阻断缺氧诱导因子-1α/血管内皮生长因子信号通路对膀胱癌生物学行为的影响

目的探讨阻断缺氧诱导因子(HIF)-1α/血管内皮生长因子(VEGF)信号通路对人膀胱癌生长及转移的影响。方法通过构建人膀胱癌小鼠原位移植瘤模型并注射基因制剂,观察肿瘤生长及盆腔淋巴结转移情况,同时采用免疫组化法检测肿瘤微血管密度及凋亡的肿瘤细胞指数。结果肿瘤大小:治疗组为(19.80±3.47)mm2,对照组为(64.58±7.31)mm2,两组比较差异有统计意义(P<0.01);肿瘤微血管密度:治疗组为(2 537±309)个,对照组为(3 846±972)个,两组相比差异有统计学意义(P<0.05);凋亡指数:治疗组为21.84,对照组为13.52,两者比较差异有统计学意义(P<0.05);制剂组无盆腔转移,对照组转移率为75.0%,两组比较差异有统计学意义(P<0.01)。结论阻断HIF-1α/VEGF信号通路能够通过抑制肿瘤微血管形成并加速肿瘤细胞凋亡,遏制实验性人膀胱癌细胞的生长转移。     

抗人膀胱癌/抗VEGF双功能基因抗体对原位种植人膀胱癌的影响

目的 研究抗人膀胱癌/抗VEGF双功能基因抗体对裸鼠原位种植人膀胱癌生长和转移的抑制作用.方法 建立人膀胱癌裸鼠皮下移植瘤模型,观察双功能基因抗体对肿瘤生长和转移的影响,并计数肿瘤内微血管密度.结果 用药组与对照组比较,肿瘤生长和转移显著减慢和延缓,肿瘤内部微血管密度亦明显低.结论 抗人膀胱癌/抗VEGF双功能基因抗体能够通过抑制肿瘤微血管的形成来遏制人膀胱癌的生长和转移,从而为该抗体进一步体内试验和临床应用提供了实验基础.     

抗人膀胱癌/抗血管内皮生长因子双功能基因抗体的动物实验研究

目的 探讨抗人膀胱癌／抗人血管内皮生长因子(VEGF)双功能基因抗体对膀胱癌生长的抑翻作用。方法 应用双功能基因抗体作用于荷瘤动物模型观察抑瘤作用，应用免疫组化技术检测体内生长肿瘤中截血管密度。结果 双功能基因抗体对体内生长的肿瘤有明显的抑制作用，经双功能基因抗体治疗的瘤体中截血管密度明显低于对照组。结论 双功能基因抗体能够抑制肿瘤血管生成，从而为膀胱癌的治疗提供一种新的辅助方法。     

血管内皮细胞生长因子反义寡核苷酸对小鼠Lewis肺癌生长和转移的抑制作用

目的探讨血管内皮细胞生长因子(VEGF)反义寡核苷酸对小鼠Lewis肺癌生长和转移的抑制作用。方法复制小鼠Lewis肺癌模型24只,随机分为对照组、VEGF反义寡核苷酸(ASODN)组、VEGF错义寡核苷酸(MSODN)组,每组8只,接种肿瘤细胞24h内分别给予生理盐水、VEGF-ASODN、VEGF-MSODN皮下注射,隔日一次,共15次。检测皮下移植瘤的变化和肺转移率,并用免疫组织化学的方法检测肿瘤组织微血管密度(MVD),及用Western blot的方法检测肿瘤组织VEGF蛋白表达。结果ASODN组和MSODN组的抑瘤率分别为47.34%和7.28%,具有显著差异(P<0.01);ASODN组肺转移率为37.5%,低于MSODN组(75.0%)和对照组(87.5%);ASODN组MVD为12.29±2.06,低于MSODN组(17.38±3.24)和对照组(20.14±3.90)(P<0.05);且ASODN组VEGF蛋白表达亦明显减弱。结论VEGF-ASODN可抑制小鼠Lewis肺癌的生长和转移,为肺癌的治疗提供新的方法。     

抗人膀胱癌/抗VEGF双功能基因抗体对血管内皮细胞增殖的影响

目的 研究抗人膀胱癌／抗VEGF双功能基因抗体体外抗血管内皮细胞增殖的活性。方法 MTT法检测抗人膀胱癌／抗VEGF双功能基因抗体对血管内皮细胞增殖的活性。结果 抗人膀胱癌／抗VEGF双功能基因抗体可以明显抑制血管内皮细胞增殖。结论 抗人膀胱癌／抗VEGF双功能基因抗体能通过抗肿瘤新生血管形成而发挥抗肿瘤作用，从而为膀胱癌的治疗提供了一种新的思路。     

一氧化氮合酶抑制剂对大肠癌裸鼠移植瘤的抗血管生成作用

目的:观察一氧化氮合酶抑制剂N-硝基精氨酸甲酯(L-NAME)对大肠癌细胞的抑制作用,以及对移植瘤内血管生成的影响.方法:建立大肠癌裸鼠移植瘤模型再随机分为生理盐水对照组(n=6,0.2 mL)、L-NAME组(n=6,1.5 mg/kg)、5-FU组(n=6,5 mg/ kg)、L-NAME 5-FU联合组(n=6,L-NAME 1.5 mg/kg,5-FU 5 mg/kg),皆以灌胃方式给药,3次/wk,共2 wk.测量各组肿瘤体积,观察L-NAME的体内抗瘤作用.采用免疫组化方法观察移植瘤的微血管密度(MVD),用Western blot方法检测肿瘤组织VEGF蛋白的表达.结果:L-NAME,5-FU,L-NAME 5-FU组抑瘤率分别为34.1%、46.0%、74.1%,与对照组比较,有显著性差异(P<0.01),联合治疗组与L-NAME,5-FU组比较,差异也有显著性(P<0.01);MVD值对照组为28.9±2.7,L-NAME组为16.2±3.1,与对照组比较,差异有显著性(P<0.05);L-NAME组移植瘤VEGF蛋白的表达(113.14±2.34),与对照组(98.56±1.76)相比,明显减弱(P<0.05).结论:L-NAME具有抑制肿瘤新生血管生成的作用,可抑制大肠癌裸鼠移植瘤的生长;和5-FU联合具有协同抗肿瘤作用.     

Survivin蛋白在前列腺癌组织中的表达和相关性研究

目的探讨Survivin蛋白在前列腺癌组织中表达及其与肿瘤增殖、微血管密度计数和肿瘤细胞凋亡的关系和临床意义。方法采用免疫组化SP法和DNA原位未端标记TUNEL法分别测定42例前列腺癌(PCa)组织和10例正常前列腺(NP)组织中Survivin、Ki-67、VEGF、CD34的表达和细胞凋亡情况。结果Survivin蛋白在PCa中的阳性表达为80.59%,与病理分级、临床分期和淋巴结转移密切相关(P<0.05),而正常前列腺组织中无阳性表达。Ki-67标记指数(LI)在PCa及NP中分别为(14.42±8.10)%和(8.10±2.50)%,其差异有统计学意义(P<0.01)。PCa中VEGF的阳性表达为69.05%,与病理分级、临床分期和淋巴结转移密切相关(P<0.05)。PCa中MVD计数(32.54±10.17)显著高于正常前列腺组织(19.68±5.14)(P<0.01)。PCa癌组织及NP组织中细胞凋亡指数(AI)分别为3.03±1.33和1.07±0.77,其差异有统计学意义(P<0.05)。Survivin蛋白的表达与Ki-67LI、VEGF、MVD计数呈正相关(r分别为0.828、0.427和0.386,P<0.05);Survivin蛋白的表达与细胞凋亡指数呈负相关(r=-0.679,P<0.001)。结论Survivin蛋白的异常表达而引起的细胞凋亡抑制或逃避、肿瘤细胞增殖和微血管增生的增加,在前列腺癌的发生、发展中起一定的作用;Survivin蛋白的检测有助于对肿瘤细胞的分化程度、病理分期作出正确评价,以指导临床治疗及估计预后。     

术前腹腔化疗对进展期胃癌细胞增值及凋亡的影响

目的探讨术前腹腔化疗对进展期胃癌细胞凋亡及增值的影响。方法40例进展期胃癌病人随机分为两组,每组20例。实验组手术前行腹腔化疗。两组手术标本检测增殖细胞核抗原和细胞凋亡,分别计算肿瘤细胞增殖指数和凋亡指数。结果腹腔化疗-手术组肿瘤细胞增殖指数为(43.5±3.6%),明显低于对照组的(57.8±5.4%),P<0.01,腹腔化疗-手术组肿瘤细胞凋亡指数为(13.2±3.8%),与对照组(5.7±2.6%)比,差异极显著(P<0.01)。结论进展期胃癌术前化疗可以抑制肿瘤细胞增殖,增加肿瘤细胞凋亡,控制肿瘤生长。腹腔化疗在临床应用安全有效。     

人肝癌组织血管内皮生长因子及微血管密度分析的临床价值

目的 探讨血管内皮生长因子(VEGF)在肝癌(HCC)微血管形成、生长和转移方面的作用。 方法 以免疫组织化学法分析36例HCC组织中VEGF表达状态和细胞内分布,采用微血管染色方法测定微血管密度(MVD),并定量检测癌及癌周组织中总RNA和VEGF水平。 结果 所有HCC组织中VEGF阳性率为63.9％,无包膜组为78.3％,伴有远处转移组为90.9％;VEGF表达与MVD密切相关(t=4.49,,P<0.01);HCC组织VEGF水平或MVD值,在肿瘤直径大小组及肿瘤分化程度高低组间差异无显著性;HCC组织总RNA水平低于癌旁及远癌组织,而VEGF水平明显高于癌旁和远癌组织(q=6.10,P<0.01)。 结论VEGF过度表达和MVD异常是反映HCC侵润生长及转移的有效指标。     

西罗莫司对人肝癌裸鼠肝脏移植瘤生长的影响

目的 探讨西罗萸司(SRL)对人肝癌裸鼠肝脏移植瘤生长的影响.方法 建立人肝癌裸鼠肝脏移植瘤模型,使用SRL、他克莫司(FK506)进行干预治疗,采用免疫组织化学方法和图像分析技术检测移植瘤血管内皮细胞生长因子、增殖细胞核抗原的表达和微血管密度,原位末端标记法检测肿瘤细胞凋亡情况.统计学处理采用方差分析或t检验.结果 (1)SRL、FK506组和对照组移植瘤质量分别为(352±38)mg、(683±53)mg、(675±45)mg;SRL组移植瘤质量较对照组明显减少(t=10.378,P<0.01);FK506组和对照组比较无明显差异(P>0.05).(2)SRL组移植瘤血管内皮细胞生长因子和增殖细胞核抗原的表达较对照组明显下凋亡(f值分别为5.753和5.296,P<0.05),FK506组和对照组比较无明显差异(P>0.05).(3)SRL组移植瘤微血管密度较对照组明显减少(t=8.637,P<0.01);FK506组和对照组相比无明显变化(P>0.05).(4)SRL组移植瘤凋亡指数明显高于对照组(t=11.518,P<0.05);FK506对移植瘤凋亡指数无明显影响(P>0.05). 结论 SRL可通过减少肿瘤血管形成、阻I卜肿瘤增殖、诱导肿瘤细胞凋亡抑制肝癌的生长.     

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.