This study provides a mechanism for continued administration of ALN-VSP02 therapy to patients with cancer who completed participation in another ALN-VSP02 clinical study. The primary objective of this study is to collect long term safety data.

Start Date01 Jul 2010

Sponsor / Collaborator

Alnylam Pharmaceuticals, Inc.

NCT00882180

/ CompletedPhase 1

A Multi-Center, Open Label, Phase 1 Dose-Escalation Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intravenous ALN-VSP02 in Patients With Advanced Solid Tumors With Liver Involvement

The purpose of the study is to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of intravenous ALN-VSP02, an RNAi therapeutic, in patients with advanced solid tumors with liver involvement.

Start Date01 Mar 2009

Sponsor / Collaborator

Alnylam Pharmaceuticals, Inc.

100 Clinical Results associated with VEGF-A x KIF11

100 Translational Medicine associated with VEGF-A x KIF11

0 Patents (Medical) associated with VEGF-A x KIF11

Literatures (Medical) associated with VEGF-A x KIF11

01 May 2015·Journal of Vascular and Interventional RadiologyQ3 · MEDICINE

Gene Expression in Hepatocellular Carcinoma: Pilot Study of Potential Transarterial Chemoembolization Response Biomarkers

Q3 · MEDICINE

Article

Author: Groth, John V ; Guzman, Grace ; Parvinian, Ahmad ; Casadaban, Leigh C ; Gaba, Ron C

PURPOSETo perform a feasibility study to explore the relationship between hepatocellular carcinoma genetics and transarterial chemoembolization treatment response to identify potential biomarkers associated with enhanced treatment efficacy.MATERIALS AND METHODSIn this single-institution study, pretreatment hepatocellular carcinoma biopsy specimens for tumors in 19 patients (14 men, five women; mean age, 59 y) treated with chemoembolization between 2007 and 2013 were analyzed for a panel of 60 chemotherapy-sensitivity, hypoxia, mitosis, and inflammatory genes with the QuantiGene Plex 2.0 mRNA detection assay. Demographic, disease, and procedure data and tumor response outcomes were collected. Quantitative mRNA levels were compared based on radiologic response between tumors exhibiting complete response (CR) versus partial response (PR).RESULTSThe study sample included 19 biopsy specimens from tumors (mean size, 3.0 cm; grade 1, n = 6; grade 2, n = 9; grade 3, n = 4) in patients treated with a mean of two conventional chemoembolization sessions. Thirteen and six tumors exhibited CR and PR, respectively, at a mean of 116 days after treatment. Tumors with CR showed a significant increase in (P < .05) or trend toward (P < .1) greater (range, 1.49-3.50 fold) pretreatment chemotherapy-sensitivity and mitosis (ATF4, BAX, CCNE1, KIF11, NFX1, PPP3CA, SNX1, TOP2A, and TOP2B) gene mRNA expression compared with tumors with PR, in addition to lower CXCL10 levels (0.48-fold), and had significantly (P < .05) higher (1.65-fold) baseline VEGFA levels.CONCLUSIONSGenetic signatures may allow prechemoembolization stratification of tumor response probability, and gene analysis may therefore offer an opportunity to personalize locoregional therapy by enhancing treatment modality allocation. Further corroboration of identified markers and exploration of their respective predictive capacity thresholds is necessary.

31 Dec 2013·Oncotarget

Impaired angiogenesis and tumor development by inhibition of the mitotic kinesin Eg5

Article

Author: Becker, Jürgen ; Nivelles, Olivier ; Ormenese, Sandra ; Herbert, John ; Wang, Baigang ; Franco, Mélanie ; Hagedorn, Martin ; Platonova, Natalia ; Winandy, Marie ; Javerzat, Sophie ; Godard, Virginie ; Pujol, Nadège ; Wilting, Jörg ; Bikfalvi, Andreas ; Bicknell, Roy ; Pineau, Raphael ; Exertier, Prisca

Kinesin motor proteins exert essential cellular functions in all eukaryotes. They control mitosis, migration and intracellular transport through interaction with microtubules. Small molecule inhibitors of the mitotic kinesin KiF11/Eg5 are a promising new class of anti-neoplastic agents currently evaluated in clinical cancer trials for solid tumors and hematological malignancies. Here we report induction of Eg5 and four other mitotic kinesins including KIF20A/Mklp2 upon stimulation of in vivo angiogenesis with vascular endothelial growth factor-A (VEGF-A). Expression analyses indicate up-regulation of several kinesin-encoding genes predominantly in lymphoblasts and endothelial cells. Chemical blockade of Eg5 inhibits endothelial cell proliferation and migration in vitro. Mitosis-independent vascular outgrowth in aortic ring cultures is strongly impaired after Eg5 or Mklp2 protein inhibition. In vivo, interfering with KIF11/Eg5 function causes developmental and vascular defects in zebrafish and chick embryos and potent inhibition of tumor angiogenesis in experimental tumor models. Besides blocking tumor cell proliferation, impairing endothelial function is a novel mechanism of action of kinesin inhibitors.

Health Information Science and Systems

Identification of circRNA-miRNA-mRNA networks to explore underlying mechanism in lung cancer

Article

Author: Wang, Yajie ; Fu, Yu

BackgroundCircular RNAs (circRNAs) are involved in the occurrence and development of various tumors. CircRNAs can act as competing endogenous RNAs (ceRNAs), which are important regulatory networks, by regulating microRNAs (miRNAs). However, the effects of ceRNA networks on lung cancer (LC), especially the circRNA-miRNA-mRNA regulatory network, remain incompletely understood. Therefore, the aim of this study was to explore novel ceRNA networks and their function and underlying mechanisms in LC.MethodsSix RNA expression datasets were obtained from the Gene Expression Omnibus microarray datasets (circRNA: GSE158695, GSE101684, GSE112214, and GSE101586; miRNA: GSE135918; mRNA: GSE98929). First, we constructed a circRNA-miRNA-mRNA ceRNA network in LC using Cytoscape. Second, we constructed a protein-protein interaction network using STRING and identified hub genes using CytoHubba. Functional analysis was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to predict the potential function of the hub genes. Third, expression and survival analysis of the hub genes were performed to identify prognostic genes.ResultsWe constructed a ceRNA network including 18 circRNAs, 32 miRNAs, and 135 mRNAs, and identified 10 hub genes (VEGFA, FOS, MAD2L1, CREBBP, TYMS, EDN1, RFC5, KIF11, SLC2A1, and TOP2A). Both GO and KEGG analyses revealed that the 10 hub genes were associated with several cancer‑related biological functions and pathways, including "oxygen levels", "nuclear division", and "HIF-1 signaling pathway". Five genes (MAD2L1, TYMS, KIF11, SLC2A1, and TOP2A) were associated with the prognosis of lung adenocarcinoma (LUAD), the most common histological type of LC.ConclusionOur study provides novel insights into the pathogenesis and therapy of LC from a ceRNA network perspective.

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