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11.
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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Anders Elm Pedersen Esben Gjerløff Wedebye Schmidt Jesper Freddie Sørensen Carsten Faber Boye Schnack Nielsen Kim Holmstrøm Silje Haukali Omland Peter Tougaard Søren Skov Bo Bang 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2015,123(7):547-555
TL1A is a TNF‐like cytokine which has been shown to co‐stimulate TH1 and TH17 responses during chronic inflammation. The expression of this novel cytokine has been investigated in inflammatory disorders like rheumatoid arthritis and inflammatory bowel disease, but little is known about expression and induction in psoriasis. Indeed, the pathogenesis in psoriasis is still not fully understood and it is speculated that cytokines other than TNF‐α are important in subsets of patients. Also, for patients with severe disease that are treated with systemic anti‐TNF‐α blockade, novel candidates to be used as disease and response biomarkers are of high interest. Here, we demonstrate TL1A expression in biopsies from psoriatic lesions. Also, we investigated spontaneous and induced TL1A secretion from PBMCs and blood levels from a cohort of psoriasis patients. Here, increased spontaneous secretion from PBMCs was observed as compared to healthy controls and a small subset of patients had highly elevated TL1A in the blood. Interestingly, activation of PBMCs with various cytokines showed a decreased sensitivity for TL1A activation in psoriasis patients compared to healthy controls.TL1A levels in blood and biopsies could not be correlated with disease activity with this patient cohort. Thus, additional large‐scale studies are warranted to investigate TL1A as a biomarker. 相似文献
15.
目的 探讨扶正消瘤颗粒对原发性肝癌血清中血管内皮生长因子(Vascular endothelial growth factor,VEGF)和缺氧诱导因子-1α(Hypoxia inducible factor-1α,HIF-1α)表达的影响及临床意义。方法 选择符合纳入标准的原发性肝癌患者66例,按1∶1随机分试验组和对照组。观察治疗过程中两组VEGF、HIF-1α水平的变化及对患者临床疗效指标的影响。结果 (1)在性别、年龄、合并乙型肝炎、Child-Pugh分级、AFP值、临床分期方面,试验组和对照组差异无统计学意义(P > 0.05)。(2)肝癌患者在治疗各时间节点的VEGF和HIF-1α表达水平呈线性正相关(r = 0.829,P < 0.001)。(3)VEGF浓度在经导管动脉化疗栓塞术(Transcatheter arterial chemoembolization,TACE)后3月降至术前水平(P > 0.05),HIF-1α在TACE后3月仍高于术前(P < 0.05)。(4)扶正消瘤颗粒可降低HIF-1α水平,下调VEGF的表达。(5)扶正消瘤颗粒可减少TACE序贯RFA治疗后的不良反应,提高患者的生活质量(P < 0.05)。(6)血清中VEGF水平与生活质量无明显相关性(P > 0.05,r = 0.251),HIF-1α水平与生活质量存在正相关性(P < 0.05,r = 0.450)。结论 扶正消瘤颗粒可明显改善TACE序贯RFA治疗后患者生活质量,降低HIF-1α水平,下调VEGF的表达,抑制肿瘤血管生成。 相似文献
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Yeon Seok Lee June Hyunkyung Lee Jae Eun Choi Joo Young Kim Tae Young Han 《Pediatric dermatology》2021,38(1):290-291
Erythema induratum of Bazin (EIB) is a form of tuberculid resulting from hypersensitivity to tuberculosis antigen. EIB occurs most commonly in middle‐aged women and is not typically seen in children. Here, we present a rare case of EIB, presenting as a chronic nodular panniculitis, in a 10‐year‐old Korean boy. 相似文献
18.
<正>第5章术前辅助措施在腹疝修补术中的作用通过Medline、PubMed、Cochrane Library以及相关期刊和参考文献进行了系统的文献检索,证据结论:(1)在腹壁疝修补术之前使用A型肉毒素(botulinum toxin type A,BTA)与阿片类镇痛的使用显著减少疼痛。证据级别:3级。(2)(1)应用BTA可使腹壁疝直径减小,腹壁外侧肌厚度显著减少,腹壁外侧肌显著延长。在大多数腹疝患者中,单独 相似文献
19.
Bielik Peter Bonczek Ondřej Krejčí Přemysl Zeman Tomáš Izakovičová-Hollá Lydie Šoukalová Jana Vaněk Jiří Vojtěšek Bořivoj Lochman Jan Balcar Vladimir J. Šerý Omar 《Clinical oral investigations》2022,26(12):7045-7055
Clinical Oral Investigations - The aim of this study was the analysis of WNT10A variants in seven families of probands with various forms of tooth agenesis and self-reported family history of... 相似文献