Multiple myeloma-associated chromosomal translocation activates orphan snoRNA ACA11 to suppress oxidative stress

10.1172/JCI63051Journal of Clinical Investigation12282793-2806JCIN

Fibroblast growth factor 19 expression correlates with tumor progression and poorer prognosis of hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Although fibroblast growth factor 19 (FGF19) can promote liver carcinogenesis in mice, its involvement in human hepatocellular carcinoma (HCC) has not been well investigated. FGF19, a member of the FGF family, has unique specificity for its receptor FGFR4. This study aimed to clarify the involvement of FGF19 in the development of HCC.</p> <p>Methods</p> <p>We investigated human FGF19 and FGFR4 expression in 40 hepatocellular carcinoma specimens using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) analysis and immunohistochemistry. Moreover, we examined the expression and the distribution of FGF19 and FGFR4 in 5 hepatocellular carcinoma cell lines (HepG2, HuH7, HLE, HLF, and JHH7) using RT-PCR and immunohistochemistry. To test the role of the FGF19/FGFR4 system in tumor progression, we used recombinant FGF19 protein and small interfering RNA (siRNA) of <it>FGF19 </it>and <it>FGFR4 </it>to regulate their concentrations.</p> <p>Results</p> <p>We found that FGF19 was significantly overexpressed in HCCs as compared with corresponding noncancerous liver tissue (<it>P </it>< 0.05). Univariate and multivariate analyses revealed that the tumor <it>FGF19 </it>mRNA expression was an independent prognostic factor for overall and disease-free survival. Moreover, we found that the FGF19 recombinant protein could increase the proliferation (<it>P </it>< 0.01, <it>n </it>= 12) and invasion (<it>P </it>< 0.01, <it>n </it>= 6) capabilities of human hepatocellular carcinoma cell lines and inhibited their apoptosis (<it>P </it>< 0.01, <it>n </it>= 12). Inversely, decreasing <it>FGF19 </it>and <it>FGFR4 </it>expression by siRNA significantly inhibited proliferation and increased apoptosis in JHH7 cells (<it>P </it>< 0.01, <it>n </it>= 12). The postoperative serum FGF19 levels in HCC patients was significantly lower than the preoperative levels (<it>P </it>< 0.01, <it>n </it>= 29).</p> <p>Conclusions</p> <p>FGF19 is critically involved in the development of HCCs. Targeting FGF19 inhibition is an attractive potential therapeutic strategy for HCC.</p

Inhibitor-Sensitive FGFR1 Amplification in Human Non-Small Cell Lung Cancer

Background Squamous cell lung carcinomas account for approximately 25% of new lung carcinoma cases and 40,000 deaths per year in the United States. Although there are multiple genomically targeted therapies for lung adenocarcinoma, none has yet been reported in squamous cell lung carcinoma. Methodology/Principal Findings Using SNP array analysis, we found that a region of chromosome segment 8p11-12 containing three genes–WHSC1L1, LETM2, and FGFR1–is amplified in 3% of lung adenocarcinomas and 21% of squamous cell lung carcinomas. Furthermore, we demonstrated that a non-small cell lung carcinoma cell line harboring focal amplification of FGFR1 is dependent on FGFR1 activity for cell growth, as treatment of this cell line either with FGFR1-specific shRNAs or with FGFR small molecule enzymatic inhibitors leads to cell growth inhibition. Conclusions/Significance These studies show that FGFR1 amplification is common in squamous cell lung cancer, and that FGFR1 may represent a promising therapeutic target in non-small cell lung cancer.Novartis Pharmaceuticals CorporationAmerican Lung AssociationUniting Against Lung CancerSara Thomas Monopoli FundSeaman FoundationIndia. Dept. of BiotechnologyNational Lung Cancer Partnershi

Membentuk Kepercayaan Konsumen untuk Meningkatkan Keputusan Pembelian

Penelitian ini bertujuan untuk menguji dan menganalisis pengaruh kesadaran merek dan citra merek untuk membentuk kepercayaan merek dan dampaknya terhadap peningkatan keputusan pembelian Biskuit Khong Guan di Kota Ambon. Populasi dalam penelitian ini masyarakat Kota Ambon yang pernah membeli dan mengonsumsi biskuit Khong Guan. Sampel dalam penelitian ini berjumlah 100 responden. Kuesioner sebagai alat pengumpul data dan non probabilty sampling sebagai teknik pengambilan sampel dengan metode purposive sampling. Dalam penelitian ini teknik analisis data menggunakan pendekatan Partial Least Square (PLS). Hasil penelitian menunjukan bahwa semua hipotesis yang diajukan dapat diterima. &nbsp

Proto-ubiquitin: A Bayesian prediction of an ancient protein during the prokaryotic-eukaryotic transition

Only recently have biologists been able to apply mathematical and biochemical tools to preview lifestyles of ancient life forms and travel back in time. In this paper, we describe an ancestral reconstruction of ubiquitin to determine its molecular properties during the rise of the eukaryotes. Although ubiquitin is one of the most conserved proteins in eukaryotes, no ubiquitin homolog has been found in prokaryotic genomes sequenced thus far. In an attempt to derive the ancestral ubiquitin, or proto-ubiquitin (proto-Ub), we applied Bayesian statistical theory to estimate posterior probabilities of protein sequences from a minimum evolution tree of 30 extant species. The inferred ancestral sequence was 100% homologous with the ubiquitin of Brugia malayi, a parasitic nematode. Among its 76 amino acids, only nine residues have undergone amino acid modification. As no major structural and functional changes happened during the evolution of ubiquitin, we hypothesize that the stressful conditions that led to the creation of this gene after the Great Oxidation Event 2.4 billion years ago may have already been buffered to date