Pleomorphic mastocytoma associated with loss of chromosome 5, PDGFRA,and HRAS mutations: A case of cutaneous mastocytosis with severe atypia and indolent behavior

A 21‐year‐old female presented with a 5‐year history of an erythematous papule on her right breast. The biopsy showed a dense, dermal nodular infiltrate, extending focally into the subcutaneous tissue. The infiltrate was composed predominantly of pleomorphic cells with bi‐lobed, multi‐lobed, horseshoe, or ring‐shaped nuclei. There was a smaller subset of monomorphous cells characterized by a round, reniform, or elongated single‐lobed nucleus. Accompanying cells included few foamy histiocytes, lymphocytes, and numerous scattered eosinophils. No necrosis, vascular invasion, or ulceration was present. The pleomorphic and monomorphic granular cells were positive for Giemsa stain as well as for tryptase, CD117, CD68, CD2, and CD30 immunohistochemistry and negative for S100, CD1a, myeloperoxidase, lysozyme, and CD56. Clinical examination was negative for any additional similar lesions and serum tryptase was within normal limits. The bone marrow was not biopsied. In addition, fluorescent in situ hybridization revealed multiple clones with loss of number 5 chromosome and PDGFRA and HRAS mutations. The lesion did not recur or progress after a 6‐year clinical follow‐up. To our full knowledge, we report the first case of pleomorphic mastocytoma with loss of chromosome 5 and PDGFRA and HRAS mutations.     

Antitumor effects of dioscin in A431 cells via adjusting ATM/p53-mediated cell apoptosis,DNA damage and migration

Skin cancer is the deadliest type of malignant disease and causes primary mortality worldwide. Dioscin, which exists in medicinal plants, has potent anticancer effects. However, its effects on skin cancer remain unknown. In the present study, the activity and mechanism of dioscin on the human skin cancer A431 cell line were investigated, MTT, colony formation, Transwell, wound-healing, TUNEL, Comet, immunofluorescence and western blot assays were used to assess the effects of dioscin on A431 cells. The results of MTT, colony formation, Transwell and wound-healing assays revealed that dioscin suppressed proliferation, colony formation and invasion of the cancer cells. TUNEL and comet assays demonstrated that dioscin exhibited significant effects on cell apoptosis and DNA damage. Investigations into the mechanism revealed that the expression levels of phosphorylated Ataxia telangiectasia-mutated (ATM) were considerably activated by dioscin, which significantly upregulated the expression levels of p53 to activate mitochondrial apoptosis signaling. Furthermore, the expression levels of BAX, cleaved caspase-3/9 and cleaved poly (ADP-ribose) polymerase were upregulated, and the expression levels of BCL-2 were downregulated by dioscin. Additionally, dioscin markedly downregulated the expression levels of matrix metalloproteinase 2 (MMP2), MMP9, RHO and cdc42, which are all associated with tumor invasion. In addition, p53-small interfering RNA transfection experiments indicated that dioscin exhibited excellent activity against skin cancer in vitro by decreasing p53 expression. Overall, the present results suggested that dioscin inhibited skin cancer cell proliferation via adjusting ATM/p53-mediated cell apoptosis, migration and DNA damage, which should be considered as a potential option for future treatments of skin cancer.     

血清p53抗体异常高水平对消化道肿瘤的早期诊断价值分析

目的:探讨血清p53抗体异常高水平对消化道肿瘤的早期诊断的价值。方法:选取2016年3月至2019年3月来我院检查确诊为消化道肿瘤的患者80例为消化道肿瘤组,选取来我院健康体检的67例健康志愿者为健康对照组。通过酶联免疫吸附实验检测血清中人体抑癌基因p53及其抗体水平;通过RT-qPCR检测血清中细胞凋亡相关基因Bcl-2、Bax和Caspase-3蛋白表达量。采用Pearson相关性分析明确消化道肿瘤p53、p53抗体水平和Bcl-2、Bax、Caspase-3蛋白表达水平的关系。结果:消化道肿瘤组p53水平降低,p53抗体水平异常升高(P<0.05)。与健康对照组相比,消化道肿瘤组Bcl-2表达量增加,Bax和Caspase-3蛋白表达量降低(P<0.05)。消化道肿瘤p53水平与Bcl-2蛋白表达水平呈负相关关系,与Bax、Caspase-3蛋白表达水平均呈正相关关系;p53抗体水平和Bcl-2蛋白表达水平呈正相关关系,与Bax、Caspase-3蛋白表达水平均呈负相关关系(P<0.05)。结论:消化道肿瘤患者血清p53抗体异常高水平,可作为临床辅助诊断消化道肿瘤的可靠指标之一。     

Efficacy of recombinant Marek’s disease virus vectored vaccines with computationally optimized broadly reactive antigen (COBRA) hemagglutinin insert against genetically diverse H5 high pathogenicity avian influenza viruses

The genetic and antigenic drift associated with the high pathogenicity avian influenza (HPAI) viruses of Goose/Guangdong (Gs/GD) lineage and the emergence of vaccine-resistant field viruses underscores the need for a broadly protective H5 influenza A vaccine. Here, we tested experimental vector herpesvirus of turkey (vHVT)-H5 vaccines containing either wild-type clade 2.3.4.4A-derived H5 inserts or computationally optimized broadly reactive antigen (COBRA) inserts with challenge by homologous and genetically divergent H5 HPAI Gs/GD lineage viruses in chickens. Direct assessment of protection was confirmed for all the tested constructs, which provided clinical protection against the homologous and heterologous H5 HPAI Gs/GD challenge viruses and significantly decreased oropharyngeal shedding titers compared to the sham vaccine. The cross reactivity was assessed by hemagglutinin inhibition (HI) and focus reduction assay against a panel of phylogenetically and antigenically diverse H5 strains. The COBRA-derived H5 inserts elicited antibody responses against antigenically diverse strains, while the wild-type-derived H5 vaccines elicited protection mostly against close antigenically related clades 2.3.4.4A and 2.3.4.4D viruses. In conclusion, the HVT vector, a widely used replicating vaccine platform in poultry, with H5 insert provides clinical protection and significant reduction of viral shedding against homologous and heterologous challenge. In addition, the COBRA-derived inserts have the potential to be used against antigenically distinct co-circulating viruses and future drift variants.     

整合素α5β1在苯妥英钠促进大鼠PDLSCs和BMMSCs黏附于牙骨质中的作用

目的 探讨在苯妥英钠(Phenytoin,PHT)促进大鼠牙周膜干细胞(Rat periodontal ligament stem cells,rPDLSCs)、大鼠骨髓间充质干细胞(Rat Bone Marrow Mesenchymal Stem Cells,rBMMSCs)黏附于牙骨质过程中,整合素α5β1(Integrin α5β1)起到的作用。方法 提取大鼠BMMSCs和PDLSCs,培养并纯化。通过细胞鉴定后,将获得的两种细胞各分为4组:40 mg/L PHT处理组、40 mg/L PHT+整合素α5抗体处理组、40 mg/L PHT+整合素β1抗体处理组、PBS处理组,每组细胞放入置有牙骨质片的96孔板处理4 h后,检测黏附于牙骨质片上的细胞量并做以比较。最后,利用qRT-PCR和Western blot检测40 mg/L PHT组与对照组细胞的整合素α5、β1亚基的mRNA与蛋白表达量。结果 40 mg/L PHT可促进rBMMSCs及rPDLSCs黏附于牙骨质片,加入整合素α5、β1抗体后,均明显抑制了40 mg/L PHT对rBMMSCs、rPDLSCs黏附于牙骨质的促进作用(P＜0.01)。qRT-PCR、Western-blot结果显示PHT处理组的整合素α5、β1亚基表达量高于空白对照组(P＜0.05)。结论 40 mg/L PHT能促进rBMMSCs、rPDLSCs黏附于牙骨质,该作用与整合素α5β1的表达上调密切相关。     

Automated synthesis of (R)-[18F]MH.MZ on the iPhase Flexlab reaction platform

(R)-[¹⁸F]MH.MZ ([¹⁸F]MH.MZ) is a promising positron emission tomography (PET) radiotracer for in vivo study of the 5-HT_2A receptor. To facilitate clinical trials, a fully automated radiosynthesis procedure for [¹⁸F]MH.MZ was developed using commercially available materials on the iPhase Flexlab module. The overall synthesis time was 100 min with a radiochemical yield of 7 ± 0.9% (n = 3). The radiochemical purity was greater than 99% for [¹⁸F]MH.MZ with a molar activity of 361 ± 57 GBq/μmol (n = 3). The protocol described herein reliably provides [¹⁸F]MH.MZ that meets all relevant release criteria for a GMP radiopharmaceutical.