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Biomedical subjects

V D Courtenay

Publications and source records attributed to V D Courtenay.

At least 19 recordsLinked to original sources
PubMed1988

Reduction of tumour bed effect after angiogenic stimulation.

A new two-tumour system has been developed to examine the effect of an angiogenic stimulus on the tumour bed effect (TBE) in C3H mouse skin treated with 20 Gy X rays. The first tumour was implanted intradermally to stimulate angiogenesis. The Lewis lung carcinoma (3LL) was used for this since it is isogeneic in C57 B1 mice and after initial growth (mean volume 69 mm3), tumours completely regressed within 24 days. The second tumour, the RIF-1 fibrosarcoma (RIF) isogeneic to C3H mice was used to assess stromal function using the TBE assay. After complete regression of the 3LL tumour, RIF cells were implanted into the centre of the stimulated sites and 24 days later the resulting RIF tumours were excised and the TBE measured from the yield of viable RIF cells obtained from each tumour. There was an approximately 10-fold increase in cell yield from tumours implanted into stimulated, pre-irradiated beds compared with those implanted into unstimulated, pre-irradiated beds. This suggests that the angiogenic stimulus provided by the growth of the 3LL tumour led to a substantial restoration of the capacity of the radiation-damaged stroma to support tumour growth. If stromal restoration, as seen during these experiments using artificially induced angiogenesis, was to occur in unstimulated stroma during the normal course of repair and regeneration, this slowly dividing tissue constituent might eventually recover given sufficient time. This raises the possibility that the role of the stroma in late radiation damage might not be as important as was previously thought.

Animals↗
PubMed1987

Tumour bed effect: hypoxic fraction of tumours growing in preirradiated beds.

The reduction in tumour growth rate seen when tumours are implanted into preirradiated sites, the tumour bed effect (TBE), is believed to be due to radiation damage to vascular stroma, leading to defective angiogenesis in the tumour. The present work examined whether or not the functional inadequacy of irradiated stroma was accompanied by an increased hypoxic fraction in tumours growing in irradiated beds. Mouse flank skin was given 0 or 20 Gy X-rays and RIF-1 fibrosarcoma cells were implanted i.d. into the centre of the treatment field one week later. Tumours of 200 mm3 were irradiated under clamped or unclamped conditions and the hypoxic fraction measured from the displacement of the corresponding survival curves, assayed in vitro. Results indicated a small increase in the hypoxic fraction. Averaging values from three independent experiments, the percentage of hypoxic cells increased from 2.5 per cent for cells in tumours growing in unirradiated beds to 4.6 per cent for those from tumours in beds given 20 Gy. Thus an irradiated vascular bed is still to some extent able to maintain the proportion of oxic: hypoxic tumour cells found in tumours growing in unirradiated beds, despite manifest changes in tumour necrosis and growth rate.

Animals↗
PubMed1987

Ultrastructural, immunocytochemical, and cytogenetic characterization of a human epithelioid sarcoma cell line (RM-HS1).

A cell line (RM-HS1) derived from a human epithelioid sarcoma was established in tissue culture. Ultrastructurally, the cells show features of those found within the primary tumor. A mixed mesenchymal-epithelial phenotype, defined by reactivity with antibodies to epithelial membrane antigen and to vimentin and keratin intermediate filaments, was found in the tumor, and a similar phenotype persisted in the cultured cells. Cytogenetic analysis revealed a mode of 66 chromosomes. With the use of a variety of banding techniques together with in situ hybridization of a 3H-labeled molecular probe for 18s and 28s ribosomal RNA genes (pX1r101), the karyotypes were shown to contain extensive numerical and structural rearrangements, with up to 24 marker chromosomes.

Adult↗
PubMed1983

The response to chemotherapy of a variety of human tumour xenografts.

The results of a series of projects on the cytotoxic drug response of human tumour xenografts are compared. All were performed in one laboratory, using conventional CBA mice that were usually immunosuppressed by thymectomy, cytosine arabinoside treatment, and whole-body irradiation. Results on human tumours arising in 9 anatomical sites are included, with the main emphasis on colo-rectal, pancreas, breast, lung and testis carcinomas, also melanomas. Growth acceleration during successive passage of most of these tumour types was observed. When therapeutic response was measured by a growth-delay method there were wide differences in response to chemotherapy. Testicular teratomas and small-cell lung tumours responded well; breast tumours showed modest response; melanomas, colo-rectal tumours and non-small-cell lung tumours responded poorly. Studies of clonogenic cell survival were made in 11 xenografted tumour lines. They confirmed the range of responsiveness and tendency towards individuality of the growth delay data. Cell survival in most cases was exponentially related to drug dose. This compilation of a large amount of experimental data supports the belief that human tumour xenografts broadly maintain the level of chemotherapeutic responsiveness of the source tumours in man.

Animals↗
PubMed1982

In vitro cellular radiosensitivity of human malignant melanoma.

The agar diffusion chamber assay was used to construct in vitro radiation cell survival for two human malignant melanoma xenografts. Both tumors had survival curves of shoulder-exponential shape with large shoulders (Dq 2.38, 2.92 Gy). Comparison with previous studies of 4 human tumor xenografts in the same system suggests that large shoulders are more common in melanomas than other tumor types. This supports the case for large fraction irradiation in the clinical therapy of melanoma.

Animals↗
PubMed1981

Enhanced cell killing in lewis lung carcinoma and a human pancreatic-carcinoma xenograft by the combination of cytotoxic drugs and misonidazole.

The "chemosensitizing" properties of the radiosensitizer misonidazole (MISO) were examined in 2 tumour systems, murine Lewis lung carcinoma and human pancreatic adenocarcinoma xenografted into immune-suppressed mice, using a soft-agar colony assay to measure tumour-cell survival. In mice bearing Lewis lung tumour, the administration of MISO simultaneously with melphalan, cyclophosphamide. CCNU, FU or vincristine gave substantial enhancement of cytotoxicity (DEFs from 1.5 to 3.5). However, no enhancement was seen with bleomycin, VP 16-213 or cis-Pt. The same level of enhancement of cyclophosphamide effect (DEF = 2.0) was seen with both cell survival and growth delay end-points effect (DEF = 2.0) was seen with both cell survival and growth delay end-points of tumour response. Enhancement was also seen in the human tumour xenograft with melphalan, cyclophosphamide and MeCCNU, using a cell survival assay, but cis-Pt was again not enhanced.

Adenocarcinoma↗
PubMed1980

Colony growth and clonogenic cell survival in human melanoma xenografts treated with chemotherapy.

A soft-agar diffusion-chamber technique was used to grow colonies from human melanoma xenografts. Plating efficiencies ranged from 0-042% to 75% and increased with serial passage of some tumours. Cells in colonies were similar to human melanoma cells in morphology, histochemistry and ultrastructure, and were shown by immunofluorescence to contain human antigens. Xenograft tumours could be regrown from the colonies when re-implanted into immune-deprived mice. Cell-survival curves were constructed from 5 xenograft lines treated with 4 cytotoxic drugs. All lines were resistant to adriamycin, but each line appeared to have an individual spectrum of sensitivity to the more effective drugs. The responses were compatible with the clinical pattern of response in melanoma, and in 2 cases the objective response of lung metastases to treatment with melphalan was consistent with the xenograft cell-survival data. Dose-response curves were exponential for treatment with methyl-CCNU and melphalan, but distinct plateaux were seen for 2 xenografts treated with doses of DTIC over 100 mg/kg. These were thought to be due to resistant subpopulations of clonogenic cells within the tumours.

Animals↗
PubMed1980

A simple method for quantitating endogenous CSA.

The enhanced colony-formation by human bone marrow cells in vitro, produced by the addition of lysed rat red blood cells, has been shown to be due to an increase in the sensitivity of the colony-forming cells (CFUc) to colony-stimulating activity (CSA). Rat red cell lysate does not contain CSA, nor does it increase CSA production by cells. The sensitivity of colong-forming cells is sufficiently increased by the lysate to give colony-formation in the absence of any added source of CSA. Consequently, it is possible to assay for locally produced (endogenous) CSA without the need for cell separation and the complications this entails. Furthermore, the linear relationship between the numbers of cells plated and the colony yield simplifies the quantitative interpretation of the results.

Animals↗
PubMed1978

Growth of human tumour cell colonies from biopsies using two soft-agar techniques.

Two techniques for growing colonies of human tumour cells in soft agar have been applied to cell suspensions derived from fresh tumour tissue from 48 patients. Colonies were obtained in 31 cases, with plating efficiencies between 0.01 and 15%. In 11 cases the plating efficiencies were 1% or above. There was evidence that some categories of tumour grew more readily than others under these conditions. The potential applications of the methods to clinical and experimental oncology are discussed.

Agar↗
PubMed1978

Improved immune-suppression techniques for the exongrafting of human tumours.

The transplantability of a xenografted human adenocarcinoma has been examined in mice that had been immune-suppressed by thymectomy and whole-body irradiation and the results have been compared with transplantation into athymic (nude) mice. Two alternative techniques were used to prevent marrow failure following whole-body irradiation: reconstituting the animals with a marrow graft, or protecting them by an injection of cytosine arabinoside (Ara-C) 2 days before the irradiation. The results show that the Ara-C-prepared mice were more receptive to transplantation than marrow-grafted or nude mice, and they were the only animals that developed regional metastases from implanted xenografts. Some recovery of immunity occurred in both types of immune-suppressed mice, which was evident more than 5 weeks after immune-suppression and which was more marked in females than in males. It was concluded that the immune-suppressed mice were superior to nude mice for short-term experiments but they may be less satisfactory for long-term experiments.

Adenocarcinoma↗
PubMed1978

An in vitro colony assay for human tumours grown in immune-suppressed mice and treated in vivo with cytotoxic agents.

An in vitro agar colony technique has been developed for the growth of tumour cells taken directly from human tumours grown in immune-suppressed mice. The novel feature of the technique is the addition of a replenishable liquid phase which permits the maintenance of relatively slowly growing cells. A number of different xenografted tumours have been cultured successfully in this system, with red blood cells added to the agar and using 5% O2 in the gas phase. The technique has been used to assay cell survival in tumours treated in vivo with cytotoxic agents, and examples are given of survival curves obtained from a pancreatic tumours irradiated with gamma-rays and a colonic tumour from mice treated with cyclophosphamide. The results obtained by this in vitro method are in agreement with those from the agar diffusion chamber technique. This culture method has also been successfully used for the growth of cells taken directly from human tumour biopsy samples obtained in the clinic.

Animals↗
PubMed1978

In vitro radiation response of cells from four human tumors propagated in immune-suppressed mice.

Two recently developed clonogenic assays for human tumor cells have been used to measure the in vitro radiation cell survival of four human tumors, a pancreatic carcinoma, a colonic carcinoma, an oat cell carcinoma of the lung, and a melanoma, propagated as xenografts in immune-suppressed mice. The slopes and shoulders of the survival curves for the first three tumors were all similar with Do's, respectively, of 94, 100, and 131 rads and with Dq's, respectively, of 8, 44, and 41 rads, However, melanoma cells from the fourth tumor had a survival curve that differed from those of the other three, both in having a wider shoulder with a Dq of 216 rads and in having a shallower slope with a Do value of 183 rads. It is suggested that the wide shoulder to the melanoma cell survival curve may in part explain the poor response to small fractionated doses of radiotherapy usually observed clinically for this tumor type. However, the data from the other three tumors suggest that differences in radiotherapeutic response seen in the clinic for these tumors cannot be attributed to differences in intrinsic radiosensitivity of the tumor cells.

Animals↗
PubMed1978

The effect of misonidazole on the radiation response of clonogenic human pancreatic carcinoma cells.

An enhancing effect of misonidazole on the in vivo radiation response of clonogenic human tumour cells from a pancreatic carcinoma xenograft has been demonstrated using both a soft agar in vitro assay and an agar in diffusion chamber assay. Enhancement ratios of 1.8 and 1.3 were found when cells were assayed at 0 h and 18 h respectively after irradiation. No enhancement was seen with in vitro irradiation of oxygenated cells. The potential of these assay systems as a perclinical screening test for new radiosensitizers is discussed.

Animals↗