A novel quantitative model based on gross tumor volume corresponding to anatomical distribution measured with multidetector computed tomography to determine the resectability of non­distant metastatic esophageal squamous cell carcinoma.

It is important to accurately determine the resectability of thoracic esophageal squamous cell carcinoma (ESCC) for treatment decision-making. Previous studies have revealed that the CT-derived gross tumor volume (GTV) is associated with the staging of ESCC. The present study aimed to explore whether the anatomical distribution-based GTV of non-distant metastatic thoracic ESCC measured using multidetector computed tomography (MDCT) could quantitatively determine the resectability. For this purpose, 473 consecutive patients with biopsy-confirmed non-distant metastatic thoracic ESCC who underwent contrast-enhanced CT were randomly divided into a training cohort (TC; 376 patients) and validation cohort (VC; 97 patients). GTV was retrospectively measured using MDCT. Univariate and multivariate analyses were performed to identify the determinants of the resectability of ESCC in the TC. Receiver operating characteristic (ROC) analysis was performed to clarify whether anatomical distribution-based GTV could help quantitatively determinate resectability. Unweighted Cohen's Kappa tests in VC were used to assess the performance of the previous models. Univariate analysis demonstrated that sex, anatomic distribution, cT stage, cN stage and GTV were related to the resectability of ESCC in the TC (all P<0.05). Multivariate analysis revealed that GTV [P<0.001; odds ratio (OR) 1.158] and anatomic distribution (P=0.027; OR, 1.924) were independent determinants of resectability. ROC analysis revealed that the GTV cut-offs for the determination of the resectability of the upper, middle and lower thoracic portions were 23.57, 22.89 and 22.58 cm3, respectively, with areas under the ROC curves of >0.9. Unweighted Cohen's Kappa tests revealed an excellent performance of the ROC models in the upper, middle and lower thoracic portions with Cohen k-values of 0.913, 0.879 and 0.871, respectively. On the whole, the present study demonstrated that GTV and the anatomic distribution of non-distant metastatic thoracic ESCC may be independent determinants of resectability, and anatomical distribution-based GTV can effectively be used to quantitatively determine resectability.

Gross tumor volume of adenocarcinoma of esophagogastric junction corresponding to cT and cN stages measured with computed tomography to quantitatively determine resectabiliy: A case control study.

Purpose: To determine whether gross tumor volume (GTV) of adenocarcinoma of esophagogastric junction (AEG) corresponding to cT and cN stages measured on CT could help quantitatively determine resectability. Materials and methods: 343 consecutive patients with AEG, including 279 and 64 randomly enrolled in training cohort (TC) and validation cohort (VC), respectively, underwent preoperative contrast-enhanced CT. Univariate and multivariate analyses for TC were performed to determine factors associated with resectability. Receiver operating characteristic (ROC) analyses were to determine if GTV corresponding to cT and cN stages could help determine resectability. For VC, Cohen's Kappa tests were to assess performances of the ROC models. Results: cT stage, cN stage and GTV were independently associated with resectability of AEG with odds ratios of 4.715, 4.534 and 1.107, respectively. For differentiating resectable and unresectable AEG, ROC analyses showed that cutoff GTV of 32.77 cm3 in stage cT1-4N0-3 with an area under the ROC curve (AUC) of 0.901. Particularly, cutoffs of 27.67 and 32.77 cm3 in stages cT3 and cT4 obtained AUC values of 0.860 and 0.890, respectively; and cutoffs of 27.09, 33.32 and 37.39 cm3 in stages cN1, cN2 and cN3 obtained AUC values of 0.852, 0.821 and 0.902, respectively. In VC, Cohen's Kappa tests verified that the ROC models had good performance in distinguishing between resectable and unresectable AEG (all Cohen's K values > 0.72). Conclusions: GTV, cT and cN stages could be independent determinants of resectability of AEG. And GTV corresponding to cT and cN stages can help quantitatively determine resectability.

A quantitative model based on gross tumor volume of gastric adenocarcinoma corresponding to N-stage measured at multidetector computed tomography for preoperative determination of resectability: A case control study.

Purpose: To develop and validate a quantitative model based on gross tumor volume (GTV) of gastric adenocarcinoma (GA) corresponding to N-stage measured at multidetector computed tomography (CT) for preoperative determination of resectability. Materials and methods: 493 consecutive patients with confirmed GA undergoing contrast-enhanced CT two weeks before treatments were randomly enrolled into the training cohort (TC, n = 271), internal validation cohort (IVC, n = 107) and external validation cohort (EVC, n = 115). GTV was measured on CT by multiplying sums of all tumor areas by section thickness. In TC, univariate and multivariate analyses were performed to select factors associated with resectability. Receiver operating characteristic (ROC) analysis was to determine if N-stage based GTV could identify resectability. In IVC and EVC, unweighted Cohen's Kappa tests were to evaluate performances of the ROC models. Results: According to univariate analysis, age, cT stage, cN stage and GTV were related to resectability in TC (all P-values < 0.05), and multivariate analysis suggested that cN stage and GTV were independent risk factors with odds ratios of 1.594 (95% confidence interval [CI]: 1.105-2.301) and 1.055 (95%CI: 1.035-1.076), respectively. ROC analysis in TC revealed the cutoffs of 21.81, 21.70 and 36.93 cm3 to differentiate between resectable and unresectable cancers in stages cN0-3, cN2 and cN3 with areas under the curves of more than 0.8, respectively, which was validated in IVC and EVC with average Cohen k-values of more than 0.72. Conclusions: GTV and cN stage can be independent risk factors of unresectable GA, and N-stage based GTV can help determine resectability.

Apparent diffusion coefficient derived from diffusion-weighted imaging to differentiate between tumor, tumor-adjacent and tumor-distant tissues in resectable rectal adenocarcinoma.

PURPOSE: To evaluate feasibility of apparent diffusion coefficient (ADC) at different b-values to differentiate between tumor, tumor-adjacent and tumor-distant tissues in rectal adenocarcinoma (RA). MATERIALS AND METHODS: Seventy consecutive patients with RA undergoing preoperative diffusion-weighted imaging were retrospectively enrolled. ADCs of tumor, proximal tumor-adjacent tissue (PTA) and tumor-distant tissue (PTD), and distal tumor-adjacent tissue (DTA) and tumor-distant tissue (DTD) were calculated with b-values of 0 and 800 sec/mm2, 0 and 1000 sec/mm2, 0 and 1500 sec/mm2, and multiple b-values of 0, 50, 100, 800, 1000 and 1500 sec/mm2. Statistical analysis was performed to determine feasibility of ADC to differentiate between pairwise tissues. RESULTS: Mean ADC of tumor was lower than those of PTA, PTD, DTA and DTD; and mean ADCs of PTA and DTA were lower than those of PTD and DTD at all b-values, respectively (all P-values < 0.001). ADC cut-offs of 1.089 × 10-3 mm2/sec (b = 0, 1000 sec/mm2) or 1.215 × 10-3 mm2/sec (b = 0, 800 sec/mm2), and 1.142 × 10-3 mm2/sec (b = 0, 1000 sec/mm2) or 0.995 × 10-3 mm2/sec (b = 0, 1500 sec/mm2) achieved excellent performance in differentiating tumor from PTA or PTD, and tumor from DTA or DTD (area under receiver operating characteristic curves [AUCs]: 0.813 or 0.952, and 0.970 or 0.996), respectively. ADC cut-offs of 1.625 × 10-3 mm2/sec (b = 0, 800 sec/mm2), and 1.165 × 10-3 mm2/sec (b = 0, 1500 sec/mm2) could differentiate PTA from PTD, and DTA from DTD (AUCs: 0.709 and 0.673), respectively. CONCLUSION: ADC can help differentiate between tumor, tumor-adjacent and tumor-distant tissues in RA.

Omeprazole inhibits α-glucosidase activity and the formation of nonenzymatic glycation products: Activity and mechanism.

In this study, the inhibitory effect and mechanism of omeprazole on α-glucosidase and nonenzymatic glycation were investigated in vitro by using multi-spectroscopic methods and molecular docking. Enzyme kinetic results showed that omeprazole inhibited α-glucosidase in a reversible and noncompetitive manner (IC50= 0.595 ± 0.003 mM). The results from fluorescence quenching and thermomechanical analyses signified that omeprazole reduced the fluorescence intensity of α-glucosidase by forming an omeprazole-α-glucosidase complex primarily driven by hydrogen bonds. Molecular docking further confirmed that hydrogen bonds and hydrophobic forces were the major driving forces for omeprazole binding to α-glucosidase. The nonenzymatic glycation assays revealed that omeprazole had a moderate inhibition against the formation of fructosamine, dicarbonyl compounds, and advanced glycation end products (AGEs). This study provides a new inhibitor of both α-glucosidase and nonenzymatic glycation and provides a practicable candidate for treating diabetes and its complications.

Tumor Stage-Based Gross Tumor Volume of Resectable Esophageal Squamous Cell Carcinoma Measured on CT: Association With Early Recurrence After Esophagectomy.

OBJECTIVE: To investigate relationship of tumor stage-based gross tumor volume (GTV) of esophageal squamous cell carcinoma (ESCC) measured on computed tomography (CT) with early recurrence (ER) after esophagectomy. MATERIALS AND METHODS: Two hundred and four consecutive patients with resectable ESCC including 159 patients enrolled in the training cohort (TC) and 45 patients in validation cohort (VC) underwent contrast-enhanced CT less than 2 weeks before esophagectomy. GTV was retrospectively measured by multiplying sums of all tumor areas by section thickness. For the TC, univariate and multivariate analyses were performed to determine factors associated with ER. Mann-Whitney U test was conducted to compare GTV in patients with and without ER. Receiver operating characteristic (ROC) analysis was performed to determine if tumor stage-based GTV could predict ER. For the VC, unweighted Cohen's Kappa tests were used to evaluate the performances of the previous ROC predictive models. RESULTS: ER occurred in 63 of 159 patients (39.6%) in the TC. According to the univariate analysis, histologic differentiation, cT stage, cN stage, and GTV were associated with ER after esophagectomy (all P-values < 0.05). Multivariate analysis revealed that cT stage and GTV were independent risk factors with hazard ratios of 3.382 [95% confidence interval (CI): 1.533-7.459] and 1.222 (95% CI: 1.125-1.327), respectively (all P-values < 0.05). Mann-Whitney U tests showed that GTV could help differentiate between ESCC with and without ER in stages cT1-4a, cT2, and cT3 (all P-values < 0.001), and the ROC analysis demonstrated the corresponding cutoffs of 13.31, 17.22, and 17.83 cm3 with areas under the curve of more than 0.8, respectively. In the VC, the Kappa tests validated that the ROC predictive models had good performances for differentiating between ESCC with and without ER in stages cT1-4a, cT2, and cT3 with Cohen k of 0.696 (95% CI, 0.498-0.894), 0.733 (95% CI, 0.386-1.080), and 0.862 (95% CI, 0.603-1.121), respectively. CONCLUSION: GTV and cT stage can be independent risk factors of ER in ESCC after esophagectomy, and tumor stage-based GTV measured on CT can help predict ER.

Effect of ascorbic acid on tyrosinase and its anti-browning activity in fresh-cut Fuji apple.

Tyrosinase (polyphenol oxidase) is the key enzyme of enzymatic browning in fruits and vegetables. In this research, the impact of ascorbic acid on tyrosinase and its anti-browning effect on fresh-cut Fuji apple were investigated. Ascorbic acid had a dual effect on tyrosinase with a half inhibitory concentration (IC50 ) of 13.40 ± 0.05 µM. Fluorescence assay demonstrated that ascorbic acid interacted with tyrosinase in a dynamic contaction caused by Förster's resonance energy transfer (FRET) and induced a conformational change of the enzyme. Thermodynamic analysis, copper interaction, and molecular docking further confirmed that ascorbic acid could chelate the copper ions located in active center and interact with amino acid residues of tyrosinase via hydrophobic interaction. In addition, ascorbic acid prevented the browning of fresh-cut apples by increasing APX activity and inhibiting PPO and POD activities which reduce the oxidation of total phenolics and flavonoids. PRACTICAL APPLICATIONS: The present study demonstrated that ascorbic acid had a strong inhibitory activity against tyrosinase (IC50 = 13.40 ± 0.05 µM) and anti-browning activity against fresh-cut Fuji apple. It could delay the browning degree of apple juice, increase APX activity, inhibit PPO and POD activities, and reduce the oxidation of total phenolics and flavonoids. These findings provided a basis for the feasible application of ascorbic acid on the preservation of fruits.

5-Methoxy-2-mercaptobenzimidazole as an efficient inhibitor on tyrosinase: Inhibitory activity and mechanism.

In this study, 5-methoxy-2-mercaptobenzimidazole (5-M-2-MB) was confirmed as an efficient tyrosinase inhibitor by methods of enzyme kinetic, fluorescence quenching, ANS-binding, thermodynamics, energy transfer, and molecular docking in combination. The results proved that 5-M-2-MB significantly inhibited the tyrosinase (IC50 = 60 ± 2 nM) in a reversible and competitive way with the Ki value of 80 ± 1 nM. It quenched the intrinsic fluorescence of tyrosinase through a static mechanism, and caused conformational change of the enzyme by increasing the hydrophobic region. Moreover, this compound could bind to tyrosinase and form 5-M-2-MB-tyrosinase complex by hydrogen bond and hydrophobic interaction. The interactions were generated between 5-M-2-MB and specific amino acid residues (Trp-358, Thr-308, Glu-356, and Asp-357) located on the A chain of tyrosinase. Therefore, this study would offer a theoretical foundation for developing the new tyrosinase inhibitor.

Inhibitory potential of 4-hexylresorcinol against α-glucosidase and non-enzymatic glycation: Activity and mechanism.

Inhibition of α-glucosidase as well as non-enzymatic glycation is thought as an effective method for treating type-2 diabetes mellitus. In this study, we investigated the inhibitory potential and mechanism of 4-hexylresorcinol against α-glucosidase and non-enzymatic glycation by using multispectroscopic analyses and molecular docking. The results of enzyme kinetics showed that 4-hexylresorcinol reversibly inhibited α-glucosidase activity in a noncompetitive way. Fluorescence quenching then revealed that it increased the hydrophobicity of α-glucosidase and changed the conformation of the enzyme by forming the α-glucosidase-hexylresorcinol complex. Thermodynamic analysis and molecular docking further demonstrated that the inhibition of 4-hexylresorcinol on the α-glucosidase was mainly dependent on hydrogen bond and hydrophobic interaction. Moreover, the 4-hexylresorcinol moderately inhibited the formation of fructosamine, and strongly suppressed the generation of α-dicarbonyl compounds and advanced glycation end products (AGEs). The interaction between 4-hexylresorcinol and bovine serum albumin was mainly driven by hydrophobic interaction. This study showed a novel inhibitor of α-glucosidase as well as non-enzymatic glycation, and provided a drug candidate for the prevention and treatment of type-2 diabetes.

Encodable multiple-fluorescence CdTe@carbon nanoparticles from nanocrystal/colloidal crystal guest-host ensembles.

We report herein the controllable generation of encodable multi-fluorescence CdTe@carbon nanoparticles (CdTe@C NPs) via the pyrolysis of quantum dot/photonic crystal (QD/PC) guest-host ensembles. The precursors of CdTe/poly(styrene-co-glycidylmethacrylate) (PS-co-PGMA) QD/PC guest-host ensembles were initially formed via the assembly of epoxy groups of PCs and carboxyl groups on the surface of CdTe QDs, followed by a pyrolysis process to generate CdTe@C NPs. The as-prepared CdTe@C NPs not only integrate the optical properties for both the carbon and CdTe QD constituents, but also enable an impressive enhancement of the fluorescence lifetime for CdTe QDs. The multifarious fluorescent spectra coding for CdTe@C NPs was further generated through regulating the embedded sizes or concentrations of CdTe QDs and the excitation wavelength, and their applications in DNA detection and luminescent patterns were achieved.

Facile access to versatile fluorescent carbon dots toward light-emitting diodes.

We report the facile synthesis of carbon dots with tunable fluorescence from unzipping of photonic crystals and their application in LEDs, which may provide an insight into the creation of multifunctional carbon dots adapted for various applications such as in optoelectronics, sensing, or bioimaging.