AFP阴性肝癌的肿瘤标志物诊断的研究进展

甲胎蛋白(alpha-fetoprotein,AFP)是肝细胞癌(hepatocellular carcinoma,HCC)的主要标志物,测定血清AFP水平是目前诊断HCC的主要手段.约1/3的HCC患者血清AFP水平正常,即所谓的AFP阴性肝癌,这部分患者的诊断是目前肝癌诊断中需解决的关键问题.多年来,人们一直在寻找能弥补AFP不足的肝癌标志物,以提高HCC的诊断水平.本文综述了有关AFP阴性肝癌的肿瘤标志物诊断研究进展,主要内容包括传统肝癌标志物对AFP阴性肝癌的诊断价值,新肝癌标志物对AFP阴性肝癌的诊断价值,以及对AFP阴性HCC具有潜在诊断价值的生物标志物.     

趋化因子在肝癌中的作用

<正>原发性肝癌(primary hepatocellular carcinoma,PHC)主要包括肝细胞癌(hepatocellular carcinoma,HCC)、肝内胆管细胞癌(intrahepatic cholangiocarcinoma ICC)和肝细胞癌-肝内胆管细胞癌混合型等不同病理类型,其发病机制、生物学行为、组织学形态、临床表现、治疗方法以及预后等方面均有明显的不同[1];由于其中HCC占到90%以上,故本文所指的"肝癌"主     

甲胎蛋白对肝衰竭肝细胞再生及预后判定价值的研究

甲胎蛋白(alpha fetoprotein,AFP)作为肿瘤标志物,临床上主要用于原发性肝癌、生殖腺胚胎癌、胃癌、胰腺癌等的诊断参考指标。我国最新的《慢性乙型肝炎防治指南》就明确提出AFP明显升高往往提示肝细胞癌(HCC),可用于监测HCC的发生。但AFP升高也可提示大量肝细胞坏死后的肝细胞     

肝细胞癌血清学诊断研究进展

肝细胞癌(HCC)的早期,正确诊断仍是当前研究的热点和难点.以甲胎蛋白(AFP)为代表的血清肿瘤标志物检测结合影像学及病理学检查已成为肝癌早期诊断的重要手段之一.现就其最新进展作一简述.     

磷脂酰肌醇蛋白多糖-3异常表达与肝细胞癌变相关

肝细胞癌(HCC)预后极差,延长患者生存期的关键是早期(小肝癌)诊断和早期(手术)治疗.HCC通过肝癌标记和影像检查建立诊断.甲胎蛋白(AFP)是主要肝癌标记,但有假阳性和假阴性;AFP异质体(AFP.L3)、AFP基因标志(AFP-mRNA)以及GGT-Ⅱ、PIVKA Ⅱ、AFU等其它肝癌标记可与AFP互补诊断,尤其对AFP假阴性肝癌和小肝癌的诊断甚有帮助.磷脂酰肌醇蛋白多糖-3(GPC-3)在细胞的生长发育中起重要的调控作用,与肝癌密切相关.本文就GPC-3分子构成、表达机制、与多种信号传导途径关系及对肝癌早期诊断价值等作一综述.     

甲胎蛋白异质体在原发性肝癌临床诊断中的应用

目的 通过临床大样本数据回顾性分析血清甲胎蛋白（AFP）和甲胎蛋白异质体（AFP-L3）诊断原发性肝癌（PLC）的价值。方法 2015年1月～2015年12月东方肝胆外科医院诊治的PLC患者7097例,同期诊治的肝硬化（LC）患者122例。采用化学发光法检测血清AFP水平,采用凝集素捕获微量离心柱法检测AFP-L3,将AFP-L3/AFP比值大于10%定义为AFP-L3阳性。结果 7097例PLC患者血清AFP水平为61.7（5.4,1226.0）μg/L,显著高于122例LC患者的3.6（2.5,10.95） μg/L（P<0.05）,AFP-L3阳性率为8.2（-,26.1）%,而在肝硬化患者未检出AFP-L3阳性（P<0.05）;以血清AFP≥20 μg/L或/和AFP-L3≥10%任一阳性为截断点,诊断PLC的准确度为63.1%,优于AFP（60.3%）和AFP-L3（47.9%）单独诊断的结果;AFP-L3阳性率随着AFP水平的升高而升高;血清AFP阴性的PLC和AFP阳性的LC患者AFP-L3阳性率分别为39.6%和7.7%,显著低于血清AFP阳性PLC患者的73.7%（P<0.05）;在2103例具有病理学诊断的PLC患者,1976例肝细胞癌（HCC）患者血清AFP水平为50.8（4.8,1015.0） μg/L,6例混合型肝癌患者血清AFP水平为74.9（4.55,39248.3） μg/L,AFP-L3阳性率分别为5.3（-,24.6）%和8.4（-,18.8）%,均显著高于121例肝内胆管细胞癌患者【2.8（2.2,5.15） μg/L,P<0.05】和【-（-,-）%,P<0.05】。结论 大样本的结果显示PLC患者血清AFP和AFP-L3存在较高的阳性率,其诊断效能较好。     

热休克蛋白90联合甲胎蛋白在肝细胞癌早期诊断中的价值

背景肝细胞癌是全球第六大常见癌症,早期诊断主要依靠血清学检查,随着热休克蛋白90(heat shock protein 90,HSP90)对于肝细胞癌分子研究的深入,本研究创新性采用HSP90联合甲胎蛋白(alpha fetoprotein, AFP)的方法,探究联合诊断对于肝细胞癌的诊断价值.目的评估H S P 9 0联合甲胎蛋白A F P在肝细胞癌(hepatocellular carcinoma, HCC)的诊断价值.方法选取2017-08/2020-07原发性肝癌、病毒性肝炎后肝硬化(乙型、丙型)、健康体检者共383位,采用电化学法检测AFP血清浓度, ELLISA法检测HSP90血清浓度,并使用统计学软件对结果进行处理及分析.结果单独分析AFP及HSP90对HCC的诊断价值,敏感度HSP90AFP,特异度AFPHSP90, AFP联合HSP90的灵敏度和特异度达到87.8%和91.2%.结论AFP联合HSP90建立新型HCC诊断模型能显著提高HCC诊断价值.     

甲胎蛋白诊断和筛查原发性肝癌的阈值分析

目的探讨AFP在原发性肝癌(HCC)诊断和早期筛查中的最佳阈值。方法收集2007年-2017年于南京医科大学附属淮安第一医院住院、门诊和健康体检确诊的2212例HCC和1998例非HCC患者的临床资料,统计AFP水平。将AFP水平划分为10~20μg/L、21~65μg/L、66~110μg/L、111~155μg/L、156~200μg/L、201~250μg/L、251~300μg/L、301~350μg/L、351~400μg/L、 400μg/L 10个阈值。比较各阈值、B超以及二者联合诊断HCC的联合敏感度、特异度、阳性似然比、阴性似然比、诊断优势比。构建受试者工作特征曲线(ROC曲线)测定最佳诊断阈值。结果 AFP阈值201~250μg/L组的灵敏度与特异度之和最大(1. 370 1),ROC曲线下面积最大(0. 896 4)。AFP 20μg/L联合B超诊断肝癌的敏感度最高(95. 35%),诊断优势比为26. 13。结论临床诊断HCC的AFP最佳阈值为200μg/L。应用AFP检测联合B超检查对HCC高危人群进行筛查时,可以将AFP20μg/L作为阳性指标,结合进一步的鉴别诊断、密切随访和跟踪检查,减少筛查漏诊率。     

IQGAP2在肝细胞肝癌中的表达及其临床意义

目的:认识肝细胞肝癌中含IQ模体的GTP酶活化蛋白2(IQ motif containing GTPase activating protein 2,IQGAP2)的亚细胞定位和表达,及其在肝细胞肝癌(hepatocellular carcinoma,HCC)中的作用.方法:分别通过Western blot、免疫荧光和免疫组织化学染色分析IQGAP2在7种人肝癌细胞与正常肝细胞系中的表达、定位,及其在HCC组织样本中的表达与分布.结果:IOGAP2在Bel-7402、Bel-7404、SMMC-7721、SK-HEP-1、HLE和HL-7702等肝癌和正常成人肝细胞系中不表达,仅在HepG2和Hep3B等2种甲胎蛋白(AFP)表达阳性的人肝癌细胞系中表达,IQGAP2主要分布于细胞质,此外,在HepG2细胞中还具有明显的核膜和核仁定位,IQGAP2在HCC组织中表达降低(56.9%,29/51).其中,19例配对HCC组织的IQGAP2表达与肿瘤大小,AJCC分期和血清AFP水平相关(P=0.020,P=0.017,P=0.002);38例配对组织IQGAP2在肿瘤和癌旁正常肝组织中主要定位于胞质,部分细胞伴有胞核和胞膜定位,但是,IQGAP2的表达与肿瘤大小、分化程度、AJCC分期以及血清AFP表达水平无相关性.结论:IQGAP2蛋白可能参与细胞黏附、信号转导等过程,在肝癌的发生发展中发挥重要作用,是一种潜在的抑癌基因.     

MAGE-4基因在肝细胞肝癌中的表达及临床意义

目的通过研究MAGE-4基因在肝细胞肝癌组织中的表达,并与患者临床资料进行分析,探讨 MAGE-4基因与肝细胞肝癌(HCC)患者临床指标及转移与复发的关系,为MAGE-4基因编码蛋白用于HCC患者免疫治疗提供依据. 方法用RT-PCR的方法对31例HCC患者癌组织及相应癌旁组织MAGE-4基因表达进行测定,对全部RT-PCR扩增产物中目的基因片段进行DNA测序以证实其为 MAGE-4基因,患者均测定并统计AFP、AFU、抗HCV、HBsAg、AFP mRNA、肿瘤直径等临床指标. 结果 31例HCC患者肝癌组织中MAGE-4基因表达的阳性率38.7% (12/31)明显高于癌旁组织中MAGE-4基因表达的阳性率0% (0/31),P＜0.01.HCC患者肝癌组织中MAGE-4基因表达的阳性率与患者AFP、AFU、抗HCV、HBV标志物、AFP mRNA、肿瘤直径等临床指标均无关,P＞0.05. 结论 MAGE-4基因在HCC患者肝癌组织中特异高表达,可能作为HCC患者免疫治疗攻击的靶点,HCC患者肝癌组织中 MAGE-4基因表达的阳性率与HCC患者肿瘤标志物、转移、复发均无关.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.