The TP53 tumor suppressor gene is frequently mutated in human cancers. An analysis of five data platforms in 10,225 patient samples from 32 cancers reported by The Cancer Genome Atlas (TCGA) enables ...comprehensive assessment of p53 pathway involvement in these cancers. More than 91% of TP53-mutant cancers exhibit second allele loss by mutation, chromosomal deletion, or copy-neutral loss of heterozygosity. TP53 mutations are associated with enhanced chromosomal instability, including increased amplification of oncogenes and deep deletion of tumor suppressor genes. Tumors with TP53 mutations differ from their non-mutated counterparts in RNA, miRNA, and protein expression patterns, with mutant TP53 tumors displaying enhanced expression of cell cycle progression genes and proteins. A mutant TP53 RNA expression signature shows significant correlation with reduced survival in 11 cancer types. Thus, TP53 mutation has profound effects on tumor cell genomic structure, expression, and clinical outlook.
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•TP53 mutation effects analyzed by five data platforms in 32 cancers/10,225 patients•More than 91% of cancers with TP53 mutations show loss of both functional TP53 alleles•TP53 mutation affects genomic stability, global RNA, miRNA, and protein expression•Mutant p53 RNA expression signature helps prognostic predictions in 11 cancer types
Donehower et al. performed a comprehensive analysis of the effects of TP53 gene mutation in 32 cancer types and 10,225 patients from The Cancer Genome Atlas (TCGA). Data synthesized from five different analysis platforms show how mutant TP53 increases genomic instability and induces major pathway signaling changes in cancer cells.
•The elevated temperature flow stresses of the extruded 7075 aluminum alloy with different grain size are characterized.•The safe and instable deformation domains for the hot working process with ...different grain size are obtained.•The optimum hot-working parameters with different grain size are determined.•The influences of grain sizes on hot deformation maps are discussed.
The effects of grain size on hot deformation and processing map of 7075 aluminum alloy were investigated using Gleeble-1500 test machine at 320–480°C with strain rates from 0.001 to 1s−1. The microstructural evolution observations of the alloy were carried out using ZESIS optical microscopy. The results showed that the flow stress increased with increasing strain rate and decreasing temperature. The flow stress of the alloy with coarse grains was higher than that of the alloy with fine grains. During hot-deformation, the alloy exhibited dynamic recovery at temperatures ranging from 320 to 440°C and dynamic recrystallization at 480°C. The processing maps for the alloy with different grain sizes were built at a strain of 0.6. It was found that the characteristics of the two processing maps were different. The instability deformation domain occurred at temperatures between 320 and 340°C and at a strain rate of 0.18–1s−1 for the alloy with coarse grains, but at temperatures between 380 and 420°C and also at a strain rate of 0.18–1s−1 for the alloy with fine grains. Based on the processing maps and microstructure observations, the optimum hot-working parameters were determined to be 480°C at 0.1s−1 for the coarse alloy and 480°C at 0.01s−1 for the fine alloy. The optimized hot working parameters of 7075 aluminum alloy with different grain size could be used in various hot working processes.
In this paper, cyclic expansion extrusion with an asymmetrical extrusion cavity (CEE-AEC) was proposed as a novel severe plastic deformation process for fabricating bulk ultrafine-grained (UFG) ...metals. Increasing the size of the processed sample and introducing the shear strain by attaching an asymmetrical extrusion cavity are the core advantages of this technology. The CEE-AEC process was applied to Mg-13Gd-4Y–2Zn-0.4Zr alloys for four passes deformation with the decreasing temperature, and then the microstructure evolution, texture analysis, and mechanical properties were investigated. Microstructure results show that a dramatical grain refinement is achieved from initial value of 24 ± 0.3 μm to 1.4 ± 0.3 μm which is mainly led by continuous dynamic recrystallization (CDRX) and discontinuous dynamic recrystallization (DDRX) as well as the particle-stimulated nucleation (PSN) induced by interdendritic long-period stacking ordered (LPSO) phases. With increasing CEE-AEC passes, the intensities of basal texture are gradually weakened, and the basal plane tends to incline to transverse and normal directions with different degrees of different passes, leading to a remarkable increase in Schmid factor for the activation of basal slip system. Tensile tests at room temperature (RT) indicate that the samples after three-passes of CEE-AEC exhibit the best comprehensive mechanical properties with tensile yield strength (TYS) of 302 MPa, ultimate tensile strength (UTS) of 330 MPa, and fracture elongation of 6.1%, which are mainly ascribed to the grain refinement, broken of interdendritic block-shaped LPSO phases, and texture modification.
•A novel SPD method entitled CEE-AEC was proposed.•The Mg-13Gd-4Y–2Zn-0.4Zr alloy was processed by CEE-AEC with consecutive four passes deformation.•A significant grain refinement from initial 24 ± 0.3 μm to 1.4 ± 0.3 μm was obtained.•Continuous and discontinuous dynamic recrystallizations took place during CEE-AEC.•The mechanical properties were contributed from the competitive of fine grains strengthening and texture modification.
Abstract Purpose To investigate whether dual energy computed tomography (CT) with iodine quantification can characterize primary lesions and metastatic lymph nodes from non-metastatic ones in ...non-small cell lung cancer (NSCLC). Materials and Methods Sixty-one patients with NSCLC confirmed by pathology underwent chest contrast CT scan with dual energy computed tomography before surgery. The Iodine concentration (IC) and normalised iodine concentration (NIC) values of the primary lesions, 20 metastatic and 20 non-metastatic lymph nodes were measured, respectively. The differences between the primary lesions, metastatic and non-metastatic lymph nodes were statistically analyzed. Results For the IC and NIC values of the primary lesions and their metastatic lymph nodes, there were no significant differences between lung squamous cell carcinomas and adenocarcinomas, respectively ( P > 0.05), while significant differences existed between metastatic and non-metastatic lymph nodes, respectively ( P < 0.05). The IC of 29.32 100 μg/cm3 and NIC value of 0.4328 of a lymph node represented the optimal threshold to discriminate metastatic from non-metastatic lymph nodes and yielded the following: sensitivity, 80% and 75%; specificity, 65% and 75%; PPV, 70% and 75%; NPV, 76% and 75%; accuracy, 73% and 75%, respectively. Conclusion Although its value in distinguishing primary lesions and their metastatic lymph nodes in NSCLC needs to be verified in further studies, dual energy CT with iodine quantification may be used to differentiate metastatic from non-metastatic lymph nodes in NSCLC.
Purpose
To investigate the correlations between the minimum and mean apparent diffusion coefficient (ADC) values of hepatocellular carcinoma (HCC) and pathological grade.
Materials and Methods
...Preoperative magnetic resonance imaging (MRI) images of 241 patients with HCC confirmed by pathology were retrospectively analyzed. All patients underwent preoperative diffusion‐weighted imaging (DWI) on a 1.5T MRI scanner. The mean and minimum ADC values of the tumors were measured. The ADC values were compared in tumors with different grades and the correlations between ADC values and pathological grade were analyzed. Receiver operating characteristic (ROC) curves of ADC values were obtained and compared to distinguish poorly and nonpoorly differentiated HCCs. Interobserver agreements were assessed by intraclass correlation coefficient (ICC).
Results
The mean and minimum ADC values of poorly differentiated HCCs were lower than those of nonpoorly differentiated HCCs (P = 0.000, 0.000, respectively). The mean and minimum ADC values were negatively correlated with pathological grade (rs = –0.180 and –0.202, respectively) (P = 0.005, 0.002, respectively). For the differentiation between poorly and nonpoorly differentiated HCCs, the mean ADC value provided a sensitivity of 69.57% and a specificity of 73.39% with a cutoff value of 0.96 × 10−3 mm2/s while the minimum ADC value showed a sensitivity of 78.26% and a specificity of 61.47% with a cutoff value of 0.90 × 10−3 mm2/s. No significant difference existed between both ROC curves (P = 0.64). The ICC for the measurements of the mean and minimum ADC values was 0.92 (95% confidence interval CI 0.90–0.93) and 0.91 (95% CI 0.89–0.93), respectively.
Conclusion
DWI of HCC could preoperatively provide quantitative parameters for predicting tumor histological grade. J. Magn. Reson. Imaging 2016;44:1442–1447.
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•7 age points were determined by correlating RPI curve with target stacks PISO-1500.•Visible precession cycle was observed in ARM/SIRM in the RPI chronology.•The “MIS 3 ...Mega-paleolake” hypothesis in China deduced by 14C dating was challenged.
Long and continuous lacustrine sedimentary sequences from SW China faithfully recorded the evolution of the Indian summer monsoon (ISM). However, the limited dating range (<50 ka) of 14C dating has restricted high-resolution research on the last glacial cycle.
We presented a relative paleointensity (RPI) record from a lacustrine sedimentary core from the Heqing Basin to optimize its AMS 14C chronology. Detailed rock magnetic analyses indicated that SD and vortex state magnetite (and/or maghemite) was the dominant magnetic mineral of lacustrine sediments. Moderate variations in concentration-dependent (SIRM, ARM) and grain-size-dependent (ARM/SIRM) parameters satisfied the criteria for the RPI studies. Consequently, we determined the RPI by NRM20-40 mT/SIRM20-40 mT, where NRM20-40 mT denotes the NRM after demagnetization between 20 and 40 mT. Using 6 AMS 14C dates younger than 40 ka BP as constraints, 7 age control points were determined by correlating the lows in the RPI record with those of the target paleointensity stacks PISO-1500. We established a reliable chronological framework of the upper 11.1 m of the HQ drill core by binomial fitting based on the 7 RPI age control points and the climatic transition termination II. The consistent variations in our RPI curve and other global target paleointensity curves indicated that the optimized chronology was reliable.
In our optimized chronology, the visible precession cycle in ARM/SIRM indicated that the ISM was a direct response to solar insolation during the last glacial cycle. The strong ISM suggested by the high content of Mesic conifers and tropical and subtropical trees during MIS 3 shifted to MIS 5a. Thus, the “MIS 3 Mega-paleolake” hypothesis in China, which was mainly deduced by the 14C age model, was challenged.
The evolution of partial discharge (PD) with time can provide a deep understanding on the insulation status of power cables. It is of great significance for intelligent operation and maintenance of ...power cables. In this paper, the PD pulse signal in the 10kV cable joint during accelerated electrical aging under 20kV AC voltage was acquired in the real-time for about 160h. The characteristic parameters of partial discharge-pulse number, average voltage, maximum voltage and energy per second were extracted. The results show that the phase of partial discharge is mainly concentrated at 30°-90° and 200°-270°, which can be characterized as internal discharge. PD characteristic parameters gradually increased after 50h. The pulse number, energy per second and the average voltage of PD pulse reached a peak between 60-80h. Then these parameters reached a steady state between 80-130h and showed a steep rise after 130h. The maximum voltage of PD pulse shows a steep rise at about 70h from 0.1V to 0.3V. It rises sharply from 0.3V to 0.5V after about 120h and then enters a relatively stable oscillation stage. The evolution rules of the PD characteristic parameters comply well with the electrical tree growth states-initiation period, lag period and rapid growth period. Furthermore, model for predicting and evaluating the insulation state based on BP neural network are established and the prediction accuracy is verified. The proposed models can provide early warning for the cable joint before the insulation failure, so as to ensure timely maintenance or replacement.
The chondroitin sulfate proteoglycan serglycin (SRGN), a hematopoietic cell granule proteoglycan, has been implicated in promoting tumor metastasis; however, the underlying mechanisms remain to be ...elucidated. The present study aimed to investigate the SRGN gene expression and its regulation as downstream signaling of hypoxia-inducible transcription factor 1 alpha (HIF-1α) in colorectal cancer (CRC) cells and tissues.
The expression of SRGN was analyzed in CRC specimens for its correlation with progression and metastasis. Using chromatin-immunoprecipitation (ChIP), quantitative real-time PCR, Western blot, and transwell assay, the functional role and underlying mechanism of SRGN in CRC metastasis were elucidated. Thus, this study provides evidence of a critical role of SRGN in metastatic progression of CRC.
Our results indicated that SRGN overexpression was significantly associated with poor prognosis in CRC specimens. SRGN overexpression promoted CRC cell migration and invasion in vitro; however, SRGN depletion exhibited contrasting effects. Mechanistic investigations revealed that HIF-1α regulated SRGN transcription via physically binding to a hypoxia response element in its promoter region.
In conclusion, we demonstrated that dysregulated HIF-1α/SRGN signaling promotes CRC progression and metastasis. SRGN may serve as a potential candidate therapeutic target for metastatic CRC.
Background/Aims: Gastric cancer (GC) is an important health problem. Classification based on molecular subtypes may help to determine the prognosis of patients with GC. Tumor invasion and metastasis ...are important factors affecting the prognosis of cancer. We aimed to identify genes related to tumor invasion and metastasis, which may serve as indicators of good GC prognosis. Methods: Tumor tissues and adjacent normal tissues were collected from 105 patients with primary GC who were treated by undergoing radical surgery. Samples were used for tissue microarray analysis. Identified genes with altered expression were further analyzed using the Gene Ontology (Go) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The expression levels of THBS2, COL1A2 and SPP1 were analyzed by RT-PCR, western blot and immunohistochemistry. The overall survival curves of patients with high and low expression of each gene of interest were plotted and compared. Results: Forty-three genes were identified. THBS2, COL1A2 and SPP1 were selected for further analysis. Altered expression levels of THBS2, COL1A2 and SPP1 in tumor tissues were confirmed. Patients with low THBS2 expression had a better prognosis; the expression of COL1A2 and SPP1 might not affect the prognosis of patients with GC. Conclusion: THBS2, but not COL1A2 and SPP1, may serve as an indicator of GC prognosis.
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