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Biomedical subjects

R S Camplejohn

Publications and source records attributed to R S Camplejohn.

At least 73 records · Page 4Linked to original sources

Combination heparin plus cortisone treatment of two transplanted tumors in C3H/He mice.

C3H/He inbred mice bearing either C3H mouse mammary or RIF-1 tumors of 180-mm3 volume were treated with a combination of heparin (500 anticoagulation U/ml drinking water) plus cortisone (either 250 mg/kg/day tapering to 37 mg/kg/day or a constant dose of 75 mg/kg/day). Five types of heparin were tested in this study. RIF-1 tumors shrank to approximately half the volume at the start of therapy after only 3 days of treatment; mammary tumors took longer to respond, not reaching half the starting volume until after 11 days of treatment. In both tumors response was transient, the tumors eventually regrowing. However, response to combined heparin and cortisone therapy was in fact no different from the response to cortisone used alone. Also, cortisone treatment was extremely toxic to these animals and experiments had to be terminated after about 3 weeks of therapy.

Adenocarcinoma

Mitotic and labelling activity in normal human epidermis in vivo.

Labelling and mitotic indices were studied in the epidermis of twenty-eight young men. A mean labelling index of 5.5% was found from the whole study and a mean mitotic index of 0.06%. Mitotic index particularly was extremely variable; indices between 0.002 and 0.438% were found in individual biopsies. In the first two of three experiments in which mitotic index at 09.00 hours was compared with that at 15.00 hours, significant differences were found (15.00 hours greater than 09.00 hours by a factor of 2.6, P less than 0.001). However, in the third such experiment no such difference was found, suggesting that the timing and occurrence of diurnal rhythms of mitotic activity may not be consistent in normal human epidermis. In the one experiment in which it was investigated, a significantly higher mitotic index was found at 21.00 hours compared to 09.00 and 15.00 hours. Labelling index did not vary significantly at 09.00, 15.00 or 21.00 hours. However, labelling index did show a significant pattern of change over a 12-month period in two groups of subjects; peaks of labelling were seen in July and troughs in January. Very high ratios of labelled: mitotic cells were found, the median ratio for the whole study being ninety-eight labelled: one mitotic cell. This finding supports the possibility that not all labelled cells subsequently go on to divide in normal human epidermis.

Adult

A study of diurnal proliferative activity in tumour and small intestine of C3H mice bearing a transplanted mammary carcinoma.

Diurnal changes in proliferative activity were investigated in tumour and small intestinal epithelium of mice bearing a transplanted mammary carcinoma. In addition to mitotic and labelling index studies, the metaphase-arrest technique with vincristine (VCR) was employed. In the tumour there was no clear evidence of a significant diurnal rhythm in proliferative activity but in the small intestinal epithelium such a rhythm was clearly demonstrated. A higher cell production rate (kB) measured by metaphase-arrest and higher labelling and mitotic indices were seen in the mid to late part of the dark period. The peak mitotic index was seen 3 to 6 h after the labelling peak in the small intestine. The basal third of the crypt which is believed to include the stem cell compartment of this tissue showed larger diurnal fluctuations in both labelling index and kB than the rest of the proliferative compartment.

Animals

Stathmokinetic measurement of tumour cell proliferation in relation to vascular proximity.

In this study the metaphase-arrest method with vincristine (VCR) was used, in a transplanted C3H mouse mammary tumour, to study cell proliferation relative to distance from a blood vessel. The metaphase-arrest method has a number of advantages over methods involving [3H]TdR labelling for such a study. The cell birth rate (kB) was shown to be inversely related to distance from a capillary in corded areas of tumour. Penetration of VCR, even into perinecrotic areas of tumour, appeared to be sufficient to achieve effective metaphase arrest.

Adenocarcinoma

Cell kinetic response of an experimental tumour to irradiation. Use of the stathmokinetic method.

The cell kinetic perturbations following irradiation (20 Gy) were studied by combining the metaphase arrest method using vincristine with histological indices of cell death. The metaphase arrest method yielded remarkably constant values of rate of entry into mitosis (rM) of around 24 new cells/1,000 cells/hour during a 7 day period in which there was no tumour growth. The time course of cell death as indicated by changes in the pyknotic index during this period may reflect the processes of reoxygenation and repopulation known to influence the results of fractionated radiotherapy.

Adenocarcinoma

An attempt to use vincristine and colcemid to measure proliferative rates in normal human epidermis in vivo.

A range of doses of vincristine (0.5-10 micrograms) or colcemid (5-100 micrograms) injected intradermally into normal volunteers failed to yield any significant accumulation of arrested mitoses. This was despite an apparently successful block of cells in metaphase by the highest three doses of each drug. Possible reasons for the failure to see accumulation are discussed. The results suggest that normal human epidermis is not a suitable system for application of the metaphase-arrest technique using intradermal injection.

Adult

An in vivo double labelling study of the subsequent fate of cells arrested in metaphase by vincristine in the JB-1 mouse ascites tumour.

The fate of cells arrested by Vincristine (VCR) in metaphase is of interest because of the wide use of this substance in cancer chemotherapy and, particularly, in relation to its use in so-called 'synchronization' therapy. The present study was designed to answer the question of whether cells blocked in metaphase by VCR subsequently proliferate further or whether they become infertile and die. By means of a double labelling technique with [3H] and [14C]thymidine (TdR) it was shown that all VCR-arrested metaphases in the JB-1 ascites tumour subsequently became necrotic. These cells did not re-enter a viable G2 phase following arrest and thus could not take part in a wave of synchronous proliferation. In agreement with earlier studies, VCR was found to lead to arrest in metaphase, not only of cells in or shortly prior to mitosis at the time of VCR administration, but also of the majority of cells which had at this time been in the S and G2 phase.

Animals

A critical review of the use of vincristine (VCR) as a tumour cell synchronizing agent in cancer therapy.

Vincristine (VCR) has been used clinically in so-called 'tumour cell synchronization therapy schedules'. These schedules are based on the assumption that cells, arrested in metaphase by low doses of VCR, subsequently re-enter the proliferative cycle synchronously. However, the evidence that tumour cell synchrony can be achieved under clinical conditions or that 'cell synchronization therapy schedules' yield a better therapeutic response than other efficient combination schemes, is scanty. Further, even in experimental systems, the efficacy of VCR as a cell synchronizing agent is disputed. Indeed, in some systems, cells arrested in metaphase by low doses of VCR, do not re-enter a normal proliferative cycle at all following arrest. In addition, the complex nature of the VCR-tumour interaction and the heterogeneous nature of the tumour cell populations against which it is used augurs badly for the successful application of cell synchronization therapy schedules.

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