Targeting cap-dependent translation blocks converging survival signals by AKT and PIM kinases in lymphoma

PIM kinase expression in human lymphomas can influence the outcome of chemotherapy, and blocking cap-dependent translation can reverse PIM-mediated rapamycin resistance in murine lymphomas

Mining Height Effect and Application of Upper Protected Layer Mining Pressure Relief

In order to obtain the minimum mining height that can play an effective protective role in the mining of the non-full coal protective layer in the Hongyang No. 3 coal mine and improve its economic benefits, the relationship between the mining height and the pressure relief of the protected layer is studied. Theoretical analysis is used to establish a calculation model of the goaf stress distribution law, with the mining height as a variable. The calculation model research results show that the mining height adjusts the goaf stress distribution by adjusting the range of the “three zones”. The force of the falling zone and the frustration zone on the goaf is approximately trapezoidal geostatic stress, and the roof stress in the vertical projection area of the trapezoidal waistline is not transmitted to the goaf. The development heights of the “two zones” are different at different mining heights, and the corresponding pressure-relief ranges are different from the waistline vertical projection. The curved subsidence zone transmits stress to the goaf through the fissure zone and the caving zone below, which can be calculated by the elastic foundation beam model. The falling zone is the elastic foundation, and different mining heights have different foundation coefficients. With the increase in mining heights, the foundation coefficients first decrease and then tend to be stable. The pressure-relief range of the stress transmitted from the curved subsidence zone to the goaf first increases and then tends to be stable. According to the calculation model, the minimum mining height for effective pressure relief of the upper protective layer of thin coal in the Hongyang No. 3 coal mine is 2.5 m, which can effectively relieve the pressure of the protected layer with the floor layer spacing of 48 m

Simulation test study on filling flow law of gangue slurry in goaf

Abstract The disposal and utilization of solid waste of coal gangue is one of the main problems in coal mining in China. Injecting coal gangue into goaf in the form of slurry can effectively solve the problems of ground stacking and environmental pollution prevention. In order to obtain the flow law of gangue slurry in the void of the accumulated rock in the goaf, a visualization simulation test device for gangue slurry permeation grouting in the goaf was independently designed. The flow and diffusion characteristics, flow and diffusion velocity changes, void pressure changes, and viscosity changes of three mass concentrations (76%, 78%, 80%) of gangue slurry in the void between caved rock blocks in goaf were studied by visual grouting simulation test. The results show that: (1) The seepage process of gangue slurry in the goaf simulation test is divided into three diffusion forms, namely radial diffusion, axial diffusion, and bidirectional diffusion. The three diffusion forms are interrelated and inseparable. (2) The initial flow velocity of the slurry with different concentrations is different under the same permeation grouting pressure, and the higher the slurry concentration, the smaller the initial flow velocity of the slurry. The velocity of the slurry has a nonlinear relationship with the diffusion distance of the slurry. (3) With the permeation and diffusion of slurry, pressure sensors at different positions are subjected to pressure from bottom to top and enter the pressure boost stage, gradually forming stress peaks. When the slurry exceeds the position of the pressure sensor, the pressure on the pressure sensor is weakened and begins to enter the pressure relief stage, and the stress decline trend gradually becomes gentle with time. (4) The water loss effect occurs during slurry flow interaction with rock mass, resulting in slurry viscosity increasing. The viscosity of the slurry affects the difference in the amount of viscosity change. The research results can provide a certain theoretical basis for the goaf gangue slurry filling project

PIK3CA mutation is associated with increased local failure in lung stereotactic body radiation therapy (SBRT)

Objectives: Hyperactivation of the phosphatidylinositol-3-kinase (PI3K) pathway has been associated with radioresistance. It is unclear whether such mutations confer suboptimal local control for patients who receive lung stereotactic body radiation therapy (SBRT). Our objective was to examine whether mutations in the EGFR/AKT/PIK3CA signaling pathway are associated with local failure (LF) after lung SBRT. Methods: We retrospectively reviewed 166 patients who underwent SBRT to primary or metastatic lung lesions from 2007 to 2015 for whom genetic testing data was available for EGFR, AKT, and PIK3CA genes. Association between clinical factors, including molecular mutation status, and LF was evaluated. Results: Six patients (4%) had PIK3CA mutation, 36 patients (22%) had EGFR mutation, and one patient (0.6%) had AKT1 mutation. Median lesion size was 2.0â¯cm (range, 0.6â5.6â¯cm); median dose was 48â¯Gy in 4 fractions (range, 30â70â¯Gy in 3â10 fractions). Median follow-up for survivors was 27.3â¯months (range, 3.8â66.7â¯months). LF occurred in 16 patients (10%). On univariate analysis, PIK3CA mutation was associated with LF (HR 10.44 [95% CI 2.16â50.46], pâ¯=â¯.003), while tumor histology, tumor size, primary tumor site, BED and EGFR mutation were not. At one year, probability of LF in lesions with PIK3CA mutation was 20.0% vs. 2.9% in lesions without mutation (pâ¯<â¯.001 by log rank test). Conclusion: Although the number of patients affected was small, PIK3CA mutation was significantly associated with higher risk of LF in patients undergoing lung SBRT. This association has not previously been reported for lung SBRT and indicates the need for further validation. Keywords: Lung stereotactic body radiation therapy (SBRT), PIK3CA, Radiation resistance, Local failur

Concurrent Chemoradiotherapy With Cisplatin Versus Cetuximab for Squamous Cell Carcinoma of the Head and Neck

ObjectivesWe previously reported inferior outcomes for locally advanced head and neck cancer treated with cetuximab (C225) versus cisplatin (CDDP). We now examine if this difference persists when accounting for HPV status and update outcomes on the entire cohort.Materials and methodsFrom 3/106 to 4/1/08, 174 locally advanced head and neck cancer patients received definitive treatment with RT and CDDP (n=125) or RT and C225 (n=49). Of these, 62 patients had tissue available for HPV analysis.ResultsThe median follow-up was 47 months. The 3-year loco-regional failure, disease-free survival, and overall survival for CDDP versus C225 were 5.7% versus 40.2% (P&lt;0.0001), 85.1% versus 35.4% (P&lt;0.0001), and 90.0% versus 56.6% (P&lt;0.0001), respectively. In the subset with tissue, there was no difference in rates of HPV or p16 positivity between the 2 groups. In this subset, the 3-year loco-regional failure, disease-free survival, and overall survival for CDDP versus C225 were 5.3% versus 32.0% (P=0.01), 86.8% versus 43.2% (P=0.002), and 86.7% versus 76.9% (P=0.09), respectively. Multivariate analysis continued to show a benefit for CDDP.ConclusionsWith longer follow-up and the inclusion of HPV and p16 status for about one third of patients where tissue was available, we continued to find superior outcomes with concurrent CDDP versus C225