Abstract:
:Choroid plexus carcinomas (CPCs) are rare, aggressive pediatric brain tumors with no established curative therapy for relapsed disease, and poor survival rates. TP53 Mutation or dysfunction correlates with poor or no survival outcome in CPCs. Here, we report the case of a 4 month-old female who presented with disseminated CPC. After initial response to tumor resection and adjuvant-chemotherapy, the tumor recurred and metastasized with no response to aggressive relapse therapy suggesting genetic predisposition. This patient was then enrolled to a Molecular Guided Therapy Clinical Trial. Genomic profiling of patient tumor and normal sample identified a TP53 germline mutation with loss of heterozygosity, somatic mutations including IDH2, and aberrant activation of biological pathways. The mutations were not targetable for therapy. However, targeting the altered biological pathways (mTOR, PDGFRB, FGF2, HDAC) guided identification of possibly beneficial treatment with a combination of sirolimus, thalidomide, sunitinib, and vorinostat. This therapy led to 92% reduction in tumor size with no serious adverse events, excellent quality of life and long term survival.
journal_name
Front Pharmacoljournal_title
Frontiers in pharmacologyauthors
Cornelius A,Foley J,Bond J,Nagulapally AB,Steinbrecher J,Hendricks WPD,Rich M,Yendrembam S,Bergendahl G,Trent JM,Sholler GSdoi
10.3389/fphar.2017.00652subject
Has Abstractpub_date
2017-09-25 00:00:00pages
652issn
1663-9812journal_volume
8pub_type
abstract::Tumors frequently arise as a result of an acquired genomic instability and the subsequent evolution of neoplastic populations with variable genomes. A barrier to the study of the somatic genetics of human solid tumors in vivo is the presence of admixtures of non-neoplastic cells with normal genomes in patient samples....
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2013.00002
更新日期:2013-01-28 00:00:00
abstract::DT-13, a saponin monomer 13 from the dwarf lilyturf tuber, was reported to exhibit anti-inflammatory, hepatoprotective, cardioprotective as well as antitumor activities in a number of tumor cells. Prostate cancer is the second leading cause of cancer death in males, discovery of novel antitumor drug for therapy of pro...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.01450
更新日期:2018-12-07 00:00:00
abstract::There are three members of the endogenous gas transmitter family. The first two are nitric oxide and carbon monoxide, and the third newly added member is hydrogen sulfide (H2S). They all have similar functions: relaxing blood vessels, smoothing muscles, and getting involved in the regulation of neuronal excitation, le...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.00702
更新日期:2020-05-14 00:00:00
abstract::Interest is increasing in the development of non-animal methods for toxicological evaluations. These methods are however, particularly challenging for complex toxicological endpoints such as repeated dose toxicity. European Legislation, e.g., the European Union's Cosmetic Directive and REACH, demands the use of altern...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2016.00321
更新日期:2016-09-21 00:00:00
abstract::Random-pattern skin flap replantation is commonly used to repair skin defects during plastic and reconstructive surgery. However, flap necrosis due to ischemia and ischemia-reperfusion injury limits clinical applications. Betulinic acid, a plant-derived pentacyclic triterpene, may facilitate flap survival. In the pres...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.01017
更新日期:2019-09-13 00:00:00
abstract::Neutrophil killing of bacteria is mediated by oxidative and non-oxidative mechanisms. Oxidants are generated through the NADPH oxidase complex, whereas antimicrobial proteins and peptides rank amongst non-oxidative host defenses. Mucus hypersecretion, deficient hydration and poor clearance from the airways are promine...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.554353
更新日期:2020-09-30 00:00:00
abstract::Several studies have pointed to soluble oligomers of beta amyloid peptide (SOAβ) as the principal neurotoxic agents responsible for the generation of synaptotoxic events that can explain the main symptoms of Alzheimer's disease (AD). Among the toxic features associated with SOAβ, one of the most notorious is the forma...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2019.01330
更新日期:2019-11-07 00:00:00
abstract::Purpose: Gender differences exist in the prevalence of asthma and allergic diseases, partially due to the effects of sex hormones on the development of allergic manifestations. Women, compared with men, are more prone to suffer allergic asthma, experience difficulties in controlling asthma symptoms, and show adverse r...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.01094
更新日期:2019-09-24 00:00:00
abstract::Over recent years, utilization of green synthesized nanomaterials has been widely growing on human body because of its special properties. With the increasing acceptance of nanoparticle approach for various clinical treatments, the biosafety and toxicological effects on the vital organs such as central nervous system,...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00549
更新日期:2018-05-23 00:00:00
abstract::Flavonoids are the largest class of plant polyphenols, with common structure of diphenylpropanes, consisting of two aromatic rings linked through three carbons and are abundant in both daily diets and medicinal plants. Fueled by the recognition of consuming flavonoids to get better health, researchers became intereste...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00918
更新日期:2018-08-15 00:00:00
abstract::The genus Ononis has important value as traditional drugs and foods. In the present work, we aimed to assess the chemical profiles and biological effects of Ononis natrix subsp. hispanica extracts (ethyl acetate, methanol, and water). For chemical profile, total and individual phenolic components were detected. For bi...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00600
更新日期:2017-09-01 00:00:00
abstract::Kyotorphin (KTP, l-tyrosyl-l-arginine) is an endogenous dipeptide initially described to have analgesic properties. Recently, KTP was suggested to be an endogenous neuroprotective agent, namely for Alzheimer's disease (AD). In fact, KTP levels were shown to be decreased in the cerebrospinal fluid of patients with AD, ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00985
更新日期:2020-07-09 00:00:00
abstract::Gut microbiome maintains local gut integrity and systemic host homeostasis, where optimal control of intestinal lipopolysaccharides (LPS) activity may play an important role. LPS mainly produced from gut microbiota are a group of lipid-polysaccharide chemical complexes existing in the outer membrane of Gram-negative b...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.00554
更新日期:2020-04-30 00:00:00
abstract::The inflammatory airway disease cystic fibrosis (CF) is characterized by airway obstruction due to mucus hypersecretion, airway plugging, and bronchoconstriction. The cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is dysfunctional in CF, leading to defects in epithelial transport. Although...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2019.00003
更新日期:2019-01-29 00:00:00
abstract::Marantodes pumilum (Primulaceae) has been used in Malaysian folk medicine to help women regain strength after delivery and for "sickness in the bones." It was previously revealed that its extracts inhibited xanthine oxidase (XO) activity in vitro. The leaves and roots of M. pumilum var. alata (MPA), var. pumila (MPP),...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00289
更新日期:2020-03-17 00:00:00
abstract::γ-aminobutyric acid (GABA) or glucagon-like peptide-1 based drugs, such as sitagliptin (a dipeptidyl peptidase-4 inhibitor), were shown to induce beta cell regenerative effects in various diabetic mouse models. We propose that their combined administration can bring forth an additive therapeutic effect. We tested this...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00362
更新日期:2017-06-20 00:00:00
abstract:BACKGROUND:Abiraterone Acetate (AA) is approved for the treatment of mCRPC after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated and for treatment of mCRPC progressed during or after docetaxel-based chemotherapy regimen. The aim of this study is to evaluate the role of early...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2016.00123
更新日期:2016-05-18 00:00:00
abstract::Bone-related infection rates are 4-64% in long open bone fractures and nearly 1% in joint-related surgeries. Treating bone infections and infection-related bone loss is very important. The present study prepared strontium ranelate (SR)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (PM) with assembled silver...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00368
更新日期:2018-04-18 00:00:00
abstract::Animal poisons and venoms are comprised of different classes of molecules displaying wide-ranging pharmacological activities. This review aims to provide an in-depth view of toxin-based compounds from terrestrial and marine organisms used as diagnostic tools, experimental molecules to validate postulated therapeutic t...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.01132
更新日期:2020-07-24 00:00:00
abstract::Recent advances in fluorescent ligand technology have enabled the study of G protein-coupled receptors in their native environment without the need for genetic modification such as addition of N-terminal fluorescent or bioluminescent tags. Here, we have used a non-imaging plate reader (PHERAstar FS) to monitor the bin...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00908
更新日期:2017-12-13 00:00:00
abstract:Background:Patients with locally advanced rectal cancer (LARC) are at higher risk of local and distant recurrence and are thus more vulnerable to metastatic diseases. Neoadjuvant chemoradiotherapy (nCRT) and subsequent curative resection with total mesorectal excision (TME) followed by adjuvant chemotherapy have been r...
journal_title:Frontiers in pharmacology
pub_type:
doi:10.3389/fphar.2020.00706
更新日期:2020-05-15 00:00:00
abstract::In a screening of Sudanese medicinal plants for antiprotozoal activity, the chloroform fractions obtained by liquid-liquid partitioning from ethanolic extracts of fruits of Croton gratissimus var. gratissimus and stems of Cuscuta hyalina Roth ex Schult. exhibited in vitro activity against axenically grown Leishmania d...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.01246
更新日期:2020-08-14 00:00:00
abstract::The psoralen-related compound, 4,6,4'-trimethylangelicin (TMA) potentiates the cAMP/PKA-dependent activation of WT-CFTR and rescues F508del-CFTR-dependent chloride secretion in both primary and secondary airway cells homozygous for the F508del mutation. We recently demonstrated that TMA, like lumacaftor (VX-809), stab...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00719
更新日期:2018-07-04 00:00:00
abstract::Pulmonary fibrosis is closely associated with the recruitment of fibroblasts from capillary vessels with damaged endothelial cells, the epithelial mesenchymal transition (EMT) of type II alveolar epithelial cells, and the transformation of fibroblasts to myofibroblasts. Recent studies suggest that EMT is a key factor ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.590972
更新日期:2020-12-04 00:00:00
abstract::Cytochrome P450 enzymes are often responsible for the toxic and carcinogenic effects of toxicants, such as aflatoxin B1 (AFB1). The human hepatic CYP2A6 enzyme mediates the oxidative metabolism of several procarcinogens. In this study, we characterized a partial sequence of CYP2A6 gene from Arbor Acres (AA) broiler an...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00143
更新日期:2017-03-21 00:00:00
abstract::The conjugate 8 was obtained as a result of condensation of 3-hydroxyiminooleanolic acid morfolide (7) and aspirin in dioxane. Analgesic effect of OAO-ASA (8) for the range of doses 0.3-300.0 mg/kg (p.o.) was performed in mice using a hot-plate test. Anti-inflammatory activity was assessed on carrageenan-induced paw e...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2016.00202
更新日期:2016-07-12 00:00:00
abstract::Purpose: The present study compared the risk of ischemic stroke in atrial fibrillation (AF) patients receiving digoxin and amiodarone. Methods: A retrospective cohort study was conducted using the longitudinal population-based database of Taiwan's National Health Insurance program. Patients with AF who received amioda...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00448
更新日期:2018-05-07 00:00:00
abstract::Studies proved that among all α1-adrenoceptors, cardiac myocytes functionally express only α1A- and α1B-subtype. Scientists indicated that α1A-subtype blockade might be beneficial in restoring normal heart rhythm. Therefore, we aimed to determine the role of α1-adrenoceptors subtypes (i.e., α1A and α1B) in antiarrhyth...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2016.00229
更新日期:2016-08-03 00:00:00
abstract::Saikosaponin d (SSd) is a major hepatoprotective component of saikosaponins derived from Radix Bupleuri, which was also linked to hepatotoxicity. Previous studies have demonstrated that caspases play a key role in SSd-induced liver cell death. Our in vitro and in vivo studies also showed that treatment with caspase in...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00732
更新日期:2018-07-06 00:00:00
abstract::The use of therapeutic peptides in various inflammatory diseases and autoimmune disorders has received considerable attention; however, the identification of anti-inflammatory peptides (AIPs) through wet-lab experimentation is expensive and often time consuming. Therefore, the development of novel computational method...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00276
更新日期:2018-03-27 00:00:00