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.The short-term effect of aortic sinoplasty on repairing aortic roots of patients with acute type A aortic dissection
Yi CHANG ; Xiangyang QIAN ; Hongwei GUO ; Yizhen WEI ; Yi SHI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2021;28(12):1441-1446
Objective To investigate the feasibility, effectiveness and durability of aortic sinoplasty in repairing aortic roots of patients with acute type A aortic dissection. Methods From January 2014 to July 2017, 43 consecutive patients with acute type A aortic dissection underwent aortic sinoplasty to repair aortic root in our institution, including 34 males and 9 females, aged 32-65 (50.1±8.1) years. The perioperative and follow-up data were retrospectively analyzed, and statistical analysis on the preoperative, postoperative and follow-up ultrasound indicators was performed. Results Thirty-day mortality was 4.7%. Preoperative aortic regurgitation was corrected and false lumen was eliminated immediately after operation in all patients. There was no late death, or aortic root or valve re-intervention and two patients were lost during a follow-up of 18-45 (27.9±6.7) months. There was no residual dissection found. No patients had significant dilation of aortic root. No statistically significant difference was found when comparing the maximum of root diameter and aortic regurgitation grade between at discharge and follow-up. Conclusion Aortic sinoplasty for aortic root repair in acute type A aortic dissection is a simple and reliable technique and demonstrates excellent early outcomes.
3.Advances in multimodality therapy for hepatocellular carcinoma
Journal of Clinical Hepatology 2020;36(10):2179-2183
Primary liver cancer is one of the most common malignances worldwide, among which hepatocellular carcinoma (HCC) accounts for about 90% of all cases. Multidisciplinary multimodality therapy involving surgery, ablation, interventional treatment, targeted therapy, and immunotherapy is an effective strategy for the treatment of liver cancer. In recent years, great achievements have been made in multimodality therapy for liver cancer, especially the advances in combination therapy for advanced liver cancer and drug research and development, which improves the overall prognosis of liver cancer patients, and the improvement in targeted drug therapy and immunotherapy is expected to change the pattern of multimodality therapy for liver cancer. This article systematically reviews the recent advances in multimodality therapy for liver cancer from the aspects of local treatment and systemic therapy.
4.Toxicity effect of cadmium stress exposure to insects and defense mechanism of insects
Weili FU ; Yizhen DU ; Min ZHANG
Chinese Journal of Pharmacology and Toxicology 2015;(6):1001-1006
Cadmium is one of the important heavy metal pollutants with strong toxicity and wide distribution. It poses a threat to human health and invertebrates,especially to insects. It has been demonstrated that cadmium can infiltrate into insects through respiration ,food intake and so on. It can affect their development,and even induce apoptosis via oxidative damage. Insects can gradually develop defense mechanisms against cadmium with the help of metallothionein,antioxidant enzymes, excretion and heat shock protein. Toxicity effect varies among different species. This paper reviewsed the effect of cadmium on development,cell apoptosis mechanism and defense mechanism in insects.

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