Plasma mRNA expression levels of BRCA1 and TS as potential predictive biomarkers for chemotherapy in gastric cancer

OBJECTIVE: Personalized chemotherapy based on predictive biomarkers can maximize efficacy. However, tumor tissue obtained at the time of initial diagnosis will not reflect genetic alterations observed at the time of disease progression. We have examined whether plasma mRNA levels can be a surrogate for tumor levels in predicting chemosensitivity. METHODS: In 150 gastric cancer patients, mRNA levels of BRCA1 and TS were assessed in plasma and paired tumor tissue. The Mann-Whitney U-test was used to compare mRNA expression levels between tumor samples exhibiting in vitro sensitivity or resistance to docetaxel and pemetrexed. All statistical tests were two-sided. RESULTS: There were significant correlations between plasma and tumor mRNA levels of BRCA1 (rho = 0.696, P < 0.001) and TS (rho = 0.620, P < 0.001). BRCA1 levels in plasma (docetaxel-sensitive: 1.25; docetaxel-resistant: 0.50, P < 0.001) and tumor (docetaxel-sensitive: 8.81; docetaxel-resistant: 4.88, P < 0.001) were positively associated with docetaxel sensitivity. TS levels in plasma (pemetrexed-sensitive: 0.90; pemetrexed-resistant: 1.82, P < 0.001) and tumor (pemetrexed-sensitive: 6.56; pemetrexed-resistant: 16.69, P < 0.001) were negatively associated with pemetrexed sensitivity. CONCLUSIONS: Plasma mRNA expression levels mirror those in the tumor and may have a promising role as potential predictive biomarkers for chemotherapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-014-0355-2) contains supplementary material, which is available to authorized users

Influence of the binder jetting process parameters and binder liquid composition on the relevant attributes of 3D-printed tablets

Binder jetting has the potential to revolutionize the way we produce medicine. However, tablets produced by binder jetting technology can be quite fragile and hard to handle. In this study, the printing process and ink composition were examined to optimize the mechanical properties of tablets. A model formulation containing the ketoprofen drug was developed and used as a base for optimization. Firstly, important printing parameters were identified with a fractional factorial design. Saturation and layer height critically influenced selected tablet properties. Relevant process parameters were optimized for tablet mechanical strength by using the D-optimization DoE approach. The best mechanical properties were achieved when saturation was set to 1 and layer height to 150 µm. On the other hand, binder ink composition did not appear to impact tablet mechanical strength as much as process parameters did. Three ethanol-water mixtures were tested at three tablet strength levels and no definitive conclusions could be drawn. The binder jetting process can be wasteful, especially if the unbound powder cannot be reused. To determine the suitability of powder blend recycling, the ketoprofen content was measured for 27 subsequent batches of tablets. While the trendline did indicate a slight reduction in ketoprofen content, the powder blend reuse can nevertheless be employed

Ablative potential of four different pulses of Er: YAG lasers and low-speed hand piece

Abstract Objective: The aim of the study was to evaluate the ablation rate of caries in dentin with fluorescence-feedback controlled Er:YAG, Variable Square Pulse technology (VSPt) based Er:YAG working in different pulse durations, and steel bur. Materials and methods: Sixty human molar teeth with caries in dentin, extracted for periodontal reasons, were selected for this study. All selected teeth were randomly divided into five groups, each containing twelve specimens: (1) group FFC, fluorescence feedback-controlled Er:YAG laser; (2) group SSP (super short pulse: 50 μs); (3) group MSP (medium short pulse; 100 μs); (4) group SP (short pulse; 300 μs); and (5) group SB, steel bur in a slow-speed hand piece. A profilometer was used to determine the volume of the ablated caries in dentin. The clinical and real ablation rates of caries in dentin were calculated. Two specimens from each experimental group were selected randomly and subjected to SEM examination. Results: The volumes of the ablated caries in dentin in the SSP and SB groups were statistically significantly different in comparison with other experimental groups (p<0.05). The clinical and real ablation rate of caries in dentin was the highest for the SSP group (0.15±0.05 and 0.17±0.05 mm(3)/sec, respectively) and statistically significantly different in comparison with the MSP and SB groups (p<0.05). The SB and FFC groups revealed a dentin surface with a smear layer and closed dentinal tubules on SEM micrographs. In the SSP, MSP, and SP groups, an irregular surface without a smear layer was found. Conclusions: Taking into consideration the experimental conditions of the present study, SSP was the most efficient in ablation of caries in dentin, providing a smear layer-free surface with open dentinal tubules