PubMed HealthSearch

Biomedical subjects

R S Camplejohn

Publications and source records attributed to R S Camplejohn.

27 records · Page 2Linked to original sources

Perioperative bromocriptine adjuvant treatment for operable breast cancer.

Blood levels of prolactin are consistently raised in women who have undergone mastectomy for breast cancer, probably because of the stress of surgery. Since this increase in concentration of a known breast epithelial growth promoter might stimulate proliferation in micrometastatic cells shed at the time of surgery, a pilot study was conducted to try to abolish this effect. 38 patients with suspected operable breast cancer were given either bromocriptine (18) or placebo (20) tablets for 5 days preoperatively and thereafter for 3-10 days. Bromocriptine-treated patients showed significant reductions in prolactin levels and in S-phase fraction of tumour cells within the primary infiltrating carcinoma. There were no major side-effects. Perioperative bromocriptine may provide another approach to adjuvant therapy, possibly combined with endocrine or cytotoxic treatment for patients with axillary nodal metastases.

Breast Neoplasms

The flow cytometry of melanocytic skin lesions.

DNA flow cytometry was performed on formalin fixed, paraffin embedded melanocytic naevi. DNA aneuploidy was detected in all three types of naevus but was significantly more frequent in those naevi accepted as precursors of malignancy: that is, dysplastic and congenital pigmented hairy naevi. It may be that the presence of DNA aneuploidy has prognostic significance in these naevi. Technical problems were encountered in the analysis of data from melanocytic lesions so that caution is recommended in interpretation of studies using formalin fixed tissue.

Aneuploidy

Comparison of monoclonal antibody Ki-67 reactivity with grade and DNA flow cytometry of breast carcinomas.

The reactivity of 95 breast carcinomas with the antibody Ki-67, which recognises a nuclear antigen in proliferating cells, has been assessed and compared to their histological grade and, for 47 tumours, DNA index and S-phase content. The effects of freezing and section handling on the stability of the nuclear antigen have been assessed. Evidence of nuclear staining was seen in 56% of carcinomas, with a range of positive cells from less than 1% to 60%. Cytoplasmic rather than nuclear staining was observed in 26% and 18% of carcinomas were negative. A significant correlation was observed between the presence of nuclear staining and poorer histological grade and higher S-phase content, and between the percentage of positive nuclei and S-phase content, but not grade. Three groups of carcinomas were identified: those in which Ki-67 reactivity, grade and S-phase content were similar; ones in which there was prominent nuclear reactivity with Ki-67 but low grade and S-phase content; and a group showing the converse. These patients will be followed to assess which of these three markers of proliferation is of greatest prognostic value.

Antibodies, Monoclonal

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

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

Assessment of inherent fluctuations of mitotic and labelling indices of human tumours.

A method is presented to evaluate the influence of statistical errors and inherent variation on the determination of mitotic and labelling indices of human tumours. In most of the experiments reported here, sufficient cells were counted to yield a statistical error which is small in comparison to the inherent differences in the proliferative indices, both between different sites in the same tumour and between different tumours of the same histological type. These inherent fluctuations are, theefore, a critical factor in cell kinetic studies of human tumours.

Cell Count

In vivo cell synchrony in the L1210 mouse leukaemia studied with 5-fluorouracil or 5-fluorouracil followed by cold thymidine infusion.

[3H]-TdR and [3]-udR labelling indices and mitotic indices were followed in tumour-bearing mice after application of either 5-fluorouracil (FU) alone or of FU followed by cold TdR infusion. With FU alone, accumulation of cells at the beginning of S was found, but there was no indication of a synchronous passage of the accumulated cells further round the cycle. When FU injection was followed by cold TdR infusion, a synchronous passage of the accumulated cells through the cycle was observed. However, there was a large variation in the response of individual mice to this treatment.

Animals

Measurement of cell production rates in human gastro-intestinal cancer--a guide to treatment?

Cell production rates were measured in 19 cases of rectal carcinoma and in 11 cases of gastric carcinoma using a stathmokinetic technique. These measurements were compared with results from normal rectal and gastric mucosa. It was found that most of the cases of rectal cancer were proliferating more slowly than morphologically normal rectal mucosa. This was true for the majority of gastric cancers, but a small proportion appeared to be proliferating more rapidly. These results are discussed with their relevance to appropriate therapy.

Biopsy