1.Safety, dosimetry, and efficacy of an optimized long-acting somatostatin analog for peptide receptor radionuclide therapy in metastatic neuroendocrine tumors: From preclinical testing to first-in-human study.
Wei GUO ; Xuejun WEN ; Yuhang CHEN ; Tianzhi ZHAO ; Jia LIU ; Yucen TAO ; Hao FU ; Hongjian WANG ; Weizhi XU ; Yizhen PANG ; Liang ZHAO ; Jingxiong HUANG ; Pengfei XU ; Zhide GUO ; Weibing MIAO ; Jingjing ZHANG ; Xiaoyuan CHEN ; Haojun CHEN
Acta Pharmaceutica Sinica B 2025;15(2):707-721
Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as 177Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of 177Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, 177Lu-LNC1010, for PRRT. In preclinical studies, 177Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of 177Lu-LNC1010 in patients with advanced/metastatic NETs. 177Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of 177Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two 177Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.
2.LncRNA SBF2-AS1 Regulates Invasion and Proliferation of Hepatocellular Carcinoma Cells Through miR-372-3p/CDK6 Axis
Wei SONG ; Rong XU ; Yupeng LI ; Zhide LI ; Jinguo WANG ; Chao MA ; Yuan MENG ; Xiong CHEN
Cancer Research on Prevention and Treatment 2023;50(7):666-674
Objective To investigate the effects of lncRNA SBF2-AS1 on the proliferation and invasion of hepatoma cells by regulating the miR-372-3p/CDK6 pathway. Methods Bel7402 and SK-hep1 cells were selected as research objects. The expression levels of SBF2-AS1, miR-372-3p, and CDK6 were up- or down-regulated according to different experimental stages, while the expression levels of miR-372-3p and CDK6 in cells were detected by real-time fluorescence quantitative PCR and Western blot. Dual luciferase reporter assay verified the targeting relationships between SBF2-AS1 and miR-372-3p as well as miR-372-3p and CDK6, respectively. CCK-8, colony formation assay, Transwell, cell cycle assay, and flow cytometry were used to analyze cell proliferation, colony formation, migration/invasion ability, cell cycle activity, and apoptosis. Results SBF2-AS1 was highly expressed in hepatocellular carcinoma cells (
3.Catalytic Spectrophotometric Determination of Osmium (Ⅳ) Using Osmium (Ⅳ)-KIO4-Chlorophosphonazo-mA System
Hongping XU ; Jiang LI ; Xingguo CHEN ; Zhide HU
Chinese Journal of Analytical Chemistry 2001;29(5):546-548
A catalytic spectrophotometric method for the determination of micro amounts of osmium has been established based on the catalytic action of Os(Ⅳ) on the oxidation fading reaction of chlorophosphonazo-mA with KIO4 in alkaline-medium. The reaction conditions were optimized by orthogonal experimental design. The detection limit for osmium was 2.0 μg/L.Beer's law was obeyed in the range from 7.0 to 25.0 μg/L for Os(Ⅳ). The method has been applied to the determination of micro amounts of Os(Ⅳ) in concentrate of noble metals and secondary alloy,both of the relative errors were 0.9%. Recoveries varied from 95.38% to 106.0%.
4.Clinical Study of Using Cinobufotalin and Chemotherapeutic Agents by Transcatheter Arterial with Oily Chemoembolization in the Treatment of Primary Liver Cancer
Yiping ZHANG ; Shaoxiong XU ; Guoyan SHANG ; Zhide XU ; Yingke LIU ; Shuanlin JIAO
Journal of Practical Radiology 1992;0(11):-
Objective To evaluate the effect of cinobufotalin and chemotherapeutic agents by transcatheter arterial with oilychemoembolization(TACE) in the treatment of primary liver cancer.Methods 144 patients with HCC proved histopathologically were divided into 2 groups.76 of them(group A) were treated by transcatheter arterial infusion(TAI) with cinobufotalin 100 ml,DDP and 5-FU,then embolism with iodized oil mixed ADM;while the other 68 patients(group B) were treated by TAI with DDP and 5-FU,then embolism with iodized oil mixed ADM.The serum T lymphocytes,HBV DNA,AFP and CT scan were acquired before and after treatment.Results The effective rate(PR+MR) of group A was 86.64%,the lymphocyte transformation rate(LTT),T lymphocytes CD_3~+,CD_4~+proportion and CD_4~+/CD_8~+ratio markedly increased;HBV DNA descended in 21 cases,unchanged in 46 cases,and elevated in 9 cases;1 and 2 year survival rate was 86.84%(66/76)and71.05%(54/76) respectively.The effective rate(PR+MR) of group B was 72.73%,LTT,T lymphocytesCD_3~+,CD_4~+proportion and CD_4~+/CD_8~+ratio markedly descended;HBV DNA descended in 2 cases,unchanged in 20 cases and elevated in 46 cases;1 and 2 year survival rate was 72.73%(48/68) and 54.41%(37/68) respectively.There were significant statistical differences between the two groups(P

Result Analysis
Print
Save
E-mail