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Melanoma models for the next generation of therapies.

下一代疗法的黑色素瘤模型。

  • 影响因子:15.04
  • DOI:10.1016/j.ccell.2021.01.011
  • 作者列表:"Patton EE","Mueller KL","Adams DJ","Anandasabapathy N","Aplin AE","Bertolotto C","Bosenberg M","Ceol CJ","Burd CE","Chi P","Herlyn M","Holmen SL","Karreth FA","Kaufman CK","Khan S","Kobold S","Leucci E","Levy C","Lombard DB","Lund AW","Marie KL","Marine JC","Marais R","McMahon M","Robles-Espinoza CD","Ronai ZA","Samuels Y","Soengas MS","Villanueva J","Weeraratna AT","White RM","Yeh I","Zhu J","Zon LI","Hurlbert MS","Merlino G
  • 发表时间:2021-02-04
Abstract

:There is a lack of appropriate melanoma models that can be used to evaluate the efficacy of novel therapeutic modalities. Here, we discuss the current state of the art of melanoma models including genetically engineered mouse, patient-derived xenograft, zebrafish, and ex vivo and in vitro models. We also identify five major challenges that can be addressed using such models, including metastasis and tumor dormancy, drug resistance, the melanoma immune response, and the impact of aging and environmental exposures on melanoma progression and drug resistance. Additionally, we discuss the opportunity for building models for rare subtypes of melanomas, which represent an unmet critical need. Finally, we identify key recommendations for melanoma models that may improve accuracy of preclinical testing and predict efficacy in clinical trials, to help usher in the next generation of melanoma therapies.

摘要

: 缺乏可用于评价新型治疗方式的功效的合适的黑素瘤模型。在这里,我们讨论了黑色素瘤模型的现状,包括基因工程小鼠、患者来源的异种移植物、斑马鱼以及离体和体外模型。我们还确定了使用这些模型可以解决的五个主要挑战,包括转移和肿瘤休眠,耐药性,黑色素瘤免疫反应,以及衰老和环境暴露对黑色素瘤进展和耐药性的影响。此外,我们讨论了为罕见的黑色素瘤亚型建立模型的机会,这是一个未满足的关键需求。最后,我们确定了黑色素瘤模型的关键建议,这些建议可能会提高临床前测试的准确性,并在临床试验中预测疗效,以帮助引领下一代黑色素瘤疗法。

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发表时间:2021-02-01
DOI:10.1007/s11033-021-06155-w
作者列表:["Juan-Carlos PM","Perla-Lidia PP","Stephanie-Talia MM","Mónica-Griselda AM","Luz-María TE"]

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影响因子:2.68
发表时间:2021-02-01
DOI:10.1080/14656566.2020.1814255
作者列表:["Sawada H","Oeda T","Kohsaka M","Tomita S","Umemura A","Park K","Yamamoto K","Kiyohara K"]

METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.

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影响因子:2.06
发表时间:2021-03-24
DOI:10.1007/s11033-021-06299-9
作者列表:["Louvrier A","Terranova L","Meyer C","Meyer F","Euvrard E","Kroemer M","Rolin G"]

METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.

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