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Chen H.-H.,Head and Neck Surgery | Chen H.-H.,Head and Neck Oncology Group | Chen H.-H.,Chang Gung University | Wang H.-M.,Internal Medicine | And 23 more authors.

The levels of squamous cell carcinoma antigen (SCC-Ag) and C-reactive protein (CRP) can be used to predict tumor invasion, lymph node metastasis, staging and survival in patients with oral cavity cancer. The present study analyzed the relationship between pre-treatment levels of SCC-Ag and CRP in relation to clinicopathological factors in patients with pharyngolaryngeal cancer (PLC) and determined whether elevated levels of CRP and SCC-Ag were associated with tumor metabolic activity via [18F] fluorodeoxyglucose positron emission tomography (FDG-PET). We retrospectively recruited one hundred and six PLC patients between June 2008 and December 2011. All patients received computed tomography (CT)/magnetic resonance imaging (MRI) and FDG-PET staging analyses, and the serum levels of SCC-Ag and CRP in these patients were measured prior to treatment. A SCC-Ag level ≥2.0 ng/ml and a CRP level ≥5.0 mg/L were significantly associated with clinical stage (P<0.001), clinical tumor status (P<0.001), and clinical nodal status (P<0.001). The elevation of both SCC-Ag and CRP levels was correlated with the standardized uptake value (SUV) max of the tumor (≥8.6 mg/L) and lymph nodes (≥5.7 ng/ml) (P = 0.019). The present study demonstrated that the presence of high levels of both pre-treatment SCC-Ag and CRP acts as a predictor of clinical stage, clinical tumor status, and clinical nodal status in patients with PLC. Moreover, elevated levels of SCC-Ag and CRP were associated with a high metabolic rate as well as the proliferative activity measured according to the SUVmax of the tumor and lymph nodes. Therefore, elevated levels of these two factors have the potential to serve as biomarkers for the prediction of tumor aggressiveness in cases of PLC. © 2013 Chen et al. Source

Lin Y.-J.,National Tsing Hua University | Chen Y.-T.,National Tsing Hua University | Hsu S.-N.,National Tsing Hua University | Peng C.-H.,Chang Gung Memorial Hospital | And 5 more authors.

Copy number variation (CNV) has been reported to be associated with disease and various cancers. Hence, identifying the accurate position and the type of CNV is currently a critical issue. There are many tools targeting on detecting CNV regions, constructing haplotype phases on CNV regions, or estimating the numerical copy numbers. However, none of them can do all of the three tasks at the same time. This paper presents a method based on Hidden Markov Model to detect parent specific copy number change on both chromosomes with signals from SNP arrays. A haplotype tree is constructed with dynamic branch merging to model the transition of the copy number status of the two alleles assessed at each SNP locus. The emission models are constructed for the genotypes formed with the two haplotypes. The proposed method can provide the segmentation points of the CNV regions as well as the haplotype phasing for the allelic status on each chromosome. The estimated copy numbers are provided as fractional numbers, which can accommodate the somatic mutation in cancer specimens that usually consist of heterogeneous cell populations. The algorithm is evaluated on simulated data and the previously published regions of CNV of the 270 HapMap individuals. The results were compared with five popular methods: PennCNV, genoCN, COKGEN, QuantiSNP and cnvHap. The application on oral cancer samples demonstrates how the proposed method can facilitate clinical association studies. The proposed algorithm exhibits comparable sensitivity of the CNV regions to the best algorithm in our genome-wide study and demonstrates the highest detection rate in SNP dense regions. In addition, we provide better haplotype phasing accuracy than similar approaches. The clinical association carried out with our fractional estimate of copy numbers in the cancer samples provides better detection power than that with integer copy number states. © 2014 Lin et al. Source

Chen Y.Y.,National Tsing Hua University | Chao C.-C.,National Tsing Hua University | Liu F.-C.,National Tsing Hua University | Hsu P.-C.,National Tsing Hua University | And 6 more authors.

Candida albicans is responsible for a number of life-threatening infections and causes considerable morbidity and mortality in immunocompromised patients. Previous studies of C. albicans pathogenesis have suggested several steps must occur before virulent infection, including early adhesion, invasion, and late tissue damage. However, the mechanism that triggers C. albicans transformation from yeast to hyphae form during infection has yet to be fully elucidated. This study used a systems biology approach to investigate C. albicans infection in zebrafish. The surviving fish were sampled at different post-infection time points to obtain time-lapsed, genome-wide transcriptomic data from both organisms, which were accompanied with in sync histological analyses. Principal component analysis (PCA) was used to analyze the dynamic gene expression profiles of significant variations in both C. albicans and zebrafish. The results categorized C. albicans infection into three progressing phases: adhesion, invasion, and damage. Such findings were highly supported by the corresponding histological analysis. Furthermore, the dynamic interspecies transcript profiling revealed that C. albicans activated its filamentous formation during invasion and the iron scavenging functions during the damage phases, whereas zebrafish ceased its iron homeostasis function following massive hemorrhage during the later stages of infection. Most of the immune related genes were expressed as the infection progressed from invasion to the damage phase. Such global, inter-species evidence of virulence-immune and iron competition dynamics during C. albicans infection could be crucial in understanding control fungal pathogenesis. © 2013 Chen et al. Source

Huang W.-C.,National Health Research Institute | Huang W.-C.,National Central University | Chan S.-H.,National Health Research Institute | Jang T.-H.,National Health Research Institute | And 13 more authors.
Cancer Research

MicroRNAs offer tools to identify and treat invasive cancers. Using highly invasive isogenic oral squamous cell carcinoma (OSCC) cells, established using in vitro and in vivo selection protocols from poorly invasive parental cell populations, we used microarray expression analysis to identify a relative and specific decrease in miR-491-5p in invasive cells. Lower expression of miR-491-5p correlated with poor overall survival of patients with OSCCs. miR- 491-5p overexpression in invasive OSCC cells suppressed their migratory behavior in vitro and lung metastatic behavior in vivo. We defined the G-protein-coupled receptor kinase-interacting protein 1 (GIT1)-as a direct target gene for miR-491-5p control. GIT1 overexpression was sufficient to rescue miR-491-5p-mediated inhibition of migration/invasion and lung metastasis. Conversely, GIT1 silencing phenocopied the ability of miR-491-5p to inhibit migration/invasion and metastasis of OSCC cells. Mechanistic investigations indicated that miR-491-5p overexpression or GIT1 attenuation reduced focal adhesions, with a concurrent decrease in steady-state levels of paxillin, phospho-paxillin, phospho-FAK, EGF/EGFR-mediated extracellular signal-regulated kinase (ERK1/2) activation, and MMP2/9 levels and activities. In clinical specimens of OSCCs, GIT1 levels were elevated relative to paired normal tissues and were correlated with lymph node metastasis, with expression levels of miR-491-5p and GIT1 correlated inversely in OSCCs, where they informed tumor grade. Together, our findings identify a functional axis for OSCC invasion that suggests miR-491-5p and GIT1 as biomarkers for prognosis in this cancer. © 2013 AACR. Source

Tseng J.-R.,Nuclear Medicine and Molecular Imaging Center | Chen K.-Y.,Chang Gung Memorial Hospital at Linkou | Lee M.-H.,Chang Gung Memorial Hospital at Linkou | Huang C.-T.,Chang Gung Memorial Hospital at Linkou | And 2 more authors.

Purpose:The role of FDG PET in the evaluation of patients with sepsis of unknown origin remains unclear. We sought to assess the value of FDG PET/CT in patients with sepsis of unknown cause and to define its priority in this group of subjects.Methods:A total of 53 patients with sepsis of unknown origin underwent FDG PET/CT within two weeks of diagnosis. All of the patients were followed up for at least 3 months after discharge to determine the clinical outcomes. The impact of FDG PET/CT was assessed according to the number of cases who had their treatment modified on the basis of the imaging results. Logistic regression analysis was used to identify the independent predictors of positive FDG PET/CT findings.Results:Of the 53 study patients, 35 (66%) had positive FDG PET/CT findings, and 13 (25%) had their treatment modified on the basis of the imaging results. Logistic regression analysis identified normal serum aspartate aminotransferase (odds ratio [OR] = 6.134; 95% confidence interval [CI] = 1.443-26.076, P = 0.014) and increased serum alkaline phosphatase levels (OR = 5.813; 95% CI = 1.386-24.376, P = 0.016) at diagnosis as independent predictors of positive FDG PET/CT findings. A scoring system using these two covariates was developed, which defined three distinct priority groups for FDG PET/CT imaging.Conclusion:Our findings suggest that FDG PET/CT may be clinically useful for the detection of occult foci of infection in patients with sepsis of unknown origin. © 2013 Tseng et al. Source

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