We have examined the biological activity of keto-C-glycosides (KCGs), a new family of drugs displaying anti-proliferative and cytotoxic properties on tumor cells. KCG1, the most powerful drug tested on epithelial derived neoplastic cells, was 25–125 times more cytostatic on epithelial cells than on lymphoma. By contrast, KCG10 proved to be more cytostatic on lymphoma than on epithelial cells. Correlations were found between the cytostaticity of KCGs and their lipophflicity, and are discussed within the framework of the structure-activity and the structure-selectivity relationships.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSystematic Fractionation of Swine Pancreatic Hydrolases. I. Fractionation of Enzymes Soluble in Ammonium Sulfate Solution at 0.40 Saturation*José Uriel and Stratis AvrameasCite this: Biochemistry 1965, 4, 9, 1740–1749Publication Date (Print):September 1, 1965Publication History Published online1 May 2002Published inissue 1 September 1965https://doi.org/10.1021/bi00885a010RIGHTS & PERMISSIONSArticle Views33Altmetric-Citations21LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (2 MB) Get e-Alerts Get e-Alerts
Abstract The binding to resting and activated T lymphocytes of two radiolabelled fatty acids (oleic and arachidonic) was studied in the presence or in the absence of alphafetoprotein (AFP) as carrier protein. Fatty acid binding by resting and activated T lymphocytes was determined at 4°C as a function of the concentration of fatty acid and AFP. Under the conditions employed, the following observations were made: (1) in the presence of AFP, fatty acids (oleic and arachidonic acid) are bound to cells by a two‐component pathway; one is a saturable process, evidenced when the fatty acid to AFP (FA/AFP) molar ratio was fixed at 1 and the concentration of the fatty acid and the protein varied from 0.1 to 3.2 μM, and the second is a nonsaturable function of FA/AFP molar ratio and was linearly related to the unbound fatty acid concentration in the medium over the entire range studied; (2) in the absence of AFP, the nonsaturable process appears to be the only component of fatty acid binding; (3) at all tested concentrations of free (unbound) fatty acid in the medium, net fatty acid binding by either resting or activated T cells was considerably greater in the presence than in the absence of AFP; (4) in the presence of AFP, fatty acid binding was much higher in activated T cells than in resting T cells, whereas in the absence of AFP, nonsignificant differences were observed between activated and resting T cells; and (5) the time course of fatty acid and AFP binding at 4°C revealed that, at equilibrium, the number of fatty acid molecules bound to the cell was much greater than that of AFP suggesting an accelerated dissociation of the fatty acid upon interaction of the AFP‐fatty acid complex with putative cell receptors. It is concluded to the existence of an AFP/AFP‐receptor pathway that facilitates the binding of fatty acids to T lymphocytes, particularly upon their blast transformation. This pathway may fulfill the increased requirement for fatty acids characteristic of proliferating cells and may serve to regulate the endocytosis of fatty acids with modulatory effects on lymphocyte function and to protect cells from their cytotoxic potential when internalized in excess.
Sera from 813 patients were examined independently by 3 test centers for the presence of alpha-fetoprotein (AFP). The sera were collected at 5 different African centers and 2 non-African centers. There was disagreement in the serologic results among the 3 test laboratories in only 27, or 3.3%, of cases. A clinical and/or histologic diagnosis of primary liver cancer had been made in 231 of the cases in which there was serologic agreement, and 151, or 65.4%, of these were positive for AFP. If only those cases with histologic confirmation of liver cell cancer were included, the percentage of cases with AFP increases to 75%. Analysis of the results from each collection center has been made, and the basis for "false-positives" and serologic disagreements is discussed. The test has proven to be highly specific for primary liver cell cancer and may be used with advantage in differential diagnosis of this disease and in epidemiologic studies.
Α-Fetoprotein (AFP) and AFP-gene transcripts were demonstrated in vitro in Schwann (S) cell and fibroblast (F) cell cultures of neonatal mouse origin. All S and F cells of primary cultures and of established cell lines expressed the AFP gene. AFP mRNA was detected by an in situ hybridization technique using a 35S-AFP-cDNA probe. AFP was localized by immunocytoperoxidase labelling using purified anti-AFP antibodies. The amounts of stained endogenous AFP, estimated semiquantitatively, were about 3-fold higher in S cells than in F cells. After incubating the cultures with exogenous mouse AFP, both S and F cells showed significant ability to take up the protein; the amount of internalized protein was found to be higher in F cells than in S cells. Moreover, the uptake of AFP fluorescein conjugates (FITC-AFP), estimated quantitatively by fluorometry, also gave higher values for F cells. The cytoplasm of F cells exhibited a characteristic fluorescence pattern, strongly illuminated and dispersed grains; the cytoplasm of S cells was regularly labelled. If exogenous FITC-AFP uptake could be used to distinguish labelled F cells from S cells (with application for identification and selection of F cells), the immunocytochemically stained endogenous AFP could allow S cells to be distinguished from F cells (using the dilutions of antibodies still staining the S cells but which lead to the absence of F-cell labelling). The two procedures, which can be used independently or together, may constitute differential markers for S cell and F cultures in, i.e., nerve regeneration of neurofibroma studies using the model of mixed S and F culture also containing other types of cells.