成人急性髓系白血病治疗现状及新药研究进展

急性髓系白血病（Acute myeloid leukemia, AML）是一类高度异质性疾病,过去常规诱导化疗和各类支持治疗为主,但随着二代测序等技术应用以来,AML药物迅速发展。本文从细胞毒药物、小分子靶向药物以及免疫靶向药物等方面,系统概述AML的致病机制,以及临床研究中较为前沿的各类新型药物（如FLT3抑制剂Midostaurin、IDH抑制剂AG-221和CPX-351等）的研究进展,旨在为AML的新药研发提供参考。     

Selective induction of apoptosis in MCF7 cancer-cell by targeted liposomes functionalised with mannose-6-phosphate

Liposomes are versatile platforms to carry anticancer drugs in targeted drug delivery; they can be surface modified by different strategies and, when coupled with targeting ligands, are able to increase cellular internalisation and organelle-specific drug delivery. An interesting strategy of antitumoral therapy could involve the use of lysosomotropic ligand-targeted liposomes loaded with molecules, which can induce lysosomal membrane permeabilization (LMP), leakage of cathepsins into the cytoplasm and subsequent apoptosis. We have previously demonstrated the ability of liposomes functionalised with a mannose-6-phosphate to reach lysosomes; in this research we compare the behaviour of M6P-modified and non-functionalised liposomes in MCF7 tumour cell and in HDF normal cells. With this aim, we first demonstrated by Western blotting the overexpression of mannose-6-phosphate/insulin-like growth factor (M6P/IGF-II) receptor in MCF7. Then, we prepared calcein-loaded liposomes and we revealed the increased uptake of M6P-functionalised liposomes in MCF7 cells respect to HDF cells by flow cytometry analysis. Finally, we loaded functionalised and not functionalised liposomes with N-hexanoyl-d-erythro-sphingosine (C6Cer), able to initiate LMP-induced apoptosis; after having studied the stability of both vesicles in the presence of serum by Dynamic Light Scattering and Spectrophotometric turbidity measurements, we showed that ceramide-loaded M6P-liposomes significantly increased apoptosis in MCF7 with respect to HDF cells.     

Drug delivery targets and systems for targeted treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease that selectively attacks human joints. The common non-targeted treatment approaches lead to obvious side effect and systemtic complication for RA patients. Therefore, targeted drug delivery for treatment of RA has gained much attetntion in the past few years. In this paper, we reviewed the potential targets (folate receptor, angiogenesis, matrix metalloproteases, selectins, vasoactive intestinal peptide receptor andFc-γ receptor) that could be utilised to facilitate the specific delivery of drugs to the inflammed synovium and also presented different drug delivery systems for targeting RA, including the liposomes, various types of nanoparticles, polymeric micelles and the macromolecular prodrugs. The strategies combining nanotechnologies and ligand mediated active targeting for RA would be emphatically illustrated, which was expected to be helpful for identifying technologies and drug delivery methods for targeted treatment of RA.     

Aptamer micelles targeting fractalkine-expressing cancer cells in vitro and in vivo

In this work we hypothesized that the chemokine fractalkine can serve as a cancer molecular target. We engineered aptamer micelles functionalized with an outer poly(ethylene glycol) (PEG) corona, and investigated the extent and efficacy of using them as a targeting tool against fractalkine-expressing colon adenocarcinoma cells. In vitro cell binding results showed that aptamer micelles bound and internalized to fractalkine-expressing cancer cells with the majority of the micelles found free in the cytoplasm. Minimal surface binding was observed by healthy cells. Even though partial PEGylation did not prevent serum adsorption, micelles were highly resistant to endonuclease and exonuclease degradation. In vivo biodistribution studies and confocal studies demonstrated that even though both aptamer and control micelles showed tumor accumulation, only the aptamer micelles internalized into fractalkine-expressing cancer cells, thus demonstrating the potential of the approach and showing that fractalkine may serve as a specific target for nanoparticle delivery to cancer cells.     

Dépistage néonatal ciblé de la drépanocytose : limites du test de falciformation (test d’Emmel) dans le bilan prénatal en zone ouest africaine

Background

Newborn screening for sickle cell anemia is necessary in Africa where the disease is more frequent. Hemoglobin electrophoresis is used for screening, but is limited by a high cost and difficult access. Sickling test (Emmel test), which is more affordable and technically more accessible, is often requested for prenatal assessment of pregnant women in West African areas to reserve screening for newborns from mothers in whom the positive sickling test attests the presence of hemoglobin S. This study aims to evaluate the number of undetected sickle cell anemia newborns by a screening policy targeting only newborns from mothers in whom a sickling test would have been positive.

DC-CIK细胞联合EGFR-TKI治疗35例老年晚期EGFR突变肺癌的效果

目的 探讨树突状细胞-细胞因子诱导的杀伤细胞(DC-CIK)联合表皮生长因子受体酪氨酸激酶抑制剂(EGRF-TKI)治疗老年晚期表皮生长因子受体(EGFR)突变肺癌的临床疗效。 方法 将70例Ⅳ期EGFR突变肺癌患者分为治疗组和对照组。治疗组35例,给予DC-CIK细胞治疗联合吉非替尼或厄洛替尼靶向治疗;对照组35例,给予吉非替尼或厄洛替尼靶向治疗。 结果 治疗组的疾病控制率(DCR)为88.6%,高于对照组的68.6%(P=0.041),治疗组生活质量评分改善率为71.4%,高于对照组的45.7%(P=0.029),差异均有统计学意义。治疗组和对照组的1年、2年和3年总生存(OS)率分别为62.9% vs 57.1%、37.1% vs 31.4%和8.6% vs 2.9%,两组比较差异无统计学意义(P=0.217)。治疗组和对照组的1年、2年和3年无进展生存(PFS)率分别为57.1% vs 31.4%、20.0% vs 5.7%和2.9% vs 0%,两组差异有统计学意义(P=0.005)。多因素分析显示,腺癌(HR=0.178,95%CI:0.061~0.523)及高分化(HR=0.058,95%CI:0.015~0.228)患者OS更长,腺癌(HR=0.271,95%CI:0.094~0.777)及高分化(HR=0.089,95%CI:0.029~0.272)患者PFS也更长。治疗组和对照组不良反应发生率差异无统计学意义(P>0.05)。 结论 DC-CIK细胞联合EGRF-TKI可以提高晚期老年EGFR突变肺癌患者的疾病控制率和生活质量,延长患者的PFS。     

Adequate sentinel node harvest is associated with low false negative rate in breast cancer managed with neoadjuvant chemotherapy and targeted axillary dissection

IntroductionAfter neoadjuvant chemotherapy (NAC) for clinically node-positive breast cancer (NPBC), targeted axillary dissection (TAD) reduces the false negative rate (FNR) of axillary node sampling. Axillary lymph node dissection (ALND) is indicated if the clipped node cannot be identified. Prior studies have indicated that a sentinel lymph node harvest (SLNH) of ≥3 also leads to low FNR. We investigated the performance of SLNH thresholds at inferring the status of the axilla during TAD.MethodsRetrospective review of the Legacy Health System Tumor Registry was performed. We identified NPBC patients between 2011 and 2016 managed with NAC and TAD.ResultsIn 29 patients, the FNR of the SLNB component of TAD was 11% with SLNH of ≥3; with SLNH of ≤2 nodes the FNR was 20%.ConclusionsIn patients with NPBC receiving NAC, adequate SLNH is associated with acceptably low FNR. The decision to pursue ALND for clip identification should be made on a case-by-case basis.     

El problema de la estadificación axilar en el cáncer de mama tras quimioterapia neoadyuvante. Papel de la disección axilar dirigida y tipos de marcadores ganglionares

Targeted axillary dissection (TAD) consists of a new axillary staging technique that combines sentinel lymph node biopsy (SLNB) and clipped lymph node biopsy (CLNB) in the same surgery, in order to re-stage patients with breast cancer and positive axillary lymph nodes undergoing neoadjuvant chemotherapy (NAQT). Prior to the NAQT, the affected lymph node is punctured and a solid marker is left inside echo-guided, in order to biopsy it in the subsequent surgery. There are numerous types of markers: metallic (steel, titanium or polyglycolic acid clips), radioiodine or ferromagnetic seeds, which differ in the method of location (wire, gamma-detection or magnetic probe). The aim of this study is to perform a systematic review about the current status of the TAD, as well as to explain the different techniques and types of axillary marking, based on the current available evidence.     

Prognosis of HER2-positive pregnancy-associated breast cancer: Analysis from the French CALG (Cancer Associé à La Grossesse) network

IntroductionThe prevalence of pregnancy-associated breast cancer is increasing. HER2-positive breast cancers typically have a poor prognosis. The objective of our study was to compare the prognosis of patients with HER2-positive breast cancer diagnosed during pregnancy (HER2-positive BCP) to young women diagnosed with HER2-positive breast cancer outside of pregnancy (HER2 non-BCP).MethodsData of patients managed for invasive breast carcinoma between January 2005 and 2020 were retrospectively collected from the database of Tenon University Hospital (Paris, France), part of the “Cancer lié à la Grossesse” network.ResultsFifty-one patients with HER2-positive BCP were matched on age at diagnosis with 51 HER2-positive non-BCP patients. Locally advanced disease with axillary lymph node involvement were frequent. Tumors were frequently aggressive with high grade (p = 0.57) and high Ki67 (p = 0.15). Among the HER2-positive BCP patients, the mean term at diagnosis was 19.3 week of gestation (WG). Eighty-four percent of the patients continued their pregnancy with a mean term at delivery of 34.2WG. Chemotherapy modalities differed between the two groups: neoadjuvant chemotherapy was more frequent in the HER2-positive BCP group (p = 0.03) and adjuvant chemotherapy more frequent in the HER2 non-BCP group (p = 0.009). The recurrence rate was 10% (n = 5) and 18% (n = 9) in the HER2-positive BCP and HER2 non-BCP groups, respectively, p = 0.25. Breast cancer-free survival was poorer in the HER2-positive BCP group with earlier recurrence, p = 0.008. No difference in type of recurrence was found between the groups (p = 0.58).ConclusionThis matched case-control study implies that patients with HER2-positive BCP still have a poorer prognosis than non-pregnant HER-positive patients.     

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。