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131.
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
132.
《Journal of vascular surgery》2020,71(1):149-157
ObjectiveVascular Ehlers-Danlos syndrome (vEDS) is a rare disorder and 1 of 13 types of EDS. The syndrome results in aortic and arterial aneurysms and dissections at a young age. Diagnosis is confirmed with molecular testing via skin biopsy or genetic testing for COL3A1 pathogenic variants. We describe a multi-institutional experience in the diagnosis of vEDS from 2000 to 2015.MethodsThis is a multi-institutional cross-sectional retrospective study of individuals with vEDS. The institutions were recruited through the Vascular Low Frequency Disease Consortium. Individuals were identified using the International Classification of Diseases-9 and 10-CM codes for EDS (756.83 and Q79.6). A review of records was then performed to select individuals with vEDS. Data abstraction included demographics, family history, clinical features, major and minor diagnostic criteria, and molecular testing results. Individuals were classified into two cohorts and then compared: those with pathogenic COL3A1 variants and those diagnosed by clinical criteria alone without molecular confirmation.ResultsEleven institutions identified 173 individuals (35.3% male, 56.6% Caucasian) with vEDS. Of those, 11 (9.8%) had nonpathogenic alterations in COL3A1 and were excluded from the analysis. Among the remaining individuals, 86 (47.7% male, 68% Caucasian, 48.8% positive family history) had pathogenic COL3A1 variants and 76 (19.7% male, 19.7% Caucasian, 43.4% positive family history) were diagnosed by clinical criteria alone without molecular confirmation. Compared with the cohort with pathogenic COL3A1 variants, the clinical diagnosis only cohort had a higher number of females (80.3% vs 52.3%; P < .001), mitral valve prolapse (10.5% vs 1.2%; P = .009), and joint hypermobility (68.4% vs 40.7%; P < .001). Additionally, they had a lower frequency of easy bruising (23.7% vs 64%; P < .001), thin translucent skin (17.1% vs 48.8%; P < .001), intestinal perforation (3.9% vs 16.3%; P = .01), spontaneous pneumothorax/hemothorax (3.9% vs 14%, P.03), and arterial rupture (9.2% vs 17.4%; P = .13). There were no differences in mortality or age of mortality between the two cohorts.ConclusionsThis study highlights the importance of confirming vEDS diagnosis by testing for pathogenic COL3A1 variants rather than relying on clinical diagnostic criteria alone given the high degree of overlap with other forms genetically triggered arteriopathies. Because not all COL3A1 variants are pathogenic, the interpretation of the genetic testing results by an individual trained in variant assessment is essential to confirm the diagnosis. An accurate diagnosis is critical and has serious implications for lifelong screening and treatment strategies for the affected individual and family members. 相似文献
133.
《The Journal of emergency medicine》2020,58(6):e237-e241
BackgroundThe anatomic course of the phrenic nerve runs in the fascia covering the anterior scalene muscle. Interscalene blocks are commonly performed by an anesthesiologist for shoulder surgery, such as a rotator cuff repair, total shoulder replacement, humeral fracture, or other arm surgery. Phrenic nerve palsy or paralysis is a known complication from interscalene block and is covered in multiple case reports and series in both Anesthesia and Neurosurgical literature, but only one case report in the Emergency Medicine literature.Case ReportThis case involves a 57-year-old man who had an uncomplicated arthroscopic rotator cuff repair with placement of interscalene block under care of anesthesia. He was discharged with a pain pump in place and then subsequently presented to the Emergency Department (ED) later that same day for evaluation of dyspnea. Using point-of-care ultrasound, his right diaphragm did not appear to be moving. Chest x-ray study revealed an elevated right hemidiaphragm. He was diagnosed with iatrogenic right phrenic nerve paralysis from interscalene block.Why Should an Emergency Physician Be Aware of This?Emergent diagnosis of phrenic nerve paralysis in the ED is complicated by a distressed patient and need for quick intervention. Most formal tests for this diagnosis are not immediately available to emergency physicians. Ultrasound is a rapid and reproducible, noninvasive resource with high sensitivity and specificity, making it an ideal imaging modality for the emergent evaluation of possible phrenic nerve palsy or paralysis. 相似文献
134.
《Journal of PeriAnesthesia Nursing》2020,35(2):125-134
PurposeThis article reviews state of the science of preoperative risk factors associated with postanesthesia care unit (PACU) pediatric respiratory complications.DesignAn integrative review.MethodsA search of PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), MEDLINE, Scopus, Cochrane, and Joanna Briggs Institute databases was performed. Thirty-one articles, published between 2006 and 2018, were appraised for quality and the level of evidence using the Johns Hopkins Nursing Evidence-Based Practice Model.FindingsThese articles were grouped into the following categories: age, American Society of Anesthesiologists status, gender, airway comorbidities, syndromes, anomalies, pulmonary comorbidities, ethnicity, obesity, neurologic comorbidities, and cardiac comorbidities.ConclusionsEvidence identified significant preoperative and anesthesia risk factors that are associated with PACU pediatric respiratory complications. This article reveals the importance for the perioperative team to identify, assess for, communicate, and develop a management plan for pediatric respiratory complications. 相似文献
135.
新型冠状病毒肺炎(新冠肺炎)对人民的生命健康造成了巨大的威胁。在新冠肺炎疫情下,如何应对肝胆外科肝癌患者的门诊筛查、病房管理以及安全地实施肝癌手术,都是对肝胆外科医师提出的新挑战。我们认为,该病的临床处置应在筛查新冠肺炎的前提下,遵循正规操作流程,做好充分防护。对于需要急诊治疗但无法排除新冠肺炎的肝癌患者,须综合考虑患者的病情严重程度、手术方式及手术室条件,慎重制定个体化治疗方案。整个诊疗过程必须遵从既保证患者的安全及疗效,又要降低医护人员感染风险的原则。 相似文献
136.
137.
Rafiye Ciftciler Haluk Demiroglu Yahya Buyukasık Elifcan Aladag Salih Aksu Ibrahim C. Haznedaroglu Nilgun Sayınalp Osman Ozcebe Umit Yavuz Malkan Hakan Goker 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(3):177-182
Background
Refractory acute myeloid leukemia (AML) includes AML includes failure of disease to respond to standard induction chemotherapy, relapse within 6 months after first CR, and 2 or more relapses. The outcome of these patients is usually very poor; only a small proportion can be rescued by allogenic hematopoietic stem-cell transplantation (allo-HSCT). The aim of this study was to evaluate the efficacy and feasibility of allo-HSCT in patients with refractory AML.Patients and Methods
We retrospectively analyzed the clinical outcome of 91 patients who were diagnosed with treatment-refractory AML at Hacettepe University Hospital between January 2002 and June 2018. Patients' disease status included refractory AML, defined as failure to respond to standard induction chemotherapy and relapse within 6 months after first complete remission.Results
The median follow-up was 12 months (range, 0.5-184 months) for the entire group. Kaplan-Meier estimates of the 3-year overall survival for patients who underwent allo-HSCT and patients who received only salvage chemotherapy were 67% and 12%, respectively. Additionally, the Kaplan-Meier estimates of 5-year overall survival for patients who underwent allo-HSCT and patients who received only salvage chemotherapy were 44% and 4%, respectively (P < .001). Complete remission was obtained in 25 patients (83.3%) who underwent allo-HSCT; however, the disease of only 3 patients (3.8%) exhibited complete response after salvage chemotherapy.Conclusion
Allo-HSCT is still the best-known treatment option with curative potential in patients with treatment-refractory AML. Therefore, all efforts should be made in an attempt to find a suitable matched donor in order to perform allo-HSCT. 相似文献138.
目的观察比较CO2点阵激光早期控制唇裂术后二期整复术术区瘢痕的临床疗效。方法治疗组为43例接受唇裂术后鼻唇畸形二期整复术的患者,早期采用CO2点阵激光治疗,对照组为70例曾接受一期唇裂手术的患者,对两组6个月后的瘢痕恢复情况进行比较;分析术后距离激光开始治疗时间的长短,性别两因素对激光治疗瘢痕疗效的差异。结果1)治疗组的疗效优于对照组(P<0.000 1),治疗组中显效和有效所组成的总有效率达90.7%;2)男女疗效差异无统计学意义(P=0.487),手术后1年内的患者,手术后距离开始瘢痕治疗的时间<3个月与≥3个月之间,疗效无明显统计学差异(P=0.055)。结论CO2点阵激光在唇裂二期整复术术后瘢痕的治疗中具有较为确切的疗效。且与患者的性别无明显相关性。手术后1年内的患者,术后距离开始瘢痕治疗的时间<3个月和≥3个月疗效无差异,因此在唇裂二期手术后的1年内早期对瘢痕进行干预可获得良好的效果。 相似文献
139.
Alexandra Katsimardou Konstantinos Imprialos Konstantinos Stavropoulos Alexandros Sachinidis Michalis Doumas 《Expert opinion on pharmacotherapy》2020,21(10):1241-1252
ABSTRACT
Introduction
Type 1 diabetes mellitus (T1DM) is a chronic, autoimmune disease that is characterized by total absence of insulin production. Hypertension is a common comorbidity in T1DM with complex pathophysiology, while it is also a well-recognized risk factor for the development of cardiovascular disease (CVD), as well as other microvascular diabetic complications. 相似文献140.