Activation of phagocytosis by immune checkpoint blockade

Inhibition of macrophage-mediated phagocytosis has emerged as an essential mechanism for tumor immune evasion. One mechanism inhibiting the innate response is the presence of the macrophage inhibitory molecule, signal regulatory protein-α (SIRPα), on tumor-associated macrophages (TAMs) and its cognate ligand cluster of differentiation 47 (CD47) on tumor cells in the tumor microenvironment. On the basis of a recently discovered programmed death protein 1 (PD-1) in TAMs, we discuss the potential inhibitory receptors that possess new functions beyond T cell exhaustion in this review. As more and more immune receptors are found to be expressed on TAMs, the corresponding therapies may also stimulate macrophages for phagocytosis and thereby provide extra anti-tumor benefits in cancer therapy. Therefore, identification of biomarkers and combinatorial therapeutic strategies, have the potential to improve the efficacy and safety profiles of current immunotherapies.     

Expression of CD68+ tumor-associated macrophages in patients with diffuse large B-cell lymphoma and its relation to prognosis

Tumor-associated macrophages (TAM) have been ascribed both pro- and anti-tumor properties, but the majority of clinical cancer studies have shown that the presence of a high number of TAM is related to poor prognosis, suggesting that TAM predominantly exert pro-tumoral activity. The prognostic role of TAM in patients with diffuse large B-cell lymphoma (DLBCL), however, is so far unknown. Therefore, TAM were immunohistochemically stained with a CD68 antibody in a retrospective, population-based study including 176 DLBCL patients treated with curative intent. With the exception that patients >60 years of age had a larger number of CD68+ cells (1143 vs 1018 cells/mm²; P  = 0.05), no significant differences were found between the number of CD68+ cells and other clinical factors. Similarly, germinal center B-cell (GCB)/non-GCB immunophenotype or low/high Ki-67 percentage were not associated with CD68 expression. Finally, no significant correlation was found between the number of CD68+ cells and progression-free survival ( P  = 0.34) or overall survival ( P  = 0.94). These data indicate that the pro-tumor effect of TAM has limited clinical relevance in DLBCL patients, which could imply that therapeutic strategies aimed at enhancing their anti-tumor activity are of continuous clinical interest.     

三苯氧胺治疗乳腺增生病635例分析

本文报道用三苯氧胺治疗乳腺增生病635例。年龄20~55岁，其中20~30岁70例（26．77%）；31~40岁306例（48．18％）；41－50岁107例（16．85％）。全部病例均用三苯氧胺治疗，显效540例（85％），有效51例（8％）。三苯氧胺治疗乳腺增生病，副作用少，疗效好，是目前较为理想的药物，值得推广应用。     

北豆根总碱对氢化可的松模型小鼠的免疫调节作用

北豆根总碱２５ｍｇ／ｋｇ、５０ｍｇ／ｋｇｉｐ能显著增强氢化可的松所致免疫功能低下模型小鼠单核巨噬细胞吞噬功能、迟发型超敏反应及血清溶血素的生成；北豆根总碱５０ｍｇ／ｋｇｉｐ能显著增加模型鼠外周血淋巴细胞ＡＮＡＥ阳性百分率，增加脾脏空斑形成细胞溶血能力。提示北豆根总碱对免疫功能低下小鼠有免疫增强作用。     

夏枯草口服液治疗乳腺增生症100例

为观察夏枯草口服液治疗乳腺增生症的疗效 ,2 0 0例乳腺增生症患者随机分成两组。治疗组 10 0例服用夏枯草口服液 ,疼痛明显者加三苯氧胺 ,肿块明显者加软坚散结中成药。对照组10 0例服用三苯氧胺。结果 :治疗组有效率 10 0 % ,对照组有效率 95 % ,(P <0 0 5 )。提示夏枯草口服液对乳腺增生症疗效确切     

乳腺癌pS2蛋白表达与内分泌治疗的关系研究

目的：探讨乳腺癌pS2蛋白的表达与内分泌治疗的关系。方法：应用免疫组化S－P法检测100例原发性乳腺癌组织中pS2蛋白的表达情况，并结合治疗及随访资料进行分析。结果100例原发性乳腺癌组织中，pS2蛋白阳性表达组与ER阳性表达组用TAM治疗后的生存率曲线显示，前者生存率高于后者（P＜0．05），结论：pS2蛋白表达的检测对乳腺癌患者的内分泌治疗有一定的指导意义。     

Quaternary ammonium-linked glucuronidation of tamoxifen by human liver microsomes and UDP-glucuronosyltransferase 1A4

Tamoxifen (TAM), a nonsteroidal antiestrogen, is the most widely used drug for chemotherapy of hormone-dependent breast cancer in women. In the present study, we found a new potential metabolic pathway of TAM via N-linked glucuronic acid conjugation for excretion in humans. TAM N(+)-glucuronide was isolated from a reaction mixture consisting of TAM and human liver microsomes fortified with UDP-glucuronic acid (UDPGA) and identified with a synthetic specimen by high-performance liquid chromatography-electrospray ionization-mass spectrometry. However, no TAM-glucuronidating activity was detected in microsomes from rat, mouse, monkey, dog, and guinea pig livers. A strong correlation (r(2) =0.92 ) was observed between N-glucuronidating activities toward TAM and trifluoperazine, a probe substrate for human UDP-glucuronosyltransferase (UGT) 1A4, in human liver microsomes from eight donors (five females, three males). However, no correlation ( (r(2) =0.02 )) was observed in the activities between 7-hydroxy-4-(trifluoromethyl)coumarin and TAM. Only UGT1A4 catalyzed the N-linked glucuronidation of TAM among recombinant UGTs (UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B4, UGT2B7, UGT2B15, and UGT2B17) expressed in insect cells. Apparent K(m) values for TAM N-glucuronidation by human liver microsomes and recombinant UGT1A4 were 35.8 and 32.4 microM, respectively. These results strongly suggested that UGT1A4 could play a role in metabolism and excretion of TAM without Phase I metabolism in human liver. TAM N(+)-glucuronide still had binding affinity similar to TAM itself for human estrogen receptors, ERalpha and ERbeta, suggesting that TAM N(+)-glucuronide might contribute to the biological activity of TAM in vivo.     

腹腔镜下子宫肌瘤剔除术与开腹手术的比较

目的:评价应用腹腔镜与传统开腹方式进行子宫肌瘤剔除术的优缺点。方法:回顾分析应用传统开腹手术方法62例和应用腹腔镜技术40例进行子宫肌瘤剔除术的临床资料,对手术适应症、并发症和手术时间、术中出血量以及术后恢复情况进行比较分析。结果:腹腔镜手术时间较开腹手术组长,差异有显著性(P<0.05);腹腔镜手术术中出血量、术后肛门排气时间、术后病率和术后住院时间均明显低于开腹手术组,差异有显著性(P<0.05)。40例病人均在腹腔镜下完成手术,无中转开腹及严重并发症。结论:腹腔镜下子宫肌瘤剔除术较传统开腹手术具有创伤小、恢复快,住院时间短,术中、术后并发症少等优点,值得在有条件的医院广泛开展。     

rhTIMP-3与TAM联合应用对乳腺癌细胞MCF-7生长与凋亡的影响

目的:探讨重组金属蛋白酶组织抑制因子-3(rhTIMP-3)和三苯氧胺(tamoxifen,TAM)联合应用对乳腺癌细胞株MCF-7(ER )生长和凋亡的影响。方法:分别或联合应用不同浓度的rhTIMP-3、TAM作用于MCF-7细胞,应用四甲基偶氮唑蓝(MTT)比色法分析细胞生长抑制作用,应用流式细胞技术测定细胞周期分布和凋亡率。结果:rhTIMP-3与TAM均可抑制MCF-7细胞增殖,呈时间、浓度依赖性,并可诱导凋亡。rhTIMP-3使细胞阻滞在S和G2/M期;TAM可造成细胞G0/G1期的阻滞,当两者联合时对MCF-7的生长抑制明显增加,在诱导凋亡方面有明显协同作用。结论:rhTIMP-3、TAM均可抑制MCF-7细胞的增殖,并可诱导其凋亡;二者联合应用不仅能增加细胞生长的抑制作用,而且在诱导细胞凋亡方面有协同作用。     

Biogenesis and function of the autotransporter adhesins YadA,intimin and invasin

Bacteria often express numerous virulence factors. These virulence factors make them successful pathogens, by e.g. mediating attachment to host cells and thereby facilitating persistence or invasion, or by contributing to the evasion of the host immune system to allow proliferation and spread within the host and in the environment. The site of first contact of Gram negative bacteria with the host is the bacterial outer membrane (OM). Consisting of an asymmetrical lipid bilayer with phospholipids forming the inner, and lipopolysaccharides forming the outer leaflet, the OM harbors numerous integral membrane proteins that are almost exclusively β-barrel proteins. One distinct family of OM β-barrel proteins strongly linked to bacterial virulence are the autotransporter (AT) proteins. During the last years huge progress has been made to better understand the mechanisms underlying the insertion of AT proteins into the OM and also AT function for interaction with the host. This review shortly summarizes our current knowledge about outer membrane protein (OMP) and more specifically AT biogenesis and function. We focused on the AT proteins that we haved studied in most detail: i.e. the Yersinia adhesin A (YadA) and invasin of Yersinia enterocolitica (Ye) as well as its homolog intimin (Int) expressed by enteropathogenic Escherichia coli. In addition, this review provides a short outlook about how we could possibly use this knowledge to fight infection.