Non-canonical role of Hippo tumor suppressor serine/threonine kinase 3 STK3 in prostate cancer

1. Download : Download high-res image (207KB)
2. Download : Download full-size image

     

Synthesis and automated fluorine-18 radiolabeling of new PSMA-617 derivatives with a CuAAC radiosynthetic approach

In the last decade, the development of new radiopharmaceuticals for the imaging and therapy of prostate cancer has been a highly active and important area of research, especially focusing on the prostate-specific membrane antigen (PSMA), an antigen which is upregulated in prostate, as well as in other tumor cells. A large variety of PSMA ligands have been radiolabeled, to date. Among the various derivatives, PSMA-617 resulted to be one of the most interesting in terms of interaction with the antigen and clinical properties, and its lutetium-177 labeled version has recently been approved by regulatory agencies for therapeutic purposes. For this reasons, the radiolabeling with fluorine-18 of a PSMA-617 derivative might be of interest. Beside other methodologies to radiolabel macromolecules with fluorine-18, the “click-chemistry” approach resulted to be very useful, and the copper-catalyzed azide-alkyne cycloaddition (CuAAC) is considered one of most efficient and reliable. This paper proposes the synthesis of a suitable precursor for the radiolabeling with fluorine-18 of a new PSMA-617 derivative. The whole radiosynthetic procedure has been fully automated, and the final product, which proved to be stable in plasma, has been obtained with radiochemical yield and purity suitable for subsequent preclinical studies.     

Delayed haemolytic transfusion reaction due to Kidd antibodies

A delayed haemolytic transfusion reaction (DHTR) encompasses a positive direct antiglobulin test (DAT) developed anytime between 24 hours to 28 days after cessation of transfusion, a positive eluate or a newly identified alloantibody in the plasma or serum along with features of haemolysis in the patient. Routinely, it is expected that with the transfusion of one unit of packed red cells in a patient of average height and weight, the haemoglobin level and hematocrit increase by 1 g/dL and 3% respectively. However, in a patient with DHTR, an inadequate rise of post-transfusion haemoglobin (< 1 g/dL) or rapid fall in haemoglobin back to pre-transfusion levels is observed. Kidd antibodies are particularly known to cause DHTR, maybe alone or in unison with other antibodies. Detection of these alloantibodies is consequential in providing good transfusion support to these patients. These events may be difficult to detect as they may present as varied clinical features or immunological nuisances. In this case series, we have presented three cases of DHTR with special emphasis on their clinical presentations, immunohaematological evaluations, laboratory parameters and the role of proper transfusion support in these patients to avoid further complications.     

前列腺癌早期诊断的研究进展北大核心

前列腺癌(prostate cancer, PCa)是中老年男性常见恶性肿瘤之一,目前尚缺乏有效的晚期癌症治疗方法,因此早期诊断对于降低PCa死亡率至关重要。近年来,较多研究开发出多种新型诊断方法以改善对PCa诊断的准确性,同时避免过度诊疗,但其有效性及实用性尚需进一步验证。本文对目前新型生物标志物、联合成像技术及风险预测模型等的早期诊断技术进行总结,以期为临床研究提供指导作用。     

术前SCC与CYFRA21-1在肺鳞癌患者表达上调及临床意义

目的 分析术前SCC、CYFRA21-1与肺鳞癌临床病理特征、预后之间的关系。方法 收集2017年3月~2018年4月在云南省肿瘤医院确诊的肺鳞癌患者100例为观察组，确诊为肺良性肿瘤患者90名为肺良性肿瘤组、以及正常人群90名为健康人群组。通过电化学发光法对SCC、CYFRA21-1两种指标进行检测。检测SCC、CYFRA21-1含量，分析在肺鳞癌中表达的临床意义。结果 SCC、CYFRA21-1在肺鳞癌中比在肺良性肿瘤、健康人群中含量要高，差异有统计学意义（P＜0.001），并且敏感性均高于其他两组；男性患者的SCC、CYFRA21-1含量高于女性患者，差异具有统计学意义（P＜0.05）；SCC、CYFRA21-1含量在年龄≥60岁的含量高于＜60岁患者，差异无统计学意义（P＞0.05）；有吸烟史患者的SCC含量高于无吸烟史患者，差异无统计学意义（P＞0.05）。CYFRA21-1在吸烟史患者中高表达，差异有统计学意义（P＜0.05）；SCC、CYFRA21-1在有淋巴结转移、远处转移、肿瘤直径≥5 cm、病理分期为晚期时高表达，差异具有统计学意义（P＜0.05）；SCC、CYFRA21-1阳性患者OS、PFS比阴性患者短；SCC、CYFRA21-1两者之间呈正相关,相关系数（r）为0.630。结论 SCC、CYFRA21-1在肺鳞癌中表达上调；SCC、CYFRA21-1与性别之间存在某种内在联系；SCC、CYFRA21-1与肺鳞癌的TNM分期呈正相关；SCC、CYFRA21-1阳性患者OS、PFS比阴性患者短；SCC、CYFRA21-1两者之间呈正相关,相关系数（r）为0.630。     

Role of site-directed mutagenesis and adjuvants in the stability and potency of anthrax protective antigen

Anthrax is a zoonotic infection caused by the gram-positive, aerobic, spore-forming bacterium Bacillus anthracis. Depending on the origin of the infection, serious health problems or mortality is possible. The virulence of B. anthracis is reliant on three pathogenic factors, which are secreted upon infection: protective antigen (PA), lethal factor (LF), and edema factor (EF). Systemic illness results from LF and EF entering cells through the formation of a complex with the heptameric form of PA, bound to the membrane of infected cells through its receptor. The currently available anthrax vaccines have multiple drawbacks, and recombinant PA is considered a promising second-generation vaccine candidate. However, the inherent chemical instability of PA through Asn deamidation at multiple sites prevents its use after long-term storage owing to loss of potency. Moreover, there is a distinct possibility of B. anthracis being used as a bioweapon; thus, the developed vaccine should remain efficacious and stable over the long-term. Second-generation anthrax vaccines with appropriate adjuvant formulations for enhanced immunogenicity and safety are desired. In this article, using protein engineering approaches, we have reviewed the stabilization of anthrax vaccine candidates that are currently licensed or under preclinical and clinical trials. We have also proposed a formulation to enhance recombinant PA vaccine potency via adjuvant formulation.     

Metastasis-directed Therapy in Prostate Cancer: Prognostic Significance of the ESTRO/EORTC Classification in Oligometastatic Bone Disease

AimsOligometastatic disease (OMD) represents a spectrum of clinical scenarios and various classification systems have been proposed. Bone-only OMD can occur in patients with advanced prostate cancer and validated decision-making tools are needed to assist patient selection for metastasis-directed therapy. The aim of the present study was to determine the prognostic utility of a classification system for OMD.Materials and methodsA retrospective review was conducted of all patients with bone-only oligometastatic prostate cancer treated with stereotactic body radiotherapy (SBRT) since November 2011. SBRT was delivered using CyberKnife® and gantry-based linear accelerator platforms. All patients were classified into oligometastatic states based on the European Society for Radiotherapy and Oncology/European Organisation for Research and Treatment of Cancer (ESTRO/EORTC) classification system. Kaplan–Meier and Cox regression analyses were carried out to determine the prognostic utility of this classification system.ResultsIn total, 105 patients with 145 osseous metastases were treated over 119 sessions. The median follow-up after SBRT was 23 months (interquartile range 10–39.8). Twelve patients had died after a median time of 31 months. The 3-year metastatic progression-free survival was 23% (95% confidence interval 13–32) and the 3-year overall survival was 88% (95% confidence interval 80–96). Patients in a metachronous oligometastatic state were 4.50 (95% confidence interval 1.19–17.10, P = 0.03) times more likely to experience metastatic progression compared with those with synchronous oligometastases, and 6.69 (95% confidence interval 1.05–42.50, P = 0.04) times more likely to experience any failure. Hazard ratio magnitudes increased for patients in a repeat oligometastatic state. The multivariate model for both metastatic progression-free survival and failure-free survival found prostate-specific antigen doubling time <4 months (P = 0.002; P = 0.05) to independently predict for progression.ConclusionThe ESTRO/EORTC classification of OMD predicts for progression in patients treated with SBRT for bone-only oligometastatic prostate cancer at our institution. Further validation in prospective series over multiple tumour sites is needed. These characterisation factors should be assessed in patients considered for metastasis-directed therapy together with established prognostic features.