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Molecular therapy

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https://www.readbyqxmd.com/read/28743166/second-tyrosine-kinase-inhibitor-discontinuation-attempt-in-patients-with-chronic-myeloid-leukemia
#1
Laurence Legros, Franck E Nicolini, Gabriel Etienne, Philippe Rousselot, Delphine Rea, Stéphane Giraudier, Agnès Guerci-Bresler, Françoise Huguet, Martine Gardembas, Martine Escoffre, Jean-Christophe Ianotto, Marie-Pierre Noël, Bruno R Varet, Thomas Pagliardini, Irit Touitou, Stéphane Morisset, Francois-Xavier Mahon
BACKGROUND: Several studies have demonstrated that approximately one-half of patients with chronic myeloid leukemia (CML) who receive treatment with tyrosine kinase inhibitors (TKIs) and achieve and maintain a deep molecular response (DMR) are able to successfully discontinue therapy. In patients who have a molecular relapse, a DMR is rapidly regained upon treatment re-initiation. METHODS: The authors report the results from RE-STIM, a French observational, multicenter study that evaluated treatment-free remission (TFR) in 70 patients who re-attempted TKI discontinuation after a first unsuccessful attempt...
July 25, 2017: Cancer
https://www.readbyqxmd.com/read/28743118/disappearance-of-bone-marrow-fibrosis-in-a-patient-with-chronic-myeloid-leukemia-treated-with-dasatinib
#2
Ernesto Vigna, Bruno Martino, Francesco Bacci, Anna Grazia Recchia, Francesco Mendicino, Rosellina Morelli, Francesca Romana Mauro, Caterina Musolino, Rosa Greco, Eugenio Lucia, Elena Sabattini, Fortunato Morabito, Massimo Gentile
We report a case of a chronic myeloid leukemia patient showing progressive bone marrow fibrosis and anemia during imatinib therapy. Given the loss of major molecular response, we switched treatment to dasatinib 100 mg daily, observing a reduction in BCR-ABL transcript, a significant improvement of anemia, and a gradual disappearance of fibrosis. After 7 years of dasatinib therapy the patient maintains a complete cytogenetic response and a deep molecular response; the last bone biopsy confirmed the absence of fibrosis...
July 26, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28742937/models-for-discovery-of-targeted-therapy-in-genetic-epileptic-encephalopathies
#3
REVIEW
Snezana Maljevic, Christopher A Reid, Steven Petrou
Epileptic encephalopathies are severe disorders emerging in the first days to years of life that commonly include refractory seizures, various types of movement disorders, and different levels of developmental delay. In recent years, many de novo occurring variants have been identified in individuals with these devastating disorders. To unravel disease mechanisms the functional impact of detected variants associated with epileptic encephalopathies is investigated in a range of cellular and animal models. This review addresses efforts to advance and use such models to identify specific molecular and cellular targets for the development of novel therapies...
July 25, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28742586/summary-of-future-developments
#4
Jessica R Zolton, Alan Decherney
Endometriosis is a chronic disease with the potential to cause devastating clinical manifestations such as infertility and chronic pelvic disease. Current treatment is limited to surgical intervention and pharmacologic therapy targeting estrogen and progesterone to suppress ectopic endometrial tissue proliferation. Undesired side effects and contraindications to the use of hormonal medications may reduce treatment options. As the pathogenesis of endometriosis continues to be investigated, new therapies will emerge...
September 2017: Clinical Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28742111/axonal-outgrowth-neuropeptides-expression-and-receptors-tyrosine-kinase-phosphorylation-in-3d-organotypic-cultures-of-adult-dorsal-root-ganglia
#5
Estrela Neto, Cecília J Alves, Luís Leitão, Daniela M Sousa, Inês S Alencastre, Francisco Conceição, Meriem Lamghari
Limited knowledge from mechanistic studies on adult sensory neuronal activity was generated, to some extent, in recapitulated adult in vivo 3D microenvironment. To fill this gap there is a real need to better characterize the adult dorsal root ganglia (aDRG) organotypic cultures to make these in vitro systems exploitable for different approaches, ranging from basic neurobiology to regenerative therapies, to address the sensory nervous system in adult stage. We conducted a direct head-to-head comparison of aDRG and embryonic DRG (eDRG) organotypic culture focusing on axonal growth, neuropeptides expression and receptors tyrosine kinase (RTK) activation associated with neuronal survival, proliferation and differentiation...
2017: PloS One
https://www.readbyqxmd.com/read/28741662/molecular-breakdown-a-comprehensive-view-of-anaplastic-lymphoma-kinase-alk-rearranged-non-small-cell-lung-cancer
#6
Ka-Won Noh, Mi-Sook Lee, Seung Eun Lee, Ji-Young Song, Hyun-Tae Shin, Yu Jin Kim, Doo Yi Oh, Kyungsoo Jung, Minjung Sung, Mingi Kim, Sungbin An, Joungho Han, Young Mog Shim, Jae Ill Zo, Jhingook Kim, Woong-Yang Park, Se-Hoon Lee, Yoon-La Choi
Most anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancers (NSCLCs) show good clinical response to ALK inhibitors. However, some ALK-rearranged NSCLC patients show various primary responses with unknown reasons. Previous studies focused on the clinical aspects of ALK fusions in small cohorts, or were conducted in vitro and/or in vivo to investigate the function of ALK. One of the suggested theories describes how Echinoderm microtubule-associated protein-like 4 (EML4)-ALK variants play a role towards different sensitivities in ALK inhibitors...
July 25, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28741517/filling-the-gap-on-caveolin-1-in-liver-carcinogenesis
#7
Manuel A Fernandez-Rojo, Grant A Ramm
Caveolin-1 (CAV1) has emerged as a promoter of proliferation, metastasis, and chemoresistance in hepatoma cells, as well as a marker of poor prognosis in liver cancer. We discuss here current knowledge and future approaches to elucidating the molecular mechanisms underlying CAV1 action during hepatocarcinogenesis and evaluate its potential use in clinical therapies.
December 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28741502/immune-priming-of-the-tumor-microenvironment-by-radiation
#8
REVIEW
Wen Jiang, Charles K Chan, Irving L Weissman, Betty Y S Kim, Stephen M Hahn
Ionizing irradiation can induce a multitude of alterations within the tumor microenvironment. Unlike targeted therapies, radiation delivered to the tumor bed can prompt phenotypic changes in both normal stromal and cancer cells, leading to molecular and physiological alterations within the tumor microenvironment. These environmental modulations directly influence the degree of immunogenicity of the tumor microenvironment and may ultimately affect tumor responsiveness to cancer immunotherapies. Here we review the preclinical evidence for tumor microenvironment-mediated immune suppression and how radiation can modulate immune properties within a tumor...
November 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28741493/derisking-drug-induced-carcinogenicity-for-novel-therapeutics
#9
REVIEW
Jonathan G Moggs, Timothy MacLachlan, Hans-Joerg Martus, Philip Bentley
Assessing the carcinogenic potential of innovative drugs spanning diverse therapeutic modalities and target biology represents a major challenge during drug development. Novel modalities, such as cell and gene therapies that involve intrinsic genetic modification of the host genome, require distinct approaches for identification of cancer hazard. We emphasize the need for customized weight-of-evidence cancer risk assessments based on mode of action that balance multiple options for preclinical identification of cancer hazard with appropriate labeling of clinical products and risk management plans...
August 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28741479/colorectal-cancer-subtypes-developmental-origin-and-microenvironmental-regulation
#10
REVIEW
Evelyn Fessler, Jan Paul Medema
Cancer is a heterogeneous disease and many cancer types do not represent a single entity, but are composed of biologically and clinically diverse subtypes. The subtype affiliation can influence prognosis and response to therapy. Recently, a multicenter colorectal cancer (CRC) subtyping consortium introduced a consensus molecular classification system for CRC. This will be of great benefit for future basic and clinical research since it enables uniform categorization of CRC specimens across different institutes and studies...
September 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28741454/nanovesicular-formulations-for-cancer-gene-therapy
#11
Lorena Tavano, Elisabetta Mazzotta, Rita Muzzalupo
In the last decades, gene therapy has become a novel therapeutic strategy for cancer treatment, including immunologic and molecular approaches. Among molecular avenue, the design of efficient and effective gene delivery systems, like cationic liposomes and niosomes, has been widely investigated and proposed as the most promising research area. The advantages of cationic vesicles rely on their natural ability to form complexes with anionic genetic molecules and deliver them into the cells via the endosomal pathway...
May 18, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28740920/pathologic-response-after-neoadjuvant-chemotherapy-predicts-locoregional-control-in-patients-with-triple-negative-breast-cancer
#12
Victor E Chen, Erin F Gillespie, Kaveh Zakeri, James D Murphy, Catheryn M Yashar, Sharon Lu, John P Einck
PURPOSE: Our goal was to determine the impact of pathologic response after neoadjuvant chemotherapy in triple negative breast cancer (TNBC) on the subsequent risk of locoregional recurrence (LRR) and disease-free survival (DFS) in the setting of adjuvant radiation therapy. METHODS AND MATERIALS: This was an institutional review board-approved retrospective chart review of patients with clinical stage I-III breast cancer treated with neoadjuvant chemotherapy, local surgery (breast conservation or mastectomy), and adjuvant radiation therapy between 1997 and 2015...
April 2017: Advances in Radiation Oncology
https://www.readbyqxmd.com/read/28740727/structure-modeling-of-human-tyrosyl-dna-phosphodiesterase-1-and-screening-for-its-inhibitors
#13
I V Gushchina, D K Nilov, A L Zakharenko, O I Lavrik, V K Švedas
The DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (Tdp1) represents a potential molecular target for anticancer therapy. A human Tdp1 model has been constructed using the methods of quantum and molecular mechanics, taking into account the ionization states of the amino acid residues in the active site and their interactions with the substrate and competitive inhibitors. The oligonucleotide- and phosphotyrosine-binding cavities important for the inhibitor design have been identified in the enzyme's active site...
April 2017: Acta Naturae
https://www.readbyqxmd.com/read/28740516/pge2-promotes-the-migration-of-mesenchymal-stem-cells-through-the-activation-of-fak-and-erk1-2-pathway
#14
Xiaomin Lu, Jibin Han, Xiuping Xu, Jingyuan Xu, Ling Liu, Yingzi Huang, Yi Yang, Haibo Qiu
A critical step of MSCs therapy is dependent on its ability to migrate into the sites of injury, so various approaches have been introduced to boost the migratory ability of MSCs. PGE2 is the major prostaglandin generated by COX enzymes and has been implicated in inflammatory response. Evidence indicates that PGE2 can facilitate MSCs migration. Further exploration of the underlying molecular mechanism participating in the promigratory ability of PGE2 may provide a novel strategy to improve MSC transplantation efficacy...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28740507/mir-195-inhibits-tumor-growth-and-metastasis-in-papillary-thyroid-carcinoma-cell-lines-by-targeting-ccnd1-and-fgf2
#15
Yali Yin, Shubin Hong, Shuang Yu, Yanrui Huang, Shuwei Chen, Yujie Liu, Quan Zhang, Yanbing Li, Haipeng Xiao
BACKGROUND: MicroRNA (miRNA) dysregulation was commonly seen in papillary thyroid carcinoma (PTC), and miR-195 was verified to be downregulated in PTC by the large data set analysis from The Cancer Genome Atlas (TCGA). Our study aimed to explore the biological functions and the underlying molecular mechanisms of miR-195 in PTC. METHODS: The relative expression of miR-195 and its target genes were assessed by quantitative RT-PCR assay in 38 pairs of PTC and the adjacent thyroid tissues...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28740441/detection-of-ros1-rearrangement-in-non-small-cell-lung-cancer-current-and-future-perspectives
#16
REVIEW
Giulio Rossi, Genny Jocollé, Antonia Conti, Marcello Tiseo, Federica Zito Marino, Giovanni Donati, Renato Franco, Francesca Bono, Francesca Barbisan, Francesco Facchinetti
ROS1 rearrangement characterizes a small subset (1%-2%) of non-small cell lung cancer and is associated with slight/never smoking patients and adenocarcinoma histology. Identification of ROS1 rearrangement is mandatory to permit targeted therapy with specific inhibitors, demonstrating a significantly better survival when compared with conventional chemotherapy. Detection of ROS1 rearrangement is based on in situ (immunohistochemistry, fluorescence in situ hybridization) and extractive non-in situ assays. While fluorescence in situ hybridization still represents the gold standard in clinical trials, this technique may fail to recognize rearrangements of ROS1 with some gene fusion partner...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28740365/spotlight-on-ceritinib-in-the-treatment-of-alk-nsclc-design-development-and-place-in-therapy
#17
REVIEW
Mariacarmela Santarpia, Maria Grazia Daffinà, Alessandro D'Aveni, Grazia Marabello, Alessia Liguori, Elisa Giovannetti, Niki Karachaliou, Maria Gonzalez Cao, Rafael Rosell, Giuseppe Altavilla
The identification of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) fusion gene in non-small cell lung cancer (NSCLC) has radically changed the treatment of a subset of patients harboring this oncogenic driver. Crizotinib was the first ALK tyrosine kinase inhibitor to receive fast approval and is currently indicated as the first-line therapy for advanced, ALK-positive NSCLC patients. However, despite crizotinib's efficacy, patients almost invariably progress, with the central nervous system being one of the most common sites of relapse...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28739796/multicenter-and-international-study-of-mic-mec-distributions-for-definition-of-epidemiological-cutoff-values-ecvs-for-species-of-sporothrix-identified-by-molecular-methods
#18
A Espinel-Ingroff, D P B Abreu, R Almeida-Paes, R S N Brilhante, A Chakrabarti, A Chowdhary, F Hagen, S Córdoba, G M Gonzalez, N P Govender, J Guarro, E M Johnson, S E Kidd, S A Pereira, A M Rodrigues, S Rozental, M W Szeszs, R Ballesté Alaniz, A Bonifaz, L X Bonfietti, L P Borba-Santos, J Capilla, A L Colombo, M Dolande, M G Isla, M S C Melhem, A C Mesa-Arango, M M E Oliveira, M M Panizo, Z Pires de Camargo, R M Zancope-Oliveira, J F Meis, J Turnidge
Clinical and Laboratory Standards Institute (CLSI) conditions for testing the susceptibilities of pathogenic Sporothrix species to antifungal agents are based on a collaborative study that evaluated five clinically relevant isolates of Sporothrix schenckii sensu lato and some antifungal agents. With the advent of molecular identification, there are two basic needs: to confirm the suitability of these testing conditions for all agents and Sporothrix species and to establish species-specific epidemiologic cutoff values (ECVs) or breakpoints (BPs) for these species...
July 24, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28739795/clinical-characteristics-and-treatment-outcomes-of-patients-with-acquired-macrolide-resistant-mycobacterium-abscessus-lung-disease
#19
Hayoung Choi, Su-Young Kim, Dae Hun Kim, Hee Jae Huh, Chang-Seok Ki, Nam Yong Lee, Seung-Heon Lee, Soyoun Shin, Sung Jae Shin, Charles L Daley, Won-Jung Koh
Macrolide antibiotics are mainstays in the treatment of lung disease due to the Mycobacterium abscessus complex. Although previous studies have reported development of acquired macrolide resistance in this species, limited data are available on the outcomes of lung disease due to macrolide-resistant M. abscessus subspecies abscessus (hereafter M. abscessus). This study evaluated the clinical features, treatment outcomes, and molecular characteristics of macrolide-resistant isolates of M. abscessus We performed a retrospective review of medical records and genetic analysis of clinical isolates from 13 patients who had acquired macrolide-resistant M...
July 24, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28739642/animal-models-of-ocular-angiogenesis-from-development-to-pathologies
#20
REVIEW
Chi-Hsiu Liu, Zhongxiao Wang, Ye Sun, Jing Chen
Pathological angiogenesis in the eye is an important feature in the pathophysiology of many vision-threatening diseases, including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration, as well as corneal diseases with abnormal angiogenesis. Development of reproducible and reliable animal models of ocular angiogenesis has advanced our understanding of both the normal development and the pathobiology of ocular neovascularization. These models have also proven to be valuable experimental tools with which to easily evaluate potential antiangiogenic therapies beyond eye research...
July 24, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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