三种有机锗（Ge—132,Ge—162,Ge—164）对小鼠骨髓嗜多染红细胞…

本文以三种有机锗（Ｇｅ－１３２，Ｇｅ－１６２，Ｇｅ－１６４）对小鼠进行灌胃处理，以测定对环磷酰胺（ＣＰ）诱发的骨髓嗜多染红细胞微核率的抑制作用，结果表明，三种有机锗均能降低微核率，与阳性对照组比较有显著性差异（Ｐ〈０．０５），而三种有机锗之间抑制微核率的效能无差异（Ｐ〈０．０５）。提示，三种有机锗均可拮抗ＣＰ的致突变作用。     

有机锗（Ge—132）对大量肝细胞色素P450,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－Ｍ     

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％。     

癌症患者血清硒和全血GSH—PX的临床研究

测定８９例癌症患者血清硒（ＳＳｅ）和全血谷胱甘肽过氧化物酶（ＧＳＨ－ＰＸ）活性，并与３１例健康人进行对照，以探讨ＳＳｅ与ＧＳＨ－ＰＸ间的相互关系和临床意义。结果示ＳＳｅ与ＧＳＨ－ＰＸ活性明显低于对照组（Ｐ＜０．０１和Ｐ＜０．０５），ＳＳｅ和ＧＳＨ－ＰＸ呈显著正相关。随着临床分期不同，ＳＳｅ和ＧＳＨ－ＰＸ活性下降趋于明显，Ⅲ～Ⅳ期明显低于Ⅰ－Ⅱ期（Ｐ＜０．０５）；不同部位癌症患者之间ＳＳｅ和ＧＳＨ－ＰＸ活性均无显著性差异（Ｐ＞０．５）。提示ＳＳｅ和ＧＳＨ－ＰＸ活性与癌症的发展有关     

羧乙基锗倍半氧化物（Ge－l32）的抗诱变作用研究

本研究用果蝇伴性隐性致死（ＳＬＲＬ）实验，鼠伤寒沙门氏菌回复突变实验（Ａｍｅｓ）实验，小鼠骨髓细胞微核（ＭＮ）实验分别检测了Ｇｅ－１３２的抗诱变作用，结果表明：Ｇｅ－１３２在低浓度一定范围内（０．１％，０．０１％）对甲基磺酸乙酯诱发果蝇ＳＩＲＬ突变具有较弱的抗诱变作用Ｇｅ－１３２对２－氢基芴诱发的ＴＡ９８．ＴＡ１００回变无抗诱变作用，对环磷酰胺诱发小鼠髓细胞微核效应呈现剂量反应关系的抗诱变作用，但由于Ｇｅ－１３２处理组微核率仍远远离于阴性对照组，故认为抗诱变作用有限，并认为除在特殊适应症人群中可适量应用Ｇｅ－１３２外，健康人群中不提倡使用。     

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。     

培养人淋巴细胞分裂阻滞与常规微核测试法的比较研究Ⅲ．微核直径和微核率的检测比较

采用未照射（对照）和体外放射线照射３个供血员的全血，检测应用细胞松弛素法（ＣＢ）与常规法，对测得的淋巴细胞微核直径和微核率作了比较。结果表明：１）３．１Ｇｙ的γ－线照射，ＣＢ法微核率７．５１７％高于常规法６．１７１％（Ｐ＜０．０５）；ＣＢ法平均微核体积是常规法的１．８倍，ＤＮＡ损伤检测效率是常规法的２．２倍。２）未照射组中，ＣＢ法测的健康人自发微核率０．７６７％也高于常规法０．４９２％（Ｐ＜０．０５）；ＣＢ法平均微核体积是常规法的１．６倍，ＤＮＡ损伤检测效率是常规法的２．５倍。结合文献资料可认为，ＣＢ法在检测电离辐射的诱变性上较常规法敏感。细胞松弛素Ｂ有一定的遗传毒性，实际工作中应有选择地使用ＣＢ法。     

大蒜、大蒜绿茶合剂对MNNG诱发实验性胃癌及癌前病变PBL微核率的影响

本文研究大蒜、大蒜绿茶合剂对ＭＮＮＧ诱发大鼠胃癌及癌前病变过程中ＰＢＬ微核率的影响。结果显示，ＭＮＮＧ组（ＭＧ）ＭＮＦ在１０月与１６月时无明显差异，但较对照组（ＣＧ）始终显著增高（Ｐ＜０．００１），胃癌及癌前病变均高于ＣＧ（Ｐ＜０．００１），癌前病变明显低于胃癌（Ｐ＜０．００１），预防组（ＰＧ）、治疗１（ＴＧⅠ）与Ⅱ组（ＴＧⅡ）皆低于ＭＧ（Ｐ＜０．００１），ＰＧ在１６月较１０月时显著降低（Ｐ＜０．００１），与ＴＧⅠ无明显区别，而ＴＧⅡ较ＰＧ１０月时差异明显（Ｐ＜０．００５），但与ＰＧ１６月时和ＴＧⅡ无差异。证明ＭＮＮＧ的致突变、致癌变性可持续作用，大蒜、绿茶具有明显的抗突变、抗癌变效果，微核先于胃癌出现于癌前病变，从而检测ＰＢＬ微核可作为胃癌危险和早期的新标志。     

大肠癌酶细胞化学及电镜观察

对７５例大肠癌组织中的碱性磷酸酶（ＡＫＰａｓｅ）、酸性磷酸酶（ＡＣＰａｓｅ）、琥珀酸脱氢酶（ＳＤＨａｓｅ）、葡萄糖－６－磷酸酶（Ｇ－６－Ｐａｓｅ）、焦磷酸硫胺素酶（ＴＰＰａｓｅ）活性进行了细胞化学检测及电镜观察，结果表明；ＡＫＰａｓｅ活性多呈阴性反应，ＡＣＰａｓｅ、ＳＤＨａｓｅ、Ｇ－６－Ｐａｓｅ、ＴＰＰａｓｅ四种酶活性在大肠癌明显低于大肠正常粘膜及腺瘤（Ｐ＜０．０１），在高分化癌组明显高于低分化癌组（Ｐ＜０．０５），在淋巴结无转移组明显高于有转移组（Ｐ＜０．０５），提示：对大肠癌组织同时测定ＡＣＰａｓｅ、ＳＤＨａｓｅ、Ｇ－６－Ｐａｓｅ、ＴＰＰａｓｅ活性，并在超微结构上对酶反应颗粒定位观察，能在一定程度上反映大肠癌细胞的功能状态，可以作为判断大肠癌生物学行为及预后的重要指标之一。     

胃癌组织中肥大细胞与C－erbB－2癌基因蛋白

用俾士麦棕法和免疫组织化学方法检测了５７例胃癌组织中肥大细胞（ＭＣ）和Ｃ－ｅｒｂＢ－２癌基因蛋白。结果表明：（１）ＭＣ计数与胃癌的分化程度和转移有关，高、中分化腺癌高于低分化腺癌和未分化癌（Ｐ＜０．０５），无转移者高于有转移者（Ｐ＜０．０５）；（２）Ｃ－ｅｒｂＢ－２癌基因蛋白阳性表达与胃癌的分化程度和转移无关（Ｐ＞０．０５）；（３）Ｃ－ｅｒｂＢ－２癌基因蛋白阳性表达与ＭＣ计数有关，ＭＣ高计组，Ｃ－ｅｒｂＢ２癌基因蛋白阳性表达低于ＭＣ低计组（Ｐ＜０．０５）。     

Importance of T-cells and macrophages in the antitumor activity of carboxyethylgermanium sesquioxide (Ge-132)

The purpose of this study was to investigate the effective mechanisms of Ge-132, an organogermanium compound with immunomodulatory activity, on experimental murine ascites tumors. The antitumor effects of Ge-132 were observed when mice inoculated with Ehrlich carcinoma (allogeneic) or RL male 1 leukemia (syngeneic) cells were treated orally. However, Ge-132 had no activity on EL-4 lymphoma (syngeneic) or Meth A fibrosarcoma (syngeneic). The antitumor activity of Ge-132 was not observed when tumor-bearing mice were treated with trypan blue, carrageenan, or monoclonal anti-Thy 1.2 antibody. However, when natural killer (NK) cells were eliminated from mice bearing RL male 1 or Ehrlich ascites tumors by treatment with anti-asialo GM1 antiserum, the antitumor activity of the compound was unchanged. This suggests that Ge-132 was effective against certain ascites tumors regardless of whether the tumor was syngeneic or allogeneic. Furthermore, its effect might be expressed through host defense mechanisms, including macrophages and/or T-cells.     

Suppression of tumor growth by peritoneal macrophages isolated from mice treated with carboxyethylgermanium sesquioxide (Ge-132)

In a murine model it has been shown that the antitumor activity of carboxyethylgermanium sesquioxide (Ge-132) can be depleted by administration of macrophage (M phi) blockers. In the present study, the role that M phi play in the antitumor activity of the compound was investigated. Oral administration of Ge-132 in mice was demonstrated to be effective in activating M phi (Ge-132-cytotoxic M phi), and the cytotoxic activity of these M phi appeared in the peritoneal cavity of mice 48 hours after the oral administration of the compound. Co-cultivation of RL male-1 leukemia or Ehrlich carcinoma cells with Ge-132-cytotoxic M phi in vitro resulted in marked suppression of the growth of tumor cells. The transfer of peritoneal exudate cells (PEC), or purified M phi fractions of PEC from Ge-132-treated mice to mice bearing Ehrlich or RL male-1 ascites tumors resulted in significant protection. However, when the cytotoxic M phi were depleted by carbonyl-iron treatment in vitro, no antitumor effect was demonstrated in mice bearing Ehrlich or RL male-1 ascites tumors. Macrophage fractions obtained from PEC of Ge-132-treated mice exhibited an inhibitory effect against certain tumors both in vivo and in vitro suggesting that the antitumor effect of Ge-132 observed in vivo resulted from the activation of M phi.     

羧乙基锗倍半氧化物在黄曲霉毒素B1致大鼠肝癌过程中的抗氧化作用研究

目的与方法：本文采用ＡＦＢ１致大鼠肝癌体内短期实验模型，测定血清与肝组织的ＳＯＤ活力，进一步研究摄入Ｇｅ－１３２的剂量、时间与抗氧化作用的关系。结果：发现Ｇｅ－１３２具有抵抗ＡＦＢ１降低ＳＯＤ活力的作用，Ｇｅ－１３２的摄入时间、剂量可影响ＳＯＤ活力大小。结论：Ｇｅ－１３２的抗氧化作用与抑癌作用有关，并具有一定的防癌作用。     

Ability of sera from mice treated with Ge-132, an organo-germanium compound, to inhibit experimental murine ascites tumors

Serum specimens from mice treated orally with Ge-132 (100 mg/kg) exhibited antitumor activity against Ehrlich (allogeneic) and RL 1 (syngeneic) ascites tumors in BALB/c mice. Sera obtained from mice 24 hours after Ge-132 administration displayed the highest antitumor effect and the antitumor activity was dose-dependent. Sera prepared from mice 12, 36 or 48 hours after Ge-132 treatment had no protective effect. Circulating interferon (IFN) was induced at 24 hours after administration. The antiviral activity of serum from Ge-132-treated mice was inactivated by treatment with trypsin, low pH, and anti-IFN-gamma antiserum. The inactivated preparations of serum IFN induced by Ge-132 did not show antitumor activity when administered to mice bearing Ehrlich ascites tumors. These results suggest that the antitumor activity in the sera of Ge-132-treated mice may have been expressed through IFN-gamma which was induced by Ge-132.     

Ability of sera from mice treated with Ge-132, an organic germanium compound, to inhibit experimental murine ascites tumours

Sera from C57Bl/6 mice treated orally with Ge-132 exhibited antitumour activity against Ehrlich (allogeneic) and RL male 1 (syngeneic) ascites tumours in BALB/c mice. Sera obtained from mice 24 h after Ge-132 administration displayed the greatest antitumour effect and this was dose dependent. Sera prepared from mice 12, 36, or 48 h after Ge-132 treatment had no protective effect. Circulating interferon (IFN) was induced at 24 h after administration of Ge-132 but was not detected in the sera at 12, 36, or 48 h after administration. The antiviral activity of sera from Ge-132-treated mice was inactivated by treatments with trypsin, low pH, and anti-IFN gamma antiserum. The inactivated preparations of serum IFN induced by Ge-132 did not exhibit antitumour activity when administered to tumour-bearing mice. These results suggest that antitumour activity in the sera of Ge-132-treated mice may be expressed through activities of Ge-132-induced lymphokine(s), such as IFN gamma.     

Effect of combination immunochemotherapy with an organogermanium compound, Ge-132, and antitumor agents on C57BL/6 mice bearing Lewis lung carcinoma (3LL)

The antitumor effect of combination immunochemotherapy with Ge-132 and antitumor agent was studied using C57BL/6 mice bearing Lewis lung carcinoma (3LL). Ge-132 was administered orally at a daily dose of 100 mg/kg. Antitumor agents were administered intraperitoneally once a week. Initially, the effect of combination immunochemotherapy with Ge-132 and 5-fluorouracil (5-FU) was studied on 3LL local tumor growth, pulmonary metastases, survival, delayed type hypersensitivity (DTH) and body weight in tumor-bearing mice, and the following results were obtained: Inhibition of tumor growth in the combined group; Enhanced anti-metastatic effect; Prolonged survival time, and; Recovery of loss of both DTH and body weight as a result of combination therapy. These antitumor effects were also obtained by adoptive transfer of Ge-132-stimulated splenocytes in 5-FU-treated mice bearing 3LL. These results therefore suggest that the effects of Ge-132 were expressed through modification of immunocytes. Furthermore, Ge-132 enhanced the antitumor activity of bleomycin as well as that of 5-FU. These facts suggested that Ge-132 is useful for antitumor combination immunochemotherapy.     

两种不同剂量Ge—132对二甲肼诱发大鼠大肠癌的作用

在以二甲肼(DMH)诱发大鼠大肠癌的同时,给大鼠灌胃Ge-132 100mg/kg体重或300mg/kg体重共27周。Ge-132 100mg/kg体重组大鼠的平均癌灶数和平均癌灶体积,均显著少于对组照和Ge-132 300mg/kg体重组(P均<0.01)。Ge-132 300mg/kg体重组与对照组差异无显著意义(P>0.05)。肠镜检查显示,Ge-132 100mg/kg体重组致癌物所致结肠粘膜的炎症、萎缩和不典型增生明显轻于对照组(P<0.05),癌肿发生的潜伏期比对照组长3周。Ge-132 300mg/kg体重组与对组照差异无显著意义(P>0.05)。结果表明,Ge-132对化学诱癌的预防作用具有剂量依赖性。     

Antitumor activity of Ge-132, a new organogermanium compound, in mice is expressed through the functions of macrophages and T lymphocytes

The antitumor activity of Ge-132 against a variety of allogeneic and syngeneic murine ascites tumors was first evaluated. The antitumor effects of Ge-132 were observed when mice inoculated with Ehrlich carcinoma (allogeneic) or RL male 1 leukemia (syngeneic) cells were treated orally. However, Ge-132 had no activity on a T-cell lymphoma (EL 4, syngeneic) or a methylcholanthrene-induced fibrosarcoma (Meth-A, syngeneic). The antitumor effect of Ge-132 in mice was related to the dose administered as well as the administration schedule. The antitumor activity of Ge-132 was next studied in mice pretreated with some blockers against immunocompetent cells. The antitumor efficacy of Ge-132 was not observed when tumor-bearing mice were treated with trypan blue and carrageenan or monoclonal anti-Thy 1.2 antibody. However, when natural killer cells were eliminated from mice bearing RL male 1 or Ehrlich ascites tumors by treatment with anti-asialo GM 1 antiserum, the antitumor efficacy of the compound was unchanged. These results suggest that Ge-132 is effective against certain ascites tumors regardless of whether the tumor is syngeneic or allogeneic. Further, its effect might be expressed through host defense mechanisms, including macrophages and/or T lymphocytes.     

羧乙基锗倍半氧化物对实验诱发小鼠前胃癌变率的影响

 用羧乙基锗倍半氧化物（Ge-132）处理NSEE诱发的小鼠前胃鳞状上皮增生、癌变，结果发现实验组的癌变率显着低于对照组（P<0.05）,抑癌率为42.9%,实验组核仁组成区相关嗜银蛋白（Ag-NOR）数目及不规则型颗粒的比例显着低子对照组（P<0.05）,而实验组之癌周淋巴细胞浸润反应程度较对照组显着增强（P<0,05）.以上结果表明Ge-132可显着降低NSEE诱发小鼠前胃癌的癌变率，并可影响Ag-NOR在小鼠前胃鳞状上皮细胞中的表达，Ge-132的以上作用可能与其提高小鼠局部细胞免疫力有关。     

Antitumor effect in mice of an organic germanium compound (Ge-132) when different administration methods are used

The antitumor effect of an organic germanium compound, carboxyethylgermanium sesquioxide (Ge-132), was examined in mice using two systems: one, the ascitic form of Ehrlich carcinoma in DDI mice, and the other, the solid form of Meth-A fibrosarcoma in BALB/c mice. In the mice with Ehrlich ascitic tumors, a remarkable prolongation in life span was observed after intraperitoneal (i.p.) or per oral (p.o.) administration of Ge-132 (300 mg/kg), but not after intravenous (i.v.) injection of the same compound. Following i.p. or p.o. administration, cytotoxic macrophages (M?) were induced in the peritoneal cavity after 48 h. although this was not the case after i.v. injections. When the in vivo effect of these in vitro active M? was examined after adoptive transfer to mice bearing Ehrlich ascitic tumor cells, a significant antitumor effect was noted. In the mice bearing solid Meth-A tumors, i.v. injections of Ge-132 (100 mg/kg) were found to inhibit tumor growth remarkably, although i.p. and p.o. administrations did not have the same result. This inhibitory effect of Ge-132 by i.v. administration was explained by the continued augmentation of NK activity in peripheral blood, which was followed by the induction of specific killer cells appearing in the spleen. When the mice which had recovered from Meth-A tumor growth, following i.v. injections of Ge-132, were challenged with the same tumor on day 30, all mice were able to tolerate the challenge, but not a challenge of RL male 1 tumor cells. These observations may indicate that the differing antitumor effects of Ge-132 produced when different administration methods are used can be explained by the variation in effector cells induced by such different administration routes.