大肠癌中nm23-H1的表达及其与临床病理特征的关系

目的:观察nm23-H1的表达与临床病理特征的关系,探讨nm23-H1的表达与大肠癌发生、发展、转移的作用.方法:选取行结、直肠癌根治术的患者63例,并取腺瘤组织16例做对照.应用免疫组化S-P法检测大肠癌患者癌组织、同源癌旁组织及正常黏膜组织和大肠腺瘤组织nm23-H1的表达.结果:nm23-H1在癌组织中表达(58.7%)显著低于癌旁组织(90.5%)、正常黏膜组织(96.0%)及腺瘤组织(93.8%)(P＜0.05).在大肠癌组织中,无淋巴结转移者nm23-H1表达(73.3%)显著高于有淋巴结转移者(45.5%)(P＜0.05).大肠癌中nm23-H1表达与肿瘤分化程度呈正相关(r=0.192,P＜0.05),与肿瘤浸润深度呈负相关(r=-0.263,P＜0.05).nm23-H1表达程度与患者年龄、性别、肿瘤大体分型、组织学类型、同期肿瘤大小均无关.结论:nm23-H1表达下调是大肠癌发生、发展中的重要分子生物学事件,可作为提示肿瘤分化、侵袭和淋巴结转移的一项指标.     

SFRP2和β-catenin在大肠癌中的表达及其临床意义

目的:探讨分泌型Frizzled相关蛋白2(Secreted Frizzled-related proteins 2,SFRP2)和β-连接素(β-catenin)在大肠癌发生、发展中的作用.方法:采用免疫组化SP法检测20例正常大肠黏膜、加例非腺瘤性息肉、36例大肠腺瘤和42例大肠癌组织中的SFRP2和β-catenin蛋白的表达情况,分析二者表达的差异及其与临床病理参数的关系.结果:大肠癌和大肠腺瘤组SFRP2的阳性表达率显著低于正常大肠黏膜和非腺瘤性息肉组(28.57% VS 100.0%,95.0%;36.11% VS 100.0%,95.0%,均P＜0.05);大肠癌中β-catenin膜表达缺失率显著高于正常大肠黏膜、非腺瘤性息肉及大肠腺瘤组(52.4% VS 0%,0%,11.1%,均P＜0.05);大肠癌和大肠腺瘤组β-catenin异位表达率显著高于正常大肠黏膜和非腺瘤性息肉组(64.3% VS 0%,0%;30.6% VS 0%,0%,均P＜0.05),大肠癌β-catenin异位表达率高于大肠腺瘤(P＜0.05);SFRP2表达、β-catenin膜表达缺失及异位表达与大肠癌患者的肿瘤部位、大体形态、肿瘤直径、淋巴转移和Dukes分期无明显关系,而与大肠癌的分化程度密切相关,其中SFRP2表达还与大肠癌的浸润深度密切相关:SFRP2表达与β-catenin膜表达缺失、异位表达均呈明显负相关(r=-0.452,P=0.003;r=-0.519,P=0.000),而β-catenin膜表达缺失与异位表达呈明显正相关(r=0.782,P=0.000).结论:SFRP2和β-catenin的表达与大肠癌的发生、发展密切相关,可能是大肠癌发生的早期事件,且SFRP2表达与β-catenin膜表达缺失、异位表达均呈负相关,前者起抑癌作用,后者起促癌作用.     

VEGF在大肠癌中的表达及意义

采用免疫组化技术检测15例正常人大肠黏膜，27例大肠腺瘤及81例大肠癌患者瘤组织中血管内皮生长因子（VEGF）表达。结果VEGF在大肠正常黏膜、大肠腺瘤、大肠癌组织中表达逐渐增高、增强，两两比较均存在显著差别（P〈0．01）；VEGF表达与大肠癌的浸润深度、淋巴结转移、远处转移、Dukes分期呈正相关。认为VEGF在大肠正常黏膜发展到腺瘤及癌的过程中具有重要作用，可作为预测组织癌变的因子；VEGF可促进大肠癌组织的生长和转移，可作为大肠癌的预后评估因子；降低VEGF的表达和活性可能成为抗肿瘤转移治疗的新途径。     

Survivin、MMP-9在大肠腺瘤癌变过程中的表达及其临床意义

目的研究存活素(Survivin)和MMP-9在大肠腺瘤癌变过程中的表达,探讨他们在大肠癌发生、发展、浸润和转移中的作用及其相互关系。方法用免疫组化SABC法和原位杂交技术检测59例大肠腺癌、35例大肠腺瘤(包括21例低度异型增生和14例高度异型增生)和12例癌旁正常大肠黏膜组织中Survivin蛋白、SurvivinmRNA和MMP-9的表达。结果在大肠腺瘤-癌序列演变过程中,Survivin蛋白、mRNA和MMP-9的表达率逐渐升高;正常大肠黏膜、低度异型增生腺瘤与高度异型增生腺瘤、大肠癌间Survivin、MMP-9表达有显著性差异(P<0.05),大肠癌和高度异型增生腺瘤的Survivin、MMP-9表达无显著性差异(P>0.05);SurvivinmRNA阳性强度均低于蛋白表达水平;大肠癌组织中,Survivin的表达与临床病理分型之间均无相关性(P>0.05);MMP-9的表达与浸润深度、Dukes分期、淋巴道转移之间有显著性差异(P<0.05);Survivin与MMP-9两者在大肠腺瘤癌变过程中的表达密切相关(r=0.573,P<0.01)。结论Survivin在大肠腺瘤至癌的演变阶段起重要作用;MMP-9在大肠癌浸润、转移过程中起重要作用;Survivin蛋白表达的调控可能发生在转录以后水平;Survivin与MMP-9存在协同作用或相互调节机制,共同促进肿瘤的发生、发展、浸润和转移。     

E-cadherin、MMP-9及TIMP-1表达与大肠癌生物学行为及预后的关系

目的 探讨E-钙粘素(E-cadhefin)、基质金属蛋白酶-9(MMP-9)及其抑制剂(TIMP-1)表达与大肠癌生物学行为及预后的关系.方法 采用免疫组化染色法检测54例大肠癌组织标本中E.钙粘素、MMP-9及TIMP-1的表达情况,经结肠镜活检的大肠腺瘤组织标本15例作为正常对照.结果 E-cadherin的表达率在大肠腺瘤中为86.7%,显著高于大肠癌中55.6%的表达率,两者存在显著性差异(P<0.05).E-cadherin的表达与大肠癌的大体类型有关,且随着大肠癌分化程度的降低而减少.与浸润深度、淋巴结转移呈负相关(P<0.05).其表达率越高,患者的预后越好.大肠癌MMP-9和TIMP-1蛋白表达存在显著正相关(r=0.374,P<0.01).MMP-9的表达率在大肠腺瘤中为33.3%,显著低于大肠癌中的70.4%(P<0.05).其表达与大肠癌的浸润深度、Dukes分期、淋巴结转移及生存期均密切相关(P均<0.05).TIMP-1的表达在大肠腺瘤及大肠癌组织中没有显著性差异(P>0.05),但其表达与大肠癌组织学类型、分化程度、淋巴结转移密切相关,对预后无显著性影响(P>0.05).结论 E.钙粘素、MMP-9及TIMP-1对大肠癌生物学行为均有明显影响.E-钙粘素的正常表达将显著降低大肠癌的浸润和转移能力.MMP-9蛋白阳性表达促进大肠癌浸润和转移,患者预后欠佳.E-钙粘素、MMP-9和TIMP-1的检测可以成为临床判断大肠癌的生物学行为及预后的重要参考指标.     

PTEN与VEGF在大肠癌组织中的表达及其临床意义

目的 通过对张力蛋白同源物基因(PTEN)和血管内皮生长因子(VEGF)在大肠癌中表达的研究,探讨PTEN和VEGF的相关性.方法 应用免疫组织化学S-P法检测58例大肠癌组织及20例正常大肠组织中PTEN和VEGF的表达.结果 大肠癌组织中PTEN蛋白表达显著低于正常大肠组织(P＜0.01),与淋巴结转移及Dukes分期相关(P＜0.05),而与大肠癌组织分化程度不相关(P＞0.05).VEGF在大肠癌中的表达显著高于正常大肠黏膜的表达(P＜0.01),与淋巴结转移及Dukes分期相关(P＜0.05),而与大肠癌组织分化程度不相关(P＞0.05).PTEN在大肠癌中的表达与VEGF呈负相关(P＜0.05).结论 PTEN失活或蛋白表达降低与大肠癌淋巴结转移及Dukes分期相关,且与VEGF呈负相关.联合检测PTEN、VEGF有助于提高大肠癌侵袭转移能力的评估,对大肠癌的预后判断具有重要的临床意义.     

COX-2、EGFR和Ki67在大肠癌组织中的表达及其意义

目的 探讨环氧合酶-2(COX-2)、表皮生长因子受体(EGFR)和Ki67在大肠癌组织中的表达及其意义.方法 选取大肠癌70例、大肠腺瘤21例和正常大肠组织15例,采用免疫组织化学Envision方法检测COX-2、EGFR和Ki67的表达.结果 在正常大肠黏膜、大肠腺瘤和大肠癌组织中,COX-2的阳性表达率分别为33.3%、71.4%和80.0%,大肠癌和腺瘤组显著高于正常组(P均＜0.05);EGFR的阳性表达率依次为0、23.8%和65.7%,两两比较有统计学差异(P均＜0.05);Ki67的阳性表达率依次为40.0%、76.2%和82.8%,大肠癌和腺瘤组织中的表达均高于正常大肠组织(P均＜0.05).COX-2在有淋巴结转移的大肠癌组中的表达明显高于无淋巴结转移组(P＜0.05);EGFR在低分化、高分期和有淋巴结转移大肠癌中的表达明显增强(P均＜0.05),且COX-2与EG-FR、COX-2与Ki67、EGFR与Ki67之间均具有相关性(r=0.316,0.435,0.314,P均＜0.05).结论 COX-2、EGFR和Ki67对大肠癌的发生、发展有协同作用.     

DR-nm23在大肠癌组织中的蛋白表达及意义

目的:探讨DR-nm23蛋白在大肠癌组织中的表达及其与大肠癌发生发展和转移的关系. 方法:应用SP免疫组织化学法检测98例大肠癌、57例大肠腺瘤及42例正常大肠黏膜组织中DR-nm23蛋白的表达,统计学分析比较DR-nm23蛋白表达差异与大肠癌的发生、进展、淋巴结转移以及大肠癌组织学分型、病理分级的相关性. 结果:DR-tnm23蛋白在正常组、腺瘤组和大肠癌组的表达逐渐下调,3组间表达差异具有显著性(71.4% vs 38.6%,35.7%,均P<0.01).腺瘤组中,高级别上皮内肿瘤的表达率低于低级别上皮内肿瘤(25.7% vs 59.1%,P<0.05);大肠癌无淋巴结转移组表达率高于淋巴结转移组,表达与淋巴结转移呈负相关(44.1% vs 23.1%,P<0.05);DR-nm23表达与组织学分型(χ2=13.731,P<0.01)及病理分级(χ2=12.198,P<0.01)均有相关性.转移组中,淋巴结转移癌DR-nm23蛋白表达率较原发癌高,但二者差异无显著性(P>.05). 结论:DR-nm23参与大肠癌细胞的分化,其表达下调与大肠癌发生发展转移密切相关,可作为反映大肠癌生物学行为和判断预后的潜在重要指征.     

COX-2基因在大肠癌的表达及其意义

目的 探讨COX-2基因在大肠癌中表达的意义.方法 收集手术切除的大肠癌标本58例,同时选取大肠癌远端正常黏膜组织10例,应用流式细胞术(FCM)检测大肠癌及正常黏膜中COX-2表达情况,根据平均荧光强度计算荧光指数(FI). 结果 COX-2表达平均FI值正常黏膜组为1.00±0.28,高、中、低分化及黏液癌组分别为2.47±1.41、2.70±1.08、3.16±1.34和2.01±1.43,高、中、低分化及黏液癌组COX-2表达均明显高于正常黏膜组(P＜0.01);大肠癌淋巴结转移组平均FI值(2.45±1.41)显著高于无淋巴结转移组(1.61±1.27)(P＜0.05).COX-2的表达与患者的年龄、性别、肿瘤的发生部位等无关.结论 COX-2在大肠癌中表达异常增高,并与淋巴结转移密切相关.     

IGF-Ⅱ和IGF-ⅠR在大肠癌中的表达

目的研究胰岛素样生长因子-Ⅱ(IGF-Ⅱ)和胰岛素样生长因子Ⅰ受体(IGF-ⅠR)在国人大肠癌中的表达情况及其与临床病理的关系.方法应用免疫组织化学过氧化物酶标记链霉卵白素法(S-P)对40例大肠癌患者的大肠癌组织、距大肠癌原发灶1cm癌旁组织、距大肠癌原发灶10cm以上大肠组织和10例非肿瘤患者的正常大肠组织标本,进行IGF-Ⅱ和IGF-ⅠR的抗原染色.结果①大肠癌组织和癌旁组织中IGF-Ⅱ和IGF-ⅠR的表达率显著高于切缘组织和正常大肠组织的表达率(P＜0.05).癌组织和癌旁组织中IGF-Ⅱ和IGF-ⅠR的表达率无显著性差异(P＞0.05).切缘组织和正常大肠组织中IGF-Ⅱ和IGF-ⅠR的表达率无显著性差异(P＞0.05).②在有淋巴结转移和Dukes分期C期及浸透全层组中IGF-Ⅱ和IGF-ⅠR的表达率分别显著高于无淋巴结转移组和Dukes分期A、B期及未浸透全层组中ⅠGF-Ⅱ和ⅠGF-ⅠR的表达率(P＜0.05).结论 IGF-Ⅱ、IGF-ⅠR的高表达与大肠癌的发生发展和侵袭转移密切相关.     

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.     

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.     

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.     

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.