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41.
Vilde Yuli Stenberg Roy Hartvig Larsen Li-Wei Ma Qian Peng Petras Juzenas
yvind Sverre Bruland Asta Juzeniene 《International journal of molecular sciences》2021,22(9)
Radioligand therapy targeting the prostate-specific membrane antigen (PSMA) is rapidly evolving as a promising treatment for metastatic castration-resistant prostate cancer. The PSMA-targeting ligand p-SCN-Bn-TCMC-PSMA (NG001) labelled with 212Pb efficiently targets PSMA-positive cells in vitro and in vivo. The aim of this preclinical study was to evaluate the therapeutic potential of 212Pb-NG001 in multicellular tumour spheroid and mouse models of prostate cancer. The cytotoxic effect of 212Pb-NG001 was tested in human prostate C4-2 spheroids. Biodistribution at various time points and therapeutic effects of different activities of the radioligand were investigated in male athymic nude mice bearing C4-2 tumours, while long-term toxicity was studied in immunocompetent BALB/c mice. The radioligand induced a selective cytotoxic effect in spheroids at activity concentrations of 3–10 kBq/mL. In mice, the radioligand accumulated rapidly in tumours and was retained over 24 h, while it rapidly cleared from nontargeted tissues. Treatment with 0.25, 0.30 or 0.40 MBq of 212Pb-NG001 significantly inhibited tumour growth and improved median survival with therapeutic indexes of 1.5, 2.3 and 2.7, respectively. In BALB/c mice, no signs of long-term radiation toxicity were observed at activities of 0.05 and 0.33 MBq. The obtained results warrant clinical studies to evaluate the biodistribution, therapeutic efficacy and toxicity of 212Pb-NG001. 相似文献
42.
Rikako Tabata SungGi Chi Junichiro Yuda Yosuke Minami 《International journal of molecular sciences》2021,22(4)
Several immune checkpoint molecules and immune targets in leukemic cells have been investigated. Recent studies have suggested the potential clinical benefits of immuno-oncology (IO) therapy against acute myeloid leukemia (AML), especially targeting CD33, CD123, and CLL-1, as well as immune checkpoint inhibitors (e.g., anti-PD (programmed cell death)-1 and anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) antibodies) with or without conventional chemotherapy. Early-phase clinical trials of chimeric antigen receptor (CAR)-T or natural killer (NK) cells for relapsed/refractory AML showed complete remission (CR) or marked reduction of marrow blasts in a few enrolled patients. Bi-/tri-specific antibodies (e.g., bispecific T-cell engager (BiTE) and dual-affinity retargeting (DART)) exhibited 11–67% CR rates with 13–78% risk of cytokine-releasing syndrome (CRS). Conventional chemotherapy in combination with anti-PD-1/anti-CTLA4 antibody for relapsed/refractory AML showed 10–36% CR rates with 7–24 month-long median survival. The current advantages of IO therapy in the field of AML are summarized herein. However, although cancer vaccination should be included in the concept of IO therapy, it is not mentioned in this review because of the paucity of relevant evidence. 相似文献
43.
Form selection of concomitant polymorphs: A case study informed by crystallization kinetics modeling
Weiwei Tang Yufeng Quan Junbo Gong Jingkang Wang Qiuxiang Yin Tonglei Li 《American Institute of Chemical Engineers》2021,67(4):e17129
Molecular mechanisms and process kinetics of crystallizing concomitant polymorphs remain poorly understood. Solvent-mediated phase transformation and concomitant crystallization are difficult to be distinguished in practice, as multiple forms can be detected at the same time. Herein, we developed a population balance model to simulate a concomitant crystallization process of two polymorphs of tolfenamic acid. Our kinetic modeling aims to understand concomitant crystallization and help guide form selection of such a molecular system. Crystallization kinetics of ethanolic solutions were uncovered from induction time measurements, as well as seeded and unseeded crystallization experiments. Experimental and simulation results demonstrate that the stable form I crystallizes concomitantly with the metastable form II. The faster growing form II results in an intermediate decline in the composition of form I in crystallized samples, a characteristic feature of the concomitantly crystallized system. A four-quadrant scheme of attainable polymorph outcome was simulated under various crystallization conditions. 相似文献
44.
为了建立一种准确性高、成本低的植物油中苯并(a)芘测定的样品前处理方法,基于GB 5009.7—2016以自制氧化铝柱为固相萃取柱,采用单因素试验对称样量、洗脱剂量、洗脱流速、吸附剂存放时间、吸附剂量这5个影响植物油中苯并(a)芘洗脱的因素进行研究,优化前处理条件,并对测定方法进行考察。结果表明:优化的前处理条件为称样量0.100 0 g、洗脱剂量120 mL、吸附剂(氧化铝)量22 g、洗脱流速1滴/2 s、吸附剂存放时间少于12周;方法检出限为0.2 μg/L,样品加标回收率为94.23%~100.00%,RSD为1.20%~7.36%;同一样品测定结果与SGS测定值接近,相对平均偏差为2.36%~3.50%。说明本试验方法测定结果准确,可应用于油脂企业植物油中痕量苯并(a)芘的测定。 相似文献
45.
Cheng-Chin Huang Ching-Yao Yang Chin-Chuan Su Kai-Min Fang Cheng-Chieh Yen Ching-Ting Lin Jui-Min Liu Kuan-I Lee Ya-Wen Chen Shing-Hwa Liu Chun-Fa Huang 《International journal of molecular sciences》2021,22(9)
4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), a major active metabolite of bisphenol A (BPA), is generated in the mammalian liver. Some studies have suggested that MBP exerts greater toxicity than BPA. However, the mechanism underlying MBP-induced pancreatic β-cell cytotoxicity remains largely unclear. This study demonstrated the cytotoxicity of MBP in pancreatic β-cells and elucidated the cellular mechanism involved in MBP-induced β-cell death. Our results showed that MBP exposure significantly reduced cell viability, caused insulin secretion dysfunction, and induced apoptotic events including increased caspase-3 activity and the expression of active forms of caspase-3/-7/-9 and PARP protein. In addition, MBP triggered endoplasmic reticulum (ER) stress, as indicated by the upregulation of GRP 78, CHOP, and cleaved caspase-12 proteins. Pretreatment with 4-phenylbutyric acid (4-PBA; a pharmacological inhibitor of ER stress) markedly reversed MBP-induced ER stress and apoptosis-related signals. Furthermore, exposure to MBP significantly induced the protein phosphorylation of JNK and AMP-activated protein kinase (AMPK)α. Pretreatment of β-cells with pharmacological inhibitors for JNK (SP600125) and AMPK (compound C), respectively, effectively abrogated the MBP-induced apoptosis-related signals. Both JNK and AMPK inhibitors also suppressed the MBP-induced activation of JNK and AMPKα and of each other. In conclusion, these findings suggest that MBP exposure exerts cytotoxicity on β-cells via the interdependent activation of JNK and AMPKα, which regulates the downstream apoptotic signaling pathway. 相似文献
46.
47.
传统通信模拟系统设计较为复杂,导致模拟过程消耗能量较大,不能准确模拟稳频通信质量。因此,提出基于Matlab的量子激光雷达稳频通信模拟系统。由于振荡器是雷达形成初始信号源的基础,通过分析振荡电路与相位噪声,获得相位噪声函数与通信频率存在的关系;为确保通信过程的稳定,将准确性与稳定性作为信号质量的评价指标,并采用锁频环稳频技术计算频率偏移程度,根据PID控制算法控制频率,量子激光雷达稳频通信;利用Matlab确定激光器、探测器等硬件组成结构,通过时序与数字阵列的设置完成模拟系统设计。仿真结果表明所提系统结构简便、性能稳定,能够真实模拟出稳频通信的信号质量。 相似文献
48.
49.
50.
《Ceramics International》2022,48(21):31491-31499
In this study, an all-solid-state electrochromic device (ECD) with the structure of ITO/WO3/Al2SiO5/NiOx/ITO was prepared, and the effect of the Al2SiO5 solid electrolyte thicknesses on the opto-electrical performance was investigated. The microstructure and surface morphology were characterized using XRD, SEM and AFM, and the surface morphology and degree of surface looseness demonstrate a significant influence on the opto-electrical properties of ECDs. The charge transfer dynamics at the solid-solid interface were characterized using EIS to obtain an ionic conductivity of 4.637 × 10-8 S/cm. CV, CA and UV–Visible spectra were employed to record the in situ electrochemical and optical properties. The results revealed that the highest optical modulation was 44.58%, the coloring and bleaching times were 14.8 s and 3.7 s, and the highest coloring efficiency was 98.17 cm2/C, which indicates that excellent opto-electrical properties were obtained. When the thickness increases, the degree of surface dense morphology transforms, and the loose morphology is more favorable for ion conductivity, which improves the opto-electrical properties. The results in this study provide insights into the understanding of Al3+-based all-solid-state ECDs, which promote the exploration of new types of Al3+ ionic conductors for all-solid-state ECDs. 相似文献