TY  - JOUR
A1  - Lv, Xiaoqun
A1  - Zhang, Lingyun
A1  - Zhu, Yanyan
A1  - Said, Harun M.
A1  - Shi, Jimin
A1  - Xu, Guoxiong
T1  - Regulative effect of Nampt on tumor progression and cell viability in human colorectal cancer
JF  - Journal of Cancer
N2  - Colorectal cancer (CRC) is the third most common cancer disease. Here we examined Nampt expression in patients with CRC and the effect of Nampt on cell viability in CRC cells. Nampt protein was overexpressed in colorectal adenoma as well as colorectal carcinoma. The immunoreactive staining of Nampt was negative in the adjacent normal colorectal tissue, weak in colorectal adenoma, and strong in colorectal carcinoma, which may represent tumor progression. Further evaluation of clinical data showed that Nampt expression was not correlated with the clinicopathological characteristics of CRC. Additionally, our in vitro studies demonstrated that Nampt promotes CRC cell viability, whereas the Nampt inhibitor FK866 suppressed CRC cell viability, which was in concordance with the previous studies in other cancer cells. Treatment with Nampt-siRNA reduced the Nampt protein expression resulting in the inhibition of the cell viability of HCT116 and Caco2. Thus, the involvement of Nampt in cell growth indicates that Nampt may play an important role in colorectal tumorigenesis. As a consequence, our results suggest that Nampt may be considered as a progression marker of colorectal tumor and a potentially therapeutic target for the treatment of CRC.
KW  - nicotinamide phosphoribosyltransferase
KW  - signaling pathways
KW  - gastric cancer
KW  - overexpression
KW  - cell proliferation
KW  - tumor biomarker
KW  - adenocarcinoma
KW  - Nampt
KW  - visfatin
KW  - PBEF
KW  - breast cancer
KW  - prognostic value
KW  - visfatin levels
KW  - inhibitor
KW  - expression
KW  - adipocytokines
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-144516
VL  - 6
IS  - 9
ER  - 
TY  - JOUR
A1  - Said, Harun M.
A1  - Polat, Buelent
A1  - Stein, Susanne
A1  - Guckenberger, Mathias
A1  - Hagemann, Carsten
A1  - Staab, Adrian
A1  - Katzer, Astrid
A1  - Anacker, Jelena
A1  - Flentje, Michael
A1  - Vordermark, Dirk
T1  - Inhibition of N-Myc down regulated gene 1 in in vitro cultured human glioblastoma cells
JF  - World Journal of Clinical Oncology
N2  - AIM: To study short dsRNA oligonucleotides (siRNA) as a potent tool for artificially modulating gene expression of N-Myc down regulated gene 1 (NDRG1) gene induced under different physiological conditions (Normoxia and hypoxia) modulating NDRG1 transcription, mRNA stability and translation.

METHODS: A cell line established from a patient with glioblastoma multiforme. Plasmid DNA for transfections was prepared with the Endofree Plasmid Maxi kit. From plates containing 5 x 10(7) cells, nuclear extracts were prepared according to previous protocols. The pSUPER-NDRG1 vectors were designed, two sequences were selected from the human NDRG1 cDNA (5'-GCATTATTGGCATGGGAAC-3' and 5'-ATGCAGAGTAACGTGGAAG-3'. reverse transcription polymerase chain reaction was performed using primers designed using published information on -actin and hypoxia-inducible factor (HIF)-1 mRNA sequences in GenBank. NDRG1 mRNA and protein level expression results under different conditions of hypoxia or reoxygenation were compared to aerobic control conditions using the Mann-Whitney U test. Reoxygenation values were also compared to the NDRG1 levels after 24 h of hypoxia (P < 0.05 was considered significant).

RESULTS: siRNA- and iodoacetate (IAA)-mediated downregulation of NDRG1 mRNA and protein expression in vitro in human glioblastoma cell lines showed a nearly complete inhibition of NDRG1 expression when compared to the results obtained due to the inhibitory role of glycolysis inhibitor IAA. Hypoxia responsive elements bound by nuclear HIF-1 in human glioblastoma cells in vitro under different oxygenation conditions and the clearly enhanced binding of nuclear extracts from glioblastoma cell samples exposed to extreme hypoxic conditions confirmed the HIF-1 Western blotting results.

CONCLUSION: NDRG1 represents an additional diagnostic marker for brain tumor detection, due to the role of hypoxia in regulating this gene, and it can represent a potential target for tumor treatment in human glioblastoma. The siRNA method can represent an elegant alternative to modulate the expression of the hypoxia induced NDRG1 gene and can help to monitor the development of the cancer disease treatment outcome through monitoring the expression of this gene in the patients undergoing the different therapeutic treatment alternatives available nowadays.
KW  - Strahlentherapie
KW  - brain cancer
KW  - radiotherapy
KW  - human cancer diseases
KW  - Short dsRNA oligonucleotides
KW  - N-Myc down regulated gene 1
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123385
VL  - 3
IS  - 7
ER  -