Human carcinoma cell lines xenografted in athymic mice: biological and antigenic characteristics of an intraabdominal model

Summary In order to investigate in vivo clinical applications of murine monoclonal antibodies directed against human ovarian carcinoma a preclinical in vivo model was developed using BALB/c athymic mice. Three human carcinoma cell lines (MCF7, HT29, and SW626) were injected into the peritoneal cavity of pristane-primed animals and the biological and antigenic characteristics of the i.p. grown tumors were studied. The animals were killed when moribund or 6–8 weeks after tumor injection. At autopsy tumor take was observed in 85% of the injected animals, whereas palpable nodules were evident in only 83%. Examination of the peritoneal cavity revealed intraabdominal carcinomatosis with tumor masses varying in size between 0.2 and 0.5 cm in diameter and tumor sheets. The most frequently affected organs were the diaphragm, the liver, and the reproductive system. Ascitic fluid formation was rare and no animal developed tumors outside the peritoneal cavity. To determine whether the in vivo tumors retained the same antigenic characteristics as the in vitro cell lines, four monoclonal antibodies (MBrl, MOv2, MOv8, and MOv15) directed against ovarian carcinoma-associated antigens and two different experimental approaches (immunofluorescence and immunoblotting) were used. Variations at either a quantitative or a qualitative level were observed for some antigens, whereas no evident changes were apparent for others. In particular, the antigens detected by MBr1 and MOv15 on the MCF7 line both maintained high levels of expression and immunoblotting staining pattern, whereas the antigens detected by MOv2 on the HT29 and SW626 lines, although present at a high level, clearly changed their staining pattern. As regards the antigens recognized by MOv8 and MOv15 on the HT29 and SW626 lines, we observed a drastic decrease in the level of their expression and in many cases a drop below the threshold of detectability of the test. The intraabdominal carcinomatosis described partially mimics the growth characteristics of human ovarian cancer and maintains the expression of some antigenic markers associated with epithelial tumors of the ovary and may therefore be useful in devising immunodiagnostic and/or immunotherapeutic strategies for ovarian carcinoma.     

田螺科五种螺的核型研究

以早期胚胎细胞为材料,用火焰干燥法制片,对分布于我国湖北省武汉市近郊的常见田螺科(Viviparidae)五种螺的核型进行了分析。结果:两种圆田螺的染色体数和国外报道的同一属的种类的一致。而三种环棱螺的染色体数,则较国外报道的另两种的少得多。在铜锈环棱螺的核型中,其m组的第一对和sm组的第四对染色体上,具有明显的随体,出现频率甚高。     

中国鲤科鱼类染色体组型的研究 Ⅱ.鲴亚科四种鱼的染色体组型

鲴亚科(Xenocyprininae)鱼类多为中小型鱼类,常见于江河湖泊等较宽阔的水域中,我国长江、黑龙江、黄河及珠江诸流域皆有分布,共有10种,隶属4个属(伍献文等,1964)。迄今尚未见有该亚科鱼类染色体组型的研究报道。本文是对其中三属四种鱼的染色体组型的观察结果。这四种鱼是银鲴(Xenocypris argentea)、黄尾鲴(Xenocypris davidi)、细鳞斜颌鲴(Plagiognathops microlepis)和逆鱼(Acanthobrama simoni)。其中黄尾鲴和细鳞斜颌鲴均为新的淡水养殖鱼(沈德长等,1981;陈楚星,1979)。     

植物冷锻炼对于胁强敏感度的影响(英文)

前文由柑桔枝条在不同低温下、不同冷冻时间的电解质外渗测定,提出胁强(stress)、作用时间与胁变(strain)之间关系的数学模型。在这个模型中共有3个参数:屈服点温度(yield point temperature),胁强敏感度(stress sensitivity)和作用时间敏感度(sensitivity to duration),用以描述植物的抗性。抗性强的植物应表现为屈服点温度较低,胁强敏感度或者时间敏感度较低。为验证此数学模型,本工作以经冷锻炼与未经冷锻炼的盆栽柑桔枝条为材料,作不同温度与时间处理的电解质外渗率的测定,研究了冷锻炼对于上述3个参数的影响。发现胁强敏感度和屈服点温度受冷锻炼影响而下降,时间敏感度未表现明显变化。对于田间柑桔、油桐与毛竹的定期测定,在固定冷冻时间下,得到了类似于盆栽柑桔的结果。入冬时,植物抗冻性提高,3种植物都表现出下列两种变化:1.胁强敏感度的明显下降;2.屈服点温度和/或时间敏感度亦下降。开春时的变化则相反。胁强敏感度的变化与后一种变化有各自的规律,且因植物种类而不同。拐点胁强(stress at inflection point)具有与半致死温度(50％killing point temperature)不同的意义,它的变化是上述两种变化的综合结果。本试验结果表明,冷锻炼对于植物胁强敏感度有明显影响,用本数学模型的3个抗性指标描述     

Modulation of drug-induced cytotoxicity by a bispecific monoclonal antibody that recognizes the epidermal growth factor receptor and doxorubicin

A hybrid hybridoma secreting a bispecific hybrid mAb (bsmAb), which recognizes both the epidermal growth factor receptor (EGF-R) and the drug doxorubicin, was produced by somatic hybridization of two hybridomas. The bsmAb obtained was able to retarget doxorubicin cytotoxicity in vitro specifically on EGF-R-positive cells exerting at the same time an antidotal effect on cells that did not overexpress the EGF-R. Distribution studies in mice indicate that the bsmAb selectively delivers the drug to tumour cells and modifies doxorubicin biodistribution with a statistically significant decrease of drug concentration in the intestine, which is the main target of early anthracycline toxicity. In keeping with this finding is the remarkable antidotal activity exerted by bsmAb in mice treated with doxorubiein, which is proved by retardation in loss of body weight and mortality. The effectiveness on tumour growth of the mAb followed by the administration of doxorubicin appears to be equal to that of the drug alone; however, the bsmAb exerts a remarkable antidotal activity.     

微生物发酵法生产S-腺苷甲硫氨酸的研究进展

S-腺苷甲硫氨酸(S-adenosyl-l-methionine, SAM)广泛存在于生物体内,主要参与生物体内的转甲基过程、转硫过程及转氨丙基过程,具有重要的生理功能,其生产备受重视。目前SAM生产的研究主要集中于微生物发酵法,该方法与化学合成法和酶催化法相比,成本较低且更容易实现工业化生产。随着需求量的迅速增加,通过菌种改良提高SAM产量备受关注。当前SAM生产菌种改良的主要策略包括常规育种和代谢工程。本文综述了提高微生物生产SAM能力的近期研究进展并探讨了SAM生产中的瓶颈问题及解决方法,以期为进一步提高SAM产量提供思路。     

In vitro mimicry of CaMBr1 tumor-associated antigen by synthetic oligosaccharides

The murine monoclonal antibody (Mab) MBr1, raised against thebreast cancer cell line MCF7, recognizes a saccharidic epitopeoverexpressed on a high percentage of human breast, ovary, andlung carcinomas. This antigen was originally identified on theimmunogen as a globo-series glycosphingolipid with an H-likedeterminant at its terminus (globo-H). We report here the biologicalcharacterization of the entire globo-H hexasaccharide and fivesynthetic oligosaccharides representing fragments of the entirestructure andlor different anomeric configurations. Using competitivebinding assays on live cells, we identified the residues andthe linkages essential for mimicry of the cellular antigensrecognized by Mab MBr1 on the breast carcinoma cell line MCF7and small cell lung cancer cell line POVD. The terminal tetrasaccharidicfragment of globo-H is the oligosaccharide that most resemblesthe MBr1-defined epitope both on glycolipids and on glycoproteins.This information will help in the rational design of a highlyspecific reagent for active specific immunotherapy of carcinomasoverexpressing the MBr1-defined antigen. CaMBr1 immunotherapy monoclonal antibody oligosaccharides tumor-associated antigen     

A monoclonal antibody extends the half-life of an anti-HIV oligodeoxynucleotide and targets it to CD4+ cells.

An approach was sought to increase the half-life and target cell specificity of antisense oligodeoxynucleotides (oligos). A monoclonal antibody (MAb) was derived from mice immunised with an oligo complementary to a region (1-20) of the HIV genome. This MAb exerts a protective effect on the oligo from the degradation induced by plasma exonucleases in vitro and in vivo. Moreover the anti-oligo MAb dissociates from the oligo in the presence of its complementary sequence to allow hybridization of the two complementary strands. To direct the oligo to CD4+ cells the anti-oligo MAb was cross-linked to an anti-CD4 MAb. The heteroaggregate determines a 5-fold increase in the cellular membrane binding of the oligo to CD4+ lymphocytes. These findings suggest a new approach to enhancing the therapeutic action and the target specificity of antisense oligodeoxynucleotides useful for the selective inhibition of HIV replication in vivo.     

Biochemical and genetic characterization of three hamster cell mutants resistant to diphtheria toxin

We describe here three different hamster cell mutants which are resistant to diphtheria toxin and which provide models for investigating some of the functions required by the toxin inactivates elongation factor 2 (EF-2). Cell-free extracts from mutants Dtx(r)-3 was codominant. The evidence suggests that the codominant phenotype is the result of a mutation in a gene coding for EF-2. The recessive phenotype might arise by alteration of an enzyme which modifies the structure of EF-2 so that it becomes a substrate for reaction with the toxin. Another mutant, Dtx(r)-2, contained EF-2 that was sensitive to the toxin and this phenotype was recessive. Pseudomonas aeruginosa exotoxin is known to inactivate EF-2 as does diphtheria toxin and we tested the mutants for cross-resistance to pseudomonas exotoxin. Dtx(r)-1 and Dtx(r)-3 were cross-resistant while Dtx(r)-2 was not. It is known that diphtheria toxin does not penetrate to the cytoplasm of mouse cells and that these cell have a naturally occurring phenotype of diphtheria toxin resistance. We fused each of the mutants with mouse 3T3 cells and measured the resistance. We fused each of the mutants with mouse 3T3 cells and measured the resistance of the hybrid cells to diphtheria toxin. Intraspecies hybrids containing the genome of mutants Dtx(r)-1 and Dtx(r)-3 had some resistance while those formed with Dtx(r)-2 were as sensitive as hybrids derived from fusions between wild-type hamster cells and mouse 3T3 cells.