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Biomedical subjects

L M Franks

Publications and source records attributed to L M Franks.

At least 55 records · Page 3Linked to original sources
PubMed1977

A method of synchronization of normal and malignant human cells in culture.

A method is described for providing reproducible S phase parasynchrony in both normal mesenchyme and transformed epithelia. Cells were seeded at low density in medium containing 10% serum. 24 h later the serum concentration was reduced to 0.5%. After 110th the cells were collected at the G1/S boundary in fresh medium containing 10% serum plus 2.5mM hydroxyurea over 20h. After removal of hydroxyurea and trypsinization the re-plated cells entered the S phase with a high degree of synchrony, as judged by autoradiography, pulse-labelling with 3H-thymidine, cell growth and time lapse cinematography. By 6h after synchronization 80% of the population had entered the S phase and between 10-13h 70% went through mitosis.

Blood↗
PubMed1977

An organ culture method for adult colon from germfree and conventional mice: effects of donor age and carcinogen treatment on epithelial mitotic activity.

An organ culture system by which adult mouse colon epithelium could be maintained in a modified form for several weeks was described. The effects of donor age and carcinogen pretreatment were studied as a preliminary to proposed experiments on the effect of carcinogen treatment in vitro on colon epithelium from mice of different ages. Mitotic activity was compared in explants of colon from germfree C57BL mice 5 weeks, 5 months, and 9 months old; no differences were detected. The effect of old age on mitotic activity was not studied, since colon epithelium from old (30 mo) conventional mice could not be maintained in culture. Colon explants from conventional mice that had been pretreated for 32 weeks with weekly doses of a carcinogen, 1,2-dimethylhydrazine, appeared to have a higher potential for mitotic activity in vitro than did those from age-matched, untreated controls, but the difference was only significant at the 10% level. The epithelial cells were normal in ultrastructure, and the method may be valuable for studies of the direct effects of substances on adult colon epithelium.

Age Factors↗
PubMed1977

Markers of neoplastic transformation in epithelial cell lines derived from human carcinomas.

Density-dependent inhibition of growth, plating efficiency on confluent monolayers of 3T3 cells, and growth in agar have been measured in epithelial tumor cell lines to determine whether they have properties in common with transformed mesenchymal cells. Five lines (RT4, RT112, J82, T24, and EJ) were derived from different human bladder tumors and HT29 was from a human colon tumor. All the lines resembled transformed "fibroblasts" in the absence of density-dependent inhibition of growth and the cell-surface large external transformation-sensitive protein, and they could form colonies on 3T3 monolayers. Only RT112, EJ, and HT29 were tumorigenic in nude mice, and the tumors had many of the structural and ultrastructural features of both the original tumor and the tissue of origin, even though the cells had been through many in vitro passages. Four of the lines (J82, T24, EJ, HT29) grew in agar, so that in some cell lines no correlation of growth in agar with tumorigenicity in nude mice was found: J82 and T24 were nontumorigenic and grew in agar, whereas tumorigenic line RT112 did not grow in agar. The ability to grow in agar did not appear associated with the production of high levels of plasminogen activators.

Animals↗
PubMed1977

Alkaline phosphatase activity in human bladder tumor cell lines.

The cellular localization and isoenzyme pattern of alkaline phosphatase in five cell lines derived from human bladder carcinomas (T24, RT4, RT112, J82, EJ) shown not to be HeLa cells has been established. RT112 cells had a high level of alkaline phosphatase. RT4 had a moderate amount of alkaline phosphatase but in the other three lines, levels were extremely low. Prednisolone caused a small (2 to 3-fold) increase in total alkaline phosphatase in T24 and RT112 lines only. Electrophoretic separation of isoenzymes showed that RT112 and RT4 cells (derived from more highly differentiated tumor types) had three heat stable bands equivalent to placental alkaline phosphatase and three slower bands of a modified placental type. Prednisolone increased only the former. In T24 cells the enzyme resembled the liver-type alkaline phosphatase in electrophoretic mobility and sensitivity to heat denaturation. Cytochemical studies confirmed the presence of cell surface-associated extramembraneous placental type enzyme in RT112 cells. All five cell lines had small deposits of intramembraneous alkaline phosphatase in the plasma membrane and deposits associated tith the mitochondrial membranes and the endoplasmic reticulum that were not completely inhibited by phenylalanine or Levamisole.

Alkaline Phosphatase↗
PubMed1977

Stages in neoplastic transformation of adult epithelial cells by 7,12-dimethylbenz(a)anthracene in vitro.

Five tumor-producing cell lines were established from explant cultures of adult C57BL mouse submandibular gland. Four lines were from cultures treated for 24 hr on Day 4 of culture with 7,12-dimethylbenz(a)anthracene. Three of these gave rise to adenocarcinomas after transplantation into syngeneic mice; the fourth produced tumors with carcinomatous and sarcomatous areas. The fifth cell line was derived from an untreated culture and gave rise to adenocarcinomas. A series of four well-defined morphological stages occurred in the cultures before tumor-producing cell lines were established. In Stage I (0 to 30 days) there was an outgrowth of epithelium; in Stage II (30 to 70 days) ductal differentiation occurred in some epithelium; in Stage III (70 to 100 days) small, slowly proliferating foci developed either from the ducts or from flat epithelial areas. In Stage IV (over 100 days) the proliferation rate in some of the foci increased, and the cells became more irregular. The cells could not be transferred easily until about 150 days, after which time they were tumor producing. Neoplastic transformation occurred between 158 and 240 days in the treated cultures and at 325 days in the untreated culture.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1976

Salivary epithelial cells in primary culture: characterization of their growth and functional properties.

Mouse submandibular salivary gland cells were grown in primary explant culture. After an initial period of degeneration within the explant, surviving epithelial cells proliferated rapidly and duct-like structures recolonized the explant. Autoradiographic studies showed that a peak of DNA synthesis occurred after 4 days in vitro and that proliferation was enhanced by insulin and hydrocortisone. These cells retained specialized secretory function (protease activity) for at least 2 weeks in vitro. This enzyme is a differentiated product of granular tubule cells in vivo. Between 6 and 10 days, explants attached to the substrate. An outgrowth developed, consisting largely of ultrastructurally identifiable epithelial cells which formed pseudoglandular structures in the monolayer. Epithelium survived for over 6 months in primary culture but could not be serially transferred. Secondary cultures were rapidly overgrown by mesenchymal cells.

Animals↗
PubMed1976

The natural history of prostatic cancer.

There are inner and outer gland groups in the human prostate. Benign nodular hyperplasia develops from the inner group of glands. Cancer develops from the outer gland group and consequently spreads beyond the prostate at an early stage in the disease. The biological malignancy of prostatic cancer varies from patient to patient and from part to part of the same tumor. Some tumors remain biologically inactive or latent so that there must be some naturally-occurring factor which controls tumor growth in these cases. Prostatic cancer patients may be divided into groups which differ in their response to endocrine treatment. These differences in response may be due to changes in the host or in the tumor cells. The temporary state of tumor retardation or latency follows endocrine treatment - generally anti-androgenic - in about 70 - 80% of all cases of prostatic cancer, but whatever form of treatment is used, about 75% of all cases die within 3 years. Even in tumors which show a marked response, endocrine treatment does not destroy all tumor cells. Hormone sensitivity therefore is not a property of the tumor as a whole but may vary from part to part of the same tumor. We need adequate well controlled clinical trials before we can decide which method of teatment is best but before we can do this satisfactorily we need methods to allow us to assess the stage and biological activity of individual tumors, before treatment begins.

Age Factors↗
PubMed1976

Metastasizing tumors from serum-supplemented and serum-free cell lines from a C57BL mouse lung tumor.

A tissue culture cell line was established from an alveologenic lung carcinoma from a C57BL/lcrf-at mouse. The cells can be maintained in a completely defined serum-free medium. Tumors derived from the tissue culture cells grown in serum-free or serum-supplemented medium give rise to lung metastases. The ultrastructure of the tissue culture cells in both media is similar to that of spontaneous or induced alveologenic mouse lung tumors.

Animals↗
PubMed1976

Surface proteins and fibrinolytic activity of cultured mammalian cells.

Surface proteins and fibrinolysis were investigated in a variety of cell types. A large external transformation-sensitive protein was demonstrated by lactoperoxidase-catalyzed iodination. Electron microscope autoradiography confirmed that the technique labeled surface material only. The protein was present in explants of normal tissues was well as in nontumor-producing cultured cell lines. It was not lost during long-term culture. Neoplastic transformation in vitro, whether spontaneous or induced by a chemical carcinogen or virus, led to the loss of the material in most but not all cases. The protein was also absent from many but not all spontaneous and induced tumors of the different types tested. Elevated fibrinolytic activity was demonstrated in a number of normal tissues and non-tumor-producing cell lines. It was also present in most sarcomas but absent from most carcinomas that we have examined, except for a cell line from a well-differentiated bladder tumor. The correlation between absence of large external transformation-sensitive protein and fibrinolysis was examined, and it was found that activation of plasminogen was not sufficient to cause the absence of this surface protein.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1976

Tumour growth and melanogenesis in hamster tumours in vivo and in vitro: growth, cytochemistry and ultrastructure of tissue cultural cell lines.

Cell lines were established from three hamster melanomas. One was a spontaneous melanotic tumour which lost its ability to produce pigment. Two were induced with DMBA (9.10 dimethyl 1,2-benz/a/anthracene). One of these was pigmented. The two amelanotic lines (CHT-1 and 2) produced highly malignant amelanotic tumours after reimplantation of tissue culture cells. Electron microscopy showed that melanin forming organelles were absent. Tyrosinase activity was also absent. The line established from the pigmented tumour (CHT-8) retained its pigment production for the first seven transfers. Cells from these cultures produced slow growing pigmented tumours. Cells from the 7th to the 35th transfer, a period of 28 weeks, failed to produce tumours but cells from the 36th and subsequent transfers produced slow growing amelanotic tumours. The change in tumorigenicity was not related to changes in the growth rate of the cells in vitro: this remained constant after the 11th transfer generation. Tyrosinase activity and a whole range of melanin forming organelles were present in cells of transfers 1 to 7 but absent from subsequent transfers. Type A and H virus particles were present in the two amelanotic cell lines, CHT-1 and 2. Although the two amelanotic lines produced highly malignant tumours the loss of a differentiated character--melanin production--was not invariably associated with increased malignancy. Three cell lines should provide a good system for studying the relationship between tumour differentiation and growth.

Acid Phosphatase↗
PubMed1976

Cell and organ culture techniques applied to the study of carcinoma of colon and rectum.

The value of a number of in vitro systems which have been used in the investigation of carcinomas of colon and rectum is considered. Tissue culture cell ines which have been established from human and mouse rectal and colon tumours are described. Both mouse and human cells retain ultrastructural features of the tumours of origin; acinus formations, junctional complexes, microvilli with surface glycoprotein strands. Normal colo-rectal epithelium has not been established in cell culture but organ cultures of mouse colon, which retain normal ultrastructural features can be maintained for at least 28 days. The possible origin of non-epithelial cells which appear in cultures from normal colon is discussed. The areas in which the various in vitro systems may be of used are reviewed.

Animals↗
PubMed1975

The effect of age on mitochondrial ultrastructure and enzymes.

The ultrastructure of perfused livers and of mitochondrial fractions from 6 months and 30 month-old C57/BL mice were studied. In old mice the liver cell mitochondria were enlarged and rounded with a light "foamy", vacuolated matrix, short cristae and a loss of dense granules. Quantitative studies showed a 60% increase in the mean size and an increased proportion of larger mitochondria in intact 30 month-old perfused livers. Endothelial and Kupffer cell mitochondria were smaller than those of the parenchymal cells. Mitochondria in pellets prepared from 6 and 30 month-old livers were rounded and condensed although there were a few larger and "foamy" mitochondria in the preparations from old mice. Up to 47% of large mitochondria in the old livers were lost during cell fractionation. The levels of cytochrome oxidase and malate dehydrogenase were slightly decreased with age but their cytochemical localization was unchanged.

Aging↗