hu, Ying Liu, Yuan Lin, Jian-Kai Liang, Wen-Wen Zhong, Ke Li, Wen-Tao Huang, De-Juan Wang, Guang-Mei Yan, Wen-Bo Zhu, Jian-Guang Qiu, Xin Gao
Muscle-invasive bladder cancer (MIBC) is associated with low survival and high recurrence rates even in cases in which patients receive systemic treatments, such as surgery and chemotherapy. Here, we found that a naturally existing alphavirus, namely, M1, selectively kills bladder cancer cells but not normal cells, findings supported by our observations of changes in viral replication and MIBC and patient-derived MIBC cell apoptosis. Transcriptome analysis revealed that interferon-stimulated genes (ISGs) are expressed at low levels in sensitive bladder cancer cells and high levels in resistant cells...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449279/mri-with-dwi-for-the-detection-of-posttreatment-head-and-neck-squamous-cell-carcinoma-why-morphologic-mri-criteria-matter
#16
A Ailianou, P Mundada, T De Perrot, M Pusztaszieri, P-A Poletti, M Becker
BACKGROUND AND PURPOSE: Although diffusion-weighted imaging combined with morphologic MRI (DWIMRI) is used to detect posttreatment recurrent and second primary head and neck squamous cell carcinoma, the diagnostic criteria used so far have not been clarified. We hypothesized that precise MRI criteria based on signal intensity patterns on T2 and contrast-enhanced T1 complement DWI and therefore improve the diagnostic performance of DWIMRI. MATERIALS AND METHODS: We analyzed 1...
February 15, 2018: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/29449275/circulating-tumor-dna-reveals-genetics-clonal-evolution-and-residual-disease-in-classical-hodgkin-lymphoma
#17
Valeria Spina, Alessio Bruscaggin, Annarosa Cuccaro, Maurizio Martini, Martina Di Trani, Gabriela Forestieri, Martina Manzoni, Adalgisa Condoluci, Alberto Arribas, Lodovico Terzi-Di-Bergamo, Silvia Laura Locatelli, Elisa Cupelli, Luca Ceriani, Alden A Moccia, Anastasios Stathis, Luca Nassi, Clara Deambrogi, Fary Diop, Francesca Guidetti, Alessandra Cocomazzi, Salvatore Annunziata, Vittoria Rufini, Alessandro Giordano, Antonino Neri, Renzo Boldorini, Bernhard Gerber, Francesco Bertoni, Michele Ghielmini, Georg Stüssi, Armando Santoro, Franco Cavalli, Emanuele Zucca, Luigi Maria Larocca, Gianluca Gaidano, Stefan Hohaus, Carmelo Carlo-Stella, Davide Rossi
The rarity of neoplastic cells in the biopsy imposes major technical hurdles that have so far limited genomic studies in classical Hodgkin lymphoma (cHL). By using a highly sensitive and robust deep-next-generation-sequencing approach for circulating tumor DNA (ctDNA), here we aimed at tracking the genetics of cHL in different clinical phases, and its modifications upon treatment. The analysis was based on specimens collected from 80 newly diagnosed and 32 refractory cHL patients, including longitudinal samples collected under ABVD chemotherapy and longitudinal samples from relapsing patients treated with chemotherapy and immunotherapy...
February 15, 2018: Blood
https://www.readbyqxmd.com/read/29449194/prostaglandin-d2-receptor-dp1-antibodies-predict-vaccine-induced-and-spontaneous-narcolepsy-type-1-large-scale-study-of-antibody-profiling
#18
Helle Sadam, Arno Pihlak, Anri Kivil, Susan Pihelgas, Mariliis Jaago, Priit Adler, Jaak Vilo, Olli Vapalahti, Toomas Neuman, Dan Lindholm, Markku Partinen, Antti Vaheri, Kaia Palm
BACKGROUND: Neuropathological findings support an autoimmune etiology as an underlying factor for loss of orexin-producing neurons in spontaneous narcolepsy type 1 (narcolepsy with cataplexy; sNT1) as well as in Pandemrix influenza vaccine-induced narcolepsy type 1 (Pdmx-NT1). The precise molecular target or antigens for the immune response have, however, remained elusive. METHODS: Here we have performed a comprehensive antigenic repertoire analysis of sera using the next-generation phage display method - mimotope variation analysis (MVA)...
February 2, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29449192/association-of-body-mass-index-and-outcomes-in-patients-with-metastatic-melanoma-treated-with-targeted-therapy-immunotherapy-or-chemotherapy-a-retrospective-multicohort-analysis
#19
Jennifer L McQuade, Carrie R Daniel, Kenneth R Hess, Carmen Mak, Daniel Y Wang, Rajat R Rai, John J Park, Lauren E Haydu, Christine Spencer, Matthew Wongchenko, Stephen Lane, Dung-Yang Lee, Mathilde Kaper, Meredith McKean, Kathryn E Beckermann, Samuel M Rubinstein, Isabelle Rooney, Luna Musib, Nageshwar Budha, Jessie Hsu, Theodore S Nowicki, Alexandre Avila, Tomas Haas, Maneka Puligandla, Sandra Lee, Shenying Fang, Jennifer A Wargo, Jeffrey E Gershenwald, Jeffrey E Lee, Patrick Hwu, Paul B Chapman, Jeffrey A Sosman, Dirk Schadendorf, Jean-Jacques Grob, Keith T Flaherty, Dana Walker, Yibing Yan, Edward McKenna, Jeffrey J Legos, Matteo S Carlino, Antoni Ribas, John M Kirkwood, Georgina V Long, Douglas B Johnson, Alexander M Menzies, Michael A Davies
BACKGROUND: Obesity has been linked to increased mortality in several cancer types; however, the relation between obesity and survival outcomes in metastatic melanoma is unknown. The aim of this study was to examine the association between body-mass index (BMI) and progression-free survival or overall survival in patients with metastatic melanoma who received targeted therapy, immunotherapy, or chemotherapy. METHODS: This retrospective study analysed independent cohorts of patients with metastatic melanoma assigned to treatment with targeted therapy, immunotherapy, or chemotherapy in randomised clinical trials and one retrospective study of patients treated with immunotherapy...
February 12, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29448937/engineering-chimeric-antigen-receptor-t-cells-for-cancer-treatment
#20
REVIEW
Baixin Ye, Creed M Stary, Xuejun Li, Qingping Gao, Chunsheng Kang, Xiaoxing Xiong
Intratumor heterogeneity of tumor clones and an immunosuppressive microenvironment in cancer ecosystems contribute to inherent difficulties for tumor treatment. Recently, chimeric antigen receptor (CAR) T-cell therapy has been successfully applied in the treatment of B-cell malignancies, underscoring its great potential in antitumor therapy. However, functional challenges of CAR-T cell therapy, especially in solid tumors, remain. Here, we describe cancer-immunity phenotypes from a clonal-stromal-immune perspective and elucidate mechanisms of T-cell exhaustion that contribute to tumor immune evasion...
February 15, 2018: Molecular Cancer
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