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JeongYun Choi Haeseung Lee EunJi Kwon HyeonJoon Kong OkSeon Kwon HyukJin Cha 《Molecular oncology》2021,15(2):679
The acquisition of chemoresistance remains a major cause of cancer mortality due to the limited accessibility of targeted or immune therapies. However, given that severe alterations of molecular features during epithelial‐to‐mesenchymal transition (EMT) lead to acquired chemoresistance, emerging studies have focused on identifying targetable drivers associated with acquired chemoresistance. Particularly, AXL, a key receptor tyrosine kinase that confers resistance against targets and chemotherapeutics, is highly expressed in mesenchymal cancer cells. However, the underlying mechanism of AXL induction in mesenchymal cancer cells is poorly understood. Our study revealed that the YAP signature, which was highly enriched in mesenchymal‐type lung cancer, was closely correlated to AXL expression in 181 lung cancer cell lines. Moreover, using isogenic lung cancer cell pairs, we also found that doxorubicin treatment induced YAP nuclear translocation in mesenchymal‐type lung cancer cells to induce AXL expression. Additionally, the concurrent activation of TGFβ signaling coordinated YAP‐dependent AXL expression through SMAD4. These data suggest that crosstalk between YAP and the TGFβ/SMAD axis upon treatment with chemotherapeutics might be a promising target to improve chemosensitivity in mesenchymal‐type lung cancer.
Abbreviations
- AUC
- area under the curve
- AXL
- AXL receptor tyrosine kinase
- BCL2
- B‐cell lymphoma 2
- CTD2
- cancer target discovery and development
- CTGF
- connective tissue growth factor
- DEG
- differentially expressed genes
- DOXO
- doxorubicin
- EMT
- epithelial–mesenchymal transition
- Eto
- etoposide
- FDA
- Food and Drug Administration
- ITGB3
- integrin beta‐3
- MAPK
- mitogen‐activated protein kinase
- MMP2
- matrix metalloproteinase‐2
- MMP9
- matrix metalloproteinase‐9
- mRNA
- messenger RNA
- NF‐κB
- nuclear factor kappa‐light‐chain‐enhancer of activated B cells
- SBE
- SMAD binding element
- SERPINE1
- serpin family E member 1
- siRNA
- small interfering RNA
- ssGSEA
- single‐sample gene set enrichment analysis
- TCGA
- The Cancer Genome Atlas
- TGFβ
- transforming growth factor beta
- YAP
- Yes‐associated protein
- YAP8SA
- mutants of inhibitory phosphorylation site at eight serine to Alanine of YAP
- ZEB1
- zinc finger E‐box binding homeobox 1
- ZEB2
- zinc finger E‐box‐binding homeobox 2
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Cheong-Il Shin Sang Joon Park Ji-Hyun Kim Yeonyee Elizabeth Yoon Eun-Ah Park Bon-Kwon Koo Whal Lee 《Korean journal of radiology》2021,22(5):688
ObjectiveTo compare the lumen parameters measured by the location-adaptive threshold method (LATM), in which the inter- and intra-scan attenuation variabilities of coronary computed tomographic angiography (CCTA) were corrected, and the scan-adaptive threshold method (SATM), in which only the inter-scan variability was corrected, with the reference standard measurement by intravascular ultrasonography (IVUS).Materials and MethodsThe Hounsfield unit (HU) values of whole voxels and the centerline in each of the cross-sections of the 22 target coronary artery segments were obtained from 15 patients between March 2009 and June 2010, in addition to the corresponding voxel size. Lumen volume was calculated mathematically as the voxel volume multiplied by the number of voxels with HU within a given range, defined as the lumen for each method, and compared with the IVUS-derived reference standard. Subgroup analysis of the lumen area was performed to investigate the effect of lumen size on the studied methods. Bland-Altman plots were used to evaluate the agreement between the measurements.ResultsLumen volumes measured by SATM was significantly smaller than that measured by IVUS (mean difference, 14.6 mm3; 95% confidence interval [CI], 4.9–24.3 mm3); the lumen volumes measured by LATM and IVUS were not significantly different (mean difference, −0.7 mm3; 95% CI, −9.1–7.7 mm3). The lumen area measured by SATM was significantly smaller than that measured by LATM in the smaller lumen area group (mean of difference, 1.07 mm2; 95% CI, 0.89–1.25 mm2) but not in the larger lumen area group (mean of difference, −0.07 mm2; 95% CI, −0.22–0.08 mm2). In the smaller lumen group, the mean difference was lower in the Bland-Altman plot of IVUS and LATM (0.46 mm2; 95% CI, 0.27–0.65 mm2) than in that of IVUS and SATM (1.53 mm2; 95% CI, 1.27–1.79 mm2).ConclusionSATM underestimated the lumen parameters for computed lumen segmentation in CCTA, and this may be overcome by using LATM. 相似文献
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Fluid is usually restricted during thoracic surgery, and vasoactive agents are often administered to maintain blood pressure. One-lung ventilation (OLV) decreases arterial oxygenation; thus oxygen delivery to the brain can be decreased. In this study, we compared phenylephrine and dopamine with respect to maintaining cerebral oxygenation during OLV in major thoracic surgery.Sixty-three patients undergoing lobectomies were randomly assigned to the dopamine (D) or phenylephrine (P) group. The patients’ mean arterial pressure was maintained within 20% of baseline by a continuous infusion of dopamine or phenylephrine. Maintenance fluid was kept at 5 mL/kg/h. The depth of anesthesia was maintained with desflurane 1MAC and remifentanil infusion under bispectral index guidance. Regional cerebral oxygen saturation (rScO2) and hemodynamic variables were recorded using near-infrared spectroscopy and esophageal cardiac Doppler.The rScO2 was higher in the D group than the P group during OLV (OLV 60 min: 71 ± 6% vs 63 ± 12%; P = 0.03). The number of patients whose rScO2 dropped more than 20% from baseline was 0 and 6 in the D and P groups, respectively (P = 0.02). The D group showed higher cardiac output, but lower mean arterial pressure than the P group (4.7 ± 1.0 vs 3.9 ± 1.2 L/min; 76.7 ± 8.1 vs 84.5 ± 7.5 mm Hg; P = 0.02, P = 0.02). Among the variables, age, hemoglobin concentration, and cardiac output were associated with rScO2 by correlation analysis.Dopamine was superior to phenylephrine in maintaining cerebral oxygenation during OLV in thoracic surgery. 相似文献
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The cingulum, connecting the orbitofrontal cortex to the medial temporal lobe, involves in diverse cognition functions including attention, memory, and motivation. To investigate the relationship between the cingulum injury and cognitive impairment in patients with chronic mild traumatic brain injury, we evaluated the integrity between the anterior cingulum and the basal forebrain using diffusion tensor tractography in 73 patients with chronic mild traumatic brain injury(39 males, 34 females, age 43.29 ± 11.42 years) and40 healthy controls(22 males, 18 females, age 40.11 ± 16.81 years). The patients were divided into three subgroups based on the integrity between the anterior cingulum and the basal forebrain on diffusion tensor tractography: subgroup A(n = 19 patients)-both sides of the anterior cingulum were intact; subgroup B(n= 36 patients)-either side of the anterior cingulum was intact; and subgroup C(18 patients)-both sides of the anterior cingulum were discontinued. There were significant differences in total Memory Assessment Scale score between subgroups A and B and between subgroups A and C. There were no significant differences in diffusion tensor tractography parameters(fractional anisotropy, apparent diffusion coefficient, and fiber volume) between patients and controls. These findings suggest that the integrity between the anterior cingulum and the basal forebrain, but not diffusion tensor tractography parameter, can be used to predict the cognitive function of patients with chronic mild traumatic brain injury. This study was approved by Yeungnam University Hospital Institutional Review Board(approval No. YUMC-2014-01-425-010) on August 16, 2017. 相似文献