Precision medicine for cancer patients aims to adopt the most suitable treatment options during diagnosis and treatment of individuals. Detecting circulating tumor cell (CTC) or circulating tumor DNA (ctDNA) in plasma or serum could serve as liquid biopsy, which would be useful for numerous diagnostic applications. Liquid biopsies can help clinicians screen and detect cancer early, stratify patients to the most suitable treatment and real-time monitoring of treatment response and resistance mechanisms in the tumor, evaluate the risk for metastatic relapse, and estimate prognosis.We summarized the advantages and disadvantages of tissue and liquid biopsies.We also further compared and analyzed the advantages and limitations of detecting CTCs, ctDNAs, and exosomes. Furthermore, we reviewed the literature related with the application of serum or plasma CTCs, ctDNAs, and exosomes for diagnosis and prognosis of cancer.We also analyzed their opportunities and challenges as future biomarkers. In the future, liquid biopsies could be used to guide cancer treatment. They could also provide the ideal scheme to personalize treatment in precision medicine.
BackgroundThe plasma protein hemopexin (HPX) exhibits the highest binding affinity to free heme. In vitro experiments and gene-knock out technique have suggested that HPX may have a neuroprotective effect. However, the expression of HPX in the brain was not well elucidated and its expression after cerebral ischemia-reperfusion injury was also poorly studied. Furthermore, no in vivo data were available on the effect of HPX given centrally on the prognosis of focal cerebral ischemia.ResultsIn the present study, we systematically investigated expression of HPX in normal rat brain by immunofluorescent staining. The results showed that HPX was mainly expressed in vascular system and neurons, as well as in a small portion of astrocytes adjacent to the vessels in normal rat brain. Further, we determined the role of HPX in the process of focal cerebral ischemic injury and explored the effects of HPX treatment in a rat model of transient focal cerebral ischemia. After 2 h’ middle cerebral artery occlusion (MCAO) followed by 24 h’ reperfusion, the expression of HPX was increased in the neurons and astrocytes in the penumbra area, as demonstrated by immunohistochemistry and Western blot techniques. Intracerebroventricular injection of HPX at the onset of reperfusion dose-dependently reduced the infarct volumes and improved measurements of neurological function of the rat subjected to transient focal cerebral ischemia. The neuroprotective effects of HPX sustained for up to 7 days after experiments.ConclusionsOur study provides a new insight into the potential neuroprotective role of HPX as a contributing factor of endogenous protective mechanisms against focal cerebral ischemia injury, and HPX might be developed as a potential agent for treatment of ischemic stroke.
Differential activation of various signaling pathways and genes contributes to the tumor-promoting properties of CSCs. Therapeutic targets identified in the analysis may contribute to improving treatment options for patients.
A novel Penicillium oxalicum strain YC-WM1, isolated from activated sludge, was found to be capable of completely degrading 100 mg/L of nicosulfuron within six days when incubated in GSM at 33 °C. Nicosulfuron degradation rates were affected by GSM initial pH, nicosulfuron initial concentration, glucose initial concentration, and carbon source. After inoculation, the medium pH was decreased from 7.0 to 4.5 within one day and remained at around 3.5 during the next few days, in which nicosulfuron degraded quickly. Besides, 100 mg/L of nicosulfuron were completely degraded in GSM medium at pH of 3.5 without incubation after 4 days. So, nicosulfuron degradation by YC-WM1 may be acidolysis. Based on HPLC analysis, GSM medium acidification was due to oxalate accumulation instead of lactic acid and oxalate, which was influenced by different carbon sources and had no relationship to nicosulfuron initial concentration. Furthermore, nicosulfuron broke into aminopyrimidine and pyridylsulfonamide as final products and could not be used as nitrogen source and mycelium didn’t increase in GSM medium. Metabolomics results further showed that nicosulfuron degradation was not detected in intracellular. Therefore, oxalate secretion in GSM medium by strain YC-WM1 led to nicosulfuron acidolysis.
BackgroundInduced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) share many common features, including similar morphology, gene expression and in vitro differentiation profiles. However, genomic stability is much lower in iPSCs than in ESCs. In the current study, we examined whether changes in DNA damage repair in iPSCs are responsible for their greater tendency towards mutagenesis.MethodsMouse iPSCs, ESCs and embryonic fibroblasts were exposed to ionizing radiation (4 Gy) to introduce double-strand DNA breaks. At 4 h later, fidelity of DNA damage repair was assessed using whole-genome re-sequencing. We also analyzed genomic stability in mice derived from iPSCs versus ESCs.ResultsIn comparison to ESCs and embryonic fibroblasts, iPSCs had lower DNA damage repair capacity, more somatic mutations and short indels after irradiation. iPSCs showed greater non-homologous end joining DNA repair and less homologous recombination DNA repair. Mice derived from iPSCs had lower DNA damage repair capacity than ESC-derived mice as well as C57 control mice.ConclusionsThe relatively low genomic stability of iPSCs and their high rate of tumorigenesis in vivo appear to be due, at least in part, to low fidelity of DNA damage repair.
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