人原发性肝细胞癌核基质蛋白的研究

目的比较正常肝与原发性肝细胞癌（ＨＣＣ）核基质蛋白的异同,观察是否有ＨＣＣ特异性核基质蛋白的存在。方法用双向电泳方法比较了３例正常肝和８例ＨＣＣ核基质蛋白成分。结果正常肝和ＨＣＣ的核基质蛋白组成极为相似,但在ＨＣＣ中发现至少有４个ＨＣＣ的特异性核基质蛋白。其中以分子量为６２０００、等电点为５．３的蛋白最具代表性,它存在于所研究的８例ＨＣＣ中。其余３个ＨＣＣ特异性蛋白亦存在于大多数ＨＣＣ中。３例正常肝组织中未见有这４个ＨＣＣ特异性核基质蛋白。结论ＨＣＣ确实有ＨＣＣ特异性核基质蛋白的存在,它的发现可能会为ＨＣＣ的发生、发展、发病机理的研究提供一个新途径。     

B超对肺癌急症的诊断及疗效评估

目的评价Ｂ超对肺癌急症的快速鉴别诊断价值。方法应用Ｂ超诊断肺癌急症３５例,其中有中央型右上肺癌肿块压迫引起的上腔静脉综合征（ＳＶＣ）５例,探查取胸骨右缘第２、３肋间;中大量心包积液伴亚急性心包填塞症１０例,包括心肌与心包转移癌致急性出血性心包积液２例,探查取心前区及左腋前线第５、６肋间;恶性胸腔大量积液２０例,探查位于两侧背部膈上。介入性治疗,Ｂ超定位穿刺抽液并腔内注入中药榄香烯乳,配合临床化疗药物、输血等综合治疗。结果在４周内急症得到暂时缓解者占８２．８％,稳定占８．５％,无效占８．５％。结论简便、可重复性的超声诊断及时、可靠,并可提供疗效参考依据,证实榄香烯乳对控制急性心肌心包出血有特效,起乳剂微栓止血作用。对部分包裹性胸腔积液无效。Ｂ超对ＳＶＣ诊断有一定局限性。     

PF方案化放治疗晚期鼻咽癌的远期疗效

目的探索用ＰＤＤ／５－Ｆｕ方案化放治疗晚期鼻咽癌的疗效。方法１９８９年１２月～１９９０年１２月间,选择７６例Ⅲ、Ⅳ期鼻咽癌患者,先作３周期ＰＤＤ（２０ｍｇ（ｍ２）－１ｄ－１,ｉｖ,第１～５天）和５－Ｆｕ［７００ｍｇ（ｍ２）－１ｄ－１,连续静脉滴注,第１～５天］诱导化疗,随后尽快作放疗,此为综合治疗组。以１９８９年作单纯放疗的８６例晚期鼻咽癌患者作对照组。两组放疗方法、时间／剂量分割均相同。结果化疗有效率为８９．３％,完全缓解率为１８．４％。综合治疗组（综合组）总的５年生存率为４８．７％,对照组为３３．７％（Ｐ＞０．０５）。综合组Ｔ２Ｎ３和Ｔ２～４Ｎ３患者的５年生存率为４４．１％和３９．５％,均明显高于对照组的２１．６％及２０．４％（Ｐ＜０．０５）。结论ＰＦ方案化放治疗提高了Ｔ２～４Ｎ３患者的５年生存率。     

Dietary flavonoids, quercetin, luteolin and genistein, reduce oxidative DNA damage and lipid peroxidation and quench free radicals

Several dietary flavonoids such as quercetin, luteolin and genistein have been suggested to have cancer chemopreventive effects, although the mechanisms are not fully understood. In the present study, the effects of these flavonoids as antioxidants were investigated in the following systems: (1) production of hydrogen peroxide (H2O2) and superoxide anion (O2*-), (2) lipid peroxidation induced by FeCl2 in rat liver, and (3) formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) induced by either UV or Fenton reaction in calf thymus DNA. The results showed that quercetin and luteolin were equally potent in scavenging H2O2, with genistein having a moderate effect. Quercetin and luteolin had a potent inhibitory effect on O2*- generation by xanthine/xanthine oxidase while genistein had a moderate effect. Quercetin and luteolin were potent in inhibiting lipid peroxidation induced by FeCl2 in rat liver while genistein had a very weak inhibitory effect. All the test compounds had a potent quenching effect on 8-OHdG formation induced by UV light irradiation, with the order of effects being genistein > luteolin > quercetin. Of the test compounds, luteolin exhibited the most potent quenching effect on Fenton-induced 8-OHdG formation. The scavenging of oxygen free radicals, the inhibitory effect on lipid peroxidation and the quenching effect on 8-OHdG formation by quercetin, luteolin and genistein may, at least in part, be responsible for their anticarcinogenic effects.     

Antitumor activity and pharmacokinetics following oral administration of natural product DNA topoisomerase I inhibitors 10-hydroxycamptothecin and camptothecin in SCID mice bearing human breast cancer xenografts

The DNA topoisomerase I inhibitors, 10-hydroxycamptothecin (HCPT) and camptothecin (CPT), are indole alkaloids isolated from the Chinese tree, Camptotheca acuminata. They have been shown to have a wide spectrum of anticancer activity both in vitro and in vivo. However, their use has been limited due to their water-insolubility. The purpose of the present study was 2-fold, to determine the in vitro and in vivo activity of HCPT and CPT against human breast cancer and to determine the pharmacokinetics of the two drugs to better understand how they can best be used therapeutically. The bl vitro inhibitory effect on tumor growth was observed with breast cancer cell line MDA-MB-468. The in vivo antitumor effects were then determined using severe combined immunodeficient (SCID) mice bearing MDA-MB-468 xenografts. The tumor-bearing mice were orally administered HCPT (1, 3, 6, 9 mg/kg/day, 5 days per week) or CPT (1, 3, 6 mg/kg/day, 5 days per week) for 3 weeks. Growth of the MDA-MB-468 cells was inhibited by HCPT and CPT in vitro and in vivo in a dose-dependent manner. Complete regression of the tumor xenografts, determined by tumor measurement and microscopic examination, occurred in the groups of animals treated with doses of HCPT or CPT of 3 mg/kg/day or more. In general, HCPT was more effective and less toxic than CPT. To determine the potential mechanisms for the pharmacologic differences, the comparative pharmacokinetics of HCPT and CPT were determined in tumor-bearing SCID mice following i.v. or oral administration of H-3-HCPT or H-3-CPT. Parent drugs and their metabolites in plasma, urine, feces, and various tissues were quantified by a recently developed reversed-phase HPLC method. Significant absorption of both HCPT and CPT was observed after oral administration, with CPT having a higher bioavailability. HCPT and CPT were distributed widely into various tissues including the tumor, enterohepatic system, kidneys, and bone marrow. These studies indicate that HCPT and CPT are of potential use in treatment of breast cancer, providing the basis for the design of future human trials with these anticancer drugs.     

人眼小梁细胞体外表达表皮生长因子mRNA和表皮生长因子受体

目的 了解培养的小梁细胞分泌表皮生长因子（ｅｐｉｄｅｒｍａｌ ｇｒｏｗｔｈ ｆａｃｔｏｒ,ＥＧＦ）及细胞膜上表皮生长因子受体（ｅｐｉｄｅｒｍａｌ ｇｒｏｗｔｈ ｆａｃｔｏｒ ｒｅｃｅｐｔｏｒ,ＥＧＦＲ）的情况。方法 进行人眼小梁细胞体外培养。用ＥＧＦ ｃＤＡＮ探针,α＾－３２ｐ同位素标记及斑点杂交放射自显影法,检测小梁细胞分泌ＥＧＦｍＲＮＡ的情况。结果 人眼小梁细胞体外培养成功。免疫组化染色显示小     

Focal hepatic glycogenosis

Foci of altered hepatocytes (FAH) including clear cell foci excessively storing glycogen (focal hepatic glycogenosis) are well known as preneoplastic lesions in animal models of hepatocarcinogenesis induced by chemical, physical or viral agents. The occurrence of similar lesions has been studied in a series of 67 explanted and 2 resected human livers using histological and histochemical approaches. A high incidence of FAH was found in the liver of patients suffering from hepatocellular carcinoma(HCC, 14/14) and liver cirrhosis (21/42). FAH were also detected in one patient each with inborn hepatic glycogenosis type 1a, and cholangiocellular carcinoma. Two patients with focal nodular hyperplasia had FAH-like enzymatic changes within these lesions. No FAH were found in 5 donor livers. FAH excessively storing glycogen including clear and mixed cell foci predominated in most cases with these lesions. The focal hepatic glycogenosis was associated with a significantly increased cell proliferation compared to the extrafocal parenchyma, and with alterations in the activity of various enzymes. In the 175 FAH studied by enzyme histochemistry, two enzymes involved in glycogen breakdown, namely glycogen phosphorylase and glucose-6-phosphatase, showed the most consistent changes, being reduced in 98% and 95%, respectively. In addition, the activities of adenosine triphosphatase and gamma-glutamyltransferase were reduced in 46% and 53% of FAH, respectively. Inconsistent changes were observed in FAH concerning a number of other enzymes. The 14 HCCs investigated histochemically often contained clear cell populations rich in glycogen in well differentiated portions, but were poor in glycogen in moderately and poorly differentiated tumors or tumor components. There were some similarities in the enzyme histochemical pattern of HCC and FAH but also important differences were evident. In contrast to FAH, all HCCs (except one carcinoma of the fibrolamellar type) showed an increase in the activity of the mitochondrial glycerol-3-phosphate dehydrogenase, and 50% of the cases had increased glucose-6-phosphate dehydrogenase activity. The activities of glucose-6-phosphatase and gamma-glutamyltransferase usually showed a reactivation, or even an increase compared to the extrafocal parenchyma, in moderately and poorly differentiated HCCs. Our results indicate that the focal hepatic glycogenosis is a putative preneoplastic lesion in human beings similar to laboratory animals. The focal hepatic glycogenosis appears to be a frequent initial step in neoplastic transformation of hepatocytes, a process associated with a fundamental shift in energy metabolism.     

Postnatal development of vascular β-adrenoceptor-mediated responses and the increase in the adrenaline content of the adrenal gland have a parallel time course

The present study was undertaken to analyse the relationship between postnatal development of vascular ₂-adrenoceptor-mediated responses and the content of adrenaline in the adrenal gland and its concentration in plasma. Dog saphenous vein tissue from newborn, two-weeks old and adult animals were either preloaded with ³H-noradrenaline (or ³H-adrenaline) to study prejunctional -adrenoceptor-mediated effects or mounted in organ baths to determine isoprenaline-induced relaxation of preparations contracted by phenylephrine to about 65010 of the maximum. The adrenal glands and samples of blood from the same animals were taken for estimation of adrenaline and noradrenaline.At birth, there were no -adrenoceptor-mediated effects pre- or postjunctionally. At two weeks, while the results at the prejunctional level were not significantly different from those obtained in newborns, at the postjunctional level there was a relaxant response to isoprenaline, which antagonised about 35010 of the previous contraction to 1.75 mol·l^–1 phenylephrine. In adults, isoprenaline (50 nmol·l^–1) increased by 24% tritium overflow evoked by electrical stimulation of tissues preloaded with ³H-noradrenaline but not that of tissues preloaded with ³H-adrenaline. On the other hand, propranolol (1 mol·l^–1) reduced by 21% the overflow of tritium evoked by electrical stimulation of tissues preloaded with ³H-adrenaline but not that of tissues preloaded with ³H-noradrenaline; postjunctionally, the maximal response to isoprenaline antagonised 70% of the previous contraction to 1.75 mol·l^–1 phenylephrine.At birth the catecholamine content of the adrenals was relatively low (2.9 ol·g^–1) and the adrenaline/noradrenaline ratio was 0.26; two weeks later, the catecholamine content was 14.5 mol·g-1and the adrenaline/noradrenaline ratio was 0.74; in adults, the catecholamine content was 24.5 mol·g^–1 and the adrenaline/noradrenaline ratio was 2.3. In plasma, the highest concentration of adrenaline was observed at birth (11.8 nmol·l^–1); two weeks later it was 5.5 nmol·l^–1 and in adulthood it fell to 3.1 nmol·l^–1.On the basis of these results, it is concluded that some link between the postnatal increase in adrenaline adrenal content and the development of ₂-adrenoceptor-mediated pre- and postjunctional effects may exist. Additionally it is suggested that circulating adrenaline may trigger the development of ₂-adrenoceptor-mediated responses as well as some hypertensive states occurring as a consequence of an overreactivity of the sympathoadrenal system. Correspondence to: S. Guimarães at the above address     

Identification of residues linked to the slow-->fast transition of thrombin.

Residues energetically linked to the allosteric transition of thrombin from its anticoagulant slow form to the procoagulant fast form have been identified by site-directed mutagenesis. The energetics of recognition by the two forms of the enzyme were probed by using a synthetic chromogenic substrate, fibrinogen, and hirudin. The thrombin residues E39, W60d, E192, D221, and D222 are linked to the slow-->fast transition and are part of an "allosteric core" through which events originating at the Na+ binding loop propagate to other regions of the enzyme. The thrombin residues Y76, W96, W148, and R173 lie at the periphery of the allosteric core, affect recognition of fibrinogen and hirudin to the same extent in both forms, and are not linked to the slow-->fast transition.