载多柔比星人血清白蛋白毫微粒和两种免疫毫微粒的体内外靶向性研究

目的 构建载多柔比星的普通毫微粒、全抗体免疫毫微粒和抗体F(ab’)2片段免疫毫微粒，比较它们对肿瘤的体外和体内靶向性，寻找对肿瘤组织具有特异性靶向作用的制剂。方法 采用异型双功能交联剂琥珀酰亚胺基-3-(2-吡啶二硫)丙酸酯(SPDF)，将兔抗大鼠乳腺癌细胞系Walker-256细胞的多克隆抗体(Wab)和其F(ab’)2片段即WF(ab’)2与载多柔比星(Doxorubicin，DRB)的人血清白蛋白毫微粒(DRB-HSA-NP)交联，制备全抗体免疫毫微粒Wab-DRB-HSA-NP和F(ab’)2片段免疫毫微粒WF(ab’)2-DRB-HSA-NP，比较它们的体外肿瘤细胞靶向性和体内组织器官靶向性。结果 与DRB-HSA-NP相比，两种免疫毫微粒均有较好的体外肿瘤特异靶向性，瘤体内给药后在瘤体内的滞留量也显著增高，特别是WF(ab’)2-DRB-HSA-NP，由于所偶联的抗体切除了FC段，降低了抗体与巨噬细胞的结合。结论 免疫毫微粒，特别是WF(ab’)2-DRB-HSA-NP具有较好的肿瘤肥向性，是一种很有价值的靶向制剂。     

PEG-PLGA纳米颗粒载体药物靶向治疗肿瘤的研究进展

肿瘤是近年来临床多发的难治性疾病,是导致死亡的主要原因之一,手术及放、化疗是常规治疗手段.但晚期转移者无法手术,传统放、化疗缺乏针对性,且多有严重不良反应,致使人们普遍关注靶向治疗,因此,其已成为一个热点问题.本文纳入大量相关中外文献,综述并讨论近年来以PEG-PLGA纳米粒子为载体治疗肿瘤的靶向给药系统的研究进展,并分析了存在的问题.     

Enhancing effect of cetylmannoside on targeting of liposomes to Kupffer cells in rats

In order to evaluate whether surface modification of liposomes by cetylmannoside (Man) could be useful for targeting to Kupffer cells, the effect of Man on disposition of liposomes was examined after intravenous administration to rats. In the case of small unilamellar vesicles (SUV), no difference in disposition was observed between control liposomes (PC-SUV) and modified liposomes (Man-SUV). On the other hand, in the case of multilamellar vesicles (MLV), modified liposomes (Man-MLV) were rapidly eliminated from the circulation, and showed higher accumulation (51.4% of dose) in the liver as compared with control liposomes (PC-MLV, 25.7% of dose). In the spleen, splenic clearance of Man-MLV (0.068 ml/min) was comparable to that of PC-MLV (0.068 ml/min), although Man-MLV showed lower accumulation (5.7% of dose) than PC-MLV (14.7% of dose). This lower accumulation in the spleen of Man-MLV might be due to the low blood concentration caused by the high accumulation in the liver. Thus, it is considered that liposomal size is important in revealing the effects of Man, and Man-MLV is able to enhance only the affinity for the liver. The cellular distribution in the liver of Man-MLV 2 h after intravenous administration to rats gave encouraging evidence that Kupffer cells might be involved in the enhanced hepatic uptake of the liposomes. These results suggest the usefulness of Man-MLV for targeting to Kupffer cells. Furthermore, the involvement of plasma protein(s) in the uptake of Man-MLV is suspected.     

Transcatheter arterial embolization in unresectable hepatocellular carcinoma

Seven hundred thirty-nine patients with unresectable hepatocellular carcinoma have been treated by transcatheter arterial chemoembolization using gelatin sponge particles soaked in a solution of Mitomycin C and Adriamycin. This therapy can be equal, or superior to surgical resection and serves both as embolic therapy and targeted chemotherapy.     

Being targeted: Young women's experience of being identified for a teenage pregnancy prevention programme

Research on the unintended consequences of targeting ‘high-risk’ young people for health interventions is limited. Using qualitative data from an evaluation of the Teens & Toddlers Pregnancy Prevention programme, we explored how young women experienced being identified as at risk for teenage pregnancy to understand the processes via which unintended consequences may occur. Schools' lack of transparency regarding the targeting strategy and criteria led to feelings of confusion and mistrust among some young women. Black and minority ethnic young women perceived that the assessment of their risk was based on stereotyping. Others felt their outgoing character was misinterpreted as signifying risk. To manage these imposed labels, stigma and reputational risks, young women responded to being targeted by adopting strategies, such as distancing, silence and refusal. To limit harmful consequences, programmes could involve prospective participants in determining their need for intervention or introduce programmes for young people at all levels of risk.     

Which parameters are needed for targeting a multitined radiofrequency device—an approach to a simple algorithm

Background  The use of radiofrequency ablation (RFA) for treatment of liver malignancies is limited by the high rate of local recurrences. The aim of this experimental study was to evaluate parameters describing the reproducible target volume of a RFA procedure in order to facilitate better applicator placement. Materials and methods  RFA was performed in perfused and nonperfused pig livers. The following parameters were measured: axial and transverse diameter, front margin, coagulation center, diameter of sphere ablated (D _S), distance to center (DC), and volume. Graphic overlays were utilized to visualize variability. Parameters were evaluated for Rita XL (2 algorithms), LeVeen, and Rita Xli applicators. Results  The best prediction of a reproducibly ablated target volume can be made by the diameter of the sphere ablated and the distance of the applicator tip to center of the sphere (DC). The spheres were significantly different in diameter (D _S) depending on the applicator Rita XL 29 ± 6 mm, Rita XL^wet 35 ± 5 mm, LeVeen 35 ± 8 mm, Rita Xli 44 ± 5 mm (perfused livers, p < 0.001). Graphic overlay demonstrated differences in variability that can influence the reliability of the system. Conclusions   D _S and DC as specific values for each applicator and algorithm facilitate a placement of the applicator relative to the target volume that maximizes the chance of complete ablation.     

Response of olfactory axons to loss of synaptic targets in the adult mouse

Glomerular convergence has been proposed to rely on interactions between like olfactory axons, however topographic targeting is influenced by guidance molecules encountered in the olfactory bulb. Disruption of these cues during development misdirects sensory axons, however little is known about the role of bulb-derived signals in later life, as new axons arise during turnover of the olfactory sensory neuron (OSN) population. To evaluate the contribution of bulb neurons in maintaining topographic projections in adults, we ablated them with N-methyl-d-aspartate (NMDA) in P2-IRES-tauLacZ mice and examined how sensory axons responded to loss of their postsynaptic partners. NMDA lesion eliminated bulb neurons without damage to sensory axons or olfactory ensheathing glia. P2 axons contained within glomeruli at the time of lesion maintained convergence at these locations; there was no evidence of compensatory growth into the remnant tissue. Delayed apoptosis of OSNs in the target-deprived epithelium led to declines in P2 neuron number as well as the gradual atrophy, and in some cases complete loss, of P2 glomeruli in lesioned bulbs by 3 weeks. Increased cell proliferation in the epithelium partially restored the OSN population, and by 8 weeks, new P2 axons distributed within diverse locations in the bulb remnant and within the anterior olfactory nucleus. Prior studies have suggested that initial development of olfactory topography does not rely on synapse formation with target neurons, however the present data demonstrate that continued maintenance of the sensory map requires the presence of sufficient numbers and/or types of available bulbar synaptic targets.     

Advances in targeting the WNT/β-catenin signaling pathway in cancer

WNT/β-catenin signaling orchestrates various physiological processes, including embryonic development, growth, tissue homeostasis, and regeneration. Abnormal WNT/β-catenin signaling is associated with various cancers and its inhibition has shown effective antitumor responses. In this review, we discuss the pathway, potential targets for the development of WNT/β-catenin inhibitors, available inhibitors, and their specific molecular interactions with the target proteins. We also discuss inhibitors that are in clinical trials and describe potential new avenues for therapeutically targeting the WNT/β-catenin pathway. Furthermore, we introduce emerging strategies, including artificial intelligence (AI)-assisted tools and technology-based actionable approaches, to translate WNT/β-catenin inhibitors to the clinic for cancer therapy.     

一种新型抗体替代品——亲和体的研究进展

作为抗体的一种新型替代品,亲和体不仅以高亲和力与靶蛋白特异性结合,同时又具备相对分子质量小（~6 500）、穿透性强、免疫原性弱和制备过程简单等诸多特性。因此,亲和体在肿瘤靶向治疗、体内成像诊断和生物技术应用等方面具更突出的优势和可行性。此文对其特性和应用研究进展做一综述。     

Functions of tumorigenic and migrating cancer progenitor cells in cancer progression and metastasis and their therapeutic implications

The in vitro and in vivo characterization of adult stem cells has allowed researchers to identify certain specific functional features to each tissue-specific stem cell. Moreover, recent studies revealed that their malignant counterparts, the cancer progenitor cells with stem cell-like properties, may assume a crucial role for the initiation and progression of locally invasive cancers into disseminated and incurable disease states. Therefore, a new direction in cancer research appears necessary in considering the critical functions of cancer progenitor cells. In this review, we discuss recent concepts on the critical roles of tumorigenic and migrating cancer progenitor cells in carcinogenesis. Particularly, we describe the tumorigenic cascades that are frequently activated through the interplay of diverse hormones, growth factors, cytokines and integrins in cancer progenitor cells versus their further differentiated progeny. The emphasis is on the oncogenic signaling pathways activated during the localized cancer progression and micrometastatic events involved in tumor formation at distant sites such as bone marrow. Of therapeutic interest, important information for the selective molecular targeting of cancer progenitor cells, which must now be considered in developing new effective diagnostic and prognostic methods and curative treatments against the most locally advanced and metastatic cancers, is also described.