Search PubMed⌕ Search

Biomedical subjects

B E Miller

Publications and source records attributed to B E Miller.

At least 109 records · Page 6Linked to original sources
PubMed1985

Factors affecting growth and drug sensitivity of mouse mammary tumor lines in collagen gel cultures.

A series of mouse mammary tumor subpopulation lines were compared for growth properties and sensitivity to chemotherapeutic drugs when grown as boluses in a collagen gel matrix versus in monolayer culture. Although the cell lines exhibited characteristic rates of bolus expansion in collagen, this growth was not paralleled by an exponential increase in cell number with time. Cell boluses contained a higher proportion of cells in G0-G1 phases of the cell cycle than did the same cell lines in monolayer cultures. Histological examination revealed areas of necrosis in boluses. Thus cells growing in collagen cultures resembled cells growing as solid tumors and cells from other three-dimensional culture systems. The growth of cell boluses in collagen gel cultures was reduced nonexponentially by melphalan, methotrexate, and 5-fluorouracil in contrast to the exponential decrease in growth measured in cloning assays. The lowest concentration to which cells first responded to drug was in general similar for collagen gel assays and for cloning assays. The rank order of sensitivity of different cell lines in the two assays was identical for methotrexate (four cell lines), similar for melphalan (four of five lines), but quite different for 5-fluorouracil. In contrast to cloning assays cell boluses continued to grow, albeit at a reduced rate, in the presence of high drug concentrations. This was not due to either diminished drug availability in collagen gel or drug penetration into the bolus.

Animals↗
PubMed1984

Assessing tumor drug sensitivity by a new in vitro assay which preserves tumor heterogeneity and subpopulation interactions.

We have designed an in vitro assay to assess the influence of tumor subpopulation interactions on drug response. The assay is based upon inhibition of growth of 1 mm3-pieces of tumor embedded in a collagen gel matrix. Tumor growth is quantitated by planimetry of each colony's image, formed with a split image tracing device attached to an inverted microscope. That expansion of the colonies in collagen gel represents growth through cell replication was demonstrated by releasing and counting cell nuclei. Outgrowths from pieces of tumors produced by a series of mouse mammary tumor subpopulation lines expanded in collagen gel at a rate characteristic of each cell line: the growth rate of tumor pieces was similar to that of the corresponding tumor line embedded as a cell bolus of cultured cells, indicating that growth of pieces of tumor is due to the tumor cells rather than to stromal components. When two cell lines were grown together in collagen cultures, interactions affecting growth rate were observed. Both tumor pieces and cell boluses from cultured cells of the relatively homogeneous cell lines displayed similar, characteristic sensitivities to adriamycin (ADR) in the collagen gel assay. Advantages of the collagen assay over cloning assays are (1) preservation of potential cellular interactions which may be important in assessing tumor drug sensitivity; (2) maximization of growth of all cell populations within the tumor, as compared to growth in agar; and (3) reflection of the zonal distribution of different subpopulations within tumors; and (4) simulation of the three-dimensional growth architecture found in vivo.

Animals↗
PubMed1984

Carcinoma of the cervical stump.

This review is a retrospective analysis of 263 patients with carcinoma of the cervical stump treated at The University of Texas M. D. Anderson Hospital and Tumor Institute between 1963 and 1975. Symptomatology, stage distribution, and histology of carcinoma of the cervical stump showed no significant differences from cervical carcinoma of the intact uterus. Depending on the tumor stage, tumor volume, and distorted anatomy, treatment consisted of various combinations of intracavitary radium and transvaginal and external radiation. The 5-year survival was 100% in stage 0, 91% in stage I, 77% in stage II, 46% in stage III, and 37% in stage IV. The results achieved are similar to those in cervical cancer of the intact uterus. The complication rate was 30% and there were 9 (3.7%) deaths related to radiation complications.

Adenocarcinoma↗
PubMed1983

Morphine tolerance is associated with elevated levels of an uncharacterized endorphin (peak B) in mouse brain with no change in 3H-dihydromorphine binding.

A partially characterized mouse brain endorphin was shown to be elevated (p 0.01 U-Test) in ICR strain mice that had been made tolerant but not dependent upon morphine (5 mg/kg sc., given for 32 days). The animals were tolerant to the antinociceptive effect of morphine as judged by the tail immersion assay (48 degrees C) but showed no detectable dependence or withdrawal syndrome effects following the administration of naloxone (writhing, jumping, diarrhea or hypermotility) on day 33. No significant changes were seen in any other mouse brain endorphins (p 0.05 U-Test). Also there was no apparent change in the number of binding properties of 3H-dihydromorphine (3H-DHM) receptors (mu-receptors) in chronic morphine (CM) treated, as compared with chronic saline (CS) treated animals.

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↗
PubMed1983

Quantitative selectivity of contact-mediated intercellular communication in a metastatic mouse mammary tumor line.

We have examined contact-mediated intercellular communication by measuring the transfer of thioguanine sensitivity to a hypoxanthine phosphoribosyltransferase (EC 2.4.2.8)-negative clone (66cl-4) selected from one subline isolated previously from a spontaneously arising mammary tumor of a BALB/cfC3H mouse. We tested other sublines from the same tumor and unrelated cell types for their ability to serve as 6-thioguanine nucleotide donors to 66cl-4 cells. The degree of communication, measured by the number of donor cells required to reduce the number of thioguanine-resistant colonies, varied with the donor cell type. The 66cl-4 line communicated with the parent cell line from which the thioguanine-resistant cell was selected and with other sublines from the parent tumor, with some unrelated tumor cells, and with some nonneoplastic cells (3T3, hamster kidney and lung fibroblasts, and mouse mammary epithelial cells). There was a quantitative difference in the amount of communication which took place with the various cells tested, but no pattern of difference could be discerned. Line 66cl-4 did not preferentially communicate with cells of epithelial versus fibroblast morphology, nor with tumor versus nontumor cells. The 66cl-4 cells retained the ability of their parent line to form metastatic tumors when injected s.c. into BALB/c mice. A quantitative selectivity of communication is thus expressed in these malignant metastatic cells, but it is apparently unrelated to either the morphological or malignant phenotype of the donor. Contact-mediated communication between tumor subpopulations may differentially affect growth and drug sensitivity within a tumor.

Animals↗
PubMed1982

A survey of calmodulin-activated protein kinase activity in several tissues of Rattus rattus.

1. In each of five tissues (brain, heart, spleen, mammary acini and pancreatic acini) the prominent endogenous protein substrate possessed a molecular weight between 51,900 and 56,800 on SDS gel electrophoresis. 2. Evidence was obtained for two species of protein substrate, differing slightly in molecular weight, which appear to be distributed in a tissue-specific manner. 3. One species, with a molecular weight of 52,900, was found in spleen, mammary acini and brain; the other species, with a molecular weight of 56,200, was found in heart and pancreatic acini. 4. The specific activity of calmodulin-activated protein kinase in homogenates varied from a high of 44 pmol/min/mg in brain to 4.2 pmol/min/mg in mammary acini. 5. Subcellular fractionation of these tissues demonstrated that most of the activity was found in the cytosolic fraction and a "light-particle" fraction obtained by ultracentrifugation, but the kinase was not associated with endoplasmic reticulum. 6. High concentrations of calmodulin were required to activate the protein kinase activity from each tissue. 7. Calmodulin concentrations producing half-maximal activation were 94 nM for brain, 377 nM for spleen, 132 nM for pancreatic acini, 350 nM for heart, and 117 nM for mammary acini. 8. The calmodulin-activated protein kinase activity in these tissues were similar, but the few differences in properties from tissue to tissue left open the possibility that multiple, calmodulin-activated kinase activities exist in these tissues.

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

Calmodulin resolution of multiple peaks of activity by preparative electrofocusing.

When the supernatant fractions from rat brain homogenates were subjected to preparative electrofocusing in a bed of Sephadex G75, several peaks of calmodulin were resolved. A minor peak representing free calmodulin migrated with a pI of 3.8 --4.4. Other peaks of calmodulin activity were observed with isoelectric points at pH 4.8, 5.2, 6.0 and 6.8. The peak of calmodulin activity at 5.2 co-migrated with phosphodiesterase activity which was stimulated 1.8-fold by calcium. A second peak of phosphodiesterase activity detected at pH 8.0 was stimulated 1.2-fold by calcium and occurred in an area where no calmodulin activity could be detected. If isoelectric focusing was done in the presence of 8 M urea only one peak of calmodulin activity was observed with a pI of 4.0--4.4. It is suggested that the multiple peaks of calmodulin resolved by electrofocusing represent calmodulin associated with various proteins which are subject to modulation by calmodulin and calcium.

Animals↗