Search PubMed⌕ Search

Biomedical subjects

G H Heppner

Publications and source records attributed to G H Heppner.

At least 73 records · Page 4Linked to original sources
PubMed1983

Significance of three-dimensional growth patterns of mammary tissues in collagen gels.

Five tumor cell lines that originated from a single mouse mammary adenocarcinoma, normal mammary tissue, a preneoplastic alveolar nodule line, and a tumor developing spontaneously from that preneoplastic line were used to study the different three-dimensional growth patterns that mammary tissues produce in collagen gel. We describe five different outgrowth morphologies, one of which may represent normal stromal tissue and infiltrating cells. One type was produced both by tumors and by normal mammary gland tissue in an age-related fashion, i.e. more outgrowths of this type were produced by mammary tissue from older mice. The outgrowth patterns for the tumor cell lines were not related to morphology in monolayer culture. Certain of the tumor lines, including one variant-producing line, produced multiple outgrowth patterns. Our results indicate that this cultivation technique may be a useful method for studying the heterogeneity of mammary tumors and may facilitate the isolation of mammary tumor subpopulations.

Aging↗
PubMed1983

Tumor-associated macrophages of mouse mammary tumors. II. Differential distribution of macrophages from metastatic and nonmetastatic tumors.

Macrophage subpopulations were isolated by counterflow centrifugal elutriation from a number of closely related mammary tumors originally derived from a single spontaneous tumor in a BALB/cfC3H mouse. Each tumor line had its own distinct characteristics with regard to tumor cell distribution, macrophage size (density), macrophage content, and macrophage distribution. Although there is no correlation with the metastatic potential of the tumors for the first three characteristics listed, distinct differences are apparent between metastatic and nonmetastatic tumors in macrophage distribution into the elutriated fractions. The distribution of the tumor-associated macrophages was shifted toward the later fractions in the metastatic tumors (lines 66 and 410.4), with approximately 40% more macrophages in fractions 3 and 4 than in those fractions from the nonmetastatic tumors (lines 67 and 168). The levels of three ectoenzymes, leucine aminopeptidase (LAP), alkaline phosphodiesterase I (APD), and 5' nucleotidase (5'N) were determined for macrophages from the elutriated fractions as well as for the total tumor digest. No significant differences were observed in absolute levels of either LAP or APD between most of the fractions from the different tumor lines. Differences were seen between the fractions in levels of 5'N among the lines and in ADP levels between lines 66 and 168 from the total tumor digest. Striking differences in ectoenzyme levels were apparent when the activity was normalized to macrophage surface area: macrophages from line 66 tumors were 3- to 17-fold higher in their LAP concentrations than were macrophages from either 67 or 168 tumors. Each tumor line had a unique and reproducible pattern of macrophage-associated prostaglandin E (PGE) synthesis. The three nonmetastatic tumor lines showed peak PGE levels in fraction three with lower levels in fraction 2, whereas the highly metastatic tumor yielded more active macrophages in fraction 2 vs fraction 3. Changes in PGE levels were associated with differing ectoenzyme levels. Macrophages in fraction 3 from metastatic tumors were enriched for populations with high LAP activity and low PGE levels. Conversely, macrophages from nonmetastatic tumors exhibited lower LAP activity in fraction 3 vs 2 and increasing PGE levels. Thus, differences between metastatic and nonmetastatic mammary tumors were seen in 1) distribution of macrophages in the elutriation fractions, 2) size of infiltrating macrophages, 3) macrophage ectoenzyme concentrations, and 4) macrophage-associated PGE levels.

Animals↗
PubMed1983

Tumor-associated macrophages of mouse mammary tumors. I. Differential cytotoxicity of macrophages from metastatic and nonmetastatic tumors.

Macrophages were isolated from a series of transplanted mouse mammary tumors, originally derived from a single spontaneously arising tumor, to determine whether macrophage content or function correlated with any of a wide range of tumor properties. None of the tumor cell lines differed significantly in susceptibility to killing by MVE-2-activated peritoneal macrophages (cytotoxicity ranged from 40 to 63%). No significant differences were observed in macrophage content among the five tumor lines, nor was there any correlation between macrophage content and tumor weight, time since transplantation, or ability to metastasize. A significant association was observed, however, between a tumor's ability to metastasize to lung spontaneously and the tumoricidal activity of that tumor's infiltrating macrophages. Significant tumoricidal activity was seen when macrophages isolated from every metastatic tumor studied were used, whereas macrophage-mediated tumoricidal activity was observed in only 35% (6 of 17) of nonmetastatic tumors. Macrophage cytotoxicity was associated with spontaneous metastasis and not with lung colony formation per se.

Animals↗
PubMed1983

Characterization of metastatic heterogeneity among subpopulations of a single mouse mammary tumor: heterogeneity in phenotypic stability.

The frequency of metastasis formed by tumor cells injected into lateral tail veins, mammary fatpads, or the subcutis are described for eight subpopulations of a single, spontaneously arising BALB/cfC3H mouse mammary tumor. These subpopulations display a spectrum of metastatic behavior from all three injection sites. The proportion of animals with metastases does not depend upon the site of primary tumor growth (i.e., mammary fatpad versus subcutis). One subpopulation can grow as lung nodules after intravenous injection but is only poorly metastatic from subcutaneous or fatpad implants. Heterogeneity among the subpopulations in the stability of the metastatic phenotype is evident. Although most of the subpopulations and their clones remained stable for periods of 2-5 years, one subpopulation rapidly lost metastatic ability within 3 months and another gradually became more metastatic over 2 years.

Animals↗
PubMed1982

Prognostic significance of serum IgE levels in primary breast cancer.

Serum IgE was measured in presurgical sera from 166 nonallergic women admitted to a comprehensive, multidisciplinary study of primary, operable breast cancer. During the follow-up period, which averaged 48 months, there were 71 recurrences. Patients were divided into two groups: those with IgE levels greater than the geometric mean value of 24 I.U. and those with levels less than the mean. The rate of tumor recurrence was significantly greater for the IgE greater than 24 group (p less than 0.03). IgE remained a significant prognostic indicator when evaluated by Cox regression analysis in conjunction with other known prognostic factors including: number of positive lymph nodes, clinical stage, menopausal status, estrogen receptor status, mitotic grade, tumor diameter, breast feeding history, and age of patient (p less than 0.015). IgE was not correlated with any of these known prognostic factors in individual analyses. We conclude that serum IgE level is a significant, independent prognostic indicator in primary breast cancer.

Actuarial Analysis↗
PubMed1982

Heterogeneity of expression and induction of mouse mammary tumor virus antigens in mouse mammary tumors.

Seven spontaneous BALB/cfC3H mouse mammary tumors were heterogeneous in expression of murine mammary tumor virus-associated cell surface antigens. To determine the basis of this heterogeneity, cells from spontaneous tumors and from five subpopulations isolated from a single spontaneous tumor were examined for expression of viral antigens under both conventional conditions and conditions known to induce synthesis of murine mammary tumor virus antigens (5-iodo-2'-deoxyuridine and dexamethasone). Induction with 5-iodo-2'-deoxyuridine resulted in further manifestation of the antigenic heterogeneity of spontaneous tumors. The five subpopulations from a single tumor differed in the amount of viral antigens present in untreated and in induced cultures. Coculturing showed that viral antigen expression was independent in each subpopulation within a heterogeneous mixture and was not influenced by the presence of other subpopulations with different potentials for viral antigen synthesis. The expression of murine mammary tumor virus structural antigens, a protein with a molecular weight of 28,000 and a glycoprotein with a molecular weight of 52,000, differed within the heterogeneous subpopulations, and was noncoordinate. The data suggest that the antigenic heterogeneity in spontaneous tumors reflects the existence of cells within them that differ in both expression of viral antigens and in their response to inducers of viral antigen synthesis.

Animals↗
PubMed1982

Tumoricidal macrophages isolated from liver granulomas of Schistosoma mansoni-infected mice.

In murine schistosomiasis, inflammatory macrophages (M phi) are a major cell type of the granulomata that encase eggs of the tropical helminth Schistosoma mansoni as they are deposited in the liver by adult worm pairs. The granulomatous response is vigorous during acute infection (8 wk) and spontaneously undergoes immunomodulation during chronic infection (20 wk). Inflammatory M phi isolated from liver granulomas of 8 and 20-wk schistosome-infected CBA/J mice were assessed for their cytolytic potential. Macrophages from vigorous liver granulomas displayed significant cytolytic activity against 3 mammary tumor lines of strain BALB/cfC3H origin, while leaving untransformed embryo fibroblasts relatively unharmed. The cytolytic activity of inflammatory M phi from immunomodulated lesions was markedly less than that of cells from vigorous lesions at equivalent effector to target (E:T) cell ratios. Granuloma cell preparations depleted of the inflammatory macrophage component were marginally cytolytic at the higher E:T cell ratio; supernatant fluids from cultured inflammatory M phi-enriched cell preparations possessed no tumoricidal activity. The cytolytic potential of the vigorous granuloma M phi was lost subsequent to prolonged in vitro culture. We conclude that inflammatory M phi in S. mansoni egg-elicited granulomas are sufficiently activated to lyse allogeneic tumor cells. The degree of activation appears to correlate directly with the intensity of the granulomatous response.

Acute Disease↗
PubMed1981

Alterations of immune reactivity by haloperidol and delta-9-tetrahydrocannabinol.

Studies were performed to determine whether delta 9-tetrahydrocannabinol (THC) or haloperidol suppress or ablate humoral or cellular immune responses against sheep erythrocytes. Both agents produced dose-dependent reductions in hemolytic plaque-forming cell (PFC) numbers at the time or peak reactivity (Day 4) in vehicle-treated, control mice. However, both delta 9-THC and haloperidol only delayed the time of peak PFC formation by 24-48 hours. These changes in kinetics of humoral immune responsiveness took place at doses of delta 9-THC and haloperidol that produced signs of gross behavioral toxicity. Neither Delta-9-THC, cannabinol (CBN) or cannabidiol (CBD) had an effect on the titer of serum hemagglutinating antibody measured seven days after immunization. Further, haloperidol did not alter the delayed-type hypersensitivity response to dinitroflorobenzene (DNFB).

Animals↗
PubMed1981

Epithelial characteristics of five subpopulations of a heterogeneous strain BALB/cfC3H mouse mammary tumor.

We have described previously the isolation and characterization of five distinct subpopulations of tumor cells from a single spontaneous strain BALB/cfC3H mouse mammary tumor (Cancer Res., 38: 3174--3181, 3758--3763, 1978). Subpopulations 68H and 4.10 are polygonal and grow in epithelioid patterns in vitro, whereas subpopulations 66, 67, and 168 are fusiform and grow in lattice or fibroblast-like patterns. Line 4.10 produces tumors with distinctly glandular architecture, whereas the other four subpopulations produce poorly differentiated tumors with mixed epithelial-sarcomatous histological patterns. All five lines were evaluated for epithelial characteristics. Dome formation, characteristic of transporting epithelial cells, could be induced by dexamethasone or dimethyl sulfoxide only in line 4.10 cells. Antibodies to cell type-specific mammary epithelial antigens reacted with each of the subpopulations. All five subpopulations had ultrastructural features of epithelial cells, including desmosomes (all five lines), junctional complexes (68H, 4.10, early-passage 66 and 67 only; poorly defined in 168), and growth in cords demonstrating polarity (68H cells). Less definitive myoepithelial characteristics were also seen in four of the lines, including an incomplete reaction for Na+-K+-ATPase (4.10 cells), hemidesmosome-like junctions (168 and early-passage 66 cells), and pinocytotic vesicles at lower than normal frequency (66, 67, and 168 cells). Thus, none of the lines were distinctly myoepithelial. We conclude that the five subpopulations are epithelial cells that express a spectrum of epithelial characteristics.

Animals↗
PubMed1981

Preferential growth of mammary tumors in intact mammary fatpads.

Four transplantable tumors, three (66, 410, and 168cl) isolated from a spontaneously occurring strain BALB/cfC3H mammary tumor and one (D2) arising from a BALB/c hyperplastic alveolar nodule were found to grow better in mammary fatpads than at s.c. sites. Furthermore, tumor growth was better (p less than 0.05) in intact mammary glands than in cleared mammary fatpads for the D2, 410, and 66 tumors (168cl was not tested). The role of immunity in these differences was investigated using the highly immunogenic 410 tumors. Tumor 410 induced equally effective immunity to subsequent challenge whether it was implanted s.c. or in intact fatpads. Furthermore, in immunized animals, Tumor 410 was rejected equally well when the challenge site was intact fatpad as when s.c. Similarly, Tumor 410 induced immunity after implantation into cleared fatpads and, in immunized animals, was rejected when the challenge site was the cleared fatpad. We thus found no evidence that the mammary fatpad is immunologically privileged, as compared to the s.c. site, with respect to tumor transplantation antigens.

Adipose Tissue↗
PubMed1980

Activity of lymphoid cells separated from mammary tumors in blastogenesis and Winn assays.

Lymphoid cells isolated from mouse mammary tumors by isokinetic gradients were not stimulated in vitro by either phytohemagglutinin or a soluble, tumor-associated antigen extract even though splenocytes from the tumor-bearing mice were responsive to both. In in vivo Winn assays, lymphoid cells isolated from tumors markedly stimulated tumor growth rate. The effect on growth rate was abrogated by exposure of the isolated lymphoid cells to antilymphocyte serum and complement.

Animals↗
PubMed1980

Growth interaction in vivo between tumor subpopulations derived from a single mouse mammary tumor.

Our laboratory has previously isolated several tumor cell populations from a single, spontaneously arising mammary tumor of a BALB/cfC3H mouse and established them in tissue culture as independent sublines. These subpopulations differ according to many criteria including growth parameters and expression of tumor-associated antigens. We have tested the interaction in vivo of several of these subpopulations by injecting cell suspensions of the same or different sublines into opposite flanks of BALB/cfC3H or BALB/c mice. The growth characteristics of certain subpopulations were altered by the presence of a different subpopulation on the opposite side. In order to understand the mechanism of interaction, we chose two subpopulations (410 and 168) for further study. In BALB/cfC3H mice, the presence of line 410 tumors on one flank inhibited both 410 and 168 tumors on the other flank. Line 168 tumors did not inhibit either 410 or 168 tumors. The inhibitory effect of line 410 appeared to be immunological, since (a) it was increased by injecting line 410 several weeks before line 168, (b) it was abrogated in mice subjected to 400-rad X-irradiation 2 days prior to tumor cell injection, (c) mice could be made resistant to both line 410 and line 168 tumors by implantation followed by surgical removal of line 410 but not of line 168, and (d) resistance could be adaptively transferred with lymph node cells from line 410-sensitized mice in Winn assays. Thus, immunity to tumor-associated antigens may be one way by which cells of a heterogeneous tumor can interact.

Animals↗
PubMed1979

Bioactivities and the effect of dilution on various milk-borne murine mammary tumor viruses.

Infectivity titrations of milk-borne murine mammary tumor virus (MuMTV) from different sources or prepared in different ways or stored for periods of time have been compared. Titration curves were in general reproducible for MuMTVs of different sources or handled in different ways and for different methods of measurement, such as hyperplastic alveolar nodule (HAN) development, tumor development, or MuMTV antigen secretion in third-lactation milk, The curves had characteristic shapes with a low incidence of infection at low dilutions of milk, high incidences at intermediate dilutions, and low incidences at high dilutions. Infectivity incidences were unaffected by dilution over the range 10(-2) to 10(-5). The curves did not change appreciably with time of storage of milk at liquid N2 temperature for periods up to 3 years. Rate zonal fractionation of RIII milk gave zones with bioactivities which were not proportional to B-particle content. Upon dilution, the bioactivity of Zone 3, rich in B particles, and Zone 5, poor in B particles, increased, while the bioactivity of all the other zones usually decreased with dilution. The low incidence of infection at low dilutions may have been due, in part, to an immune response of the inoculated mouse. Administration of inactivated virions 4 h prior to or with MuMTV inoculations gave some evidence in support of this hypothesis but the complexity of the bioassay system for MuMTV lends uncertainty to interpretation of results.

Age Factors↗