DESIGNING HIGH-THROUGHPUT CANCER BIOMARKER MONITORING PLATFORM USING NANOPARTICLES

Developing high throughput cancer biomarker monitoring platform has been a long demand in cancer research. It can enable early diagnosis and help tracking recurrence of disease which will eventually increase patient’s survival rate without deteriorating quality of patient’s life. This will help doctors selectively treat patients and utilize precision medicine Most cancer biomarker monitoring studies take following two approaches; invasive and non-invasive method. First requires introduction of functionalized nanoparticles with an invasive way such as needle injection. It is designed to perform in vivo experiment where nanoparticles circulate in the body and target specific cancer cells of interest. Current obstacles in biomedical imaging for in vivo cancer diagnosis is the synthesis of hydrophilic Quantum Dots (QDs) with emission wavelength in the near-IR, a high quantum yield, stability in water, and relatively small sizes. The optimum wavelength for in vivo optical imaging, taking into account the absorbance from melanin in the epidermis, hemoglobin in blood, and water in tissue, is in the range of 700-900 nm. In this study, we successfully synthesized NIR-QDs that meets all these requirements for in vivo optical imaging. NIR QDs with emission wavelength > 700 nm, 60% QY, and high stability. High quantum yield was maintained for about 100 hours in water. We also studied circulation and retention of QDs in vivo. Fluorescent images showed that after 5 minutes of tail vein injection, QDs traveled throughout whole body and even big veins were easily visible. High fluorescence was maintained up to 100 minutes post injection (p.i.). NIR-QDs mostly cleared out by urine and feces and only 10% accumulated in RES system (especially in liver and spleen) after 24 hours p.i. Non-invasive method is also widely studied because it is more patient friendly, does not require a large amount of tumor tissue, and enables regular monitoring. Targeting cancer specific biomarkers from a collection of patients’ bodily fluids such as urine and blood is actively investigated. For example, about 10 million men take a serum prostate specific antigen (PSA) test for prostate cancer, the second leading cause of cancer death in men in the USA. Due to its high controversy, alternate test methods are developed, including testing genomic biomarkers such as PCA3 and fusion genes. Identifying genetic diversity is important as it can provide insights on disease progression and treatment. In our study, we have tested a panel of prostate cancer genetic biomarkers (AMACR, PCA3, PSMA, TMPRSS2-ERG fusion genes) with oligonucleotide sandwich assay using gold nanoparticles (AuNPs). We established high sensitivity and throughput by controlling oligos conjugated to AuNPs. Using this in vitro test, patient urine samples are tested to find correlation between expression of panel of genetic biomarkers and clinical outcomes. We found that patients with same Gleason score and PSA result showed different TMPRSS2-ERG fusion gene expressions. This indicates that oligonucleotide sandwich assay can provide a very important insight on disease progression that conventional tests could not

Selenoprotein W enhances skeletal muscle differentiation by inhibiting TAZ binding to 14-3-3 protein

AbstractSelenoprotein W (SelW) is expressed in various tissues, particularly in skeletal muscle. We have previously reported that SelW is up-regulated during C2C12 skeletal muscle differentiation and inhibits binding of 14-3-3 to its target proteins. 14-3-3 reduces myogenic differentiation by inhibiting nuclear translocation of transcriptional co-activator with PDZ-binding motif (TAZ). Phosphorylation of TAZ at Ser89 is required for binding to 14-3-3, leading to cytoplasmic retention of TAZ and a delay in myogenic differentiation. Here, we show that myogenic differentiation was delayed in SelW-knockdown C2C12 cells. Down-regulation of SelW also increased TAZ binding to 14-3-3, which eventually resulted in decreasing translocation of TAZ to the nucleus. However, phosphorylation of TAZ at Ser89 was not affected. Although phosphorylation of TAZ at Ser89 was sustained by the phosphatase inhibitor okadaic acid, nuclear translocation of TAZ was increased by ectopic expression of SelW. This result was due to decreased binding of TAZ to 14-3-3. We also found that the interaction between TAZ and MyoD was increased by ectopic expression of SelW. Taken together, these findings strongly demonstrate that SelW enhances C2C12 cell differentiation by inhibiting TAZ binding to 14-3-3

Impact of Body Mass Index on the relationship of epicardial adipose tissue to metabolic syndrome and coronary artery disease in an Asian population

<p>Abstract</p> <p>Background</p> <p>In a previous study, we demonstrated that the thickness of epicardial adipose tissue (EAT), measured by echocardiography, was increased in patients with metabolic syndrome (MS) and coronary artery disease (CAD). Several studies on obese patients, however, failed to demonstrate any relationship between EAT and CAD. We hypothesized that body mass index (BMI) affected the link between EAT and MS and CAD.</p> <p>Methods</p> <p>We consecutively enrolled 643 patients (302 males, 341 females; 59 ± 11 years), who underwent echocardiography and coronary angiography. The EAT thickness was measured on the free wall of the right ventricle at the end of diastole. All patients were divided into two groups: high BMI group, ≥27 kg/m²(n = 165), and non-high BMI group, < 27 kg/m²(n = 478).</p> <p>Results</p> <p>The median and mean EAT thickness of 643 patients were 3.0 mm and 3.1 ± 2.4 mm, respectively. In the non-high BMI group, the median EAT thickness was significantly increased in patients with MS compared to those without MS (3.5 vs. 1.9 mm, p < 0.001). In the high BMI group, however, there was no significant difference in the median EAT thickness between patients with and without MS (3.0 vs. 2.5 mm, p = 0.813). A receiver operating characteristic (ROC) curve analysis predicting MS revealed that the area under the curve (AUC) of the non-high BMI group was significantly larger than that of the high BMI group (0.659 vs. 0.506, p = 0.007). When compared to patients without CAD, patients with CAD in both the non-high and high BMI groups had a significantly higher median EAT thickness (3.5 vs. 1.5 mm, p < 0.001 and 4.0 vs. 2.5 mm, p = 0.001, respectively). However, an ROC curve analysis predicting CAD revealed that the AUC of the non-high BMI group tended to be larger than that of the high BMI group (0.735 vs. 0.657, p = 0.055).</p> <p>Conclusions</p> <p>While EAT thickness was significantly increased in patients with MS and CAD, the power of EAT thickness to predict MS and CAD was stronger in patients with BMI < 27 kg/m². These findings showed that the measurement of EAT thickness by echocardiography might be especially useful in an Asian population with a non-high BMI, less than 27 kg/m².</p

Mild Encephalopathy with Reversible Lesion in the Splenium of the Corpus Callosum and Bilateral Frontal White Matter

A 59-year-old man visited an emergency room due to the sudden onset of severe dysarthria with a drowsy mental status. MRI demonstrated T2 prolongation and restricted diffusion involving the splenium of the corpus callosum and bilateral frontal white matter neurological signs and symptoms were mild, and the recovery was complete within a week. Follow-up MRI performed one month later revealed complete resolution of the lesions. The clinical and radiological courses were consistent with previously reported reversible isolated splenial lesions in mild encephalitis/encephalopathy except for the presence of frontal lesions. This case suggests that such reversible lesions can occur outside the splenium

Sirolimus- Versus Paclitaxel-Eluting Stents for the Treatment of Coronary Bifurcations Results From the COBIS (Coronary Bifurcation Stenting) Registry

ObjectivesWe aimed to compare the long-term clinical outcomes of patients treated with sirolimus-eluting stents (SES) or paclitaxel-eluting stents (PES) for coronary bifurcation lesions.BackgroundThere are limited data regarding comparisons of SES and PES for the treatment of bifurcation lesions.MethodsPatients who received percutaneous coronary intervention for non-left main bifurcation lesions were enrolled from 16 centers in Korea between January 2004 and June 2006. We compared major adverse cardiac events (MACE [cardiac death, myocardial infarction, or target lesion revascularization]) between the SES and PES groups in patients overall and in 407 patient pairs generated by propensity-score matching.ResultsWe evaluated 1,033 patients with bifurcation lesions treated with SES and 562 patients treated with PES. The median follow-up duration was 22 months. Treatment with SES was associated with a lower incidence of MACE (hazard ratio [HR]: 0.53, 95% confidence interval [CI]: 0.32 to 0.89, p < 0.01) and target lesion revascularization (HR: 0.55, 95% CI: 0.31 to 0.97, p = 0.02), but not of cardiac death (HR: 2.77, 95% CI: 0.40 to 18.99, p = 0.62) and cardiac death or myocardial infarction (HR: 0.97, 95% CI: 0.38 to 2.49, p = 0.94). After propensity-score matching, patients with SES still had fewer MACE and target lesion revascularization incidences than did patients with PES (HR: 0.52, 95% CI: 0.30 to 0.91, p = 0.02, and HR: 0.48, 95% CI: 0.25 to 0.91, p = 0.02, respectively). There was no significant difference in the occurrences of stent thrombosis between the groups (0.7% vs. 0.7%, p = 0.94).ConclusionsIn patients with bifurcation lesions, the use of SES resulted in better long-term outcomes than did the use of PES, primarily by decreasing the rate of repeat revascularization. (Coronary Bifurcation Stenting Registry in South Korea [COBIS]; NCT00851526

Randomized Trial of Stents Versus Bypass Surgery for Left Main Coronary Artery Disease 5-Year Outcomes of the PRECOMBAT Study

AbstractBackgroundIn a previous randomized trial, we found that percutaneous coronary intervention (PCI) was not inferior to coronary artery bypass grafting (CABG) for the treatment of unprotected left main coronary artery stenosis at 1 year.ObjectivesThis study sought to determine the 5-year outcomes of PCI compared with CABG for the treatment of unprotected left main coronary artery stenosis.MethodsWe randomly assigned 600 patients with unprotected left main coronary artery stenosis to undergo PCI with a sirolimus-eluting stent (n = 300) or CABG (n = 300). The primary endpoint was a major adverse cardiac or cerebrovascular event (MACCE: a composite of death from any cause, myocardial infarction, stroke, or ischemia-driven target vessel revascularization) and compared on an intention-to-treat basis.ResultsAt 5 years, MACCE occurred in 52 patients in the PCI group and 42 patients in the CABG group (cumulative event rates of 17.5% and 14.3%, respectively; hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 0.84 to 1.90; p = 0.26). The 2 groups did not differ significantly in terms of death from any cause, myocardial infarction, or stroke as well as their composite (8.4% and 9.6%; HR, 0.89; 95% CI, 0.52 to 1.52; p = 0.66). Ischemia-driven target vessel revascularization occurred more frequently in the PCI group than in the CABG group (11.4% and 5.5%, respectively; HR: 2.11; 95% CI: 1.16 to 3.84; p = 0.012).ConclusionsDuring 5 years of follow-up, our study did not show significant difference regarding the rate of MACCE between patients who underwent PCI with a sirolimus-eluting stent and those who underwent CABG. However, considering the limited power of our study, our results should be interpreted with caution. (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease [PRECOMBAT]; NCT00422968