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https://www.readbyqxmd.com/read/27926740/a-17-gene-stemness-score-for-rapid-determination-of-risk-in-acute-leukaemia
#1
Stanley W K Ng, Amanda Mitchell, James A Kennedy, Weihsu C Chen, Jessica McLeod, Narmin Ibrahimova, Andrea Arruda, Andreea Popescu, Vikas Gupta, Aaron D Schimmer, Andre C Schuh, Karen W Yee, Lars Bullinger, Tobias Herold, Dennis Görlich, Thomas Büchner, Wolfgang Hiddemann, Wolfgang E Berdel, Bernhard Wörmann, Meyling Cheok, Claude Preudhomme, Herve Dombret, Klaus Metzeler, Christian Buske, Bob Löwenberg, Peter J M Valk, Peter W Zandstra, Mark D Minden, John E Dick, Jean C Y Wang
Refractoriness to induction chemotherapy and relapse after achievement of remission are the main obstacles to cure in acute myeloid leukaemia (AML). After standard induction chemotherapy, patients are assigned to different post-remission strategies on the basis of cytogenetic and molecular abnormalities that broadly define adverse, intermediate and favourable risk categories. However, some patients do not respond to induction therapy and another subset will eventually relapse despite the lack of adverse risk factors...
December 7, 2016: Nature
https://www.readbyqxmd.com/read/27926493/developmental-therapeutics-for-inflammatory-breast-cancer-biology-and-translational-directions
#2
REVIEW
Ricardo Costa, Cesar A Santa-Maria, Giovanna Rossi, Benedito A Carneiro, Young Kwang Chae, William J Gradishar, Francis J Giles, Massimo Cristofanilli
Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer, which accounts for approximately 3% of cases of breast malignancies. Diagnosis relies largely on its clinical presentation, and despite a characteristic phenotype, underlying molecular mechanisms are poorly understood. Unique clinical presentation indicates that IBC is a distinct clinical and biological entity when compared to non-IBC. Biological understanding of non-IBC has been extrapolated into IBC and targeted therapies for HER2 positive (HER2+) and hormonal receptor positive non-IBC led to improved patient outcomes in the recent years...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925796/a-severe-asthma-disease-signature-from-gene-expression-profiling-of-peripheral-blood-from-u-biopred-cohorts
#3
Jeannette Bigler, Michael Boedigheimer, James P R Schofield, Paul J Skipp, Julie Corfield, Anthony Rowe, Ana R Sousa, Martin Timour, Lori Twehues, Xuguang Hu, Graham Roberts, Andrew A Welcher, Wen Yu, Kian F Chung, Ian M Adcock, Peter J Sterk, Ratko Djukanović
RATIONALE: Stratification of asthma at the molecular level, especially using accessible biospecimens, could greatly enable patient selection for targeted therapy. OBJECTIVES: To determine the value of blood to identify transcriptional differences between clinically defined asthmatic and non-asthmatic groups, identify potential patient subgroups based on gene expression, and explore biological pathways associated with identified differences. METHODS: Transcriptomics profiles were generated by microarray analysis of blood from 610 asthmatic and control participants in U-BIOPRED...
December 7, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27925201/vascular-inter-regulation-of-inflammation-molecular-and-cellular-targets-for-cns-therapy
#4
REVIEW
Marta Machado-Pereira, Tiago Santos, Liliana Bernardino, Raquel Ferreira
Angiogenesis and inflammation are clearly interconnected and interdependent processes that are dysregulated in a series of systemic and brain pathologies. Herein, key aspects regarding endothelial cell function and tissue remodelling that are particularly affected or aggravated by inflammation are presented. Most importantly, the cellular and molecular mechanisms involved in the vascular regulation of the inflammatory processes occurring in several brain disorders and how they impact on disease/injury progression are detailed, highlighting potential targets for therapy...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27924725/anticancer-drug-targets-of-salvia-phytometabolites-chemistry-biology-and-omics
#5
Da-Cheng Hao, Guang-Bo Ge, Pei-Gen Xiao
Salvia displays diverse anticancer properties, which are attributable to their diterpene and phenolic contents. There is no comprehensive review on the anticancer diversity and molecular targets of Salvia components. We investigate the diversity and molecular targets of Salvia phytometabolites responsible for the prevention and treatment of cancer and sarcoma. Traditional therapeutic knowledge suggests that Salvia species can be used to develop anticancer drugs. Lots of concerns have been raised for tanshinone (Tan) IIA and cryptotanshinone...
December 7, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27924634/the-promise-of-circulating-tumor-cells-for-precision-cancer-therapy
#6
William L Hwang, Katie L Hwang, David T Miyamoto
The rapidly growing array of therapeutic options in cancer requires informative biomarkers to guide the rational selection and precision application of appropriate therapies. Circulating biomarkers such as circulating tumor cells have immense potential as noninvasive, serial 'liquid biopsies' that may be more representative of the complete spectrum of a patient's individual malignancy than spatially and temporally restricted tumor biopsies. In this review, we discuss the current state-of-the-art in the isolation and molecular characterization of circulating tumor cells as well as their utility in a wide range of clinical applications such as prognostics, treatment monitoring and identification of novel therapeutic targets and resistance mechanisms to enable real-time adjustments in the clinical management of cancer...
December 7, 2016: Biomarkers in Medicine
https://www.readbyqxmd.com/read/27924606/oral-epithelial-cell-culture-model-for-studying-the-pathogenesis-of-chronic-inflammatory-disease
#7
Mike R Milward, Martin R Ling, Melissa M Grant, Iain L C Chapple
The interactions between bacteria, epithelium, and neutrophilic polymorphonuclear leukocytes (neutrophils) are the key to the initiation and progression of many chronic inflammatory-immune diseases. In addition, all can be influenced by external factors, such as micronutrients, thereby providing potentially novel approaches to therapy. This chapter will therefore provide detailed methods for core techniques involved in studying cellular and molecular epithelial responses to a bacterial challenge in relation to chronic inflammatory disease pathogenesis and therapy...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924487/antagonists-of-the-mirna-argonaute-2-protein-complex-anti-mir-agos
#8
Marco F Schmidt, Oliver Korb, Chris Abell
microRNAs (miRNAs) have been identified as high-value drug targets. A widely applied strategy in miRNA inhibition is the use of antisense agents. However, it has been shown that oligonucleotides are poorly cell permeable because of their complex chemical structure and due to their negatively charged backbone. Consequently, the general application of oligonucleotides in therapy is limited. Since miRNAs' functions are executed exclusively by the Argonaute 2 protein, we therefore describe a protocol for the design of a novel miRNA inhibitor class: antagonists of the miRNA-Argonaute 2 protein complex, so-called anti-miR-AGOs, that not only block the crucial binding site of the target miRNA but also bind to the protein's active site...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924485/small-molecules-targeting-the-mirna-binding-domain-of-argonaute-2-from-computer-aided-molecular-design-to-rna-immunoprecipitation
#9
Teresa Bellissimo, Silvia Masciarelli, Elena Poser, Ilaria Genovese, Alberto Del Rio, Gianni Colotti, Francesco Fazi
The development of small-molecule-based target therapy design for human disease and cancer is object of growing attention. Recently, specific microRNA (miRNA) mimicking compounds able to bind the miRNA-binding domain of Argonaute 2 protein (AGO2) to inhibit miRNA loading and its functional activity were described. Computer-aided molecular design techniques and RNA immunoprecipitation represent suitable approaches to identify and experimentally determine if a compound is able to impair the loading of miRNAs on AGO2 protein...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924159/in-vitro-and-in-vivo-evaluation-of-89-zr-ds-8273a-as-a-theranostic-for-anti-death-receptor-5-therapy
#10
Ingrid J G Burvenich, Fook-Thean Lee, Nancy Guo, Hui K Gan, Angela Rigopoulos, Adam C Parslow, Graeme J O'Keefe, Sylvia J Gong, Henri Tochon-Danguy, Stacey E Rudd, Paul S Donnelly, Masakatsu Kotsuma, Toshiaki Ohtsuka, Giorgio Senaldi, Andrew M Scott
Background: DS-8273a, an anti-human death receptor 5 (DR5) agonistic antibody, has cytotoxic activity against human cancer cells and induces apoptosis after specific binding to DR5. DS-8273a is currently being used in clinical Phase I trials. This study evaluated the molecular imaging of DR5 expression in vivo in mouse tumor models using SPECT/CT and PET/MRI, as a tool for drug development and trial design. Methods: DS-8273a was radiolabeled with indium-111 and zirconium-89. Radiochemical purity, immunoreactivity, antigen binding affinity and serum stability were assessed in vitro...
2016: Theranostics
https://www.readbyqxmd.com/read/27924071/the-combination-therapy-of-imatinib-and-dasatinib-achieves-long-term-molecular-response-in-two-imatinib-resistant-and-dasatinibintolerant-patients-with-advanced-chronic-myeloid-leukemia
#11
Yu Zhu, Liangqin Pan, Ming Hong, Weixing Liu, Chun Qiao, Jianyong Li, Sixuan Qian
For patients with chronic myeloid leukemia (CML) failing imatinib therapy, second-generation tyrosine kinase inhibitors (TKIs) are recommended. Here, we describe two patients with advanced CML who failed imatinib therapy and did not tolerate the recommended dose of dasatinib, but then achieved a major molecular response with the combination of imatinib and dasatinib with no significant extramedullary toxicity. Our observations suggest that combination of TKIs may provide an additive/synergistic antileukemic effect...
November 2016: Journal of Biomedical Research
https://www.readbyqxmd.com/read/27924064/toward-the-use-of-precision-medicine-for-the-treatment-of-head-and-neck-squamous-cell-carcinoma
#12
REVIEW
Wang Gong, Yandi Xiao, Zihao Wei, Yao Yuan, Min Qiu, Chongkui Sun, Xin Zeng, Xinhua Liang, Mingye Feng, Qianming Chen
Precision medicine is a new strategy that aims at preventing and treating human diseases by focusing on individual variations in people's genes, environment and lifestyle. Precision medicine has been used for cancer diagnosis and treatment and shows evident clinical efficacy. Rapid developments in molecular biology, genetics and sequencing technologies, as well as computational technology, has enabled the establishment of "big data", such as the Human Genome Project, which provides a basis for precision medicine...
December 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27923830/a-myc-activity-signature-predicts-poor-clinical-outcomes-in-myc-associated-cancers
#13
MoonSun Jung, Amanda J Russell, Bing Liu, Joshy George, Pei Yan Liu, Tao Liu, Anna DeFazio, David D L Bowtell, Andre Oberthuer, Wendy B London, Jamie I Fletcher, Michelle Haber, Murray D Norris, Michelle J Henderson
Myc transcriptional activity is frequently deregulated in human cancers, but a Myc-driven gene signature with prognostic ability across multiple tumor types remains lacking. Here we selected 18 Myc-regulated genes from published studies of Myc family targets in epithelial ovarian cancer (EOC) and neuroblastoma. A Myc family activity score derived from the 18 genes was correlated to MYC/MYCN/MYCL1 expression in a panel of 35 cancer cell lines. The prognostic ability of this signature was evaluated in neuroblastoma, medulloblastoma, diffuse large B-cell lymphoma (DLBCL), and EOC microarray gene expression datasets using Kaplan-Meier and multivariate Cox-regression analyses, and was further validated in 42 primary neuroblastomas using qPCR...
December 6, 2016: Cancer Research
https://www.readbyqxmd.com/read/27923827/preclinical-evidence-that-3-deoxy-3-18f-fluorothymidine-pet-can-visualize-recovery-of-hematopoiesis-after-gemcitabine-chemotherapy
#14
Sonja Schelhaas, Annelena Held, Nicole Bäumer, Thomas Viel, Sven Hermann, Carsten Müller-Tidow, Andreas H Jacobs
Molecular imaging with the PET tracer 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) allows assessment of the proliferative state of organs in vivo Although used primarily in the oncology clinic, it can also shed light on the proliferation of other tissues, as demonstrated here for monitoring hematopoietic organs that recover after myelosuppressive chemotherapy. In the NMRI nude mouse model, we observed up to a 4.5-fold increase in [(18)F]FLT uptake in bone marrow and spleen on days 2, 3, and 5 after treatment with gemcitabine, a chemotherapeutic agent that is powerfully myelosuppressive in the model...
October 20, 2016: Cancer Research
https://www.readbyqxmd.com/read/27923825/rational-selection-of-syngeneic-preclinical-tumor-models-for-immunotherapeutic-drug-discovery
#15
Suzanne I S Mosely, John E Prime, Richard C A Sainson, Jens-Oliver Koopmann, Dennis Y Q Wang, Danielle M Greenawalt, Miika J Ahdesmaki, Rebecca Leyland, Stefanie Mullins, Luciano Pacelli, Danielle Marcus, Judith Anderton, Amanda Watkins, Jane Coates Ulrichsen, Philip Brohawn, Brandon W Higgs, Matthew McCourt, Hazel Jones, James A Harper, Michelle Morrow, Viia Valge-Archer, Ross Stewart, Simon J Dovedi, Robert W Wilkinson
Murine syngeneic tumor models are critical to novel immuno-based therapy development but the molecular and immunological features of these models are still not clearly defined. The translational relevance of differences between the models is not fully understood, impeding appropriate preclinical model selection for target validation, and ultimately hindering drug development. Across a panel of commonly-used murine syngeneic tumor models, we showed variable responsiveness to immunotherapies. We employed array comparative genomic hybridization, whole-exome sequencing, exon microarray analysis, and flow cytometry to extensively characterize these models, which revealed striking differences that may underlie these contrasting response profiles...
December 6, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27923814/mir-483-targeting-of-ctgf-suppresses-endothelial-to-mesenchymal-transition-therapeutic-implications-in-kawasaki-disease
#16
Ming He, Zhen Chen, Marcy Martin, Jin Zhang, Panjamaporn Sangwung, Brian Woo, Adriana Tremoulet, Chisato Shimizu, Mukesh K Jain, Jane C Burns, John Shyy
RATIONALE: Endothelial-to-mesenchymal transition (EndoMT) is implicated in myofibroblast-like cell-mediated damage to the coronary arterial wall in acute Kawasaki disease (KD) patients, as evidenced by positive staining for connective tissue growth factor (CTGF) and EndoMT markers in KD autopsy tissues. However, little is known about the molecular basis of EndoMT involved in KD. OBJECTIVE: We investigated the microRNA (miRNA) regulation of CTGF and the consequent EndoMT in KD pathogenesis...
December 6, 2016: Circulation Research
https://www.readbyqxmd.com/read/27923571/a-simple-dried-blood-spot-method-for-in-vivo-measurement-of-ureagenesis-by-gas-chromatography-mass-spectrometry-using-stable-isotopes
#17
Gabriella Allegri, Sereina Deplazes, Hiu Man Viecelli, Déborah Mathis, Ralph Fingerhut, Johannes Häberle, Beat Thöny
BACKGROUND: Clinical management of inherited or acquired hyperammonemia depends mainly on the plasma ammonia level which is not a reliable indicator of urea cycle function as its concentrations largely fluctuate. The gold standard to assess ureagenesis in vivo is the use of stable isotopes. METHODS: Here we developed and validated a simplified in vivo method with [(15)N]ammonium chloride ([(15)N]H4Cl) as a tracer. Non-labeled and [(15)N]urea were quantified by GC-MS after extraction and silylation...
December 3, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/27923552/preleukaemic-clonal-haemopoiesis-and-risk-of-therapy-related-myeloid-neoplasms-a-case-control-study
#18
Koichi Takahashi, Feng Wang, Hagop Kantarjian, Denaha Doss, Kanhav Khanna, Erika Thompson, Li Zhao, Keyur Patel, Sattva Neelapu, Curtis Gumbs, Carlos Bueso-Ramos, Courtney D DiNardo, Simona Colla, Farhad Ravandi, Jianhua Zhang, Xuelin Huang, Xifeng Wu, Felipe Samaniego, Guillermo Garcia-Manero, P Andrew Futreal
BACKGROUND: Therapy-related myeloid neoplasms are secondary malignancies that are often fatal, but their risk factors are not well understood. Evidence suggests that individuals with clonal haemopoiesis have increased risk of developing haematological malignancies. We aimed to identify whether patients with cancer who have clonal haemopoiesis are at an increased risk of developing therapy-related myeloid neoplasms. METHODS: We did this retrospective case-control study to compare the prevalence of clonal haemopoiesis between patients treated for cancer who later developed therapy-related myeloid neoplasms (cases) and patients who did not develop these neoplasms (controls)...
December 2, 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27923545/ten-plus-one-challenges-in-diseases-of-the-lysosomal-system
#19
Gregory A Grabowski, Chester Whitley
The advent of the first effective specific therapy for a lysosomal storage disease (LSDs), Gaucher disease type 1, by Roscoe O. Brady was foundational for development of additional treatments for this group of rare diseases. The past 26years, since the approval of enzyme therapy for Gaucher disease type 1, have witnessed a burgeoning understanding of LSDs at genetic, molecular, biochemical, cell biologic, and clinical levels. Simultaneously, this expansion of knowledge has exposed our incomplete understanding of the individual pathophysiologies of LSDs as well as difficult challenges for improvement in therapy and therapeutic outcomes for afflicted individuals...
November 29, 2016: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/27923508/surfacing-role-of-probiotics-in-cancer-prophylaxis-and-therapy-a-systematic-review
#20
REVIEW
Subramanyam Dasari, Chandrasekhar Kathera, Avilala Janardhan, Arthala Praveen Kumar, Buddolla Viswanath
Cancers figure among the most important causes of morbidity and mortality worldwide. Cancer and its associated infections are always complicated even when specific cancer regimens are available. It is well proved that Lactobacillus and other probiotic bacteria can modulate-ameliorate specific mechanisms against various infections including cancers. The present systematic review is intended to focus on the 'cellular and molecular mechanisms' of probiotic bacteria in the prevention and treatment of various cancers...
November 24, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
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