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https://www.readbyqxmd.com/read/28449418/hif-prolyl-hydroxylases-as-therapeutic-targets-in-erythropoiesis-and-iron-metabolism
#1
REVIEW
Volker H Haase
A classic response to systemic hypoxia is the increase in red blood cell production. This response is controlled by the prolyl hydroxylase domain/hypoxia-inducible factor (HIF) pathway, which regulates a broad spectrum of cellular functions. The discovery of this pathway as a key regulator of erythropoiesis has led to the development of small molecules that stimulate the production of endogenous erythropoietin and enhance iron metabolism. This review provides a concise overview of the cellular and molecular mechanisms that govern HIF-induced erythropoietic responses and provides an update on clinical experience with compounds that target HIF-prolyl hydroxylases for anemia therapy...
June 2017: Hemodialysis International
https://www.readbyqxmd.com/read/28449246/review-article-hepatitis-e-a-concise-review-of-virology-epidemiology-clinical-presentation-and-therapy
#2
REVIEW
M C Donnelly, L Scobie, C L Crossan, H Dalton, P C Hayes, K J Simpson
BACKGROUND: Hepatitis E virus (HEV) is a leading cause of acute icteric hepatitis and acute liver failure in the developing world. During the last decade, there has been increasing recognition of autochthonous (locally acquired) HEV infection in developed countries. Chronic HEV infection is now recognised, and in transplant recipients this may lead to cirrhosis and organ failure. AIM: To detail current understanding of the molecular biology of HEV, diagnostic and therapeutic strategies and propose future directions for basic science and clinical research...
April 27, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28448599/simulation-of-the-dynamics-of-primary-immunodeficiencies-in-cd4-t-cells
#3
Gabriel N Teku, Mauno Vihinen
Primary immunodeficiencies (PIDs) form a large and heterogeneous group of mainly rare disorders that affect the immune system. T-cell deficiencies account for about one-tenth of PIDs, most of them being monogenic. Apart from genetic and clinical information, lots of other data are available for PID proteins and genes, including functions and interactions. Thus, it is possible to perform systems biology studies on the effects of PIDs on T-cell physiology and response. To achieve this, we reconstructed a T-cell network model based on literature mining and TPPIN, a previously published core T-cell network, and performed semi-quantitative dynamic network simulations on both normal and T-cell PID failure modes...
2017: PloS One
https://www.readbyqxmd.com/read/28448556/a-highly-specific-and-sensitive-massive-parallel-sequencer-based-test-for-somatic-mutations-in-non-small-cell-lung-cancer
#4
Yoshiaki Inoue, Jun Shiihara, Hitoshi Miyazawa, Hiromitsu Ohta, Megumi Higo, Yoshiaki Nagai, Kunihiko Kobayashi, Yasuo Saijo, Masanori Tsuchida, Mitsuo Nakayama, Koichi Hagiwara
Molecular targeting therapy for non-small cell lung cancer (NSCLC) has clarified the importance of mutation testing when selecting treatment regimens. As a result, multiple-gene mutation tests are urgently needed. We developed a next-generation sequencer (NGS)-based, multi-gene test named the MINtS for investigating driver mutations in both cytological specimens and snap-frozen tissue samples. The MINtS was used to investigate the EGFR, KRAS, BRAF genes from DNA, and the ERBB2, and the ALK, ROS1, and RET fusion genes from RNA...
2017: PloS One
https://www.readbyqxmd.com/read/28448514/a-new-gtf2i-braf-fusion-mediating-mapk-pathway-activation-in-pilocytic-astrocytoma
#5
Tajana Tešan Tomić, Josefin Olausson, Annica Wilzén, Magnus Sabel, Katarina Truvé, Helene Sjögren, Sándor Dósa, Magnus Tisell, Birgitta Lannering, Fredrik Enlund, Tommy Martinsson, Pierre Åman, Frida Abel
Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. A recurrent feature of PA is deregulation of the mitogen activated protein kinase (MAPK) pathway most often through KIAA1549-BRAF fusion, but also by other BRAF- or RAF1-gene fusions and point mutations (e.g. BRAFV600E). These features may serve as diagnostic and prognostic markers, and also facilitate development of targeted therapy. The aims of this study were to characterize the genetic alterations underlying the development of PA in six tumor cases, and evaluate methods for fusion oncogene detection...
2017: PloS One
https://www.readbyqxmd.com/read/28448023/induction-of-mesenchymal-epithelial-transitions-in-sarcoma-cells
#6
Kathryn E Ware, Shivee Gilja, Shenghan Xu, Samantha Shetler, Mohit K Jolly, Xueyang Wang, Suzanne Bartholf Dewitt, Alexander J Hish, Sarah Jordan, William Eward, Herbert Levine, Andrew J Armstrong, Jason A Somarelli
Phenotypic plasticity refers to a phenomenon in which cells transiently gain traits of another lineage. During carcinoma progression, phenotypic plasticity drives invasion, dissemination and metastasis. Indeed, while most of the studies of phenotypic plasticity have been in the context of epithelial-derived carcinomas, it turns out sarcomas, which are mesenchymal in origin, also exhibit phenotypic plasticity, with a subset of sarcomas undergoing a phenomenon that resembles a mesenchymal-epithelial transition (MET)...
April 7, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28447912/targeting-ret-in-patients-with-ret-rearranged-lung-cancers-results-from-the-global-multicenter-ret-registry
#7
Oliver Gautschi, Julie Milia, Thomas Filleron, Juergen Wolf, David P Carbone, Dwight Owen, Ross Camidge, Vignhesh Narayanan, Robert C Doebele, Benjamin Besse, Jordi Remon-Masip, Pasi A Janne, Mark M Awad, Nir Peled, Chul-Cho Byoung, Daniel D Karp, Michael Van Den Heuvel, Heather A Wakelee, Joel W Neal, Tony S K Mok, James C H Yang, Sai-Hong Ignatius Ou, Georg Pall, Patrizia Froesch, Gérard Zalcman, David R Gandara, Jonathan W Riess, Vamsidhar Velcheti, Kristin Zeidler, Joachim Diebold, Martin Früh, Sebastian Michels, Isabelle Monnet, Sanjay Popat, Rafael Rosell, Niki Karachaliou, Sacha I Rothschild, Jin-Yuan Shih, Arne Warth, Thomas Muley, Florian Cabillic, Julien Mazières, Alexander Drilon
Purpose In addition to prospective trials for non-small-cell lung cancers (NSCLCs) that are driven by less common genomic alterations, registries provide complementary information on patient response to targeted therapies. Here, we present the results of an international registry of patients with RET-rearranged NSCLCs, providing the largest data set, to our knowledge, on outcomes of RET-directed therapy thus far. Methods A global, multicenter network of thoracic oncologists identified patients with pathologically confirmed NSCLC that harbored a RET rearrangement...
May 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28447761/mir-21-inhibitor-suppresses-cell-proliferation-and-colony-formation-through-regulating-the-pten-akt-pathway-and-improves-paclitaxel-sensitivity-in-cervical-cancer-cells
#8
Guohui Du, Dongmei Cao, Lingzheng Meng
The present study aimed to investigate the role and the molecular mechanisms underlying the effects of microRNA-21 (miR-21) on the proliferation, apoptosis and colony formation of cervical cancer cells, and to examine the role of miR-21 in mediating the sensitivity of cervical cancer cells to paclitaxel (PTX). Reverse transcription‑quantitative polymerase chain reaction was employed to determine the level of miR‑21 in various cervical cancer and normal cervical cells. The results revealed that the expression levels of miR-21 in cervical cancer cells were markedly higher when compared with normal cervical cells...
March 16, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28447336/review-of-recent-molecular-landscape-knowledge-of-gastric-cancer
#9
REVIEW
Dai Shimizu, Mitsuro Kanda, Yasuhiro Kodera
Gastric cancer (GC) is one of the most frequently diagnosed cancers worldwide and its prognosis remains dismal. One reason for poor outcomes of GC patients is that most are diagnosed when the cancer has already advanced. Novel biomarkers with high sensitivity and specificity are needed to diagnose GC in the early stage. In addition, to improve the outcome of patients with GC, patient stratification according to prognostic factors and sensitivity to chemo(radio)therapy are necessary. Appropriate follow-up criteria and individualized treatment will contribute to improvement in prognosis...
April 27, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/28447218/pertuzumab-trastuzumab-ct-versus-trastuzumab-ct-therapy-for-her2-breast-cancer-results-from-the-prospective-neoadjuvant-breast-registry-symphony-trial-nbrst
#10
Peter Beitsch, Pat Whitworth, Paul Baron, Michael C Rotkis, Angela M Mislowsky, Paul D Richards, Mary K Murray, James V Pellicane, Carrie L Dul, Charles H Nash, Lisette Stork-Sloots, Femke de Snoo, Sarah Untch, Laura A Lee
BACKGROUND: Pertuzumab became a standard part of neoadjuvant therapy for human epidermal growth factor receptor 2-positive (HER2+) breast cancers approximately halfway through Neoadjuvant Breast Registry Symphony Trial (NBRST) enrollment, providing a unique opportunity to determine biologically which clinical HER2+ patients benefit most from dual targeting. As a neoadjuvant phase 4 study, NBRST classifies patients by both conventional and molecular subtyping. METHODS: Of 308 clinical HER2+ patients enrolled in NBRST between 2011 and 2014 from 62 U...
April 26, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28447036/recent-translational-research-into-targeted-therapy-for-liposarcoma
#11
REVIEW
Rashi Bharat Patel, Ting Li, Zhichao Liao, Jivani Aakash Jaldeepbhai, H A Pavanika N V Perera, Sujani Kaushalya Muthukuda, Dholiya Hardeep Dhirubhai, Vaibhav Singh, Xiaoling Du, Jilong Yang
Liposarcomas (LPS) are among the most common soft tissue sarcomas, originating from adipocytes. Treatment for LPS typically involves surgical resection and radiation therapy, while the use of conventional cytotoxic chemotherapy for unresectable or metastatic LPS remains controversial. This review summarizes the results of recent translational research and trials of novel therapies targeting various genetic and molecular aberrations in different subtypes of LPS. Genetic aberrations such as the 12q13-15 amplicon, genetic amplification of MDM2, CDK4, TOP2A, PTK7, and CHEK1, point mutations in CTNNB1, CDH1, FBXW7, and EPHA1, as the fusion of FUS-DDIT3/EWSR1-DDIT3 are involved in the pathogenesis LPS and represent potential therapeutic candidates...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28446964/strategies-for-the-acquisition-of-transcriptional-and-epigenetic-information-in-single-cells
#12
REVIEW
Guang Li, Elda Dzilic, Nick Flores, Alice Shieh, Sean M Wu
As the basic unit of living organisms, each single cell has unique molecular signatures and functions. Our ability to uncover the transcriptional and epigenetic signature of single cells has been hampered by the lack of tools to explore this area of research. The advent of microfluidic single cell technology along with single cell genome-wide DNA amplification methods had greatly improved our understanding of the expression variation in single cells. Transcriptional expression profile by multiplex qPCR or genome-wide RNA sequencing has enabled us to examine genes expression in single cells in different tissues...
March 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28446882/modified-low-dose-triiodo-l-thyronine-therapy-safely-improves-function-following-myocardial-ischemia-reperfusion-injury
#13
Viswanathan Rajagopalan, Youhua Zhang, Christine Pol, Clifford Costello, Samantha Seitter, Ann Lehto, Olga V Savinova, Yue-Feng Chen, A Martin Gerdes
Background: We have shown that thyroid hormones (THs) are cardioprotective and can be potentially used as safe therapeutic agents for diabetic cardiomyopathy and permanent infarction. However, no reliable, clinically translatable protocol exists for TH treatment of myocardial ischemia-reperfusion (IR) injury. We hypothesized that modified low-dose triiodo-L-thyronine (T3) therapy would confer safe therapeutic benefits against IR injury. Methods: Adult female rats underwent left coronary artery ligation for 60 min or sham surgeries...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28446716/targeted-alpha-therapy-using-a-novel-cd70-targeted-thorium-227-conjugate-in-in-vitro-and-in-vivo-models-of-renal-cell-carcinoma
#14
Urs B Hagemann, Dessislava Mihaylova, Steinar R Uran, Joergen Borrebaek, Derek Grant, Roger M Bjerke, Jenny Karlsson, Alan S Cuthbertson
The cell surface receptor CD70 has been previously reported as a promising target for B-cell lymphomas and several solid cancers including renal cell carcinoma. We describe herein the characterization and efficacy of a novel CD70 targeted thorium-227 conjugate (CD70-TTC) comprising the combination of the three components, a CD70 targeting antibody, a chelator moiety and the short-range, high-energy alpha-emitting radionuclide thorium-227 (227Th). In vitro analysis demonstrated that the CD70-TTC retained binding affinity to its target and displayed potent and specific cytotoxicity compared to an isotype control-TTC...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28446712/aspirin-inhibits-the-shh-gli1-signaling-pathway-and-sensitizes-malignant-glioma-cells-to-temozolomide-therapy
#15
Jianguang Ming, Bo Sun, Ziwei Li, Lin Lin, Xiangqi Meng, Bo Han, Ruijia Wang, Pengfei Wu, Jianlong Li, Jinquan Cai, Chuanlu Jiang
Aberrant activation of sonic hedgehog (SHH)/glioma-associated oncogene homolog 1 (GLI1) pathway plays an important role in the tumorigenicity of malignant glioma cells and resistance to temozolomide (TMZ). Here we investigated the aspirin's antineoplastic molecular route by targeting SHH/GLI1 pathway and examined the feasibility of aspirin combined with TMZ therapy. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) revealed that the activity of the SHH/GLI1 pathway was strongly inhibited by aspirin...
April 17, 2017: Aging
https://www.readbyqxmd.com/read/28446640/ref-1-ape1-as-transcriptional-regulator-and-novel-therapeutic-target-in-pediatric-t-cell-leukemia
#16
Jixin Ding, Melissa L Fishel, April M Reed, Erin McAdams, Magdalena Czader, Angelo A Cardoso, Mark R Kelley
The increasing characterization of childhood acute lymphoblastic leukemia (ALL) has led to the identification of multiple molecular targets, but have yet to translate into more effective targeted therapies, particularly for high-risk, relapsed T-cell ALL. Searching for master regulators controlling multiple signaling pathways in T-ALL, we investigated the multi-functional protein redox factor-1 (Ref-1/APE1), which acts as a signaling "node" by exerting redox regulatory control of transcription factors important in leukemia...
April 26, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28446532/next-generation-sequencing-ngs-analysis-on-single-circulating-tumor-cells-ctcs-with-no-need-of-whole-genome-amplification-wga
#17
Raffaele Palmirotta, Domenica Lovero, Erica Silvestris, Claudia Felici, Davide Quaresmini, Paola Cafforio, Franco Silvestris
BACKGROUND: Isolation and genotyping of circulating tumor cells (CTCs) is gaining an increasing interest by clinical researchers in oncology not only for investigative purposes, but also for concrete application in clinical practice in terms of diagnosis, prognosis and decision treatment with targeted therapies. For the mutational analysis of single CTCs, the most advanced biotechnology methodology currently available includes the combination of whole genome amplification (WGA) followed by next-generation sequencing (NGS)...
May 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/28446505/clinical-features-and-outcomes-of-patients-with-colorectal-cancers-harboring-nras-mutations
#18
Andrea Cercek, Maria Ignez Braghiroli, Joanne F Chou, Jaclyn F Hechtman, Nancy E Kemeny, Leonard Saltz, Marinela Capanu, Rona Yaeger
Purpose: NRAS mutations are now routinely included in RAS testing prior to EGFR (epidermal growth factor receptor) inhibitor therapy for metastatic colorectal cancer (mCRC).  The clinical implications of NRAS mutation beyond lack of response to anti-EGFR therapy, however, are not known.  We undertook this study to determine the clinical features and treatment outcomes of patients with NRAS mutant mCRC.<br />Experimental Design: We reviewed clinical characteristics, concurrent mutations, and outcomes for all mCRC cases with NRAS mutations undergoing standard genotyping at our institution from 2008-2015...
April 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28446320/-advances-in-diagnosis-and-treatment-of-primary-breast-lymphoma-review
#19
Zhong-Ling Wei, Dong-Ping Huang
Primary breast lymphoma(PBL) is a rare and unique type of lymphoma. Female patients are the majority, but its pathogenesis is not clear, and the estrogen may be related with the pathoganesis. Women who have breast implants have more chance to be suffered. The painless breast masses are the most common clinical manifestations, which is similar to breast cancer. Surgical resection of the mass and core needle biopsy are helpful for the diagnosis. The most common pathological type of PBL is diffuse large B cell type, with non GCB type, and it is prone to extranodal relapse in which central nervous system relapse is common which has poor prognosis...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28446316/-prognostic-value-of-recurrent-molecular-genetics-and-epigenetics-abnormity-in-t-lymphoblastic-lymphoma-leukemia-review
#20
Wei Guan, Yu Jing, Li Yu
T lymphoblastic lymphoma / leukemia is a strong invasive and has a high incidence of various molecular genetic abnormalities. The NOTCH1 / FBXW7 mutation is one of the most common mutations, and related with good prognosis in T-LBL / ALL. PTEN mutation, a poor prognostic factor, could be overcome by NOTCH1 mutations in pediatric patients to some extent. Patients with MLL gene abnormality and loss of heterozygosity 6q have worse prognosis than those with normal karyotype. The incidence of MLL gene abnormality, RUNX1 mutation and DNMT3A mutation in early precursor T-lymphoblastic leukemia was higher than that of other mature subtypes, which could be used as risk stratification factors...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
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