Search PubMed⌕ Search

Biomedical subjects

G Poste

Publications and source records attributed to G Poste.

At least 91 records · Page 5Linked to original sources
PubMed1983

New histochemical method for measuring intratumoral macrophages and macrophage recruitment into experimental metastases.

A new double-label histochemical method is described which permits accurate quantitation of macrophage recruitment into neoplastic lesions in situ. Intratumoral macrophages are identified by their capacity to ingest colloidal iron particles from the interstitial fluid. Since colloidal iron is retained in a stable form within these cells for a considerable time, new macrophages that emigrate into the tissue after injection of the colloidal iron are identified by their ability to ingest a second colloid (lanthanum) which can be reliably distinguished from the initial iron label. Preexisting (colloidal iron label) and newly recruited macrophages (lanthanum label) are identified in serial sections by histochemical methods using hydrogen peroxide oxidation to detect iron (blue reaction product) and cleavage of phosphate esters to demonstrate lanthanum (magenta reaction product). The macrophage content and macrophage recruitment were found to vary substantially in individual metastases within the same host.

Animals↗
PubMed1983

Heterogeneity of protein phosphorylation in metastatic variants of B16 melanoma.

The polypeptide and phosphoprotein profiles of a spectrum of B16 melanoma clones of defined metastatic potential have been analyzed by two-dimensional gel electrophoresis. To accommodate the documented instability of metastatic properties in B16 clones, in vitro biochemical assays were always accompanied by in vivo assays of the metastatic behavior using replicate samples of the same clonal populations harvested on the same day. To exclude differences in polypeptide and phosphoprotein profiles resulting from inherent variation in electrophoretic measurements made at different times, polypeptides and phosphoproteins were analyzed in unison for every clone, and a series of clones was examined in parallel in each experiment. Also, samples were electrophoresed simultaneously using a custom-designed apparatus capable of accommodating 20 two-dimensional samples. When tested under these stringent conditions, the polypeptide profiles of B16 clones were indistinguishable. Significant qualitative and quantitative differences in phosphoprotein expression were detected in each clone, but no correlations were found between alterations in protein phosphorylation and metastatic potential. Over 200 discrete phosphoproteins were detected in each clone, but interclonal variation was confined to approximately 10 to 15 phosphoproteins. Expression of three phosphoproteins with the following molecular weights (in kilodaltons) and isoelectric points was strictly qualitative: pp96 (7.9); pp30 (8.2); and pp30 (8.8). In any given clone, they were present individually at equal intensities or were completely absent, but their expression was not coordinate. The data indicate that expression of polypeptide gene products is similar in B16 melanoma clones with widely differing metastatic abilities, but considerable clonal variability exists in posttranslational covalent modification of cell proteins. The possible contribution of protein phosphorylation and other posttranslational pathways in generating the extensive phenotypic heterogeneity observed in tumor cell subpopulations within the same tumor and in the rapid generation of new clonal variants with altered metastatic properties are discussed.

Animals↗
PubMed1982

A high performance liquid chromatography assay for the rapid analysis of the subunit content of concanavalin A.

A high performance liquid chromatography system is described which provides a rapid and convenient assay for the relative amounts of intact (26000 dalton) and fragmented (14000 and 12000 dalton) subunits present in preparations of concanavalin A. Analyses were performed on an HPLC size exclusion column using either 8M urea or 6M guanidine hydrochloride as denaturing eluents. The efficiency and resolving power of this technique were confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. This HPLC assay facilitated the monitoring of the purification of concanavalin A to prepare a homogeneous preparation necessary for its biological evaluation.

Chromatography, High Pressure Liquid↗
PubMed1982

Macrophages and cancer metastasis.

Activated macrophages appear to be able to recognize and destroy neoplastic cells without regard to their phenotypic diversity, and macrophage-mediated cytotoxicity appears invulnerable to the problem of cellular resistance to killing which is routinely encountered in efforts to destroy tumor cells by cytotoxic drugs. However, macrophage-mediated destruction of large tumor burdens may not be feasible. In many tumors the number of macrophages is too low to destroy all tumor cells, even if the macrophages are activated to the optimal tumoricidal state. For this reason, systemically administered immunomodulators encapsulated in liposomes should be used to activate macrophages to destroy those few tumor cells resistant to other means of therapy.

Animals↗
PubMed1982

Experimental systems for analysis of the malignant phenotype.

Identification of the cellular and subcellular alterations responsible for the metastatic behavior of malignant tumor cells and development of reliable screening programs for detecting new therapeutic agents for improved treatment of metastatic disease both depend crucially on the availability of experimental systems that can serve as relevant models of human cancer. Recent advances in our understanding of the pathogenesis of cancer metastasis have raised serious doubts about the usefulness of many of the experimental approaches that have long been used in the study of metastasis. Recent findings showing that metastases are caused by specific subpopulations of metastatic tumor cells, and that not all cells in a malignant primary tumor possess metastatic properties, are of profound importance for experimental efforts to understand the mechanism of metastatic phenotype among cells from the same tumor means that the traditional, and widely used, approach of analyzing primary tumors and cultured cell lines containing multiple, phenotypically heterogeneous, subpopulations of cells may provide little or no insight into the properties of the metastatic subpopulations, particularly if they represent only a minor fraction of the entire population. Similarly, the practice of screening potential therapeutic modalities for their ability to reduce the mass and/or growth rate of a primary tumor may be inadequate in predicting the responsiveness of metastatic lesions. Solution of these problems requires that new methods must be devised to isolate and characterize the specific subpopulations of tumor cells endowed with metastatic potential. In addition, knowledge of how the extraordinary phenotypic diversity found in tumor cell subpopulations from the same tumor is generated and how subpopulation diversity is regulated during progressive growth of both the primary tumor and its metastases are of fundamental importance if we are to design meaningful experimental systems for studying the metastatic process. This article reviews our current understanding of these complex issues and their implications for the experimental analysis of the malignant phenotype. The merits and shortcomings of different experimental systems are discussed in detail together with the identification of areas in which new experimental strategies and models are now needed.'

Animals↗
PubMed1982

Evolution of tumor cell heterogeneity during progressive growth of individual lung metastases.

The metastatic properties of tumor cell clones isolated from individual lesions of B16 melanoma metastatic to lung have been examined at different stages in the evolution of metastasis. Clonal analysis of metastatic lesions produced by B16 melanoma populations containing clones with identifiable, stable drug-resistance markers revealed that the majority (greater than 80%) of experimental metastases produced by intravenous injection of tumor cells are of unicellular origin. During the early stages of their growth (less than 25 days after initial tumor cell arrest), the majority of metastatic lesions contain cells with indistinguishable metastatic phenotypes (intralesional clonal homogeneity) although different clonally homogeneous lesions from the same host contain tumor cells with different metastatic phenotypes (interlesional clonal heterogeneity). Progressive growth of metastatic lesions is accompanied by emergence, within originally clonally homogeneous lesions, of variant tumor cells with altered metastatic properties (intralesional clonal heterogeneity). By 40-45 days after initial arrest of injected tumor cells in the lung, 90% of the metastatic lesions are populated by cells with heterogeneous metastatic phenotypes.

Animals↗
PubMed1982

Inhibition of antibody synthesis by histamine in concanavalin A-treated mice: the possible role of glucocorticosteroids.

Administration of histamine (50 mg/kg) to BALB/C mice injected with concanavalin A (Con A) (100 micrograms, i.v.) 24 hr previously, results in a marked decrease in antibody synthesis to sheep red blood cells (SRBC) injected 2 hr later. This phenomenon occurs with nonimmunosuppressive doses of Con A and is strain-specific. It does not take place in the response to the T-independent antigen polyvinylpyrrolidone (PVP) or if histamine is administered after the antigen. Adoptive transfer of normal syngeneic cells at the same time as antigen does not reverse this effect. Excess suppressor cell generation was excluded by co-cultivation of treated spleen cells with normal cells in vitro and by determining their antibody response to SRBC 5 days later. 2-Methylhistamine, a histamine type 1 (H1) receptor agonist, mimicks the effect of histamine whereas dimaprit, a histamine type 2 (H2) receptor agonist, does not. Because histamine interaction with H1 receptors causes the release of adrenocorticotropic hormone (ACTH), we examined the effects of ACTH and corticosterone in this system and found that both could mimick the effect of histamine. These results suggest that the interaction of histamine with H1 receptors causes the release of glucocorticosteroids that may interfere with either Con A-activated T helper cell function or macrophage processing of T-dependent antigen.

Adrenocorticotropic Hormone↗
PubMed1982

On the genesis and regulation of cellular heterogeneity in malignant tumors.

The growing body of evidence showing that malignant tumors are heterogeneous and contain diverse subpopulations of cells with different metastatic abilities is reviewed. The factors that may influence the evolution of cellular diversity at different stages in the progression of malignant neoplasms are discussed. Particular emphasis is given to the possibility that interactions occurring between the constituent subpopulations of a malignant tumor may influence the rate at which new variant subpopulations emerge. Metastatic heterogeneity poses significant problems for experimental efforts to identify the cellular features that correlate with metastatic behavior and for the therapy of metastatic disease.

Animals↗
PubMed1982

Involvement of macrophages in the eradication of established metastases following intravenous injection of liposomes containing macrophage activators.

Liposomes containing encapsulated lymphokines or muramyl dipeptide (MDP), when injected i.v. into C57BL/6 mice, produced significant destruction of established lung and lymph node metastases from a s.c. highly metastatic B16-BL6 melanoma. We present evidence that eradication of the metastases is mediated by the activation of host macrophages to the tumoricidal state. Results from three separate types of experiments support this conclusion. (a) When macrophage-activating agents such as lymphokines of MDP were delivered in liposomes that were not efficiently retained in the lung, little or no activation of lung macrophages was observed, and growth of metastases was unaltered. (b) Eradication of metastases was not observed when tumor-bearing animals were treated with agents that impaired macrophage function (e.g., silica, carrageenan, hyperchlorinated drinking water) prior to systemic therapy with liposome-encapsulated lymphokines or liposome-encapsulated MDP. (c) Macrophages activated in vitro by liposome-encapsulated MDP and then injected i.v. into mice bearing experimental lung metastases also significantly inhibited lung metastases. These results suggest that the augmented host response against pulmonary and lymph node metastases generated by the systemic administration of liposome-encapsulated lymphokines or MDP is mediated via activated cytotoxic macrophages.

Acetylmuramyl-Alanyl-Isoglutamine↗