The anticarcinogenic effects and mechanisms of the biotechnological drugs of Panax ginseng C.A. Meyer cultivated in Russia, bioginseng, panaxel and panaxel- 5, were studied. Bioginseng was produced from a tissue culture of ginseng root cultured on standard medium, whereas panaxel and panaxel-5 were produced from ginseng tissue root cultures using standard mediums enriched with 2-carboxyethylgermanium sesquioxide and 1-hydroxygermatran-monohydrate respectively. All three ginseng drugs inhibited the development of mammary tumors induced by intramammary injections of N-methyl-N-nitrosourea (MNU) in rats, the development of the brain and spinal cord tumors induced by transplacental administration of N-ethyl-N-nitrosourea (ENU) in rats, and the development of uterine, cervical and vaginal tumors induced by intravaginal applications of 7,12-dimethylbenz(a)anthracene (DMBA) in mice. The ginseng drugs induced the cytotoxic activity of macrophages in mice, enhanced T-lymphocyte rosette formation in guinea pigs exposed to cyclophosphamide, and stimulated the production of thyroid hormones in rats. These mechanisms may contribute to the anticarcinogenic action of the ginseng drugs. The organic germanium compounds present in panaxel and panaxel-5 did not potentiate the anticarcinogenic or immuno- stimulatory effects as much as biogeinseng. Preliminary clinical trials with panaxel and bioginseng were carried out in patients with precancerous lesions of the esophagus and endometrium. Panaxel was found to have a strong therapeutic effect in patients suffering from chronic erosive esophagitis. Bioginseng induced the regression of adenomatous-cystic hyperplasia of the endometrium in some patients. Thus, we conclude that the drugs of ginseng appear to hold considerable promise for future cancer chemoprevention.
Adenocarcinoma/chemically induced/prevention & control ; Adult ; Animal ; Antineoplastic Agents, Phytogenic/*therapeutic use ; Cells, Cultured ; Cervix Neoplasms/chemically induced/prevention & control ; Clinical Trials ; Cytotoxicity Tests, Immunologic ; Disease Models, Animal ; Endometrial Neoplasms/pathology/prevention & control ; Endometrium/pathology ; Esophageal Neoplasms/pathology/prevention & control ; Esophagus/pathology ; Estradiol/blood ; Female ; Fibroadenoma/chemically induced/prevention & control ; Human ; Macrophages, Peritoneal/cytology/immunology ; Male ; Mammary Neoplasms, Experimental/chemically induced/prevention & control ; Mice ; Mice, Inbred C57BL ; Neoplasms, Experimental/chemically induced/*prevention & control ; Nervous System Neoplasms/chemically induced/prevention & control ; Panax/*metabolism ; Precancerous Conditions/pathology/*prevention & control ; Rats ; Tissue Culture ; Uterine Neoplasms/chemically induced/prevention & control ; Vaginal Neoplasms/chemically induced/prevention & control

HLA expression is altered in a large variety of human cancers. We performed immunohistochemical staining on tissues from normal, preinvasive, invasive and metastatic cervical cancer tissues using anti-HLA class I or class II antibody. In tissues from normal squamous epithelium, carcinoma in situ (CIS) and microinvasive carcinoma (MIC), the expressions of HLA-B, C heavy chains and class II heavy chain were significantly decreased as disease progressed. When the expression patterns were compared between primary and metastatic squamous cell carcinoma (SCC) lesions, statistically significant down-regulation of HLA class I and class II antigen in metastatic lesions was observed. The rates of HLA-B, C heavy chains and class II heavy chain expressions were all significantly down-regulated compared to the down-regulation rate of class I beta2-microglobulin (beta2m) in invasive squamous lesions, and the expressions of class II heavy chain in metastatic lesions was decreased further than that in primary lesions. Unlike SCC, the degree of HLA class I and class II loss was not evident as disease progressed in early stage of adenocarcinoma. In invasive adenocarcinoma lesions, only the expression of HLA-B, C heavy chains was decreased and no differences were seen in HLA-B, C heavy chain expression patterns between primary and metastatic lesions. These results suggest that alterations of HLA class I and II expressions seem to occur at a particular step in cervical cancer development and depend on tissue types: when the tumor becomes invasive and starts to metastasize.
Antibodies, Monoclonal ; Carcinoma in Situ/immunology/pathology/physiopathology ; Carcinoma, Squamous Cell/immunology/pathology/physiopathology ; Cervix Neoplasms/*immunology/pathology/physiopathology ; Disease Progression ; Female ; Genes, MHC Class I ; Genes, MHC Class II ; HLA Antigens/*analysis ; HLA-B Antigens/analysis ; Histocompatibility Antigens Class I/*analysis ; Histocompatibility Antigens Class II/*analysis ; Human ; Immunohistochemistry ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Support, Non-U.S. Gov't

Multiple in vitro immune parameters were investigated in thirty-four untreated patients with invasive carcinoma of the cervix and in twenty-five controls. The parameters measured were percentages and absolute counts of T and B cells, percentage of T cell subsets, lymphocyte response to phytohemagglutinin (PHA) and concanavalin A (Con A), natural killer (NK) activity, antibody-dependent cellular cytotoxicity (ADCC), and interleukin 2 (IL-2) activity. Patients with invasive cervical carcinoma, as compared with controls, showed a decrease in the percentage and count of T cells, a decrease in the percentage of helper-inducer (CD4+) T cells, decreased CD4+/CD8+ ratio, depressed lymphocyte response to PHA and Con A, and depressed NK and ADCC activities. There were no significant differences in these immune parameters between early and advanced tumor stages. The levels of total lymphocytes, monocytes, suppressor-effector (CD8+) T cells, and B cells were similar to those of the controls. IL-2 productivity in patients was lower than that in controls. In patients with invasive cervical carcinoma, a decrease in the percentage of CD4+ cells was associated with depressed PHA response and decreased IL-2 productivity was correlated with the reduced percentage of CD4+ cells and decreased NK activity. This study shows a significant defect in an important immune surveillance mechanism in patients with invasive carcinoma of the cervix and suggests that impaired IL-2 activity production may be related to quantitative and qualitative alterations in lymphocyte subpopulations which play a major role in immune surveillance against cervical cancer.
Cervix Neoplasms/*immunology/pathology ; Female ; Human ; Immunity, Cellular ; Interleukin-2/biosynthesis ; Lymphocyte Activation ; Lymphocytes/immunology ; Neoplasm Invasiveness ; Support, Non-U.S. Gov't