Serum tumor markers in colorectal cancer staging,grading, and follow-up

Early diagnosis of colorectal cancer, a frequent neoplasia in industrialized countries, permits curative surgery. In this study we assessed the clinical role of serum tumor markers determination in diagnosing, staging, and grading colorectal cancer; the role of carcinoembryonic antigen (CEA), CA 19-9, tissue polypeptide antigen (TPA) and CA 72-4 in colorectal cancer follow-up was also assessed. In 114 patients with colorectal cancer, the oncofetal antigen CEA was compared with the membrane-associated glycoproteins CA 19-9, CA 242, and CA 72-4 and with the cytokeratins TPA, tissue polypeptide-specific antigen (TPS) and tissue polypeptide monoclonal antigen (TPM). Overall, the most sensitive indices were TPA and TPS (67% and 70%, respectively). Tumor stage influenced the levels of CEA, CA 19-9, and TPA, but not those of TPS, while tumor grade influenced CEA and TPS, but not CA 72-4, TPA, and TPM. TPA was the most sensitive index in identifying early or well-differentiated colorectal cancers. The sensitivity was enhanced when this marker was determined in combination with CEA, in diagnosing both advanced and early colorectal tumors. Seventy-seven patients were followed up after therapy for at least 18 months. CEA was the most sensitive index of recurrence (58%); however, this sensitivity is too low to consider tumor markers useful in colorectal cancer follow-up. © 1996 Wiley-Liss, Inc.     

Recombinant human interferon α-2b (rh IFNα-2b) therapy for steroid resistant idiopathic thrombocytopenic purpura (ITP)

The efficacy of recombinant human interferon α-2b (rh IFNα-2b) in the treatment of steroid resistant idiopathic thrombocytopenic purpura (ITP) was studied in 50 cases. Forty-one patients treated with rh IFNα-2b three times a week, six of 18 (33.3%) in the low dose group (150 × 10⁴IU: 3 MIU) and four of 20 (20.0%) in the high dose group (300 × 10¹⁰IU: 3 MIU) responded with platelet counts increasing to above 50 × 10⁹/L. Because of the exacerbation of thrombocytopenia and nasal bleeding, treatment was discontinued within 2 weeks in three patients out of 41 cases. On the other hand, six of nine patients (66.7%) treated with 3 MIU of IFNα-2b once a week for 8 weeks showed satisfactory response. Treatment with either administration schedule did not result in sustaining platelet counts above 50 × 10⁹/L for a long time after treatment. The results indicate that once a week administration schedule of rh IFNα-2b is more efficacious for platelet counts increasing for short period in patients who failed to respond to steroid and other medications than other schedules. The maintenance of this treatment schedule will allow sustained increased platelet levels, resulting in relief of bleeding tendency, while also being cost effective in comparison with other IFN treatment schedules and achieving better patient compliance without flu-like symptoms. © 1996 Wiley-Liss, Inc.     

沉默神经元HIF-1α和PTEN的表达对体外培养的大鼠神经元氧糖剥夺损伤的影响

目的利用RNA干扰技术分别沉默神经元中缺氧诱导因子1α（HIF-1α）和磷酸酶并和张力蛋白同源物（PTEN）基因，论证它们在神经元体外氧糖剥夺（OGD）损伤后的功能调控作用。方法构建并筛选靶向HIF-1α及PTEN基因的shRNA慢病毒载体；提取并将原代神经元分为4组：（1）NC组，仅加空载病毒；（2）NC+OGD组，加空载病毒后缺氧；（3）Si-hif-1α+OGD组，加Si-hif-1α病毒后缺氧；（4）Si-pten+OGD组，加Si-pten病毒后缺氧，均在培养第3天感染病毒，第7天OGD损伤模拟细胞缺氧。缺氧后24 h行荧光实时定量PCR（qRT-PCR）法检测干扰效率，行乳酸脱氢酶（LDH）检测及AnnexinV-FITC/PI检测神经元细胞损伤、凋亡变化，Western blot检测相应蛋白表达变化。结果慢病毒介导的shRNA能有效沉默目的基因mRNA的表达；HIF-1α沉默后，缺氧细胞的损伤及凋亡加重，PTEN蛋白的表达升高，p-PTEN、p-AKT、NR2A及VEGFa表达降低（P < 0.05）；PTEN沉默后，缺氧细胞的损伤及凋亡有所减轻，p-PTEN、p-AKT表达升高（P < 0.05），HIF-1α、NR2A及VEGFa的表达无显著变化（P>0.05）。结论慢病毒介导的shRNA能有效沉默神经元HIF-1α及PTEN的表达，逆转神经元缺氧损伤中HIF-1α升高对PTEN活性的抑制，参与神经元损伤调控。     

Characterization of peripheral benzodiazepine type sites in a cultured murine BV-2 microglial cell line

It is known that the density of peripheral benzodiazepine receptors (PBR) increases after brain damage. Astrocytes are among the cell types where PBR ligand binding has been detected and may be involved in the response to neuronal injury and regeneration. Consistent with the hypothesis, the apparent density of PBR sites in astrocytes is increased by both cytokines and neurotoxins. However, microglia, the resident macrophages which represent 5–15% of glial cell populations have not been evaluated for the presence of the PBR. In the present study, we report the presence of [³H]Ro5-4864 binding in microglial cells. In particular, we used BV-2 cells, an immortalized cell line of murine microglial cells. High affinity binding of [³H]Ro5-4864 to a single site was detected in membranes prepared from BV-2 cells (K_D = 4.4 nM, B_max = 3,800 fmoles/mg protein). Various ligands for the PBR displaced [³H]Ro5-4864 binding with the following rank order of potencies: PK11195 = Ro5-4864 > FGIN-1-27 > triazolam = diazepam > beta-pro-pyl-beta-carboline-3-carboxylate = clonazepam > lorazepam = flurazepam >> chlordiazepoxide = clorazepate. Subcellular fractionationstudies indicate that the majority of the Ro5-4864 binding sites is in the mitochondrial fraction. The remainder is found in non-mitochondrial cell fractions. The [³H]Ro5-4864 binding observed on intact cells had characteristics similar to those found on membranes. The presence of a high density of PBRs in these cells establish the basis for additional investigations into their possible functional role, if any, in the microglial response to neuronal injury. © 1996 Wiley-Liss, Inc.     

Threonine 80 on HLA-B27 confers protection against lysis by a group of natural killer clones

Recognition of major histocompatibility complex (MHC) class I molecules on target cells by natural killer (NK) cells inhibits NK cell-mediated lysis. Although it is known that this inhibitory effect is regulated by MHC polymorphism, the precise structural determinants remain undefined. Based on the capacity of different HLA-C and HLA-B motifs specifically to inhibit cytotoxicity of some NK clones, three different NK cell specificities (NK1, NK2 and NK3) have been described. In this study, the recognition of HLA-B27 by NK clones has been analyzed using C1R cells transfected with different HLA-B27 subtypes as target cells. Cytotoxicity was inhibited by the HLA-B*2705, -B*2701 -B*2703, -B*2704 and -B*2706 alleles, but not by -B*2702. This subtype is distinguished from the other B27 subtypes by the presence of isoleucine instead of threonine at position 80. Direct involvement of this residue was assessed by showing that site-directed mutagenesis of Thr80 to Ile80 in HLA-B*2705 reverted the NK protective effect of HLA-B*2705. Based on these data, we suggest that Thr80 could act as a single residue conferring target cell protection from lysis by a group of NK clones, tentatively designated NK4.     

广西20种传统瑶药抗肿瘤筛选研究

目的:对广西20种传统瑶药进行抗肿瘤筛选研究。方法:复制小鼠S180、H22腹水瘤和肉瘤动物模型,分别观察药物对小鼠的生命延长率和肿瘤抑制率的影响。结果:经3次实验,在生命延长率方面:对S180腹水瘤小鼠平均生命延长率超过50%的有葫芦钻、双钩钻高低剂量组,上山虎高剂量组和猛老虎、小红钻低剂量组;对H22腹水瘤小鼠平均生命延长率超过50%的有六方钻和双钩钻高剂量组。在肿瘤抑制率方面:对S180肉瘤平均抑制率超过30%的有槟榔钻、四方钻、葫芦钻和麻骨钻高低剂量组,大红钻和双钩钻高剂量组,下山虎、毛老虎和九龙钻低剂量组;对H22肉瘤平均抑制率超过30%的有大红钻、铜钻、小钻和葫芦钻高低剂量组,猛老虎高剂量组,四方钻和麻骨钻低剂量组。结论:葫芦钻、双钩钻等部分广西传统瑶药对S瘤和H瘤有一定的抗肿瘤作用。     

IFI27 is a potential therapeutic target for HIV infection

BackgroundTherapeutic studies against human immunodeficiency virus type 1 (HIV-1) infection have become one of the important works in global public health.MethodsDifferential expression analysis was performed between HIV-positive (HIV+) and HIV-negative (HIV-) patients for {"type":"entrez-geo","attrs":{"text":"GPL6947","term_id":"6947"}}GPL6947 and {"type":"entrez-geo","attrs":{"text":"GPL10558","term_id":"10558"}}GPL10558 of {"type":"entrez-geo","attrs":{"text":"GSE29429","term_id":"29429"}}GSE29429. Coexpression analysis of common genes with the same direction of differential expression identified modules. Module genes were subjected to enrichment analysis, Short Time-series Expression Miner (STEM) analysis, and PPI network analysis. The top 100 most connected genes in the PPI network were screened to construct the LASSO model, and AUC values were calculated to identify the key genes. Methylation modification of key genes were identified by the chAMP package. Differences in immune cell infiltration between HIV + and HIV- patients, as well as between antiretroviral therapy (ART) and HIV + patients, were calculated using ssGSEA.ResultsWe obtained 3610 common genes, clustered into nine coexpression modules. Module genes were significantly enriched in interferon signalling, helper T-cell immunity, and HIF-1-signalling pathways. We screened out module genes with gradual changes in expression with increasing time from HIV enrolment using STEM software. We identified 12 significant genes through LASSO regression analysis, especially proteasome 20S subunit beta 8 (PSMB8) and interferon alpha inducible protein 27 (IFI27). The expression of PSMB8 and IFI27 were then detected by quantitative real-time PCR. Interestingly, IFI27 was also a persistently dysregulated gene identified by STEM. In addition, 10 of the key genes were identified to be modified by methylation. The significantly infiltrated immune cells in HIV + patients were restored after ART, and IFI27 was significantly associated with immune cells.ConclusionThe above results provided potential target genes for early diagnosis and treatment of HIV + patients. IFI27 may be associated with the progression of HIV infection and may be a powerful target for immunotherapy.     

HSP27和GST在大肠腺瘤和大肠癌中表达的临床病理研究

目的探讨热休克蛋白27（HSP27）和谷胱甘肽-S-转移酶（GST）在正常大肠黏膜、大肠腺瘤和大肠癌中的表达及其临床病理意义。方法应用免疫组织化学S-P法检测HSP27和GST在大肠组织中的表达。结果HSP27在正常肠黏膜、大肠腺瘤、无淋巴结转移的大肠癌、有淋巴结转移的大肠癌中表达阳性率分别为30％,33．3％,65％,70％,多组间比较具有显著性差异（x^2=12．723,P=0．013）。两组间比较发现,HSP27表达率在正常组与大肠癌组存在差异,在有淋巴结转移的大肠癌组中的表达具有差异最为显著（x^2=8．688,P=0．003）,而其它组间比较无显著性差异。GST在正常肠黏膜、大肠腺瘤、无淋巴结转移的大肠癌、有淋巴结转移的大肠癌中表达阳性率分别为60％,80．9％,90％,100％,多组间比较具有显著性差异（x^2=16．707,P=0．001）;进一步进行两组间比较发现,GST表达率在有淋巴结转移的大肠癌组中的表达具有差异最为显著（x^2=10．909,P=0．001）,而其它组间比较无显著性差异。GST和HSP27表达无显著相关。结论HSP27和GST在大肠癌中的表达可能在大肠癌发生发展中发挥作用,特别在大肠癌恶性演进中以及预后预测中具有重要意义,可能作为独立的生物标志物。