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991.
In recent years, the click reaction has found rapidly growing applications in the field of radiochemistry, ranging from a practical labeling method to molecular imaging of biomacromolecules. This present review details the development of highly reliable, powerful and selective click chemistry reactions for the rapid synthesis of new radiotracers for molecular imaging. 相似文献
992.
The incidence of Alzheimer’s disease (AD), a progressive neurodegenerative disorder, continues to soar with the rapid growth of the elderly population, thus creating an enormous social and economic burden. Although disease-modifying drugs to treat AD are not yet available, several candidate drugs are in clinical trials. Most of these drugs are expected to be effective at the early stages of the disease, and therefore the early and accurate diagnosis of AD will be a critical factor in efforts to improve the prognosis of patients with AD. This review focuses on lead radioligands developed to date and their preclinical data in order to facilitate the development of tau-specific positron emission tomography radioligands that are of great interest to the scientific community. 相似文献
993.
994.
Andrew K. Kwegyir-Afful Senthilmurugan Ramalingam Puranik Purushottamachar Vidya P. Ramamurthy Vincent C.O. Njar 《Oncotarget》2015,6(29):27440-27460
Galeterone (Gal) is a first-in-class multi-target oral small molecule that will soon enter pivotal phase III clinical trials in castration resistant prostate cancer (CRPC) patients. Gal disrupts androgen receptor (AR) signaling via inhibition of CYP17, AR antagonism and AR degradation. Resistance to current therapy is attributed to up-regulation of full-length AR (fAR), splice variants AR (AR-Vs) and AR mutations. The effects of gal and VNPT55 were analyzed on f-AR and AR-Vs (AR-V7/ARv567es) in LNCaP, CWR22Rv1 and DU145 (transfected with AR-Vs) human PC cells in vitro and CRPC tumor xenografts. Galeterone/VNPT55 decreased fAR/AR-V7 mRNA levels and implicates Mdm2/CHIP enhanced ubiquitination of posttranslational modified receptors, targeting them for proteasomal degradation. Gal and VNPT55 also induced significant apoptosis in PC cells via increased Bax/Bcl2 ratio, cytochrome-c release with concomitant cleavage of caspase 3 and PARP. More importantly, gal and VNPT55 exhibited strong in vivo anti-CRPC activities, with no apparent host toxicities. This study demonstrate that gal and VNPT55 utilize cell-based mechanisms to deplete both fAR and AR-Vs. Importantly, the preclinical activity profiles, including profound apoptotic induction and inhibition of CRPC xenografts suggest that these agents offer considerable promise as new therapeutics for patients with CRPC and those resistant to current therapy. 相似文献
995.
Pre-operative chemoradiotherapy followed by a total mesorectal excision (TME) is the standard of care for patients with locally advanced (stage II or III) rectal cancer. Approximately 20% of patients may achieve a pathologic complete response after chemoradiation therapy (CRT), which has been shown to be associated with better oncologic outcomes. Whether surgery can be avoided in this population is an area of active investigation. Recent studies demonstrated feasibility and safety of non-operative management in patients with clinical complete response (cCR) after chemoradiotherapy. In this article, we set out to review the current data on non-operative management and to identify areas requiring further investigation, including improvement in imaging for reassessment after CRT and identifying the optimal time frame for restaging. As the field moves forward with non-operative management in select patients with rectal cancer, there continues to be a need to better understand the prognostic factors and biomarkers that may more accurately characterize patients who are qualified for this “wait-and-see” approach and thereby avoid overtreatment, potentially leading to improvements in long-term quality of life. 相似文献
996.
997.
Chromosomal instability (CIN) is a hallmark of cancer and has been implicated in cancer initiation, progression and the development of resistance to traditional cancer therapy. Here we identify a new property of CIN cells, showing that inducing CIN in proliferating Drosophila larval tissue leads to the activation of innate immune signalling in CIN cells. Manipulation of this immune pathway strongly affects the survival of CIN cells, primarily via JNK, which responds to both Toll and TNFα/Eiger. This pathway also activates Mmp1, which recruits hemocytes to the CIN tissue to provide local amplification of the immune response that is needed for effective elimination of CIN cells. 相似文献
998.
Anxiety disorders are the most common and prevalent forms of psychiatric disease, although the biological basis of anxiety is not well understood. The dynorphin/κ opioid receptor system is widely distributed in the central nervous system and has been shown to play a critical role in modulating mood and emotional behaviors. In the present review, we summarize current literature relating to the role played by the dynorphin/κ opioid receptor system in anxiety and κ opioid receptor antagonists as potential therapeutic agents for the treatment of anxiety disorders. 相似文献
999.
1000.
目的:以特质理论中的"大五"人格结构模型为理论框架,编制中国大五人格形容词量表。方法:运用人格研究的心理语言学方法编制涵盖人格维度和特质层面的《中文形容词大五人格量表》,1208名在校大学生参与了本次测试。结果:1以双极词为条目,6点记分为记分方式,所编制的《中文大五人格形容词量表》条目数适中,测量了5个大维度和26个侧面特质,共104个条目。2测量信度方面,5个大维度的内部一致性系数(α系数)在0.902(宜人性)至0.917(开放性)之间,平均为0.910;26个侧面特质的α系数在0.628(责任心)至0.870(抑郁)之间,平均为0.741;间隔2周的重测信度在维度层面上均达到0.85以上,在0.868(宜人性)至0.935(外倾性)之间;26个侧面特质的重测信度均大于0.70,达到了同类人格测验应有的水平。结论:本研究所研制的《中文形容词大五人格量表》涵盖了人格维度和特质层面,条目数适中,具有良好的测量信度。 相似文献