牛膝多糖抗肿瘤作用及免疫机制实验研究

作者研究了牛膝多糖（ＡＢＰ）对Ｓ＿（１８０）荷瘤小鼠的抑瘤作用和脾细胞诱生ＴＮＦ和ＬＡＫ细胞活性的影响。结果证实ＡＢＰ２５～１００ｍｇ·Ｋｇ￣（－１）·ｄ￣（－１）×７的抑瘤率为３１％～４０％。环磷酰胺１２．５ｍｇ／ｋｇ单次的抑瘤率为１７％，与ＡＢＰ１００ｍｇ·ｋｇ￣（－１）·ｄ￣（－１）合用的抑瘤率为５８％，有明显协同作用。ＡＢＰ１～２μｇ／ｍｌ对小鼠肉瘤Ｓ＿（１８０）细胞和人白血病Ｋ＿（５６２）细胞的增殖均有明显抑制作用，ＡＢＰ５０及１００ｍｇ／ｋｇ腹腔注射能明显提高Ｓ＿（１８０）荷瘤小鼠ＬＡＫ细胞活性和ＴＮＦ－β生成。诱生ＴＮＦ的达峰时间是２次腹腔注射后的第８天。为探讨其抗肿瘤机理，对Ｓ＿（１８０）细胞膜成份进行了分析，结果显示ＡＢＰ与细胞接触２４小时，引起细胞膜唾液酸含量升高，膜磷脂含量降低，这些变化差异均有显著性意义（Ｐ＜０．０５或Ｐ＜０．０１）；但膜胆固醇含量、膜流动性（Ｃ／Ｐ比值）不受影响。提示ＡＢＰ的抗瘤机理与其增强宿主免疫功能及改变细胞膜生化特性有关。     

大豆皂甙对小鼠移植肿瘤生长的影响

目的探讨大豆皂甙（ＴＳ）对肿瘤细胞生长的影响及其机制。方法采用Ｃ５７ＢＬ／６小鼠皮下接种Ｓ１８０细胞后，经口连续７天注入胃内０（对照组）、１０、２０和４０ｍｇ／ｋｇＴＳ。结果第８天注入上述剂量ＳＴ组小鼠移植肿瘤平均重量分别为１．１８、０．８和０．８９ｇ，均较对照组２．２３ｇ明显减轻（Ｐ＜０．０５～０．０１）。小鼠腹腔注入Ｓ１８０细胞后，连续７天经腹腔分别注入上述剂量ＴＳ，第８天各组小鼠Ｓ１８０细胞周期进程均延缓，Ｇ０／Ｇ１期Ｓ１８０细胞平均百分数分别为３０．７６、４１．７４和３４．８４，均较对照组２４．７６增多，４０ｍｇ／ｋｇ组小鼠最明显（Ｐ＜０．０５）；Ｓ期Ｓ１８０细胞分别为１５．２８、１１．６４和１１．８０，均较对照组３０．３０明显减少（Ｐ＜０．０５）。结论ＴＳ对小鼠移植肿瘤生长有抑制作用，可能与肿瘤细胞从Ｇ０／Ｇ１期向Ｓ期进程受阻有关。     

INHIBITORY EFFECT OF A BIOLOGICAL PREPARATION A CM ON SARCOCARCINOMA S180 OF MICE

在基础饲料中加入含巯基多糖的ＡＣＭ海洋生物制剂喂养皮下接种了Ｓ１８０肉瘤的小鼠，观察记录动物的存活天数和荷瘤第１０天的瘤重与体重。实验结果为：低剂量组（２０ｇ／ｋｇ饲料）和高剂量组（１００ｇ／ｋｇ饲料）动物的生命延长率分别为７６％和２１．９％（Ｐ＜００１），肿瘤生长抑制率分别为８７％和２８１％（Ｐ＜００１），高剂量组动物的体重下降幅度低于其他各组（Ｐ＜００１）。本次实验结果提示，ＡＣＭ制剂对小鼠Ｓ１８０肉瘤的生长有一定的抑制作用。     

大蒜素对小鼠S180的抑制作用及NK细胞活性的影响

以小鼠Ｓ１８０为动物模型，观察大蒜素对其抑制作用。大蒜素腹腔注射，连续５天，当大蒜素分别给予２５ｍｇ，ｋｇ＾－１，ｄ和５０ｍｇ，ｋｇ＾－１，ｄ时，则抑瘤率分别为３２．１８％（Ｐ〈０．０５）和５８．５２％，（Ｐ〈０．０１），进一步测定小鼠ＮＫ细胞活性，大蒜素组为５１．３２％，对照组为４４．２２％，两组比较差别不显著（Ｐ〉０．０５）。本文提示：大蒜素能有效的抑制小鼠Ｓ１８０的生长，但对小鼠ＮＫ细胞活性     

子宫肉瘤54例临床研究

目的 探讨子宫肉瘤预后的相关因素。方法 回顾分析了５４例子宫肉瘤的病理类型、临床分期、子宫大小、绝经情况及治疗方法与生存率进行对照研究;统计学处理采用Ｘ＾２检验。结果 （１）病理类型：子宫平滑肌肉瘤１９例;子宫内膜间质肉瘤１０例;中胚叶混合瘤２４例,５年生存率分别为４７．３％、５０．０％及４１．７％（Ｐ〉０．０５）;（２）肿瘤分期：Ｉ期３１例、Ⅱ期１１例、Ⅲ期５例、Ⅳ期７例、５年生存率分别为６１．３％、３６．４％、０及０（Ｐ〈０．００１）。（３）子宫大小：子宫大小妊娠３个月者３８例,大于妊娠３个月者１６例,５年生存率分别为５３．３％及６．３％（Ｐ〉０．０５）;（４）绝经情况,绝经前３４例,绝经后２０例,５年生存率分别为：５８．３％及３０％（Ｐ〈０．０１）;（５）治疗方法：手术１１例,手术＋化疗３６例,手术＋化疗     

CD3AK对晚期肝癌疗效初步观察

目的观察晚期肝细胞癌（ＨＣＣ）患者采用抗ＣＤ３抗体激活的杀伤细胞（ＣＤ３ＡＫ）治疗的效果。方法５８例晚期ＨＣＣ患者分为三组，Ａ组［ＣＤ３ＡＫ＋肝动脉化学栓塞（ＴＡＣＥ）］２２例，Ｂ组（ＣＤ３ＡＫ）１５例，Ｃ组（ＴＡＣＥ）２１例。结果部分缓解率（ＰＲ）Ａ，Ｂ，Ｃ组分别为４５．５％、１３．３％（Ｐ＜０．０５）和１４．３％（Ｐ＜０．０５），中位生存期分别为１１．３月、４．９月（Ｐ＜０．０１）和４．１月（Ｐ＜０．０１），半年和１年生存率分别依次为６８．２％，３３．３％（Ｐ＜０．０５）和２３．８％以及４０．９％、６．６％（Ｐ＜０．０５）和９．５％（Ｐ＜０．０５）。结论本组结果表明ＣＤ３ＡＫ＋ＴＡＣＥ治疗晚期ＨＣＣ疗效最佳     

云芝提取液的抗瘤作用

研究云芝提取液对小鼠移植性动物实体肿瘤的抑制作用。方法；按常规方法拉种肿瘤２４小时后，云芝口服液在２０－６０ｇ干药．ｋｇ＾－１／ｄ剂量范围内，连续灌胃７天，计算其抑瘤率。结果：小鼠Ｓ－１８０的抑瘤率为３１．３－５１．８％之间，均Ｐ〈０．００１，对小鼠肝癌的抑制率为４６．２－６６．５％之间，无Ｐ〈０．００１；对小鼠Ｌ－Ⅱ的抑制率为３７．９－６４．６％之间，均Ｐ〈０．００１。     

中华眼镜蛇毒对小鼠肉瘤S180的抑制作用和血浆内皮素的影响

目的：探讨中华眼镜蛇毒（ｎａｊａ ｎａｊａ ａｔｒａ ｖｅｎｏｍ，ＮＮＡＶ）对小鼠肉瘤Ｓ１８０的抑制作用和血浆内皮素的影响。方法：通过体内实验，用不同剂量的ＮＮＡＶ对荷肉瘤Ｓ１８０小鼠进行治疗，观察其对小鼠肉瘤Ｓ１８０的影响，并利用放射免疫测定法（ＲＩＡ）测定荷瘤小鼠血浆内皮素（ＥＴ）含量。结果：经过小、中和大剂量（２０μｇ／ｋｇ，４０μｇ／ｋｇ和８０μｇ／ｋｇ）ＮＮＡＶ治疗后，其中大剂量组对小鼠肉瘤Ｓ１８０有明显的抑瘤作用，抑瘤率为４９．２５％，同时发现荷Ｓ１８０肉瘤小鼠血浆内皮素水平明显高于正常对照组（Ｐ〈０．０５），大剂量组荷Ｓ１８０肉瘤小鼠的血浆内皮素含量明显降低（Ｐ〈０．０５）。结论：ＮＮＡＶ对小鼠肉瘤Ｓ１８０的生长具有抑制作用，可能与其降低荷瘤鼠血浆内皮素水平有关。     

滑膜肉瘤术后放射治疗81例

我院１９６４一１９８７年收治了８１例滑膜肉瘤患者。本文分析不同治疗方法对预后的影响，术后放疗组和单纯手术组的３、５年生存率分别为５２０％、４２．０％和４１．９％、２５．８％（Ｐ＞０．０５），局部复发率分别为１２．８％和６８．８％（Ｐ＜０．０１）。患者年龄对预后影响较大，３０－６５岁组和１０－２９岁组的３、５年生存率分别为５８．７％，４１．３％和３４．３％，２８．６％（Ｐ＜０．０５）。而病变部位与疗效无关。本组病例治疗失败的一重要原因是血行转移（４５．８％）。我们认为发病无明显症状而延搁诊治、不恰当穿刺或活检，局部复发而多次手术可能是增加血行转移的原因。本组肺转移３１例，其中９例曾用各种不同化疗方案治疗，但均于１年内死亡。     

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。     

Antitumor activity of chlorella extract, PCM-4, by oral administration

The antitumor activity of a water-soluble substance extracted from Chlorella regulararis S-50, PCM-4, against murine transplanted tumors was investigated. PCM-4 is composed of sugar (25.7%), protein (51.5%) and nucleic acid (18.7%). By oral administration of PCM-4, both the growth of Sarcoma 180 and Meth A, subcutaneously implanted into mice, and ascites hepatoma AH 44 and AH 41C, intravenously implanted into rat, was inhibited. PCM-4 also showed antitumor activity against Sarcoma 180 and Meth A by intraperitoneal administration. The finding that PCM-4 has no direct growth-inhibition effect on tumor cells in vitro suggests that the antitumor activity of PCM-4 be elicited from the host-mediated response system.     

急性髓细胞白血病细胞CD34抗原表达的临床及生物学意义

为研究ＣＤ３４在急性髓细胞白血病（ＡＭＬ）中的临床及生物学意义，用流式细胞术检测了１０７例ＡＭＬＣＤ３４表达。结果显示４８．５％的患者ＣＤ３４阳性表达，Ｍ３（１５．８％）低于其他亚型（ｐ〈０．０５）。ＣＤ３４＾＋者肝脾肿大常见。ＣＤ３４表达在ｔ（８；２１）、正常核型及ｔ（１５；１７）组分别为７２．０％、４０?７％及１７．６％。ＣＤ３４＾＋者的完全缓解率（４１．９％）明显低于ＣＤ３４＾－者的５９．６     

Antitumor activity of Lactobacillus casei YIT 9018 (LC 9018)--effect of administration route

Antitumor activity of lactobacilli on Sarcoma 180 was investigated and was shown to be different from strain to strain. In general, Lactobacillus casei had higher antitumor activity compared with other species of lactobacilli. Among these, L. casei YIT 9018 (LC 9018) had significant antitumor activity against Meth A fibrosarcoma when administered into BALB/c mice intravenously, intraperitoneally, subcutaneously, intratumorally or orally. LC 9018 showed antitumor activity against rat ascites hepatoma by intravenous or oral administration, but this activity was lower than that against Meth A in mice.     

Cytotoxic and antitumor activity of 1-nitroacridines as an aftereffect of their interstrand DNA cross-linking

To determine whether the toxic effects and changes in many cell functions caused by antitumor 1-nitroacridines are related to their enzymatically mediated covalent interstrand DNA cross-linking (J. Konopa, J. W. Pawlak, and K. Pawlak. Chem.-Biol. Interact., 43: 175-197, 1983), the cross-linking potency of the derivatives with structural modifications in position 9 of the acridine nucleus was estimated as their in vitro threshold concentrations (0.3 to 4.5 microM), beyond which the first interstrand DNA cross-links could be detected in DNA of cultured HeLa S3 cells with a polyethylene glycol 6000-Dextran T500 assay. Statistically significant (p less than 0.05) correlations exist between the cross-linking potency of 1-nitroacridines and their in vivo antitumor activity and toxicity against mice with Sarcoma 180 tumors in solid form (3 to 1065 mumol/kg of body weight), as well as their in vitro cytotoxicity against cultured HeLa or HeLa S3 cells (0.0005 to 7.2 microM), indicating that the interstrand DNA cross-linking potency might be one of primary determinants of in vivo and in vitro biological activity of 1-nitroacridine antineoplastic drugs. Susceptibility of the parent agents to reduction does not appear to be a rate-limiting factor of DNA cross-linking potency of 1-nitroacridines and their metabolic transformations (J. W. Pawlak, and J. Konopa. Biochem. Pharmacol., 28: 3391-3402, 1979), because no significant differences were observed among the agents with respect to their polarographic half-wave potentials estimated under anaerobic conditions.     

Anticellular and antitumor activity of duocarmycins, novel antitumor antibiotics.

The anticellular and antitumor activities of novel antitumor antibiotics, duocarmycins (DUMs), were examined against human and murine tumor cells. DUMs consist of five compounds, A, B1, B2, C1 and C2, which possess a pharmacophore similar to that of CC-1065, a previously isolated antibiotic. Among them, DUMA exhibited ultrapotent growth-inhibitory activity with an IC50 value of 6 pM against human uterine cervix carcinoma HeLa S3 cells. DUMA and DUMB1 also inhibited the growth of adriamycin (ADM)-resistant lines of human nasopharynx carcinoma KB cells and breast carcinoma MCF-7 cells as well as their sensitive lines. DUMs inhibited the growth of s.c.-inoculated murine tumors such as B16 melanoma, sarcoma 180, M5076 sarcoma and colon 26. DUMs were also significantly effective in increasing the lifespan of i.p.-inoculated B16 melanoma-bearing mice, although their effect was marginal against other i.p.-inoculated tumors. As a whole, DUMB1 exhibited superior activity to the other four compounds. DUMB1 rapidly inhibited the incorporation of [3H]-TdR into macromolecules of HeLa S3 cells as compared with that of [3H]UR or [3H]leucine. DNA strand breaks were detected in DUMB1-treated HeLa S3 cells by agarose gel electrophoresis with a contour-clamped homogeneous electric field apparatus. These results indicate that DUMs possess interesting biological activities as DNA-targeting antitumor antibiotics.     

Additive inhibitory effects of retinoids and interferon-alpha on the growth of human cervical carcinoma cells

The combination of 13-cis retinoic acid (13CRA) and interferon-alpha (IFN-alpha) has shown marked antitumor activity against locally advanced cervical cancer in vivo. To begin to explore the mechanism and potential of the efficacy of this combination, the sensitivity of 9 cervical carcinoma cell lines to the growth inhibitory effects of these agents was examined after 1 to 7 days of treatment. IFN-alpha (100 U/ml) alone exerted variable effects. SiHa cell line was very sensitive showing 75% inhibition. ME180, CaSki, MS751, and C33-A cell lines were moderately inhibited (30-45% inhibition), and C41, HeLa, and HT-3 cell lines were poorly responsive (20% inhibition or less). 13CRA (10(-9) to 10(-6) M) alone also caused variable growth inhibitory effect. ME180, SiHa, and HT-3 exhibited considerable inhibition (IC(50)s of 9x10(-8), 4x10(-8), and 7x10(-8) M, respectively and maximal inhibition of 80%, 79%, and 83% at 10(-6) M) and the other cell lines showed minor responses (20-45% inhibition at 10(-6) M). ME180, MS751, C41, and HeLa demonstrated additive growth inhibitory effects of 13CRA and IFN-alpha whereas the other 4 cell lines showed no additive effects. All the cell lines expressed mRNAs for the nuclear retinoid receptors (RARs and RXRs) RAR-alpha, RAR-gamma, and RXR-alpha, however, RAR-beta mRNA was detected only in ME180, MS751, C4I, and CaSki. Treatment with retinoic acid increased RAR-alpha level in C4I, HT-3, and CaSki; RAR-beta in HT-3; and RAR-gamma in HT-3 and C4I cells. IFN-alpha treatment did not exert any effect on the level of mRNA for any of the retinoid receptors in any of the cell lines or on the level of HPV18 E6 and E7 mRNA in HeLa cells. Treatment with the combination of RA and IFN-alpha did not affect the level of receptor mRNAs differently than RA alone did. There appeared to be no correlation between the responses of the cells to these agents and the presence or type of nuclear retinoid receptor, human papillomavirus, or mutant p53 in the cells.     

细胞块制片免疫组化对胸腹腔积液转移性腺癌的诊断价值

目的 探讨细胞块制片免疫组化对胸腹腔积液转移性腺癌的诊断价值.方法 收集胸腹腔积液患者100例,经过穿刺法获取胸腹腔积液标本100 ml,病理检查,给予常规涂片和细胞块制片,均联合免疫组化法,比较两种检测方法相关蛋白阳性、阴性以及不确定性,计算细胞阳性率.结果 细胞块检测阳性率为48.0%,高于常规检测的34.0%,不确定性比例为0,低于常规的22.0%(P<0.05);两种方法对良性组织检测结果显示:CK7、MOC-31、CD51、TTF-1、CEA、CA125、Ber EP4、NapsinA、E-cad均呈低表达,WT-1、Calretinin、CK5/6均呈高表达,恶性组织检测显示CK7、MOC-31、CD51、TTF-1、CEA、CA125、Ber EP4、NapsinA、E-cad均呈高表达,并且细胞块法阳性率均高于常规涂片法(P<0.05),WT-1、Calretinin、CK5/6均呈低表达;常规涂片对不确定组织检测结果:WT-1、Calretinin、CK5/6阳性率均较高,其他均为低阳性率,CK7、MOC-31、CD51、TTF-1、CEA、CA125、Ber EP4在转移性恶性肿瘤中阳性率均较高,并且细胞块阳性率均高于相应的常规涂片法(P<0.05).结论 细胞块制片免疫组化对胸腹腔积液转移性腺癌的诊断具有重要意义,各指标间联合可以判断肿瘤类型.     

Anticancer activity of new 3-amino-pyrrolidinedione-nitrogen mustard derivatives on murine sarcoma 180

A 2,5-pyrrolidinedione linked nitrogen mustard derivative, (R,S)3-[N,N-bis(2-chloroethyl)]-amino-1-(2'-methoxyphenyl)pyrrolidine- 2,5-dione hydrochloride (I) showed a marked antiproliferative effect on mouse Sarcoma 180. Since (I) is also active against L1210 and P388 leukaemias, its toxicity in mice was evaluated. A study of acute toxicity revealed focal liver cell necrosis. Another derivative, (R,S)3-[N,N-bis-(2-chloroethyl)]amino-1-(4'-n-butoxyphenyl)pyrrolidine- 2,5-dione dihydrate (II), which also possessed significant anticancer effect on P388 and L1210 leukaemias, was inactive against Sarcoma 180.     

不同分子分型乳腺癌的临床病理特征及预后的关系

目的 探讨乳腺癌分子分型与临床病理特征及预后的关系.方法 选择126例乳腺癌患者,按孕激素受体(PR)、雌激素受体(ER)和人类表皮生长因子受体-2(HER-2)的状态分为Luminal A型、Luminal B型、HER-2过度表达型和Basal-like型,比较不同分子分型乳腺癌患者的临床病理特征、复发转移及预后情况.结果 156例乳腺癌患者中,Luminal A型68例(54.0%)、Luminal B型22例(17.5%)、HER-2过度表达型9例(7.1%)、Basal-like型27例(21.4%).乳腺癌不同分子分型间绝经状态、肿瘤直径、淋巴结转移数目、临床分期及组织学分级的差异均有统计学意义(P<0.05).HER-2过度表达型与Basal-like型的局部复发率分别为33.3%和14.8%,远处转移率分别为55.6%和40.7%,均高于其他2种亚型,差异均有统计学意义(P<0.05).4组中位无瘤生存时间的差异有统计学意义(χ2=8.002,P<0.05),HER-2过度表达型与Basal-like型的MPFS较短.结论 HER-2过表达型和Basal-like型乳腺癌的病理学特征较差,且预后不良;而Luminal A型预后较好.     

Potentiation of chemotherapeutic activity by a Chinese herb medicine juzen-taiho-toh

Antitumor activity of Juzen-Taiho-Toh (JTX) and combination effect of JTX with antitumor agents were studied using murine tumors. In order to determine the antitumor activity of JTX, mice inoculated ip with IMC carcinoma (1 X 10(6) cells/CDF1 mouse), sarcoma-180(1 X 10(6) cells/ICR mouse) or Meth-A fibrosarcoma (1 X 10(6) cells/BALB/c mouse) were treated with JTX (12.5-50 mg/kg/day) ip on day 1 through day 10, and the survival days of mice were examined. Treatment with 25 mg/kg/day produced 38.7% increase of life span against IMC carcinoma. However, no antitumor effect was observed on solid form of these tumors by the daily treatment with JTX. Combination effect of JTX and antitumor agents was also examined. ICR mice inoculated sc with 1 X 10(6) cells of sarcoma-180 on day 0 were treated with JTX (2,000 mg/kg/day) po on day-7 through day 30. In addition, some of these groups received mitomycin C (5 mg/kg), cytoxan (67 mg/kg) or adriamycin (2.5 mg/kg) iv on days 3, 8 and 11, and the size of tumor grown in sc site was measured by a caliper. In combination with JTX, mitomycin C resulted in a significantly greater tumor growth inhibition than could be obtained with mitomycin C alone. Secondly, BALB/c or C57BL/6 mice inoculated sc with 1 X 10(4) cells of Meth-A fibrosarcoma or 1 X 10(5) cells of B16 melanoma on day 0 were treated with JTX (2,000 mg/kg/day) po on day 1 through day 30. Some of these group received ip with mitomycin C (3 mg/kg), adriamycin (2 mg/kg), 5-FU (33 mg/kg) or cytoxan (67 mg/kg) on days 3, 6, 9, 12, 15 and 18. From this result, the group treated with JTX and mitomycin C also showed a higher tumor-growth inhibition. Thus, a combination of a high dose of mitomycin C with JTX was more effective than mitomycin C alone.