Modelling and structural characteristics analysis of gene networks for prostate cancer

2015 ◽  
Vol 12 (1) ◽  
pp. 14
Author(s):  
Yulin Zhang ◽  
Shudong Wang ◽  
Dazhi Meng
Keyword(s):  
Prostate Cancer ◽  
Gene Networks ◽  
Structural Characteristics ◽  
Characteristics Analysis

Abiraterone acetate (AA) with or without cabazitaxel (CBZ) in treatment of chemotherapy naive metastatic castration-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 84-84
Author(s):  
Susan F. Slovin ◽  
Karen E. Knudsen ◽  
Susan Halabi ◽  
Mark T. Fleming ◽  
Ana M. Molina ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gene Networks ◽  
Radiographic Progression ◽  
Performance Status ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Primary Objective ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Castration Resistant

84 Background: Loss of retinoblastoma tumor suppressor (RB) function has been shown to lead to CRPC and is strongly associated with poor outcome. RB functions as a transcriptional repressor; as such, loss of RB causes de-repression of pro-tumorigenic gene networks, including deregulation of the androgen receptor (AR) locus, excessive AR production, and castration-resistant (ligand independent) AR activity that can bypass hormone therapy. Our hypothesis is that leveraging RB status can direct treatment decisions. The primary objective of the trial (NCT02218606) was to determine the radiographic progression free survival (rPFS) of AA/prednisone (AAP) with and without CBZ in mCRPC patients (pts) that have progressed on primary androgen deprivation therapy and no prior AR directed therapy or chemotherapy. Methods: This is a multicenter non-comparative randomized phase 2 trial. Pts were randomized 1:1 to AAP with crossover to CBZ upon AAP failure (Arm 1), or the combination of AAP + CBZ (Arm 2). Randomization was stratified by the CALGB 90401 prognostic risk groups. The primary endpoint was rPFS (time from randomization to radiographic progression or death, whichever occurs first). Arms were analyzed separately. Results: Between October 2014 and March 2019, 93 pts were accrued; 81 were randomized. Median age was 68 years and ECOG performance status was 0 or 1. Endpoints are shown in Table. Therapies were well tolerated. Conclusions: Results of AAP + CBZ (Arm 2) in chemotherapy naïve pts suggest that men may derive benefit from the earlier use of CBZ with acceptable toxicity, supporting further study of this combination in mCRPC pts. Circulating Tumor Cells are being analyzed for changes in RB/AR expression. Managed by: Prostate Cancer Clinical Trials Consortium; Funding: Sanofi US; Support: Prostate Cancer Foundation. Clinical trial information: NCT02218606. [Table: see text]

scholarly journals c-Myc Antagonises the Transcriptional Activity of the Androgen Receptor in Prostate Cancer Affecting Key Gene Networks

EBioMedicine ◽  
2017 ◽  
Vol 18 ◽  
pp. 83-93 ◽  
Author(s):  
Stefan J. Barfeld ◽  
Alfonso Urbanucci ◽  
Harri M. Itkonen ◽  
Ladan Fazli ◽  
Jessica L. Hicks ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Gene Networks ◽  
Transcriptional Activity

scholarly journals PMEPA1 Gene Isoforms: A Potential Biomarker and Therapeutic Target in Prostate Cancer

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1221
Author(s):  
Shashwat Sharad ◽  
Albert Dobi ◽  
Shiv Srivastava ◽  
Alagarsamy Srinivasan ◽  
Hua Li
Keyword(s):  
Prostate Cancer ◽  
Solid Tumors ◽  
Cancer Progression ◽  
Therapeutic Target ◽  
Gene Networks ◽  
Transmembrane Protein ◽  
Regulatory Gene ◽  
Amino Acid Sequences ◽  
Binding Domains ◽  
Potential Biomarker

The identification of prostate transmembrane protein androgen induced 1 (PMEPA1), an androgen responsive gene, came initially from the studies of androgen regulatory gene networks in prostate cancer. It was soon followed by the documentation of the expression and functional analysis of transmembrane prostate androgen-induced protein (TMEPAI)/PMEPA1 in other solid tumors including renal, colon, breast, lung, and ovarian cancers. Further elucidation of PMEPA1 gene expression and sequence analysis revealed the presence of five isoforms with distinct extracellular domains (isoforms a, b, c, d, and e). Notably, the predicted amino acid sequences of PMEPA1 isoforms show differences at the N-termini, a conserved membrane spanning and cytoplasmic domains. PMEPA1 serves as an essential regulator of multiple signaling pathways including androgen and TGF-β signaling in solid tumors. Structure-function studies indicate that specific motifs present in the cytoplasmic domain (PY, SIM, SH3, and WW binding domains) are utilized to mediate isoform-specific functions through interactions with other proteins. The understanding of the “division of labor” paradigm exhibited by PMEPA1 isoforms further expands our knowledge of gene’s multiple functions in tumorigenesis. In this review, we aim to summarize the most recent advances in understanding of PMEPA1 isoform-specific functions and their associations with prostate cancer progression, highlighting the potentials as biomarker and therapeutic target in prostate cancer.

scholarly journals Pathway Analysis of Genes Identified through Post-GWAS to Underpin Prostate Cancer Aetiology

Genes ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 526
Author(s):  
Samaneh Farashi ◽  
Thomas Kryza ◽  
Jyotsna Batra
Keyword(s):  
Prostate Cancer ◽  
Gene Networks ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Functional Variants ◽  
Pathway Gene ◽  
Gene Sets ◽  
Genome Wide ◽  
Prostate Cancer Development ◽  
Canonical Pathways

Understanding the functional role of risk regions identified by genome-wide association studies (GWAS) has made considerable recent progress and is referred to as the post-GWAS era. Annotation of functional variants to the genes, including cis or trans and understanding their biological pathway/gene network enrichments, is expected to give rich dividends by elucidating the mechanisms underlying prostate cancer. To this aim, we compiled and analysed currently available post-GWAS data that is validated through further studies in prostate cancer, to investigate molecular biological pathways enriched for assigned functional genes. In total, about 100 canonical pathways were significantly, at false discovery rate (FDR) < 0.05), enriched in assigned genes using different algorithms. The results have highlighted some well-known cancer signalling pathways, antigen presentation processes and enrichment in cell growth and development gene networks, suggesting risk loci may exert their functional effect on prostate cancer by acting through multiple gene sets and pathways. Additional upstream analysis of the involved genes identified critical transcription factors such as HDAC1 and STAT5A. We also investigated the common genes between post-GWAS and three well-annotated gene expression datasets to endeavour to uncover the main genes involved in prostate cancer development/progression. Post-GWAS generated knowledge of gene networks and pathways, although continuously evolving, if analysed further and targeted appropriately, will have an important impact on clinical management of the disease.

Characteristics Analysis and Optimization of Flying-Wing Vehicle Structure

2014 ◽  
Vol 1077 ◽  
pp. 177-184 ◽  
Author(s):  
Hong Xia Zhou ◽  
Bin Liu
Keyword(s):  
Dynamic Model ◽  
Axial Force ◽  
Structural Characteristics ◽  
Torsional Rigidity ◽  
Bending Rigidity ◽  
Static Test ◽  
Wing Span ◽  
Resonance Test ◽  
Vehicle Structure ◽  
Characteristics Analysis

To study structural characteristics of flying-wing vehicle, static and dynamic model of half wing span, static and dynamic model of all wing span, optimization model were established. Based on associated static test and ground resonance test data, these models were modified to implement static, dynamic and optimization analysis. Results demonstrated that structural bending and torsional deformations are mainly at outer wing surface. Torsion at inner wing is positive, while torsion at outer wing is negative. Total spar axial force along the wing span increases gradually from inner wing to outer wing and then decreases gradually after reaching the inner-outer wing interface. After axial force is transmitted to the inner wing, it is going to concentrate at the rear spar obviously. Structural bending rigidity and torsional rigidity satisfy requirements of both static force and flutter, without flutter problem of main structural mode. Viewed from the optimization size, ±45° and 0° skin at inner-outer wing turn thickens significantly. This can increase structural bending and torsional rigidity, which is good for satisfying multiple constraints comprehensively.

Research on Ontology Structure Characteristics Analysis and Matching Application

2014 ◽  
Vol 556-562 ◽  
pp. 4396-4399
Author(s):  
Yue Li Li ◽  
Ai Hua Ren
Keyword(s):  
Structural Characteristics ◽  
Great Influence ◽  
Individual Characteristics ◽  
Ontology Matching ◽  
Edge Weight ◽  
Network Characteristics ◽  
Structure Characteristics ◽  
Characteristics Analysis ◽  
Ontology Structure ◽  
Selection Of

According to the similarity between ontology and complex network, the article analyzes the network characteristics of ontology and brings forward a series of theories based on structural and semantic characteristics as well as quantization criteria for nodes and edges. These theories and quantization criteria are applied to the selection of core nodes and measurement of edge weight. In this article, the problem of ontology matching is transformed into the matching of weighed label graphics, which are based on individual characteristics and organizational structure. The matching of approximately optimization is acquired through quadratic programming. Results of experiments have showed that the structural characteristics of ontology have great influence on ontology matching and the close coupled with the matching of core nodes will significantly improve the accuracy of matching.

Sign in / Sign up

Export Citation Format

Share Document