Comparative effectiveness of lymphotoxin anticarcinogenic and tumor cell growth-inhibitory activities

Prevention of ultraviolet radiation- or chemical carcinogen-induced morphologic transformation and inhibition of tumor-producing transformed cell growth by lymphotoxin and by normal spleen leukocytes were quantitatively compared to define the antineoplastic activity spectra of these natural immune mediators. When Syrian golden hamster embryo cells seeded for colony formation in culture dishes were treated simultaneously with carcinogen and lymphotoxin, the number of morphologically transformed cell colonies was irreversibly reduced by 50% in the presence of 6 units of lymphotoxin/ml. Lymphotoxin inhibition of tumor cell growth, however, was reversible and 50% reduction in tumor cell growth in three transformed lines required 124, 330, and 477 units/ml. Thus, the anticarcinogenic activity of lymphotoxin can be 20-fold or more greater than its tumor growth-inhibitory activity. Similarly spleen leukocytes also were more effective as an anticarcinogen than as an inhibitor of tumor cell growth, consistent with previous observations that naturally occurring spleen leukocyte antineoplastic activity may result from lymphotoxin secretion.     

The effect of whey protein hydrolyzates on the lactic acid fermentation

Summary The batch fermentation of whey permeate to lactic acid was improved markedly by the addition of enzymehydrolyzed whey protein. Acid concentrations greater than 90 g/l were achieved at a productivity of 4.3 g/l per h and a 98% substrate use. Cell mass concentration reached 6 g/l. The acid productivity achieved is somewhat higher than that typical for fermentation of whole whey. The process economics, based on in-house hydrolyzate preparation, look promising. Presented in this paper are the experimental results showing the effects of hydrolyzate concentration on acid and cell mass production.     

31例非特异性阴道炎病人阴道微生物群的研究

本文对31例非特异性阴道炎病人和31例正常人阴道微生物群进行定性、定量分析.结果表明,阴道炎病人的阴道乳杆菌的平均浓度明显低于正常人,而肠杆菌科、葡萄球菌、棒状杆菌、类杆菌属、支原体却明显增多,阴道炎病人未发现特异性病原体,菌群失调可能是其发病因素。乳杆菌为阴道正常优势菌,对改善阴道的微环境,防止条件致病菌引起的内源性感染具有重要的生理作用。     

Lymphocyte subpopulations of regional lymph nodes in human colon and gastric adenocarcinomas

 In order to study the host immune response to tumours, previous knowledge of the cellular composition of regional draining lymph nodes is necessary. Enlarged regional lymph nodes are a common finding in colon and gastric adenocarcinomas. We have studied the cellular composition of normal non-reactive and of regional draining lymph nodes of colon and gastric adenocarcinomas. In normal non-reactive lymph nodes, T lymphocytes (CD2⁺, CD7⁺) constituted the largest fraction of the lymphoreticular cells. These lymphocytes were mainly CD4⁺, and there were more cells expressing the CD45RA isoform of the CD45 antigen than CD45RO. Reactive lymph nodes presented a decreased proportion of CD4⁺ CD45RA⁺ cells and an increased number of B cells. Although most of the T cells in the reactive nodes were CD4⁺ CD45RO⁺, their proportion was similar to that found in normal non-reactive nodes. We studied the presence of the molecules CD28 and CD80 involved in the processes of interaction and activation of T and B lymphocytes. The CD28 molecule was found in all the T lymphocytes, while the CD80 molecule was weakly expressed on the B lymphocyte membrane. Received: 4 January 1996 / Accepted: 28 May 1996     

Intradermal administration of lipopolysaccharide in treatment of human cancer

 Lipopolysaccharide (LPS) has been recognized as a potent antitumor agent in animal tumor models; however, its use in human cancer therapy has been limited to only one trial, in which LPS from Salmonella was given intravenously. It was not very successful because of poor tumor response and was also toxic. We originally developed LPS prepared from Pantoea agglomerans (LPSp), and this was a well-purified, small-molecular-mass (5 kDa) agent. We chose intradermal rather than intravenous administration in the hope that the former would release LPS slowly into the bloodstream, and thus be less toxic while preserving antitumor activity. In our animal tumor models, intradermal administration was indeed less toxic and more beneficial for tumor regression than intravenous administration. We made a pilot study with intradermal administration of LPSp on the treatment of ten advanced cancer patients. Five of them had evaluable tumor, which had failed earlier to respond to conventional chemotherapy. Cyclophosphamide was also administered in this trial, in anticipation of its synergistic effect with LPSp. In this study LPSp was injected intradermally into each patient twice a week, starting with an initial dose of 0.4 ng/kg, and raising it to 600 or 1800 ng/kg. A 400-mg/m² dose of cyclophosphamide was given intravenously every 2 weeks. After completion of the dose escalation, the treatment was continued for at least 4 months, and it was found that 1800 ng/kg LPSp was well tolerated. A significant level of cytokines was observed in the sera for at least 8 h. These results indicate higher tolerable doses and remarkably more continuous induction of the cytokines than were reported in a previous study by others using intravenous administration. Three of the five evaluable tumors showed a significant response to our combined therapy. Intradermally administered, LPS was less toxic and elicited a tumor response in combination with cyclophosphamide; it can thus can be applied to cancer treatment even in humans. Received: 3 August 1995 / Accepted: 2 April 1996     

Tumor suppression in Drosophila is causally related to the function of the lethal(2)tumorous imaginal discs gene,a dnaJ homolog

The Drosophila melanogaster tumor suppressor gene lethal(2)tumorous imaginal discs (l(2)tid) causes in homozygotes malignant growth of cells of the imaginal discs and the death of the mutant larvae at the time of puparium formation. We describe the molecular cloning of the 1(2)tid+ gene and its temporal expression pattern in the wild-type and mutant alleles. Germ line rescue of the tumor phenotype was achieved with a 7.0 kb Hindlll-fragment derived from the polytene chromosome band 59F5. The l(2)tid+ gene spans approximately 2.5 kb of genomic DNA. The protein coding region, 1,696 bps long, is divided by an intron into two exons. The predicted Tid⁵⁶ protein contains 518 amino acids and possesses a theoretical molecular weight of 56 kDa. It shows significant homology to all known DnaJ related proteins from bacteria, yeast, and man. The possible function of the Tid⁵⁶ protein in tumor suppression is delineated. © 1995 Wiley-Liss, Inc.     

LC－CW的抗肿瘤作用及其机理的研究

提取干酪乳酸杆菌细胞壁成分（ＬＣ－ＣＷ）,研究其抗肿瘤作用及其机理。结果表明：１００μｇＬＣ－ＣＷ,ｉｐ,连续４天,可明显抑制小鼠Ｓ１８腹水瘤移植物的生长,抑瘤率为５４％。增强ＩＬ－２诱导的ＬＡＫ杀伤活性,可明显促进小鼠ＮＫ杀伤活性,明显促进小鼠Ｔ细胞转化,促进ＣｏｎＡ和ＰＨＡ－Ｐ诱导的ＩＬ－２产生,促进ＳＩＬ－２Ｒ的减少。研究结果表明ＬＣ－ＣＷ是一种重要的抗肿瘤免疫调节因子。     

Induction of Nitric Oxide Synthase in Rat C6 Glioma Cells

Abstract: We have examined the induction of nitric oxide syhthase (NOS) activity in the rat astrocyte-derived C6 glioma cell line. In contrast to the previous results with primary astrocyte cultures, incubation of C6 cells with bacterial endotoxin lipopolysaccharide (LPS; 1 μg/ml for 24 h) did not stimulate NO₂ production. However, addition of either tumor necrosis factor-a (TNF-α) or interferon-γ (IFN-γ), cytokines that by themselves had no effect on NOS activity, imparted LPS responsiveness onto these cells in a dose-dependent manner (EC₅₀ values of 39 ng/ml of TNF-α and 9.4 U/ml of IFN-γ), and the effect of TNF-α could be further potentiated (twofold) by the presence of interleukin-1β. The simultaneous presence of TNF-α and IFN-γ yielded a greater response than either cytokine alone; however, the respective EC₅₀ values were not affected. A cytoplasmic extract from induced C6 cells catalyzed the Ca²⁺-independent conversion of l -arginine to l - citrulline, with an apparent K _m of 51.2 n M , and this activity could be blocked by l -arginine analogues in the potency order amino > methyl > nitroarginine. Immunoblot analysis revealed an apparent molecular mass of 125 kDa for the NOS protein induced in C6 cells. These results indicate that the combination of LPS plus cytokines can induce NOS activity in C6 glioma cells with properties similar to those of the enzyme expressed in primary astrocyte cultures.