Multifactorial anticancer effects of digalloyl-resveratrol encompass apoptosis, cell-cycle arrest, and inhibition of lymphendothelial gap formation in vitro.

BACKGROUND: Digalloyl-resveratrol (di-GA) is a synthetic compound aimed to combine the biological effects of the plant polyhydroxy phenols gallic acid and resveratrol, which are both radical scavengers and cyclooxygenase inhibitors exhibiting anticancer activity. Their broad spectrum of activities may probably be due to adjacent free hydroxyl groups. METHODS: Protein activation and expression were analysed by western blotting, deoxyribonucleoside triphosphate levels by HPLC, ribonucleotide reductase activity by (14)C-cytidine incorporation into nascent DNA and cell-cycle distribution by FACS. Apoptosis was measured by Hoechst 33258/propidium iodide double staining of nuclear chromatin and the formation of gaps into the lymphendothelial barrier in a three-dimensional co-culture model consisting of MCF-7 tumour cell spheroids and human lymphendothelial monolayers. RESULTS: In HL-60 leukaemia cells, di-GA activated caspase 3 and dose-dependently induced apoptosis. It further inhibited cell-cycle progression in the G1 phase by four different mechanisms: rapid downregulation of cyclin D1, induction of Chk2 with simultaneous downregulation of Cdc25A, induction of the Cdk-inhibitor p21(Cip/Waf) and inhibition of ribonucleotide reductase activity resulting in reduced dCTP and dTTP levels. Furthermore, di-GA inhibited the generation of lymphendothelial gaps by cancer cell spheroid-secreted lipoxygenase metabolites. Lymphendothelial gaps, adjacent to tumour bulks, can be considered as gates facilitating metastatic spread. CONCLUSION: These data show that di-GA exhibits three distinct anticancer activities: induction of apoptosis, cell-cycle arrest and disruption of cancer cell-induced lymphendothelial disintegration.

Antibodies to intermediate filament proteins as molecular markers in clinical tumor pathology. Differentiation of carcinomas by their reaction with different cytokeratin antibodies.

Antibodies to human and bovine epidermal prekeratin and antibodies to mouse liver cytokeratin component D (Mr 49 000) have been applied in indirect immunofluorescence microscopy on sections of human tumors of mammary gland and liver. In non-neoplastic mammary gland all epithelial cells were stained with these antibodies. In pre-invasive and invasive ductal and lobular carcinomas a cell population was observed which was not significantly stained with antibodies to epidermal prekeratin but did strongly react with antibodies to liver cytokeratin D. In the liver, the antibodies to epidermal prekeratin as well as those directed against liver cytokeratin D strongly decorated bile duct epithelia. In contrast, significant staining of the hepatocytes was only achieved with antibodies to liver cytokeratin D. This different staining reaction was maintained in liver tumors of hepatocellular and cholangiocellular origin. Antibodies to vimentin stained mesenchymal cells and tumors of mesenchymal derivation but reacted not significantly with any of the epithelial and carcinoma cells examined. The difference is of practical importance for the discrimination between anaplastic carcinomas and sarcomas of unknown origin. Cytokeratin could also be detected by antibody staining using the peroxidase-antiperoxidase (PAP) technique in formaldehyde-fixed and paraffin-embedded material of skin, gastrointestinal, respiratory, urinary and genital tract as well as various glands, liver and kidney. Examples of positive reactions were shown in a squamous cell carcinoma, a basalioma and a pleomorphic adenoma of the parotis. It is concluded that the immunohistochemical analysis of intermediate filament proteins has diagnostic potential in clinical pathology and may help to elucidate histogenesis and differentiation of tumors and possibly also prognosis of tumor growth. It is further suggested to use antibodies recognizing different subsets of proteins of the cytokeratin family in order to distinguish between different types of carcinomas.

[The lung phospholipid content in newborn infants with idiopathic respiratory distress syndrome in relation to lung histology and survival time (author's transl)]. / Phospholipidgehalt von Neugeborenenlungen mit idiopathischem Atemnotsyndrom in Bezichung zu Lungenhistologie und Uberlebenszeit

In an autopsy series on 25 newborn infants who died in the perinatal period (19 with and 6 without respiratory distress syndrome [RDS]) the total phospho-lipid, lecithin, and sphingomyelin content was determined in lung homogenates as parameters of the surfactant content. Histologically, the newborn infants with RDS were subdivided into those with and those without hyaline membranes. Newborn infants with RDS hat a lower lung phospho-lipid content than mature newborn infants without RDS but there was no difference in phospholipid content in relation to the presence or absence of hyaline membranes. The lecithin content of the lungs in those infants with RDS who had survived for more than 24 hours was higher in the absence of hyaline membranes than in their presence.

Blood group isoantigens in human benign and malignant vascular tumors.

Paraffin material of 31 benign and malignant vascular tumors was investigated with respect to their blood group isoantigen (BG) content by the mixed cell agglutination reaction (MCAR). In capillary hemangioma, BG was found in endothelial cells as well as in solid buds. Benign hemangioendothelioma found in endothelial cells as well as in solid buds. Benign hemangioendothelioma found in children differed from that found in adults in that in juvenile cases only endothelial cells expressed BG whereas in adult cases BG isoantigenity was present in endothelial cells as well as in intercapillary cellular elements. In pericytomas only endothelial cells were BG positive, whereas the tumor cells lacked BG. Similar results were obtained with glomus tumors. All but one hemangiosarcoma were BG negative. In one case, however, which probably resembled a "true" malignant hemangioendothelioma (Stout and Lattes, 1967) the tumor cells contained BG in conspicuous amounts.