5 research outputs found
Paying the Toll in Nuclear Reprogramming
The ability to reverse lineage-committed cells toward pluripotent stem cells or to another cell type is one of the ultimate goals in regenerative medicine. We recently discovered that activation of innate immunity, through Toll-like receptor 3, is required during this conversion of cell fate by causing global changes in the expression and activity of epigenetic modifiers. Here we discuss, in a comprehensive manner, the recent studies on the role of innate immunity in nuclear reprogramming and transdifferentiation, the underlying mechanisms, and its role in regenerative medicine
Targeted serum metabolite profiling and sequential metabolite ratio analysis for colorectal cancer progression monitoring
Colorectal cancer (CRC) is one of the most prevalent cancers worldwide and a major cause of human morbidity and mortality. In addition to early detection, close monitoring of disease progression in CRC can be critical for patient prognosis and treatment decisions. Efforts have been made to develop new methods for improved early detection and patient monitoring; however, research focused on CRC surveillance for treatment response and disease recurrence using metabolomics has yet to be reported. In this proof of concept study, we applied a targeted liquid chromatography tandem mass spectrometry (LC-MS/MS) metabolic profiling approach focused on sequential metabolite ratio analysis of serial serum samples to monitor disease progression from 20 CRC patients. The use of serial samples reduces patient to patient metabolic variability. A partial least squares-discriminant analysis (PLS-DA) model using a panel of five metabolites (succinate, N2, N2-dimethylguanosine, adenine, citraconic acid, and 1-methylguanosine) was established, and excellent model performance (sensitivity = 0.83, specificity = 0.94, area under the receiver operator characteristic curve (AUROC) = 0.91 was obtained, which is superior to the traditional CRC monitoring marker carcinoembryonic antigen (sensitivity = 0.75, specificity = 0.76, AUROC = 0.80). Monte Carlo cross validation was applied, and the robustness of our model was clearly observed by the separation of true classification models from the random permutation models. Our results suggest the potential utility of metabolic profiling for CRC disease monitoring
Colorectal Cancer Detection Using Targeted Serum Metabolic Profiling
Colorectal cancer
(CRC) is one of the most prevalent and deadly
cancers in the world. Despite an expanding knowledge of its molecular
pathogenesis during the past two decades, robust biomarkers to enable
screening, surveillance, and therapy monitoring of CRC are still lacking.
In this study, we present a targeted liquid chromatography–tandem
mass spectrometry-based metabolic profiling approach for identifying
biomarker candidates that could enable highly sensitive and specific
CRC detection using human serum samples. In this targeted approach,
158 metabolites from 25 metabolic pathways of potential significance
were monitored in 234 serum samples from three groups of patients
(66 CRC patients, 76 polyp patients, and 92 healthy controls). Partial
least-squares–discriminant analysis (PLS–DA) models
were established, which proved to be powerful for distinguishing CRC
patients from both healthy controls and polyp patients. Receiver operating
characteristic curves generated based on these PLS–DA models
showed high sensitivities (0.96 and 0.89, respectively, for differentiating
CRC patients from healthy controls or polyp patients), good specificities
(0.80 and 0.88), and excellent areas under the curve (0.93 and 0.95).
Monte Carlo cross validation was also applied, demonstrating the robust
diagnostic power of this metabolic profiling approach