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

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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.     

同型半胱氨酸、维生素D、C、E、B12及叶酸与胃癌关系的研究进展北大核心

胃癌作为临床最常见的肿瘤之一,常因确诊疾病较晚而影响治疗效果,胃镜活检后的病理虽然作为确诊的金标准,但是由于此方式过程痛苦,操作复杂,费用较高,且具有侵入性,可能会导致患者拒绝操作而难普及于临床,因此积极找寻胃癌有效的监测指标十分必要。近年来,很多学者研究维生素与胃癌的相关关系,并试图通过摄取某些维生素降低胃癌发生率,延缓病情及改善预后,也有通过检测血清中维生素的水平给早期胃癌的诊断提供帮助。本文就同型半胱氨酸、维生素D、维生素C、维生素E、维生素B12及叶酸在胃癌中的作用机制,及其在血清中水平与胃癌关系的相关研究进展进行简要综述,为临床胃癌诊疗提供新思路。     

Effect of Replacement of Wharton Acellular Jelly With FBS on the Expression of Megakaryocyte Linear Markers in Hematopoietic Stem Cells CD34+

Objective: Animal environments for the growth of stem cells cause the transmission of some diseases and immune problems for the recipient. Accordingly, replacing these environments with healthy environments, at least with human resources, is essential.  One of the media that can be used as an alternative to animal serums is Wharton acellular jelly (AWJ).  Therefore, in this study, we intend to replace FBS with Wharton jelly and investigate its effect on the expression of megakaryocyte-related genes and markers in stem cells. Materials and Methods: In this study, cord blood-derived CD34 positive HSCs were cultured and expanded in the presence of cytokines including SCF, TPO, and FLT3-L. Then, the culture of expanded CD34 positive HSCs was performed in two groups: 1) IMDM culture medium containing 10% FBS and 100 ng / ml thrombopoietin cytokine 2) IMDM culture medium containing 10% AWJ, 100 ng / ml thrombopoietin cytokine.  Finally, CD41 expressing cells were analyzed with the flow cytometry method. The genes related to megakaryocyte lineage including FLI1 and GATA2 were also evaluated using the RT-PCR technique.  Results: The expression of CD41, a specific marker of megakaryocyte lineage in culture medium containing Wharton acellular jelly was increased compared to the FBS group. Additionally, the expression of GATA2 and FLI1 genes was significantly increased related to the control group. Conclusion: This study provided evidence of differentiation of CD34 positive hematopoietic stem cells from umbilical cord blood to megakaryocytes in a culture medium containing AWJ.     

Lymph node micrometastasis of poorly differentiated node-negative gastric cancer risks a worse-than-expected survival outcome under standard management algorithm

BackgroundInvestigation of lymph node micrometastasis (mN) of gastric cancer has been focused on either T1 disease or T1-4N0 disease. Yet, it is unclear whether standard management algorithm toward poorly differentiated gastric cancer (PDGC) is more vulnerable to existence of mN, given its inherently biological aggressiveness, as compared with other histological types.Patients and methodsA surgical series (n = 3456) of gastric cancer categorized by histological differentiation was enrolled to analyze survival stratification. Of them, a cohort of T1-T4 N0 PDGC (n = 100) were subjected to cytokeratin immunohistochemistry, a surrogate of mN.ResultsCancer-specific survival by AJCC8 staging system could be nicely differentiated in both well-/moderately differentiated and signet ring cell types, while those between stage IA versus IB (p = 0.105), and stage IB versus IIA (p = 0.141) in PDGC could not. Thirteen (13%) out of 100 node-negative PDGC cases exhibited mN, with 5, 2, 5 and 1 cases occurring in T1, T2, T3, and T4 stage, respectively, without identifiable contributing factors. Prognostic performance of AJCC8 working upon PDGC became more discriminative by incorporating mN, as hazard ratio of stage IIIC referenced to stage IA increased from 43 to 78.ConclusionDefective discriminative survival of PDGC by standard staging algorithm prompted us to survey mN occurring in T1-T4N0 PDGC. The prognostic performance of AJCC8 working upon PDGC was enhanced by incorporating mN. As so, we recommend documentation of mN exclusively on node-negative PDGC that helps unveil stage migration phenomenon and switch to appropriate adjuvant therapy in need.