Antitumor Effect of Liu-Shen-Wan on Transplanted Tumors of Mice with Colon Cancer from Perspective of Tumor Microenvironment / 肿瘤防治研究

Objective To investigate the effect of Liu-Shen-Wan on transplanted tumors in mice with colon cancer based on the polarization of M2 macrophages in the tumor microenvironment. Methods We established a subcutaneous transplantation tumor model of mice with CT26 colon cancer. Mice were randomly divided into vehicle, oxaliplatin, and oxaliplatin combined with Liu-Shen-Wan groups. Treatment was administered for three weeks, and tumor volume was measured. All mice were weighed during the administration. After the end of the treatment, the mice were dissected and tumors were photographed and weighed. Spleen index was calculated. The expression levels of IFN-γ and IL-12P40 in serum and related blood biochemical indices were measured. The expression levels of M2 macrophage polarization indices, namely, IL-10 and TGF-β, in serum and tumor tissues were detected. The infiltration degree of M2 macrophages in each group was observed by immunohistochemical experiments. Results The tumor volume and mouse weight in the oxaliplatin combined with Liu-Shen-Wan group significantly decreased compared with those in the vehicle group. The spleen index increased, and the expression levels of IFN-γ and IL-12P40 in serum also significantly increased. The mice had no obvious side effects after the drug treatment. In addition, the expression levels of IL-10 and TGF-β in the serum and tissues of mice in the oxaliplatin combined with Liu-Shen-Wan group significantly decreased. The expression levels of CD68 and CD206 in tumor tissues also decreased. Conclusion The anti-tumor effect of Liu-Shen-Wan on the transplanted tumors of mice with colon cancer is related to the inhibition of M2 macrophage polarization in the tumor microenvironment.

Establishment of transplantable rat prostate carcinomas and study of its relationship to hormone dependency / 中华泌尿外科杂志

Objective To establish transplantable rat prostate carcinoma and study its relationship to hormone dependency. Methods Six transplantable rat prostate carcinoma lines were established from primary tumors developing in the dorsolateral prostate of F344 rats receiving a combined treatment with 3, 2’-dimethyl-4-aminobiphenyl (DMAB) and testosterone propionate (TP). Results Growth in the subcutis of nude mice (ICR-nu/nu) is rapid with a doubling time of approximately 10 days and transplantability is 100%. The histological appearance of the transplanted tumors is very similar to that of the primaries and their structures have not been altered by after 8 passages. Androgen receptor immunohistochemistry revealed all to be negative. Conclusions These data indicate that the model should prove useful for studies of invasion, metastasis, and hormone dependency of prostate carcinomas.

Naphthoquinones from Zicao reverses the immunosuppression of transplantable carcinomas / 中国免疫学杂志

Objective:To observe the anti-carcinoma and immuno-regulatory effects of shikonin derivatives.Methods:A water-soluble preparation of shikonin derivatives was prepared (designated as LE)and given by lavage (2.5～10 mg/kg daily for 10 days) to the mice inoculated with either HepA22 or S180 sarcoma. Their survival duration and the in situ tumor mass were observed. Thymus and spleen indexes of the mice were measured. The parameters for immuno-functions were detected by the routine activity assays, which included NK cytotoxicity, ConA-induced lymphocyte transformation and IL-2 production by the splenocytes of the mice. Thymic and splenic morphology of the experimental animals were microscopically examined with HE staining.Results:Both thymic and splenic indexes in the tumor-bearing mice diminished extremely compared to those of the normal control, and the immunological functions analyzed were also found obviously lowered when loaded with the transplantable carcinomas. Under light microscopy, it was surprisingly exhibited that thymus cortex was almost disappeared in the organs of tumor-bearing mice, and the germinal centers of their spleens were visibly shrunk. LE inhibited propagation of the inoculated tumors and at the same time, it amended the immunosuppresive impacts by tumor-bearing, including both structures of immune organs and the bioactivities of spleen cells.Conclusion:LE can reverse the immune damages mediated by carcinomas.

Discussion on the Establishment of Animal Tumor Models and Their Standards / 中国肿瘤生物治疗杂志

Animal tumor models, as replicas of human tumors, are of important significance concerning the investigation of the mechanism of tumorigenesis, tumor progression, tumor prevention and therapy, when establishing animal tumor models, we should choose suitable species of animals and corresponding carcinogens. One species of animal differs greatly from others. The same carcinogen may induce different tumor in different species of animals. Thus it is most important that animals should be selected properly to obtain animal tumor models suitable for experiment. Animal tumor models comprise spontaneons tumor models, inducing tumor models and transplantable tumor models. This paper will focus on the transplantable animal tumor models. The sources of human tumors (transplanted to immunodeficiency animals) are mainly biopsy tissues, surgically resected tumor specimens and human tumor cell lines. The basic necessity to establish transplantable tumors includes collecting fresh, non-necrotic non-capsulated tumor tissue within 1-2 hours after resection, selecting host animal (including immunodeficiency animals) should be around 4 weeks old, and the most frequent innoculating site is dorsal subcutaneous. Successful establishment of transplantable tumor models should satisfy the following standards: 15 - 20 successive generations (at least 3 - 4 animals each generation); 100 % growth after transplantation; least self-extinction (not definitely zero); stable growth rate; similar life span of host (high reproductivity); low host response (suitable for in vivo growth in host); histological similarity with primary tumor.

Mathematical models for optimizing tumour radiotherapy. I: A simple two compartment cell-kinetic model for the unperturbed growth of transplantable tumours.

Tumour growth kinetics has been analysed on the basis of interactions between two compartments comprising the proliferating and non-proliferating cells. Starting from the differential equations of growth of the cell-populations in the two compartments and assuming the process of intercompartmental cell transfers to be linear, an analytic expression on the variation of growth-fraction with the age of the tumour is obtained. The restricted conditions on the cell-cycle time and cell-loss-rate, under which these differential equations lead to a Gompertzian growth of the tumour, are critically analysed. The formalism permits the estimation of some important cell-kinetic parameters, like growth-fraction or cell-loss-factor, from a knowledge of the tumour-growth curve, cell-cycle-time and a single measurement of the cell-loss-rate of the matured tumour, provided the tumour follows a Gompertzian growth. The validity of the model has been verified with the experimental data on 4 different transplantable murine tumour systems. Usefulness of the model has been demonstrated by making some interesting predictions regarding the radiation response of the tumours from the cell-kinetic parameters.

Effects of antisense VEGF-C gene on vegetation process of implanted gastric tumor SGC-7901 in nude mice / 重庆医科大学学报

Objective:To investigate the effects of tumorigenicity and vascular generation of nude mice on antisence vascular endothelial growth factor-C(antisense VEGF-C) gene transinfection of human gastric carcinoma cell by observing the vegetation process of implanted gastric tumor.Methods:30 nude mice were divided into three groups randomly:transgenic anti-sense VEGF-C group,transgenic pure liposome group and non-transgenic group.The cell suspension of gastric carcinoma cells SGC-7901 non-transinfected or transinfected by anti-sense VEGF-C gene or pure liposome were subcutaneously injected into those mice.After injection,the size and growth velocity of those neoplasma were detected.The Microlymphatic vessel density(MLVD) and microvessel density(MVD) of tumor were detected too.Results:The neoplasma grew more slowly and was smaller in the mice in those transinfected by anti-sense VEGF-C gene than in non-transgenic ones(P0.05).Conclusions:The antisense VEGF-C gene suppress the tumorigenicity and lymphangiogenesis in the human SGC-7901 gastric carcinoma cell apparently.but it had little effects on angiogenesis of the tumor.VEGF-C might participate the lymphangiogenesis of the gastric tumor.