Burosumab for the Treatment of Tumor-Induced Osteomalacia

Tumor-induced osteomalacia (TIO) is caused by phosphaturic mesenchymal tumors producing fibroblast growth factor 23 (FGF23) and is characterized by impaired phosphate metabolism, skeletal health, and quality of life. UX023T-CL201 is an ongoing, open-label, phase 2 study investigating the safety and efficacy of burosumab, a fully human monoclonal antibody that inhibits FGF23, in adults with TIO or cutaneous skeletal hypophosphatemia syndrome (CSHS). Key endpoints were changes in serum phosphorus and osteomalacia assessed by transiliac bone biopsies at week 48. This report focuses on 14 patients with TIO, excluding two diagnosed with X-linked hypophosphatemia post-enrollment and one with CSHS. Serum phosphorus increased from baseline (0.52 mmol/L) and was maintained after dose titration from week 22 (0.91 mmol/L) to week 144 (0.82 mmol/L, p < 0.0001). Most measures of osteomalacia were improved at week 48: osteoid volume/bone, osteoid thickness, and mineralization lag time decreased; osteoid surface/bone surface showed no change. Of 249 fractures/pseudofractures detected across 14 patients at baseline, 33% were fully healed and 13% were partially healed at week 144. Patients reported a reduction in pain and fatigue and an increase in physical health. Two patients discontinued: one to treat an adverse event (AE) of neoplasm progression and one failed to meet dosing criteria (receiving minimal burosumab). Sixteen serious AEs occurred in seven patients, and there was one death; all serious AEs were considered unrelated to treatment. Nine patients had 16 treatment-related AEs; all were mild to moderate in severity. In adults with TIO, burosumab exhibited an acceptable safety profile and was associated with improvements in phosphate metabolism and osteomalacia. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research..     

Evaluation of effectiveness,safety and cost-benefit of the 23– valent pneumococcal capsular polysaccharide vaccine for HIV-Infected patients

IntroductionDue to the lack of understanding of the protective effects and safety of 23-valent pneumococcal polysaccharide vaccine (PPV23) in immune-deficient populations, the vaccination rate of PPV23 among HIV-infected patients is still very low in China. The main objectives of this study were to determine whether the efforts to assess measures for the prevention of pneumococcal pneumonia are still worthwhile, and provide designated vaccination program of HIV-infected persons for government policy based on.Methods60 HIV-infected adults in Lanshan county who had never been vaccinated with any pneumococcal vaccine were enrolled in this study, voluntary vaccination of PPV23 and One-year follow-up after vaccination can be completed.Result76.67% patients (46/60) had serologic response at 12 months after vaccine, CD4 count(≤500 cells/ul or > 500 cells/ul) and Month from diagnosis to first antiviral therapy (≤1 month or > 1 month) were related to antibody responses (p < 0.05).In this study, PPV23 was well tolerated, no adverse reaction was reported.11 Streptococcus pneumoniae pneumonia (9.17%,11/120) occurred in the Unvaccinated group and 1 case(1.67%,1/60)in the vaccination group within one year after vaccination(Fisher's exact probability, P = 0.225). The VE was 81.79%. The per capita benefit was 39.32 dollars, the benefit-cost ratio = 1.19. There are significant statistical differences between the vaccinated group and the non-vaccinated group in outpatient costs (p < 0.05, 95 %CI: 9.29–32.11), Medicine costs (p = 0.017, 95 %CI: 2.47–24.44), and disease related indirect costs (p = 0.038, 95 %CI: 0.93–33.63) within one year of vaccination.ConclusionOur study results showed that PPV23 can be safely and effectively administered to HIV-1 infected individuals and effectively preventing Streptococcal pneumonia. Considering the cost-benefit of vaccination among HIV-infected persons, as it has been reported in our study, it is necessary to promote the widespread use of the vaccine among HIV-infected persons in the future.     

五种免疫相关性心血管疾病的免疫学研究

对扩张型心肌病、风湿性心脏病，原发性高血压，冠心病及肥厚型心肌病进行外周血清可溶性白细胞介素２受体，Ｔ淋巴细胞亚群及自然杀伤细胞活性的检测，并与健康对照组比较，结果显示：ＤＣＭ组，ＲＨＤ组及ＥＨＴ组的ｓＩＬ－２Ｒ明显高于ＮＣ组，而ＤＣＭ、ＲＨＤ风湿活动组的ＮＫ活性低于ＮＣ组，ＥＨＴ组ＮＫ活性高于ＮＣ组。     

Effect of configuration of muramyl dipeptide glycoside bond and structure of glycoside aglycon on their capacity to stimulate production of interleukin-1 and tumor necrosis factor by macrophages

Effects of 11 original glycoside derivatives of muramyl dipeptide on the production of interleukin-1 and tumor necrosis factor by mouse peritoneal macrophages were studied. The relationship between macrophage activation evaluated by induction of these cytokines and configuration of glycoside bond and aglycon structure of MDP was revealed.     

Decrease of lymphokine (interleukin-2)-activated killer activity in peripheral blood after administration of natural interferon-gamma

Interferon-gamma (IFN-gamma) acts on a large array of different types of cell and has potent immunomodulatory activities besides cytotoxic effects on tumors. In a phase I study, some immunologic parameters of blood mononuclear cells from healthy volunteers who received intramuscular injections of natural human IFN-gamma were analyzed. The percentage of Leu-11a positive cells, natural killer (NK) activity, lymphokine (interleukin-2)-activated killer (LAK) activity and monokine production were measured either in blood mononuclear cells or in purified samples of lymphocytes or monocytes of the donors before and 24 h after IFN-gamma injection. After IFN-gamma injection, the percentage of Leu-11a positive cells and the LAK activity in the blood were significantly reduced, but NK activity and monokine production remained unchanged. These findings suggest that in vivo IFN-gamma acts directly or indirectly on Leu-11a positive cells and reduces LAK activity by changing the recruitment of LAK precursors in the blood.     

Intratracheal administration of recombinant adenovirus containing IL-18 gene in treatment of experimental metastatic lung carcinoma

Objective: To study the treatment of experimental metastatic lung carcinoma by intratracheal injection of IL-18 gene recombinant adenovirus. Methods: (1)The mouse IL-18 mRNA was detected by RT-PCR, and the concentration of 1L-18 and associated cytokines in lung lavages and blood were determined by ELISA at different time points after intratracheal injection of IL-18 recombinant adenovirus. (2)The lung metastasis nodes, mouse survival periods and survival rates were evaluated. NK activity and CTL activity were determined by 51Cr 4 h release method. Results: (1)IL-18 mRNA was detectable in lung tissue 6 h after intratracheal use of IL-18 recombinant adenovirus, and the concentration of IL-18 in lung lavage was higher than that in peripheral blood. Neither IL-18 mRNA nor IL-18 was detectable in control group. (2) Intmtmcheal use of IL-18 recombinant adenovirus resulted in increased CTL and NK activity, longer survival time and higher survival rates compared with the control group, showing significant therapeutic effect on experimental lung metastasis. Conclusion: Intratracheal use of adenovirus vector containing IL-18 gene has therapeutic effect on the lung metastasis, denoting that gene therapy of lung diseases could be applied through airway directly with recombinant adenovirus.     

nm23-H1基因在人贲门癌中的表达

目的 :检测转移抑制基因 nm2 3- H1在贲门癌中的表达 ,探讨其与贲门癌生物学特性和其他病理学指标的关系。方法 :应用免疫组化染色技术对 2 8例贲门癌组织中的 nm2 3- H1进行检测并与正常组织对照。结果 :贲门癌及其相应的正常组织中 nm2 3- H1蛋白表达率分别为 67.9%和71 .4% ,两者间无显著性差异 ( P<0 .0 5)。 nm2 3- H1蛋白在贲门癌中的表达 ,随肿瘤浸润程度的增加而表达下降 ( P>0 .0 5) ;在淋巴结转移阳性组贲门癌中 ,表达阳性率为 46.2 % ,而淋巴结转移阴性组为 92 .8% ,两者差异显著 ( P<0 .0 5)。结论 :nm2 3- H1蛋白表达在肿瘤分化程度高组与低组之间 ,无显著性差异。     

纤维母细胞增强HCE16/3细胞IL-1基因表达的研究

目的 :研究纤维母细胞对HPV 16型DNA永生化的人宫颈上皮细胞 (HCE16 /3细胞 )白细胞介素 1(IL 1)基因表达的调节。方法 :应用Northern印迹法分析纤维母细胞、纤维母细胞条件培养液以及纤维母细胞分泌的角质细胞生长因子 (KGF)对HCE16 /3细胞IL 1基因表达的影响。结果 :在正常情况下 ,HCE16 /3细胞IL 1基因表达水平很低 ,但在与纤维母细胞作共同培养时 ,IL 1基因的表达水平明显上调。如使用纤维母细胞条件培养液 ,IL 1基因的表达也呈上调现象 ,上调反应明显与条件培养液所占比例有关。进一步的研究表明 ,条件培养液中刺激IL 1基因表达的物质主要为纤维母细胞分泌的KGF。结论 :在体内 ,间质细胞可影响宫颈上皮性肿瘤的生长     

喉癌微血管生成中P53 nm23蛋白和血管内皮生长因子的作用

目的　探讨P5 3、nm2 3蛋白和血管内皮生长因子 (vascularendothelialgrowthfacor,VEGF)在喉癌微血管生成及转移中的作用。方法　通过免疫组化SP法对 42例喉癌标本中P5 3、nm2 3蛋白、VEGF及微血管密度 (microvesseldensity,MVD)进行了检测。结果　喉癌中P5 3、nm2 3蛋白及VEGF的阳性表达率分别占 47 6 %、5 7 1%和 71 4%。P5 3基因和VEGF呈正相关 (P <0 0 5 ) ,在有淋巴结转移的喉癌标本中P5 3、VEGF阳性表达率及MVD明显高于非转移组 (P <0 0 5 )。而nm2 3基因和VEGF在喉癌标本中无直接相关性 ,在nm2 3蛋白表达阴性和VEGF阳性标本中MVD较高 ,这种现象多见于有淋巴结转移的喉癌中。结论　突变型P5 3基因通过调控VEGF的表达影响肿瘤内MVD ,促使喉癌发生转移 ;而nm2 3基因可能不是通过调控VEGF的表达 ,而是通过其它途径影响喉癌转移。