分子核医学在甲状腺癌影像诊断与靶向治疗中的应用分析

目的探讨分子核医学在甲状腺癌影像诊断与靶向治疗中的应用效果。方法选取我院2011年²012年间收治的60例甲状腺癌患者作为研究对象,将患者随机分为观察组与对照组,观察组40例,应用分子核医学进行诊断和治疗。结果经过分子核医学的相关技术进行影像诊断,观察组患者的病情更直观的表现出来,为临床诊治提供了重要的参考资料。观察组患者的有效率为85%,对照组有效率为60%,两组数据结果比较差异具有统计学意义(P<0.05)。结论分子核医学在甲状腺癌影像诊断与靶向治疗中具有良好的应用效果。     

Functional differentiation of cytotoxic cancer drugs and targeted cancer therapeutics

There is no nationally or internationally binding definition of the term “cytotoxic drug” although this term is used in a variety of regulations for pharmaceutical development and manufacturing of drugs as well as in regulations for protecting medical personnel from occupational exposure in pharmacy, hospital, and other healthcare settings. The term “cytotoxic drug” is frequently used as a synonym for any and all oncology or antineoplastic drugs. Pharmaceutical companies generate and receive requests for assessments of the potential hazards of drugs regularly – including cytotoxicity. This publication is intended to provide functional definitions that help to differentiate between generically-cytotoxic cancer drugs of significant risk to normal human tissues, and targeted cancer therapeutics that pose much lesser risks. Together with specific assessments, it provides comprehensible guidance on how to assess the relevant properties of cancer drugs, and how targeted therapeutics discriminate between cancer and normal cells. The position of several regulatory agencies in the long-term is clearly to regulate all drugs regardless of classification, according to scientific risk based data. Despite ongoing discussions on how to replace the term “cytotoxic drugs” in current regulations, it is expected that its use will continue for the near future.     

Hydroxyapatite nanorods loaded with parathyroid hormone (PTH) synergistically enhance the net formative effect of PTH anabolic therapy

Parathyroid hormone (PTH) has been a major contributor to the anabolic therapy for osteoporosis, but its delivery to bone without losing activity and avoiding adverse local effects remain a challenge. Being the natural component of bone, use of hydroxyapatite for this purpose brings a major breakthrough in synergistic anabolism. This study focuses on synthesis, characterization and evaluation of in vitro and in vivo efficacy of PTH (1-34) adsorbed hydroxyapatite nanocarrier for synergistic enhancement in the anabolic activity of PTH for bone regeneration. The negative zeta potential of this nanocarrier facilitated its affinity to the Ca²⁺ rich bone tissue and solubilization at low pH enhanced specific delivery of PTH to the resorption pits in osteoporotic bone. In this process, PTH retained its anabolic effect and at the same time an increase in bone mineral content indicated enhancement of the net formative effect of the PTH anabolic therapy.     

The role of tumor-associated macrophages in the development,metastasis and treatment of breast cancer

Tumor-associated macrophages (TAMs) play an important role in promoting cancer in the breast cancer microenvironment. A large number of preclinical studies have demonstrated that TAMs regulate related signaling pathways by releasing a variety of chemokines, affecting breast cancer growth, metastasis, and drug resistance. In recent years, TAMs have attracted much attention as potential biomarkers for breast cancer. This article reviews the preclinical evidence of the relationship between TAMs and the breast cancer microenvironment, the role of TAMs in prognosis, and the clinical outcomes related to targeted therapy.     

One-step mixing with humanized anti-mPEG bispecific antibody enhances tumor accumulation and therapeutic efficacy of mPEGylated nanoparticles

Methoxy PEGylated nanoparticles (mPEG-NPs) are increasingly used for cancer imaging and therapy. Here we describe a general and simple approach to confer tumor tropism to any mPEG-NP. We demonstrate this approach with humanized bispecific antibodies (BsAbs) that can bind to both mPEG molecules on mPEG-NPs and to EGFR or HER2 molecules overexpressed on the surface of cancer cells. Simple mixing of BsAbs with mPEG-NPs can mediate preferential binding of diverse mPEG-NPs to cancer cells that overexpress EGFR or HER2 under physiological conditions and significantly increase cancer cell killing by liposomal doxorubicin to EGFR⁺ and HER2⁺ cancer cells. BsAbs modification also enhanced accumulation of fluorescence-labeled NPs and significantly increased the anticancer activity of drug-loaded NPs to antigen-positive human tumors in a mouse model. Anti-mPEG BsAbs offer a simple one-step method to confer tumor specificity to mPEG-NPs for enhanced tumor accumulation and improved therapeutic efficacy.     

SM5-1-Conjugated PLA nanoparticles loaded with 5-fluorouracil for targeted hepatocellular carcinoma imaging and therapy

SM5-1 is a humanized mouse antibody which has a high binding specificity for a membrane protein of about 230 kDa overexpressed in hepatocellular carcinoma (HCC), melanoma and breast cancer. In this study, SM5-1-conjugated poly d, l (lactide-coglycolide) (PLA) PLA containing Cy7 (PLA-Cy7-SM5-1) was prepared to study the targeting specificity of the bioconjugate to HCC-LM3-fLuc cell. Then, SM5-1-conjugated PLA containing 5-fluorouracil (5-FU) (PLA-5FU-SM5-1) and PLA containing 5-FU (PLA-5FU) were prepared for treatment of subcutaneous HCC-LM3-fLuc tumor mice. The results showed that PLA-5FU-SM5-1, PLA-5FU and 5-FU induced a 45.07%, 23.56% and 19.05% tumor growth inhibition rate, respectively, on day 31 post-treatment as determined by bioluminescent intensity. In addition, in order to evaluate the antitumor efficacy of PLA-5FU-SM5-1, HCC-LM3-fLuc cells were injected into the liver to establish the experimental orthotopic liver tumor models. The experiments showed that PLA-5FU-SM5-1, PLA-5FU and 5-FU induced a 53.24%, 31.00%, and 18.11% tumor growth inhibition rate, respectively, on day 31 post-treatment determined by the bioluminescent intensity of the abdomen in tumor-bearing mice. Furthermore, we have calculated the three-dimensional location of the liver cancer in mice using a multilevel adaptive finite element algorithm based on bioluminescent intensity decay calibration. The reconstruction results demonstrated that PLA-5FU-SM5-1 inhibited the tumor rapid progression, which were consistent with the results of subcutaneous tumor mice experiments and in vitro cell experiment results.     

局部晚期甲状腺癌分子靶向药物治疗临床疗效及安全性分析

目的 探讨分子靶向药物治疗在局部晚期甲状腺癌中的临床疗效及安全性。方法 回顾性收集2020年4月至2023年4月于四川大学华西医院采用分子靶向药物治疗的91例局部晚期甲状腺癌患者的临床资料,使用实体肿瘤的疗效评价标准1.1版(RECIST 1.1)评估分子靶向药物的临床疗效,使用不良事件通用术语评价标准5.0版(CTCAE5.0)评估分子靶向药物治疗的不良反应,应用Kaplan-Meier法计算患者2年生存率并绘制生存曲线。结果 91例患者客观缓解率(ORR)和疾病控制率(DCR)分别为12.09%(11/91)和80.22%(73/91),2年总生存率和无疾病进展生存率分别为83.52%(95%CI:0.76～0.91)和72.53%(95%CI:0.60～0.85)。治疗相关3级不良反应发生率：手足综合征和疲劳均为4.40%,高血压、咽痛、蛋白尿、腹泻、谷丙转氨酶升高均为1.10%。未观察到因严重不良反应事件致治疗终止的病例发生。结论 分子靶向药物用于治疗局部晚期甲状腺癌患者总体疗效良好,药物的不良反应可控。