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91.
Increased expression of the oncogene MYC is a common feature of many B‐cell malignancies, however MYC overexpression by itself is not sufficient for transformation, and additional genetic events are required, although the exact nature of these remains unknown. In patients and in transgenic mouse models, oncogenic transformation may occur in B cells at various differentiation stages interacting with complex microenvironments. B‐cell oncogenesis often occurs after prolonged periods of time, making it difficult to accurately identify the genetic events required for transformation. An in vitro system, where malignant transformation of primary B cells could be analyzed, would facilitate the identification of genetic events required for transformation. Here, we describe such a system and show that primary murine B cells rapidly become transformed upon forced expression of MYC, in conjunction with simultaneous inhibition of the ARF/p53 axis via overexpression of BMI1, as well as through downregulation of p19ARF or expression of a dominant‐negative p53 and suppression of intrinsic apoptosis through overexpression of BCLXL or MCL1. Established tumor cells remained addicted to expression of the lymphoma‐inducing genes. In mice, transformed cells rapidly established fatal B‐cell lymphomas. Our results suggest that transformation of normal mature B cells into lymphomas can occur as a consequence of three defined events. 相似文献
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Maria G Onesti Pasquale Fino Paolo Fioramonti Vittoria Amorosi Nicolò Scuderi 《International wound journal》2015,12(4):447-450
Malignant degeneration of wounds is rare and often misdiagnosed. Delay in diagnosis may result in a worse prognosis. The aim of this study is to determine the number of skin cancers associated with chronic skin ulcers in our facility over a period of 10 years. Between January 2002 and December 2012, a total of about 1000 patients had consulted with us for chronic wounds, especially of vascular, diabetic and traumatic origin and pressure ulcers. Thirteen skin cancers had been detected: seven squamous cell and five basal cell carcinomas and one melanoma. We highlight how important it is to be aware of the signs suggesting a malignant change and the importance of biopsy at regular intervals during the life cycle of any chronic wound. 相似文献
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Ka Tik Cheung Daniel Man-yuen Sze Kwok Hung Chan Polly Hang-mei Leung 《Immunobiology》2018,223(4-5):356-364
Caspase-4 physically interacts with caspase-1 and is believed to be a proinflammatory caspase that can induce the inflammatory form of programmed cell death (pyroptosis) and the release of mature interleukin (IL)-1β. However, the function of caspase-4 in dengue virus infection is not yet fully understood. We examined the function of caspase-4 in IL-1β production and pyroptosis during dengue virus serotype-2 (DENV-2) infection in human macrophages. In this study, DENV-2 infection increased IL-1β protein level with activated caspase-4 activity. Using primary macrophages, we observed that caspase-4 induces activation of caspase-1 and secretion of IL-1β in response to DENV-2 infection, without the need for secondary signals to stimulate the assembly of the inflammasome. These findings indicate that the regulation of caspase-1 activity by capsase-4 could represent a unique mechanism. Our data suggest that caspase-4 is upstream of caspase-1 in the pathway that regulates pyroptosis and IL-1β synthesis in macrophages during DENV-2 infection. 相似文献
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Ting Liu Hong Zhang Xuesong Yang Xiaojie Li Yi Shi Weidong Niu Tingjiao Liu 《Pathology, research and practice》2018,214(2):296-302
Objective
The aim of this study is to investigate the expressions of p16 and HPV16/18(E6) in oral lichen planus (OLP) and malignant transformed OLP (MT-OLP).Study design
The expression of p16 and HPV16/18(E6) in 40 cases of OLP and 6 MT-OLP was assessed by immunohistochemical staining. Twenty four cases of normal oral mucosa were used as controls.Results
Compared to normal oral mucosa, the expression of p16 and HPV16/18(E6) protein increased in OLP and MT-OLP. And there was a correlation between p16 expression and HPV infection in OLP and OLP malignant lesions (p?<?0.0001).Conclusions
The expression of p16 protein might predict HPV16/18 infection in OLP. And HPV16/18(E6) infection might contribute to OLP malignant transformation. 相似文献96.
Background
The mucosal layer plays an important role in regulating the intestinal barrier function. However, the underlying mechanisms of intestinal barrier dysfunction caused by trauma-hemorrhagic shock (THS) are still unknown.Methods
In this study, we examined the barrier damages, inflammatory responses as well as the metabolic changes of the mucosal layer of the colon in a THS rat model.Results
The results showed that compared to the rats treated with trauma only, THS induced marked failure of intestinal barrier characterized by increased intestinal permeability, inflammatory cell infiltration and decreased expression of genes involved in epithelial integrity. Moreover, decreased colonic mucus content and goblet cell numbers indicated that the mucosal layer was also impaired in response to THS. This was companied by the anomalous inflammatory responses in the tissue. Finally, microdialysis catheter examination showed that metabolites including glycerol, glucose, lactate and pyruvate, glutamate and glutamine were also altered by THS.Conclusion
Our results provide evidence that mucus layer-associated metabolic changes may contribute to the THS-induced intestinal barrier dysfunction. 相似文献97.
《中华医学遗传学杂志》2018,(2):197-201
Objective To carry out genetic testing for a family affected with pulmonary hypertension (PH) as the initial sign of hereditary hemorrhagic telangiectasia CHHT). Methods High throughput sequencing was performed to detect potential mutation in the coding regions of endoglin (ENG), activin receptor-like kinase 1 (ACVRL1) and mothers against decapentaplegic homolog 4 (SMAD4) genes. Results A pathogenic heterozygous c. 814C>T (p. Gln272Ter) mutation of the ACVRL1 gene was identified in the proband. Her mother and two sons have carried the same mutation. Conclusion The c. 814C>T (p. Gln272Ter) mutation of the ACVRL1 gene probably underlies the disease in this family. Genetic testing should be recommended to HHT patient, in particular those with pulmonary hypertension. © 2018 West China University of Medical Sciences. All rights reserved. 相似文献
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目的 探讨脑膜瘤术后复发并恶变的靶向治疗效果。方法 回顾性分析1例鞍区脑膜瘤的临床资料,并结合相关文献进行分析。结果 52岁男性,因鞍区脑膜瘤切除术后13年伴视力进行性下降3年于2020年5月12日入院;2007年首次手术近全切除鞍区肿瘤,术后病理示脑膜瘤(WHO分级Ⅰ级);2009年复查MRI显示肿瘤明显增大,2009~2018年共行6次伽玛刀治疗;2019年复查MRI显示肿瘤无增大;2020年复查MRI显示肿瘤再次明显增大,再次手术全切除肿瘤,术后病理示不典型脑膜瘤(WHO分级Ⅱ级),6个月后肿瘤再次复发,根据基因检测和类器官培养的药敏结果,选择舒尼替尼进行靶向治疗(37.5 mg,1次/d,持续4周,停药2周);靶向治疗6个月复查MRI显示肿瘤缩小,但9个月时复查MRI显示肿瘤增大,病人拒绝继续靶向治疗,神志清楚,双目失明,能搀扶行走。结论 脑膜瘤术后复发并恶变时,靶向治疗短期内可缩小肿瘤体积,长期效果有待继续研究。 相似文献