EGFR与C－erbB－2癌基因蛋白在甲状腺乳头状腺癌中的表达

本文作者研究了上皮生长因子受体（ＥＧＦＲ）和Ｃ－ｅｒｂＢ－２癌基因蛋白在５０例甲状腺癌和６６例甲状腺良性疾患中的表达。５０例甲状腺癌中，ＥＧＦＲ阳性者２６例（５２％），Ｃ－ｅｒｂＢ－２阳性者２５例（５０％）。ＥＧＦＲ和ｃ－ｅｒｂＢ－２共同表达阳性者的淋巴结转移率（９２．８５％）明显高于两者共同表达阴性者（６１．５３％）（Ｐ＜０．０５）。ＥＧＦＲ阳性者ＡｇＮＯＲ数（２．５９±０．６４／核）也明显高于ＥＧＦＲ阴性者（１．３９±０．１８／核）（Ｐ＜０．００１）。ＥＧＦＲ与Ｃ－ｅｒｂＢ－２共同表达阳性，同时ＡｇＮＯＲ计数高的甲状腺癌具有较高的恶性度。因此，对这种病人要予以特别的治疗措施并抓紧随访工作。     

表皮生长因子及其受体在慢性萎缩性胃炎中的表达和致癌变意义的探讨

采用放射免疫法测定慢性萎缩性胃炎患者（５０例）血清、尿中表皮生长因子（ＥＧＦ）水平，同时应用免疫组化ＳＡＢＣ法检测胃粘膜组织切片中表皮生长因子受体（ＥＧＦＲ）染色的阳性率，并与正常人及胃癌患者作对照分析。结果表明：慢性萎缩性胃炎组血清、尿ＥＧＦ水平均显著高于正常对照组（Ｐ＜０．０１），但与胃癌组间差异无显著性意义（Ｐ＞０．０５）。胃粘膜组织切片ＥＧＦＲ染色阳性率的统计分析结果与体液ＥＧＦ一致。慢性萎缩性胃炎病人血清ＥＧＦ水平与胃粘膜ＥＧＦＲ表达有同步性；伴有Ⅱｂ型肠化者的血清ＥＧＦ水平较其他类型肠化者有更高水平表达（Ｐ＜０．０５）。中度与重度慢性萎缩性胃炎间血清、尿ＥＧＦ水平与胃粘膜组织切片中ＥＧＦＲ染色阳性率差异均无显著意义     

表皮生长因子及其受体在胃癌患者中的表达

采用放射免疫法测定２６例胃癌病人血清、尿液ＥＧＦ水平，同时采用免疫组化ＳＡＢＣ法检测胃粘膜组织切片中ＥＧＦＲ染色的阳性率，并与正常对照进行比较分析。结果表明：胃癌患者血清和尿ＥＧＦ水平均显著高于正常对照（３．７２±１．８３μｇ／Ｌ与１．７７±０．６０μｇ／Ｌ，Ｐ＜０．０１；１８．４４±１７．８８ｎｇ／ｍｇ与５．１９±６．３７ｎｇ／ｍｇ，Ｐ＜０．０１），胃粘膜组织切片ＥＧＦＲ染色阳性率也明显高于正常对照（７３％与１１％，Ｐ＜０．０１）。胃癌病人中，ＥＧＦＲ染色阳性者血清ＥＧＦ水平显著高于ＥＧＦＲ阴性者（Ｐ＜０．０５），但两者尿ＥＧＦ水平无显著性差异。胃癌患者血清、尿ＥＧＦ水平与胃癌大小、分化程度及淋巴结转移无显著性相关。     

ER,EGFR,p53在乳腺癌组织中的比较研究

采用免疫组化染色技术,检测７５例原发乳腺癌组织中雌激素受体（ＥＲ）,表皮生长因子受体（ＥＧＦＲ）及ｐ５３的表达。结果表明：ＥＲ、ＥＧＦＲ、ｐ５３的阳性表达率分别为４９．３％、４１．３％和３７．３％。ＥＲ、ＥＧＦＲ的表达与腋淋巴结转移、临床分期有明显相关性（Ｐ＜０．０５）;与年龄及肿瘤大小无明显相关性（Ｐ＞０．０５）。ＥＧＦＲ与ＥＲ有负相关性（Ｐ＜０．０５）。在有４个以上腋淋巴结转移的２１例病例中,ＥＧＦＲ阳性者１４例,占６６．７％。２０例临床Ⅲ期的病例,ＥＧＦＲ阳性者１５例,占７５．０％。ｐ５３的表达与腋淋巴结转移、临床分期、年龄及肿瘤大小均无明显相关性（Ｐ＞０．０５）;与ＥＲ呈负相关性（Ｐ＜０．０５）;与ＥＧＦＲ呈正相关性（Ｐ＜０．０５）。研究认为ＥＧＦＲ蛋白表达阳性的乳腺癌病人预后不良,ｐ５３蛋白表达阳性与乳腺癌病人的预后无明显相关性。     

胃癌上皮生长因子及其受体与雌激素受体的表达及相互关系

用免疫组化ＡＢＣ方法，检测胃癌和正常胃粘膜中上皮生长因子（ＥＧＦ）及其受体（ＥＧＦＲ）、雌激素受体（ＥＲ）的表达。结果：６４例胃癌中，ＥＧＦ阳性３９例（６０．９％），ＥＧＦＲ阳性３３例（５１．６％），ＥＲ阳性１２例（１８．８％）；５８例正常胃组织中，ＥＧＦ、ＥＧＦＲ阳性各３例，ＥＲ阴性。癌与正常对照组间差异有显著性（Ｐ＜０．０５）。提示，ＥＧＦ、ＥＧＦＲ、ＥＲ与胃癌有关。胃癌ＥＧＦ、ＥＧＦＲ的阳性率又非常显著高于ＥＲ（Ｐ＜０．００５），说明ＥＧＦ、ＥＧＦＲ在胃癌发展中的调节作用远较雌激素重要。结果还提示，ＥＧＦ、ＥＧＦＲ、ＥＲ的相互关系影响胃癌细胞的发生、种植和转移。     

有机锗(Ge-132)对大鼠肝细胞色素P_(450)、EROD活性抑制作用的研究

利用雄性ＳＤ大鼠每日经口给予有机锗（Ｇｅ－１３２）１００、２５０、５００ｍｇ／ｋｇ连续二十五ｄ，发现高剂量组的肝细胞色素Ｐ４５０受到明显抑制（Ｐ＜０．０５）。对Ｐ４４８的标志酶乙氧基异吩口恶唑脱乙氧基酶（ＥＲＯＤ）的抑制也近５０％；动物以Ｇｅ－１３２５００ｍｇ／ｋｇ／ｄ预先处理２０ｄ，再分别给予苯巴比妥钠盐（ＰＢ）、３－甲基胆蒽（３－ＭＣ），发现Ｇｅ－１３２对ＰＢ诱导Ｐ４５０的抑制不明显，而对３－ＭＣ诱导ＥＲＯＤ的抑制仍达３３％。     

妊娠性滋养细胞肿瘤P185和雌孕激素受体的表达及意义

以ＡＢＣ法检测了４０例妊娠性滋养细胞肿瘤石蜡标本Ｐ１８５及ＥＲ、ＰＲ的表达。其中绒毛膜癌２４例。侵蚀性葡萄胎１６例，Ｐ１８５阳性率为４０％，ＥＲ、ＰＲ阳性率分别为４５％，７５％，Ｐ１８５在侵蚀性葡萄胎中的阳性率均明显高于绒瘤（Ｐ＜０．０１）。病程小于１年者，Ｐ１８５的阳性率高于病程大于１年者（Ｐ＜０．０５），ＥＲ、ＰＲ阳性者，Ｐ１８５的阳性率分别高于其阴性者（Ｐ＜０．０５、Ｐ＜０．０１），Ｐ１８５阳性与阴性的患者，分别有８１．３％、５０％的患者于３疗程内血ｈＣＧ转阴（Ｐ＜０．０５）。资料提示：Ｐ１８５倾向于在滋养细胞肿瘤恶性转化的早期表达，Ｐ１８Ｓ阳性者对化疗较为敏感。     

乳腺癌流式细胞仪分析的临床意义

通过对８６例乳腺癌的ＦＣＭ分析：发现二倍体肿瘤２４例，异倍体６２例。前者ＳＰＦ１６．８±１０．３％，后者ＳＰＦ２２．２±９．８％（Ｐ＜０．０５）。其中进行ＥＲ检查的６４例中发现：ＥＲ阳性组异倍体占６６％，ＥＲ阴性组异倍体占９２．９％（Ｐ＜０．０５）；前者ＳＰＦ１８．１±９．１％，后者ＳＰＦ２６．０±１３．０％（Ｐ＜０．０５）。ＣＥＡ阳性与否与异倍体检出率、ＳＰＦ及ＥＲ阳性率无明显关系。月经状态、腋淋巴结转移与ＦＣＭ检测结果无关系。因此作者认为ＦＣＭ分析可了解肿瘤本身的生物学特性，并可成为新的、独立的预后指标。     

癌症患者血液高粘状态对肿瘤血管内和远处转移的作用

对９６例恶性肿瘤患者与１００例正常人进行血液流变学和纤维蛋白检测，同时对５２例恶性肿瘤血管内和远处转移患者与４４例非转移患者进行血液流变学和纤维蛋白原的对比研究。结果：恶性肿瘤组ηｂ（８０Ｓ－１）、ηｂ（２０Ｓ－１）、ηＰ、ＥＳＲ、Ｋ值、ＥＴ、ＥＭ、ＲＥ、Ｒ－ηｂ（８０Ｓ－１）、Ｒ－ηｂ（２０Ｓ－１）和Ｆｉｂ均显著高于正常人组（Ｐ＜０．０５）；ＨＣＴ两组间无明显差异（Ｐ＞０．０５）。癌症转移组ηｂ（８０Ｓ－１）、ηｂ（２０Ｓ－１）、ηＰ、ＨＣＴ、ＥＴ、ＲＥ、Ｒ－ηｂ（８０Ｓ－１）、Ｒ－ηｂ（２０Ｓ－１）和Ｆｉｂ均显著高于非转移组（Ｐ＜０．０５）；ＥＳＲ、Ｋ值、ＥＭ两组间无显著差异（Ｐ＞０．０５）。认为：血液流变性增高与恶性肿瘤有直接关系，当肿瘤转移时血液流变性和纤维蛋白原增高则更为显著。     

化疗对消化系肿瘤患者CD16及T细胞活化抗原表达的影响

目的　研究消化系肿瘤患者化疗前后的免疫状态。　方法　用流式细胞仪监测８０ 例消化系肿瘤患者化疗前后Ｔ 细胞表面３ 种抗原标志，并与良性病变患者进行对比。　结果　消化系肿瘤患者化疗前ＣＤ＋３ ／ＨＬＡＤＲ＋ 显著高于对照组（ Ｐ＜００１） ，化疗后ＣＤ１６ 、ＣＤ＋３ ／ＨＬＡＤＲ＋ 显著下降（ Ｐ＜ ００１），ＣＤ６９ 低于化疗前（Ｐ＜ ００５） ，且化疗后ＣＤ１６ 、ＣＤ４９ 低于对照组（ Ｐ＜００５） 。　结论　化疗药物损害消化系肿瘤患者的细胞免疫功能，降低机体的免疫功能活性。     

维拉帕米联合5-氟脲嘧啶腹腔内化疗对荷肝癌大鼠的抗肿瘤作用

Objective To study the antineoplastic effect of the calcium channel blocker verapamil and 5-fluorouracil intraperitoneal chemotherapy on hepatocarcinoma-bearing rats, and examine the action between calcium channel blockers and cytotoxic drugs. Methods We adopted the method of subcapsular implantation of carcinoma tissues of walker-256 in the left liver lobe as a model of liver carcinoma-bearing rats. All experimental animals were divided into four groups. On the sixth day post implantation, in group A (control group) 6 ml of saline was injected intraperitoneally once a day for 3 days. In group B (single chemotherapy group) 6 ml, of 5-Fu 75 mg/kg was injected intraperitoneally once a day for 3 days. In group C (combination of treatment group) both 5-Fu (75 mg/kg) and verapamil (25 mg/kg) were administered simultaneously as in A and B. In group D (simple verapamil group) only 6 ml of verapamil (25 mg/kg) was administered as above. Results Compared with groups A, B and D, The volume of cancer and the contents of liver cancer DNA and protein were significantly reduced. The rates of inhibiting cancer (89.9% in group C and 35.4% in group B) were significantly increased in group C. Group C had significantly long survival time compared to groups A, B and D (P<0.05). By light microscopy, a number of focal necroses were found in cancer tissue in group C. Conclusion Calcium channel blockers can enhance the antineoplastic effect of 5-Fu intraperitoneal chemotherapy to liver cancer: The use of verapamil can not increase the toxicity of 5-Fu.     

近交系F344大鼠喉移植改良模型的建立

背景与目的:喉为非生命必需器官,喉移植研究一直滞后于其它生命必需器官的移植,然而,一旦宿主对移植喉的免疫耐受诱导成功,那么,喉移植将是晚期喉癌治疗和喉功能重建的重要手段。本研究的目的在于建立改良鼠喉移植模型,提高受体鼠和移植喉的存活率,为喉移植抗免疫排斥和免疫耐受诱导研究提供动物模型。方法:采用近交系F344大白鼠建立喉移植Strome模型,并对该模型进行改良:供体喉切取时保留甲状腺上动脉和咽升动脉,形成舌骨、舌根、下咽、喉、甲状腺、部分颈段食管、气管的移植复合体,移植喉血运通过供体鼠双侧颈总动脉分别与受体鼠颈总动脉和颈前静脉端-端吻合重建,术中行对侧颈外静脉穿刺补液,术后皮下注射补液。术后1周解剖移植喉,观察移植喉大体形态和血管通畅情况,常规病理检查评价移植喉的组织变化和存活状况,对比Strome模型和改良模型的受体鼠及移植喉存活率。结果:StromeA组、StromeB组、改良组的受体鼠存活率和各组移植喉存活率分别为70%(14/20)、85%(17/20)、95%(19/20)和30%(6/20)、40%(8/20)、80%(16/20),改良模型优于Strome模型。结论:与Strome模型比较,改良模型加强围手术期的处理,降低受体鼠的死亡率;将咽升动脉及其分支包含在移植复合体中,增加移植血管蒂中喉供血动脉的侧支循环,降低侧支循环阻力,减少微循环障碍的发生率,提高移植喉的存活率。     

Increase in structural-functional tolerance of kidney to ischemia upon parenteral administration of sodium hypochlorite in the pre-ischemic period

The opportunity of raising kidney structural and functional tolerance to ischemia with parenteral injections of 0.06% solution of sodium hypochlorite for 4 days in preischemia period was studied in experiment on 22 non-inbred rats of 200-280 g body weight. 90 minute ischemia was created by ligating the left and right kidney arteries, veins, ureters. Morphological and functional kidney data, enzymuria activity of nephron epithelium cells were registered, 80 and 33% of the rats survived 7 days after ischemia in the study and control groups, respectively. The control animals showed deterioration of the tubules function, high enzymuria. Thus, it is possible to raise kidney tolerance to ischemia by preischemic parenteral injection of sodium hypochlorite solution.     

Parous rats regain high susceptibility to chemically induced mammary cancer after treatment with various mammotropic hormones.

Parity in humans and rats provides significant protection against mammary tumor development. This study was carried out to investigate whether treatment of parous rats with mammotropic hormones would affect methyl-nitrosourea (MNU)-induced mammary carcinogenesis. Parous rats were treated with 17beta-estradiol (E2), progesterone (P4) and thyroxine (T4) alone or in combination. E2 (20 microg/60 days) and P4 (20 mg/60 days) were administered by silastic tubing and T4 in the drinking water (3 microg T4/ml). Hormonal treatments commenced 7 days before MNU injection and continued for 33 weeks. Animals were palpated weekly for tumor detection. The effects of the hormonal treatments on the circulating concentrations of E2, P4, growth hormone (GH), prolactin (PRL), T4 and insulin-like growth factor-I (IGF-I) after 7 days of treatment, the time of MNU injection, was assessed. Animals treated with E2 had significantly elevated circulation concentrations of GH, PRL and P4, and serum levels of E2 were more consistent in this group than in the other animal groups. P4 treatment caused elevation in P4 concentration in serum but did not affect the circulating levels of other hormones. The proliferation of the mammary gland at the time of MNU injection was elevated in animal groups treated with E2 either alone or with P4 and T4 and in animals treated with P4 alone, but the mammary gland was most differentiated in untreated parous rats and least in animals treated with E2 either alone or with P4 and T4. Mammary tumor incidence was 10% in parous rats that did not receive any hormonal treatment. Treatments with E2 or P4 alone significantly increased the susceptibility of parous animals to 67 and 50.0%, respectively; a tumor incidence similar to that of untreated AMV rats (64%). Parous rats treated with E2 plus P4 had tumor incidence higher than 90%. T4 administered did not affect mammary carcinogenesis.     

Effect of methylprednisolone on radiotherapy of F344 rats with avian sarcoma virus induced gliomas

We have examined the impact of methylprednisolone acetate (MPA) on survival of F344 rats that were bearing avian sarcoma virus (ASV)-induced gliomas and that were treated optimally with radiotherapy. Toxicity of MPA (dose range of 0.2–5.0 mg/kg × 7 over 3 weeks) was first established in non-tumor bearing rats as assessed by their relative failure to gain weight. Doses of 2.0 or 5.0 mg/kg x 7 caused animals to be 21.8 or 43.9%, respectively, underweight compared with vehicle controls. In rats bearing ASV induced gliomas, treatment with 3 000 cGY (nine fractions over a 3-week period) alone or with 0.2 or 1.0 mg MPA/kg (× 6 during the 3-week radiotherapy course) produced a significantly prolonged survival compared with that of untreated, tumor bearing rats. However, MPA did not enhance survival when given concurrently with radiotherapy; indeed, at the higher of these two doses, median survival of tumor-bearers was slightly less than with radiotherapy alone. This trend towards interference with the beneficial effects of radiotherapy was more pronounced with the highest dose of MPA studied, 5.0 mg/kg body weight × 6. These animals had a median survival time that was significantly less than that of tumor-bearers receiving radiotherapy alone, but not significantly different from untreated rats with gliomas. The possible significance of these observations is discussed.     

Enhancement of the dimethylnitrosamine acute effects in rat liver by prior treatment with triton WR-1339

Prior administration of Triton WR-1339 (tyloxapol, an anionic surfactant) to noninbred Sprague-Dawley male rats significantly enhanced the intensity of the necrogenic effect of dimethylnitrosamine (DMN) on the liver. This phenomenon was established by determination of NADP+-linked isocitrate dehydrogenase activity in the plasma and by histologic procedures. This enhancing effect was not due to an increase in the levels of DMN that reached the liver, because the content of DMN in the livers of Triton WR-1339-treated or untreated animals at 1 or 3 hours was not significantly different. Triton WR-1339 administration had no effect on DMN liver metabolism to formaldehyde or CO2; in addition, the covalent binding of DMN metabolites to nucleic acids or proteins was not modified by pretreatment with Triton WR-1339. However, in vitro, high concentrations (1 mg/ml) of Triton WR-1339 decreased the intensity of these parameters. This effect disappeared when the concentration was lowered to 0.4 mg/ml. Results are compatible with the hypothesis that the potentiating effects of Triton WR-1339 on liver damage caused by DMN and other hepatotoxins were due to a modification of the response of liver cells to injury.     

In vivo and in vitro antitumor activity of butyroyloxymethyl-diethyl phosphate (AN-7), a histone deacetylase inhibitor, in human prostate cancer

AN-7, a prodrug of butyric acid, induced histone hyperacetylation and differentiation and inhibited proliferation of human prostate 22Rv1 cancer cells in vitro and in vivo. In nude mice implanted with these cells, 50 mg/kg AN-7 given orally thrice a week led to inhibition of tumor growth and metastasis, tumor regression in >25% of animals and increased survival. Median time to the experimental end point (tumor volume 2 cm3 or death) in the untreated was 52 days, and average tumor volume was 0.8 +/- 0.18 cm3. At the same time, 94.4% of AN-7-treated mice survived and had average tumor volumes of 0.37 +/- 0.1 cm3. PSA expression was a useful marker for 22Rv1 lung metastasis detection. Sizeable metastases positively stained for PSA and limited air gaps were found in lungs of untreated mice. In animals treated with AN-7, lung morphology appeared normal. Primary tumors of treated animals were highly positive for PSA and had an elevated level of p21 and the proapoptotic protein Bax. Sections taken from AN-7-treated animals, examined under an electron microscope, exhibited condensed chromatin and apoptotic bodies. PSA serum levels were higher in untreated compared to treated animals and correlated with tumor volume. Since prolonged oral administration with 50 mg/kg or a single oral dose of 1.2 g/kg AN-7 did not cause adverse effects and the former exhibited significant anticancer activity, AN-7 is likely to display a high therapeutic index and may be beneficial for prostate cancer patients.     

Effect of dietary vitamin A or N-acetylcysteine on ethylnitrosourea-induced rat gliomas

It is our hypothesis that low grade gliomas are the glial counterparts of other precancerous lesions such as colon polyps and, therefore, suitable targets for chemoprevention. Steps in the molecular progression of gliomas have been described, indicating that an accumulation of abnormalities is required for progression to a high grade and interruption of this progression might be possible. An animal model of chemical glial carcinogenesis was used to test this hypothesis. Pregnant rats were injected intravenously with ENU (ethylnitrosourea) on the 18th day of gestation to induce gliomas in the offspring, which were randomized to receive control diet, diet supplemented with vitamin A palmitate, or diet supplemented with N-acetylcysteine. Animals exposed to ENU and receiving a control diet developed brain tumors and had a shortened life expectancy compared with rats unexposed to ENU. The animals treated with NAC showed no statistically significant delay in the time to tumor and no change in the histologic grade of the tumors when compared with animals receiving control diet, but the time to death from any cause of NAC treated animals differed significantly from untreated animals. Animals receiving high dose VA had statistically significantly prolonged time to tumor, survived significantly longer than untreated animals, but had no reduction in the total number of tumors or change in the histologic grade of their tumors. The theoretical basis of these results is likely due to the putative mechanism of action of these agents. These data indicate that glioma chemoprevention is possible and deserves further exploration.     

Pharmacokinetic studies of menogaril (TUT-7) with rats]

Menogaril (TUT-7) is a novel antitumor antibiotic belonging to anthracyclines. The pharmacokinetic parameters derived from plasma concentration-time profiles after repeated (for 14 days) or single oral administration of TUT-7 to rats were found to be not significantly different by either administration schedule. The rats with artificial liver dysfunction were obtained by subcutaneous application of carbon tetrachloride (CCl4, 1 ml/kg) for 3 days. After oral administration of TUT-7 to the rats with CCl4-induced liver toxicity (3 daily administrations of 1mg/kg, S.C.), the maximum plasma concentrations (Cmax) and AUC of both the unchanged drug and its metabolite N-Demethyl menogaril, were increased. Also over all elimination was slower in animals with liver dysfunction.