VEGF、Ki67的表达与宫颈癌浸润、淋巴结转移关系的探讨

目的:探讨宫颈癌组织中VEGF、Ki67的表达与肿瘤浸润性及淋巴结转移的关系.方法:收集45例手术切除或活检标本,包括正常宫颈组织,宫颈鳞癌组织(按有无淋巴转移、分化及临床分期分组).进行SP免疫组化染色测定VEGF蛋白、Ki67蛋白的表达.结果:正常宫颈组织VEGF蛋白不表达,宫颈癌组织中VEGF的表达率为48.57%.VEGF阳性表达与分化程度、临床分期、淋巴结转移呈正相关(χ2＝10.3001,P＜0.01;Z.一10.1521,P＜0.0t;χ2＝5.9063,P＜0.05).Ki67阳性表达与临床分期、分化程度无正相关,与淋巴结转移呈正相关(χ2=2.6662,P＞0.05;χ2=0.8649,P＞0.05;χ2=11.9442,P＜0.01).结论:VEGF可能在宫颈癌的发生发展和袭转移中起重要作用,有望成为判断宫颈癌预后的指标.Ki67可作为反映宫颈癌细胞增殖能力的指标.     

COX-2与Fax、Ki-67在宫颈癌中表达的临床意义

目的：探讨环氧化酶-2（COX-2）、Fax、Ki-67在宫颈癌中的表达及其临床病理意义。方法采用免疫组织化学染色的方法,检测宫颈癌（cervical cancer, CC）40例,宫颈上皮内瘤变（cervical intraepithelial neoplasm, CIN）10例及正常宫颈组织（normal cervical epithelium, NCE）9例中COX-2、Fax、Ki-67的抗体表达的情况。结果 COX-2在宫颈癌中的表达率为70%-90%,而在正常宫颈组织及宫颈上皮内瘤变中表达率比较差异无统计学意义（P〉0.05）。Fax在宫颈癌中的阳性表达率明显低于正常宫颈组织和CIN组织（P〈0.05）;Ki-67在宫颈癌、CIN与正常宫颈组织中表达差异有统计学意义（P〈0.05）。结论 COX-2、Fax、Ki-67在宫颈癌的发生、发展及淋巴结转移中有着重要作用,可以作为判断宫颈癌恶性程度及淋巴结转移的生物学指标。     

Caveolin-1与Ki-67在宫颈癌中的表达及与HPV16/18的相关性

目的:研究Caveolin-1和Ki-67在正常宫颈组织、宫颈上皮内瘤样变(CIN)以及宫颈癌中的表达情况及其与人乳头状病毒(HPV)16/18感染的相关性,探讨上述指标作为宫颈癌诊治的一种新的有效指标的可行性。方法:采用免疫组化方法检测15例正常宫颈组织、35例CIN组织、50例宫颈癌组织中Caveolin-1、Ki-67及HPV16/18的表达情况。结果:Caveolin-1和Ki-67在宫颈癌组织中的阳性表达率与CIN、正常宫颈组织差异有统计学意义。在宫颈癌组织Caveolin-1的阳性表达率表现为高临床分期低于低临床分期,中、高分化程度高于低分化程度;而Ki-67的阳性表达率与之情况相反;此外,无淋巴结转移患者Caveolin-1的阳性表达率高于有转移患者。HPV16/18在宫颈癌组织中的阳性表达率高于正常宫颈和CIN组,但不同临床分期、病理分级、年龄和淋巴结有无转移差异无统计学意义。Caveolin-1与Ki-67在宫颈癌组织的异常表达与HPV16/18感染有关。结论:联合检测Caveolin-1、Ki-67和HPV16/18可作为筛查宫颈癌和判断预后的有利指标。     

宫颈癌Foxm1蛋白表达与临床意义

目的 探讨Foxm1蛋白在宫颈癌发生和进展中的作用及其检测对宫颈癌的早期发现及恶性程度评估的意义.方法 采集宫颈癌组织标本43例及正常子宫颈组织标本35例.采用免疫组化法检测标本中的Foxm1蛋白情况,分析宫颈癌组织Foxm1蛋白总体表达水平及细胞核中Foxm1蛋白表达与其病理特征的关系.结果 宫颈癌组织Foxm1蛋白阳性表达率明显高于正常宫颈组织(P＜0.001).宫颈癌组织的Foxm1蛋白表达评分明显高于正常宫颈组织(P＜0.001).宫颈癌组织的不同病理类型、分化程度、FIGO分期、淋巴结转移间的Foxm1蛋白总表达评分比较差异无统计学意义(P＞0.05).低分化、Ⅱ期、有淋巴结转移患者的肿瘤细胞核中的Foxm1蛋白表达水平明显高于高分化或中分化、0～Ⅰ期、无淋巴转移患者(P＜ 0.001).结论 Foxm1蛋白可能与宫颈癌的发生、进展相关,检测细胞核中的Foxm1蛋白的阳性表达水平可能利于在早期发现宫颈恶性病变及评估宫颈癌的恶性程度.     

P14、P16在宫颈癌中的表达及临床意义

目的 探讨P14、P16在宫颈癌组织中的表达及其与临床病理参数的相关性.方法 采用免疫组织化学链霉素抗生素-过氧化酶连接法(S-P法)检测P14、P16在56例宫颈鳞癌组织、20例CIN Ⅲ组织和30例正常宫颈组织中的表达情况.结果 P14和P16蛋白在正常宫颈组织中的阳性表达率明显低于CIN Ⅲ组织和宫颈癌组织,差异有显著性(P＜0.05).P14蛋白的表达与浸润深度、病理分级及淋巴转移有关(P＜0.05),与临床分期、年龄、肿瘤大小或脉管有无癌栓无关(P＞0.05);P16蛋白的表达与病理分级及淋巴转移有关(P＜ 0.05),与临床分期、年龄、肿瘤大小、浸润深度或脉管有无癌栓无关(P＞0.05).结论 P14、P16基因的高表达发生在宫颈癌和癌前病变阶段,对宫颈癌的诊断及预后判断有一定价值,故可作为肿瘤标记物用于宫颈癌的临床筛查及诊断.     

乳腺浸润性导管癌组织中Fas、FasL和Ki-67的表达及相关性研究

目的：探讨乳腺浸润性导管癌组织中Fas、FasL、Ki-67的表达的差异及临床病理意义及Fas/FasL与Ki-67的相关性。方法采用免疫组织化学法检测20例正常乳腺组织和60例乳腺浸润性导管癌组织标本中Fas、FasL和Ki-67的表达。结果乳腺浸润性导管癌组织中 Fas、FasL 和 Ki-67阳性表达率分别为26.7％、78.3％和65.0％,正常乳腺组织中Fas、FasL和Ki-67阳性表达率分别为85.0％、15.0％和15.0％;FasL和Ki-67在乳腺浸润性导管癌组织表达与TNN分期、病理分级及淋巴转移有相关性（P＜0.05）,与年龄无相关性（P＞0.05）,而Fas的表达与年龄、TNN分期、淋巴转移等无相关性（ P＞0.05）;同时Ki-67和FasL在乳腺浸润性导管癌组织中的表达呈正相关, Ki-67和Fas的表达呈负相关。结论乳腺浸润性导管癌组织中FasL、Ki-67高表达,Fas低表达,FasL、Ki-67过度表达可能与肿瘤进展、恶性程度及预后密切相关,且FasL和Ki-67在乳腺浸润性导管癌组织中的表达在统计分析中具有一致性,提示两者之间可能存在协同作用。     

Ki67、Survivin在早期宫颈癌中的表达与预后相关性分析

目的探讨Ki67、Survivin在早期宫颈癌组织中的表达,且与术后生存期及淋巴结转移的关系;分析Ki67和Survivin的相关性。方法收集110例手术切除或活检标本,包括正常宫颈组织,宫颈癌组织(按5年存活率及有无淋巴结转移分组),进行免疫组织化学法检测Ki67、Survivin蛋白的表达。结果宫颈癌组织中Ki67的表达率为85%,明显高于正常宫颈组织,Ki67阳性表达与术后生存时间呈负相关(x2=5.7624,P0.05),与淋巴结转移呈正相关(x2=11.4820,P0.01);宫颈癌组织中Survivin表达率为80%,高于正常宫颈组织,Survivin阳性表达与术后生存时间呈负相关(x2=5.2410,P0.05),与淋巴结转移呈正相关(x2=10.0624,P0.01)。结论 Ki67、Survivin可作为反映宫颈癌预后生存期及淋巴结转移程度的指标。     

COX-2、Ki-67在胃癌发生发展中的表达及其相关性研究

目的：研究胃癌组织和正常胃黏膜中COX-2、Ki-67的表达情况,探讨它们在胃癌发生发展中的作用及其相关性。方法：应用免疫组化SABC法。结果：1胃癌组织COX-2蛋白、Ki-67蛋白阳性表达率高于正常胃黏膜组织（P〈0.05）。2随着胃癌浸润深度的增加、分化程度的降低、淋巴结转移的出现COX-2及Ki-67阳性表达率升高（P〈0.05）。3在胃癌组织中COX-2与Ki-67的表达呈正相关（rs=0.390,P〈0.05）,均呈升高趋势。结论：COX-2、Ki-67均参与胃癌的发生和发展,二者可成为判断胃癌恶性程度有价值的指标,也可成为预后评估的指标。     

宫颈癌组织中caspase-3与nm23-H1 基因的表达及其意义

目的探讨宫颈癌组织中caspase-3与nm23-H1基因表达的特征及相关性.方法应用免疫组织化学方法(SP法)分别检测caspase-3和nm23-H4基因在41例宫颈癌组织、17例宫颈上皮内瘤样病变(CIN)和10例正常宫颈组织中的表达,分析其与临床病理特征的相关性.结果caspase-3在宫颈癌组织和CIN中的阳性表达率均明显低于正常宫颈组织中的阳性表达率(P＜0.05);caspase-3的表达与宫颈癌的组织类型、病理分级和临床分期无相关性(P＞0.05).nm23-H4基因在宫颈癌组织中的阳性表达率与CIN及正常宫颈组织相比均具有显著性差异(P＜0.05);nm23-H1的阳性表达与宫颈癌的临床分期、组织类型、病理分级无相关性(P＞0.05).caspase-3基因的表达与nm23-H1基因的表达无相关性(P＞0.05).结论caspase-3和/或nm23-H1基因的表达降低与宫颈癌的发生密切相关.     

IGFBP-3、bFGF、Ki-67蛋白在非小细胞肺癌组织中的表达及意义

目的 研究胰岛素样生长因子3(IGFBP-3)、碱性成纤维细胞生长因子(bFGF)、核增殖抗原(Ki-67)蛋白在非小细胞肺癌(NSCLC)中的表达及意义.方法 应用免疫组化技术对60例NSCLC组织中IGFBP-3、bFGF、Ki-67抗原表达进行检测和分析.结果 IGFBP-3、bFGF和Ki-67抗原农达率分别为71.67%(43/60)、56.67%(34/60)和68.33%(41/60);IGFBP-3和Ki-67表达与肿瘤分化程度、分期及淋巴结转移有关(P＜0.05);bFGF表达与淋巴结转移及分期有关(P＜0.05),与肿瘤的分化程度尤关;三种标记的阳性表达与年龄、性别、组织类型无显著相关性(P＞0.05).IGFBP-3和bFC-F、Ki-67的表达旱负相关(P＜0.05).结论 在NSCLC组织中检测IGFBP-3、bFGF、Ki-67的表达对于判断NSCLC+ 患者预后具有重要意义.     

Affective and Anxiety Disorders and Alcohol and Drug Dependence:

Depression and anxiety frequently coexist in patients with substance use disorders. This clinically-oriented article examiens the relationship between these conditions and emphasizes data showing that substances of abuse can cause signs and symptoms of both depression and anxiety. These substance-related syndromes appear to have a different course and prognosis than uncomplicated, independent anxiety and major depressive disorders, and clinicians should consider the role of alcohol and other drugs in all patients presenting with these complaints. The authors will also outline an approach for diagnosing and managing patients with the combination of a substance use and depressive or anxiety disorder.     

Modelling and simulation of variability and uncertainty in toxicokinetics and pharmacokinetics

Two important methodological issues within the framework of the variability and uncertainty analysis of toxicokinetic and pharmacokinetic systems are discussed: (i) modelling and simulation of the existing physiologic variability in a population; and (ii) modelling and simulation of variability and uncertainty when there is insufficient or not well defined (e.g. small sample, semiquantitative, qualitative and vague) information available. Physiologically based pharmacokinetic models are especially suited for separating and characterising the physiologic variability from the overall variability and uncertainty in the system. Monte Carlo sampling should draw from multivariate distributions, which reflect all levels of existing dependencies in the intact organism. The population characteristics should be taken into account. A fuzzy simulation approach is proposed to model variability and uncertainty when there is semiquantitative, qualitative and vague information about the model parameters and their statistical distributions cannot be defined reliably.     

Synthesis and anti-nociceptive and anti-inflammatory effects of gaultherin and its analogs

The synthesis of gaultherin (1) and its analogs was carried out to provide 11 glycosides under phase-transfer catalytic conditions. The activities of all synthesized compounds were evaluated by nitric oxide production inhibitory assay in vitro. Methyl 2-O-(4-O-β-d-galactopyranosyl)-β-d-glucopyranosylbenzoate (5f) showed significantly anti-nociceptive and anti-inflammatory effects by the evaluation in vivo. Structure–activity relationships within these compounds were discussed.     

成骨细胞的功能与损伤和骨质疏松的防治

骨质疏松是一种全身性骨骼疾病,导致骨折风险增加。成人的骨量通过破骨细胞的骨吸收和成骨细胞的骨形成作用来维持动态平衡,治疗骨质疏松症的理想策略是抑制破骨细胞的骨吸收和/或增强成骨细胞的骨形成功能。目前针对保护成骨细胞及增强其功能的骨质疏松疗法相对较少。因此,本文针对成骨细胞相关功能蛋白、各种细胞损伤机制（内质网应激、氧化应激、机械过载、微小RNA和长链非编码RNA的影响等）及骨质疏松的治疗与预防作一综述,以期为针对增强成骨细胞功能的骨质疏松治疗策略提供新思路。     

Antiinfective and encrustation-inhibiting materials--myth and facts

Catheters, urethral and ureteral stents and other urological implants are frequently affected by encrustration and infection due to their permanent contact with urine. Indwelling urinary catheters provide a haven for microorganisms and thus require extensive monitoring. Several surface modification techniques have been proposed to improve the performance of devices including the immobilization of biomolecules, the incorporation of hydrophilic grafts to reduce protein adsorption, the creation of hydrophobic surfaces, the creation of microdomains to regulate cellular and protein adhesion, new polymers and antimicrobial coatings. Physico-chemical explanation to elucidate the mechanism of such encrustation or infection inhibiting materials is still not available. Our series of experiments showed a marked decrease of silver-activity in biological fluids which corresponds with the controversial clinical results obtained with silver coated urinary catheters. Rifampicin/minocycline coated catheters had very low activity against Gram-negative rods, enterococci and Candida spp., the main causing organisms of urinary catheter infection. Surface engineered materials and antimicrobial drug delivery systems will be the next generation of sophisticated urinary catheters and stents, if both efficacy as well as efficiency has been proved clinically.     

益生菌与肿瘤防治

益生菌广泛存在于自然界中,通过维持宿主体内菌群平衡、影响肠屏障功能和调节免疫应答等作用,提高宿主健康水平,被公认为"肠道健康卫士".一些益生菌可以增强机体的免疫功能,抑制致癌物质,影响肿瘤细胞的基因表达,对肿瘤具有拮抗作用.大量研究表明,益生菌在未来的肿瘤防治中有很好的应用和发展前景.     

Self-stimulation and amphetamine: Tolerance to d and l isomers and cross tolerance to cocaine and methylphenidate

The effects of the d and l isomers of amphetamine on self-stimulation responding were tested following acute and chronic administration. Tolerance and post-drug depression of responding occurred in tests with both isomers, indicating no role for p-hydroxynorephedrine (PHN) which is one of the metabolites of d-amphetamine. In the second experiment, d-amphetamine, methylphenidate and cocaine all produced quantitatively and qualitatively similar effects on self-stimulation responding following acute administration. Following chronic administration of d-amphetamine, animals showed tolerance to all three drugs, indicating cross-tolerance among them. These data are consistent with an hypothesis that tolerance and post-drug depression following chronic amphetamine treatment are the result of decreases in postsynaptic receptor sensitivity, which would lead to a decreased effectiveness of all three drugs, regardless of their pre-synaptic mechanisms.     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983     

Acamprosate and naltrexone treatment effects on ethanol and sucrose seeking and intake in ethanol-dependent and nondependent rats

Rationale  Two pharmacotherapies are approved for treating alcohol craving (acamprosate and naltrexone), but both have shown mixed findings in animals and humans. Objectives  The present experiments utilized a “reinforcer blocking” approach (i.e., rats were able to consume ethanol during treatment) to better understand the efficacy of these treatments for ethanol seeking and drinking using ethanol-dependent and nondependent rats. Materials and methods  In “nondependent” experiments, drugs (acamprosate 50, 100, and 200 mg/kg; naltrexone 0.1, 0.3, and 1.0 mg/kg) were administered over 3-week periods prior to operant sessions with a low response requirement to gain access to reinforcers for 20 min. For “dependent” experiments, rats were made dependent in vapor/inhalation chambers. Results  Acamprosate and naltrexone had similar effects on intake in nondependent and dependent rats; neither drug was selective for ethanol over sucrose drinking. In nondependent animals, naltrexone was more efficacious at more doses than acamprosate, and acamprosate’s effects were limited to a dose that also had adverse effects on body weight. Both pharmacotherapies showed more selectivity when examining reinforcer seeking. In nondependent rats, acamprosate and naltrexone had response-attenuating effects in ethanol, but not sucrose, groups. In dependent animals, acamprosate had selective effects limited to a decrease in sucrose seeking. Naltrexone, however, selectively decreased ethanol-seeking in nondependent rats. Conclusions  The naltrexone-induced decreases in seeking suggested a change in incentive motivation which was selective for ethanol in nondependent rats. The “nondependent” paradigm may model early stages of “problem drinking” in humans, and the findings suggest that naltrexone could be a good intervention for this level of alcohol abuse and relapse prevention.