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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
  相似文献   
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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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随着腔镜技术的进一步发展以及微创理念应用于结直肠外科疾病的诊治中,结直肠相关疾病的诊治发生了翻天覆地的变化。由传统的经腹手术到腹腔镜手术、经自然腔道手术,再到经自然腔道取标本手术(NOSES),结直肠疾病的外科诊治在微创领域取得了巨大成果。NOSES技术是目前结直肠外科在微创领域前沿的手术方式之一,它通过经直肠、阴道取标本来避免了腹壁的辅助取标本切口,从而将结直肠外科手术进一步微创化。NOSES技术集传统腹腔镜手术的优势与现代微创外科的理念于一体,它在确保手术效果的基础上集中体现了微创、加速康复外科、功能外科、"无疤"等理念的特点。本文主要就国内外各中心开展NOSES技术在结直肠外科诊治开展中的相关经验、心得和体会进行综述。  相似文献   
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Background

Many patients undergoing below knee amputations (BKA) return for subsequent unplanned operations, hospital readmission, or postoperative complications. This unplanned medical management negatively impacts both patient outcomes and our healthcare system. This study primarily investigates the risk factors for unplanned reoperation following BKA.

Methods

Below knee amputations from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database from the years 2012–2014 were identified by CPT code 27880 for amputation through the tibia and fibula. Our query identified 4631 BKA cases, including 30 day complications. Multivariate logistic regression modeling was performed on several patient demographic and disease factors to assess for independent predictors of unplanned reoperation. Secondary outcomes of unplanned and related readmissions (related to the procedure), major complications, minor complications, and mortality were also included in the analysis.

Results

Of 4631 BKAs identified, 9.63% (446/4631) underwent unplanned reoperations and 8.75% (405/4631) had unplanned and related readmissions. Major complications were experienced by 12.8% (593/4631) and minor complications by 8.7% (401/4631). Thirty day mortality rate was 5.14% (238/4631). The most common procedures for unplanned operations were thigh amputations (128/446, 28.7%), debridement/secondary closure (114/446, 25.6%), and revision leg amputations (46/446, 10.32%). Factors associated with an increased risk of unplanned reoperation included patients transferred from another facility (Adjusted Odds Ratio [AOR]?=?1.28; p?=?.04), recent smokers (AOR?=?1.34; p?=?.02), bleeding disorder (AOR?=?1.30; p?=?.02), and preoperative ventilator use (AOR?=?2.38; p?=?.01).

Conclusion

Patients that were ongoing/recent smokers, had diagnosed bleeding disorders, required preoperative ventilator use, or were transferred in from another facility were associated with the highest risks of reoperation following BKA. This patient population experiences high rates of reoperation, readmission, complication, and mortality.  相似文献   
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刘士鑫  吴瑾 《现代肿瘤医学》2022,(18):3423-3428
卵巢癌是妇科肿瘤领域内的一个热点主题。该种恶性肿瘤疾病的发病率高且隐匿,缺乏有效的早期发现及时诊断并治疗的方式,病情容易加重发生远处转移。因此罹患卵巢癌的女性5年生存率比较低。外泌体属于一类典型的囊性泡样的小体,参与肿瘤的发病及转移机制且在肿瘤疾病的治疗中起着重要作用。本篇综述主要介绍癌细胞外泌体在卵巢恶性肿瘤疾病的诊断、转移及治疗中的研究现状。  相似文献   
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