DLL4在胰腺癌组织中的表达及其与肿瘤血管生成的关系

目的 检测delta-like ligand 4(DLL4)在胰腺癌中的表达,分析其与肿瘤血管生成及临床病理特征的关系.方法 采用免疫组化SP法检测60例胰腺癌组织及20例癌旁正常胰腺组织中DLL4的表达;观察微血管内皮细胞CD34表达,计算微血管密度(MVD);分析DLL4表达、MVD与胰腺癌临床病理特征之间的关系以及两者的相关性.结果 DLL4在胰腺癌组织中的表达明显高于正常胰腺组织(68.3％比20.0％,P＜0.01);胰腺癌组织DLL4的高表达与肿瘤分化程度、TNM分型、肿瘤转移及浸润等呈正相关(P值均＜0.05),而与肿瘤部位、大小、组织病理分型无关.胰腺癌组织MVD明显高于正常胰腺组织(34.9±13.2比18.9±2.2,P＜0.01);胰腺癌的MVD与肿瘤分化程度、TNM分期、肿瘤转移及浸润有关(P值均＜0.05),而与肿瘤部位、大小、组织病理分型等无明显相关性.DLL4表达阳性的胰腺癌组织MVD明显高于DLL4表达阴性者(38.8±10.7比29.0±15.2,P＜0.05),且DLL4表达与MVD呈显著正相关(r=0.669,P＜0.05).结论 DLL4表达可促进肿瘤血管生成,且与胰腺癌的转移、浸润相关.     

Toll样受体4在胰腺癌组织中的表达及其与肿瘤血管生成的关系

目的 探讨Toll样受体4(TLR4)在胰腺癌组织中的表达及其与肿瘤血管生成的关系.方法 采用免疫组化SP法检测62例经病理证实的胰腺癌手术切除标本及35例癌旁正常胰腺组织中TLR4蛋白表达,采用CD31抗体标记微血管内皮细胞,计算微血管密度(MVD).分析TLR4蛋白表达与胰腺癌临床病理特征以及MVD的相关性.结果 胰腺癌组织TLR4蛋白阳性表达率和MVD分别为74.2％ (46/62)和47.3±13.5,均显著高于正常胰腺组织的17.1％ (6/35)和12.6±4.8(P值均＜0.01).有淋巴结转移的胰腺癌组织中TLR4蛋白阳性表达率为83.8％,显著高于无淋巴结转移的60.0％(P=0.036);TNM分期为Ⅲ+Ⅳ期的胰腺癌组织中TLR4蛋白阳性表达率为85.3％,显著高于Ⅰ+Ⅱ期的60.7％(P =0.028).MVD与肿瘤的大小、淋巴结转移及TNM分期密切相关(P值分别为0.008、0.036、0.010).胰腺癌TLR4蛋白表达与MVD呈显著正相关(Υ=0.534,P＜0.01).结论 TLR4参与胰腺癌的发生、发展,其机制可能与促进肿瘤血管生成有关.     

转录因子Twist及其相关因子N-cadherin在胰腺癌中的表达及意义

目的 探讨转录因子Twist及其下游相关因子N-cadherin在人胰腺癌组织中的表达及与肿瘤临床病理特征、患者预后的关系.方法 采用免疫组化MaxVision两步法分别检测62例胰腺癌组织和10例正常胰腺组织中Twist及N-cadherin的表达,分析二者表达与临床病理特征及患者预后的相关性.结果 Twist在胰腺癌组织的阳性表达率明显高于正常胰腺组织(96.8％比30.0％,P＜0.01),N-cadherin在胰腺癌组织的阳性表达率也明显高于正常胰腺组织(75.8％比0,P＜0.01),但两者的表达无明显相关性(r=0.100,P=0.441).Twist及N-cadherin表达与胰腺癌TNM分期、淋巴结转移、门静脉或神经浸润、肿瘤部位均密切相关(P值均＜0.05),与患者年龄、性别及肿瘤分化程度均无明显相关性(P值均＞0.05).胰腺癌患者术后生存期随Twist表达的增强而缩短,但与N-cadherin表达强度无明显相关性.TNM分期、Twist表达强度是影响胰腺癌患者预后的独立因素.结论 胰腺癌组织Twist及N-cadherin均高表达,其表达与胰腺癌的恶性生物学行为相关,Twist的异常表达可能是评估胰腺癌患者预后的潜在指标.     

EphA7在胰腺癌组织中的表达及意义

目的 检测EphA7蛋白在胰腺癌组织中的表达,探讨其与胰腺癌发生发展的关系.方法 应用免疫组化方法 检测10例正常胰腺组织、51例胰腺癌及其配对癌旁组织中EphA7蛋白的表达,并分析其与胰腺癌病理参数的关系.结果 正常胰腺组织、胰腺癌旁组织和胰腺癌组织中EphA7蛋白的阳性表达率分别为10%(1/10)、47.1%(24/51)和94.1%(48/51),差异有显著性统计学意义(P<0.05).EphA7蛋白高表达与胰腺癌患者的年龄、性别、肿瘤部位、肿瘤大小无关(P>0.05),而与肿瘤分化程度、临床分期、淋巴结转移或远距转移密切相关(P<0.05).结论 EphA7高表达可能与胰腺癌的发生、发展及转移有关.     

非小细胞肺癌组织EGFR、CXCR4的表达及其与MVD的相关性

目的 探讨非小细胞肺癌(NSCLC)组织中表皮生长因子受体(EGFR)、趋化因子受体4(CXCR4)的表达与肺癌生物学行为以及血管形成之间的关系.方法 应用免疫组织化学方法(SP法)检测62例NSCLC癌组织、12例癌旁正常组织中EGFR、CXCR4的表达及微血管密度(MVD),并分析EGFR、CXCR4的表达及MVD与组织类型、肿瘤大小、TNM分期、分化程度、淋巴结转移的相关性.结果 CXCR4在肺癌组织中的阳性表达率为58.1%,在正常组织中的阳性表达率为16.7%,两者比较有显著性差异(P<0.05).NSCLC癌组织中,EGFR、CXCR4表达明显升高,MVD也明显高于正常组织,与肿瘤的分化程度、临床分期、淋巴结转移均有相关性(均P<0.05),与肿瘤的大小、病理分型无关(均P>0.05).EGFR、CXCR4在NSCLC中的表达与肿瘤MVD呈显著正相关.结论 同时检测NSCLC癌组织的EGFR、CXCR4的表达及MVD对判断肿瘤的恶性程度和估计预后有一定的意义.     

老年胰腺癌组织中生存素的表达及其与预后的关系

目的探讨老年胰腺癌组织中生存素（survivin）的表达及其与预后的关系。方法应用免疫组化链霉菌亲和素-过氧化物酶法（SP）检测30例手术切除的老年原发性胰腺癌组织及癌旁非肿瘤胰腺组织中survivin的表达。结果胰腺癌组织中survivin的阳性率为70.0%（21/30）,癌旁非肿瘤组织中未见表达。survivin的表达与患者的性别、年龄、肿瘤部位、肿瘤大小与肿瘤分化程度无关（P〉0.05）,而与有无淋巴结转移与TNM分期[T（肿瘤的浸润范围与程度）、N（周围淋巴结转移）及M（远处脏器转移）]显著相关（P〈0.05）。KaplanMeier生存分析显示,survivin阳性组患者的预后明显差于阴性组（P〈0.05）。结论 survivin在老年胰腺癌的发生发展及预后中发挥重要作用。     

类肝素酶在胰腺癌组织中的表达意义

目的 探讨胰腺癌组织中类肝素酶(heparanase 1,Hpal)表达与胰腺癌侵袭性、临床病理等因素之间的关系.方法 采用逆转录-聚合酶链反应(RT-PCR)、免疫组化(SP)法检测37例胰腺癌患者痛组织、癌旁组织及正常胰腺组织中Hpal表达,并统计分析Hpal表达与胰腺癌侵袭性、临床病理等因素之间的相关性.结果 Hpal在胰腺癌组织、癌旁组织、正常胰腺组织中的表达阳性率分别为64.9%(24/37)、56.8%(21/37)和10.8%(4/37).胰腺癌组织中Hpal表达与胰腺癌TNM分期、侵及神经和血管情况、包膜完整情况以及淋巴转移明显相关(P＜0.05),但与患者年龄、性别、组织学分化程度、肿瘤大小无关(P＞0.05).结论 Hpal与胰腺癌发生、发展密切相关,Hpal表达与胰腺癌的侵袭性、局部浸润、临床分期以及区域淋巴结转移有密切关系,胰腺癌Hpal过表达可促进胰腺癌浸润生长与转移,其表达对评价胰腺癌预后亦有一定的价值.     

TMPRSS4在胰腺癌组织中的表达及其临床意义

目的 检测Ⅱ型跨膜丝氨酸蛋白酶4( TMPRSS4)在胰腺癌组织中的表达及其与临床病理特征的关系.方法 采用实时PCR法和蛋白质印迹法检测16例胰腺癌和配对癌旁组织TMPRSS4 mRNA和蛋白表达;采用免疫组织化学法检测61例胰腺癌标本、26例配对癌旁组织、4例正常胰腺组织TMPRSS4蛋白的表达,分析其与临床病理特征的相关性.结果 胰腺癌组织TMPRSS4mRNA和蛋白表达明显高于配对癌旁组织(9.09±7.01比1.27±0.72;1.223±0.125比0.667 ±0.106,P值均＜0.01),胰腺癌组织TMPRSS4蛋白阳性表达率为67.2％ (41/61),显著高于癌旁组织3.8％ (1/26)的阳性表达率(P＜0.01).正常胰腺组织未见TMPRSS4蛋白表达.胰腺癌TMPRSS4表达与患者年龄、性别及肿瘤部位、肿瘤大小无关,而与肿瘤分化程度、淋巴结转移、临床分期密切相关(P值均＜0.05).结论 胰腺癌组织高表达TMPRSS4,其表达与肿瘤的恶性程度相关.     

甲基转移酶3B基因在胰腺癌中的表达

目的 检测胰腺癌组织中甲基转移酶3B(DNMT3B)基因表达,分析其与胰腺癌临床病理参数的关系.方法 应用实时定量PCR和免疫组织化学方法检测42例胰腺癌组织及相应癌旁组织、10例正常胰腺组织中DNMT3B mRNA和蛋白表达.结果 胰腺癌组织、癌旁组织和正常胰腺组织DNM33B mRNA表达量分别为9.4±5.9、1.02±0.71和0,相差非常显著(P<0.05);DNMT3B蛋白表达阳性率分别为83.3%、14.3%和10.0%,相差也非常显著(P<0.01).DNMT3B mRNA表达与I临床分期、肿瘤分化程度和淋巴结转移密切相关(P<0.05或P<0.01);DNMT3B蛋白表达与肿瘤的部位、淋巴结转移有关(P<0.01或P<0.05);DNMT3B mRNA和蛋白表达均与年龄、性别、神经浸润、肿瘤大小、血CEA和CA19-9浓度无关.结论 胰腺癌DNMT3B mRNA和蛋白高表达提示胰腺癌已发生淋巴结转移,预后较差.     

胰腺癌组织中p53、血管内皮生长因子的表达与血管生成的关系及其临床意义

目的探讨胰腺癌组织中p53、血管内皮生长因子(VEGF)和血管生成的关系.方法用免疫组织化学方法检测48例胰腺癌组织及癌旁组织、6例正常胰腺组织中p53、VEGF表达和微血管密度(MVD).结果胰腺癌组织中VEGF、p53的阳性表达率分别为54.17%和50%,显著高于癌旁组织及正常组织的表达率(P < 0.01),胰腺癌组织中MVD显著高于癌旁组织及正常组织.VEGF表达与肿瘤大小和分期有关(P=0.038,P=0.045),VEGF表达与MVD有相关性(r=0.294 P=0.043).p53与淋巴结转移及预后相关(P < 0.05)而与VEGF、MVD之间无关.MVD与胰腺癌临床病理特征无关,MVD与生存期存在负相关(r=-0.371 P=0.011).多元回归分析显示p53、VEGF和MVD都不是影响胰腺癌预后的独立因素.结论 p53基因突变为胰腺癌分子事件的晚期事件,可作为评价胰腺癌预后的一项指标,抗血管生成可能有利于胰腺癌的治疗.     

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.     

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.     

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.     

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.