A Joint Model Based on Post-Treatment Longitudinal Prognostic Nutritional Index to Predict Survival in Nasopharyngeal Carcinoma.

BACKGROUND: a low PNI in patients with NPC is linked to poor survival, but prior studies have focused on single-timepoint measurements. Our study aims to employ joint modeling to analyze longitudinal PNI data from each routine visit, exploring its relationship with overall survival. METHODS: In this retrospective study using data from the Chang Gung Research Database (2007-2019), we enrolled patients with NPC undergoing curative treatment. We analyzed the correlation between patient characteristics, including the PNI, and overall survival. A joint model combining a longitudinal sub-model with a time-to-event sub-model was used to further evaluate the prognostic value of longitudinal PNI. RESULTS: A total of 2332 patient were enrolled for the analysis. Separate survival analyses showed that longitudinal PNI was an independent indicator of a reduced mortality risk (adjusted HR 0.813; 95% CI, 0.805 to 0.821). Joint modeling confirmed longitudinal PNI as a consistent predictor of survival (HR 0.864; 95% CI, 0.850 to 0.879). An ROC analysis revealed that a PNI below 38.1 significantly increased the risk of 90-day mortality, with 90.0% sensitivity and 89.6% specificity. CONCLUSIONS: Longitudinal PNI data independently predicted the overall survival in patients with NPC, significantly forecasting 90-day survival outcomes. We recommend routine PNI assessments during each clinic visit for these patients.

On the mechanism of carrier recombination in downsized blue micro-LEDs.

The mechanism of carrier recombination in downsized µ-LED chips from 100 × 100 to 10 × 10 µm2 on emission performance was systemically investigated. All photolithography processes for defining the µ-LED pattern were achieved by using a laser direct writing technique. This maskless technology achieved the glass-mask-free process, which not only can improve the exposure accuracy but also save the development time. The multi-functional SiO2 film as a passivation layer successfully reduced the leakage current density of µ-LED chips compared with the µ-LED chips without passivation layer. As decreasing the chip size to 10 × 10 µm2, the smallest chip size exhibited the highest ideality factor, which indicated the main carrier recombination at the high-defect-density zone in µ-LED chip leading to the decreased emission performance. The blue-shift phenomenon in the electroluminescence spectrum with decreasing the µ-LED chip size was due to the carrier screening effect and the band filling effect. The 10 × 10 µm2 µ-LED chip exhibited high EQE values in the high current density region with a less efficiency droop, and the max-EQE value was 18.8%. The luminance of 96 × 48 µ-LED array with the chip size of 20 × 20 µm2 exhibited a high value of 516 nits at the voltage of 3 V.

Formation of ZnO/Zn0.5Cd0.5Se Alloy Quantum Dots in the Presence of High Oleylamine Contents.

To the best of our knowledge, this report presents, for the first time, the schematic of the possible chemical reaction for a one-pot synthesis of Zn0.5Cd0.5Se alloy quantum dots (QDs) in the presence of low/high oleylamine (OLA) contents. For high OLA contents, high-resolution transmission electron microscopy (HRTEM) results showed that the average size of Zn0.5Cd0.5Se increases significantly from 4 to 9 nm with an increasing OLA content from 4 to 10 mL. First, [Zn(OAc)2]-OLA complex can be formed by a reaction between Zn(OAc)2 and OLA. Then, Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) data confirmed that ZnO is formed by thermal decomposition of the [Zn(OAc)2]-OLA complex. The results indicated that ZnO grew on the Zn0.5Cd0.5Se surface, thus increasing the particle size. For low OLA contents, HRTEM images were used to estimate the average sizes of the Zn0.5Cd0.5Se alloy QDs, which were approximately 8, 6, and 4 nm with OLA loadings of 0, 2, and 4 mL, respectively. We found that Zn(OAc)2 and OLA could form a [Zn(OAc)2]-OLA complex, which inhibited the growth of the Zn0.5Cd0.5Se alloy QDs, due to the decreasing reaction between Zn(oleic acid)2 and Se2-, which led to a decrease in particle size.

Celecoxib induces p53-PUMA pathway for apoptosis in human colorectal cancer cells.

Celecoxib, a clinical non-steroidal anti-inflammatory drug, displays anticarcinogenic and chemopreventive activities in human colorectal cancers, although the mechanisms of apoptosis by celecoxib are poorly understood. The existence of functional p53 but not securin in colorectal cancer cells was higher on the induction of cytotoxicity than the p53-mutational colorectal cancer cells following celecoxib treatment. The p53-wild type HCT116 cells were more susceptible to increase approximately 25% cell death than the p53-null HCT116 cells after treatment with 100 microM celecoxib for 24 h. Transfection with a small interfering RNA of p53 reduced the celecoxib-induced cytotoxicity in the RKO (p53-wild type) colorectal cancer cells. Celecoxib (80-100 microM for 24 h) significantly increased total p53 proteins and the phosphorylated p53 proteins at serine-15, -20, -46, and -392 in RKO cells. However, the phospho-p53 (serine-15, -20, and -392) proteins were presented on the nuclei of cells but the phospho-p53 (serine-46) protein was located on the cytoplasma of apoptotic cells following treatment with celecoxib. Interestingly, the p53 up-regulated modulator of apoptosis (PUMA) protein, which located on the mitochondria, was induced by celecoxib in the p53-functional colorectal cancer cells but not in the p53-mutational cells. Together, this study provides the first time that celecoxib induces the various phosphorylated sites of p53 and activates p53-PUMA pathway, which potentiates the apoptosis induction in human colorectal cancer cells.

Combination of cyclooxygenase-2 inhibitors and oxaliplatin increases the growth inhibition and death in human colon cancer cells.

The cyclooxygenase-2 (COX-2) protein is highly expressed in a variety of human cancers and has been reported to promote tumor growth. Non-steroidal anti-inflammatory drugs such as etodolac and celecoxib have been shown to inhibit COX-2 activity and may play a role in the chemoprevention of cancer. Oxaliplatin is a third-generation platinum compound that exhibits a different spectrum of activity compared with cisplatin. Other cisplatin-resistant tumors can still respond to oxaliplatin. However, the anticancer ability of the combination of COX-2 inhibitors and oxaliplatin is still unknown. In this study, we investigated the effects of combination of COX-2 inhibitors and oxaliplatin on the cell growth and survival in human colon cancer cells. Treatments with etodolac (0.3-0.5 mM) or celecoxib (20-80 microM) for 24 h concentration-dependently induced the cytotoxicity in the RKO colon carcinoma cells. Etodolac and celecoxib did not alter the COX-2 protein levels but inhibited its enzyme activity to reduce prostaglandin E2 production. Furthermore, the cell survival was concentration-dependently decreased following oxaliplatin (1-100 microM, 24 h) treatment. Combination of oxaliplatin and etodolac additively increased the death and growth inhibition of RKO cells. Survivin, an inhibitor protein of apoptosis, mediates anti-apoptosis and promotes cell division in cancer cells. Oxaliplatin or COX-2 inhibitors significantly decreased the levels of survivin proteins. Moreover, survivin proteins were markedly diminished following co-treatment with oxaliplatin and etodolac. Together, this is the first report that combination of COX-2 inhibitors and oxaliplatin can increase the reduction of survivin protein expression, growth inhibition, and death in human colon cancer cells.

Activation of p38 mitogen-activated protein kinase by celecoxib oppositely regulates survivin and gamma-H2AX in human colorectal cancer cells.

Cancer cells express survivin that facilitates tumorigenesis. Celecoxib has been shown to reduce human colorectal cancers. However, the role and regulation of survivin by celecoxib in colorectal carcinoma cells remain unclear. Treatment with 40-80 muM celecoxib for 24 h induced cytotoxicity and proliferation inhibition via a concentration-dependent manner in RKO colorectal carcinoma cells. Celecoxib blocked the survivin protein expression and increased the phosphorylation of H2AX at serine-193 (gamma-H2AX). The survivin gene knockdown by transfection with a survivin siRNA revealed that the loss of survivin correlated with the expression of gamma-H2AX. Meanwhile, celecoxib increased caspase-3 activation and apoptosis. Celecoxib activated the phosphorylation of p38 mitogen-activated protein (MAP) kinase. The phosphorylated proteins of p38 MAP kinase and gamma-H2AX were observed in the apoptotic cells. SB203580, a specific p38 MAP kinase inhibitor, protected the survivin protein expression and decreased the levels of gamma-H2AX and apoptosis in the celecoxib-exposed cells. The blockade of survivin expression increased the celecoxib-induced cytotoxicity; conversely, overexpression of survivin by transfection with a survivin-expressing vector raised the cancer cell proliferation and resisted the celecoxib-induced cell death. Our results provide for the first time that p38 MAP kinase participates in the down-regulation of survivin and subsequently induces the activation of gamma-H2AX for mediating apoptosis following treatment with celecoxib in human colorectal cancer cells.