Biomedical subjects

H M Coley

Publications and source records attributed to H M Coley.

21 records · Page 2Linked to original sources

PubMedDate not supplied

Lack of prognostic significance of ploidy and S-phase measurements in advanced ovarian cancer.

DNA ploidy and S-phase measurements were made in fresh tumour samples obtained from 27 patients with either untreated or previously treated ovarian cancer. In addition, an assessment of in vitro chemosensitivity to post-operative chemotherapy was carried out. Whilst we found that patients with aneuploid tumours tended to survive longer (median survival 441 days versus 268 days for diploid tumours; p = 0.308) and this was associated with clinical response (p = 0.137) this was not statistically significant. Tumours with a high S-phase fraction (i.e. > 9% median) showed a median survival of 362 days compared with 484 days for those with a low S-phase fraction (< 9%; p = 0.79). Whilst a high level of predictability for chemosensitive patients (81%) was achieved, chemosensitivity per se was not related to the respective tumour DNA ploidy or S-phase fraction. In addition, when considering disease stage i.e. FIGO stage III or IV, or extent of residual disease between diploid and aneuploid groups, there were no statistically significant differences. However, there was a tendency for stage III tumours to be aneuploid (p = 0.189). Aneuploid tumours also showed the highest S-phase fractions (p = 0.03), indicative of a high proliferation rate. In conclusion, we have shown that DNA content and ploidy status do not appear to be major prognostic indicators for the management of ovarian cancer.

Adult↗

PubMedDate not supplied

The activity of N-(hydroxymethyl) melamines in fresh human ovarian tumour cells and xenografts.

Trimelamol (TM) was developed as a water soluble analogue of the oral chemotherapeutic agent hexamethyl-melamine (HMM), to be administered i.v., in an effort to avoid dose limiting emesis. Because of formulation difficulties due to its inherent instability the development of TM was halted. In vivo studies using a human ovarian cancer xenograft model PXN/65 showed TM to be curative in the dose range of 15-60 mg/kg i.p. daily x 5, for 4 weeks. Conversely, HMM given at the highest dose (60 mg/kg i.p., or 90 mg/kg p.o.) indicated only very modest tumour growth delays. In vitro chemosensitivity testing using primary ovarian tumour cultures showed that in 12/23 cases indicating reduced sensitivity to cisplatin or carboplatin, sensitivity to TM was increased. TM was curative in the carboplatin-resistant HX 110P human ovarian cancer xenograft and promising activity was seen in the MX-1 human breast cancer xenograft. In spite of enhanced stability in aqueous solution and good in vitro cytotoxicity, the TM analogues CB 7669 (triscyanomethyl) and CB 7639 (tristrifluoroethyl) showed disappointing in vivo antitumour activity which may be explained by the need for prolonged exposure. TM analogues with intermediate stability are currently under development in an effort to further the clinical development of this promising group of antitumour agents.

Altretamine↗

PubMedDate not supplied

Chemosensitivity testing of fresh and continuous tumor cell cultures using lactate dehydrogenase.

We have examined the use of the LDH (lactate dehydrogenase) assay for chemosensitivity testing in established and primary cultures of sarcoma, leukaemia and ovarian cancer in parallel with the MTT assay. The method we describe is rapid, sensitive and ideal for 96-well plate assays using adherent or suspension cultures. Excellent agreement between the two methods was observed (r = 0.936) using a variety of antitumour agents, with some notable exceptions. In the Bax (human synovial sarcoma) cell line MTT colour production by control cells was very low, thus MTT-->formazan production could not be relied upon as a definitive end point equating with cell number. In contrast, colour production of control cells using the LDH assay was significantly greater and all cultures tested were suitable for titration of chemosensitivity. There was a discrepancy between IC50 values obtained either by cell counting or MTT in the HTB88 (human leiomyosarcoma) line treated with 5-FU (59.9 microM vs > 200 microM, respectively). However, cell counting agreed well with the LDH assay (IC50 47.3 microM). Whilst the MTT assay remains a reliable method for chemosensitivity testing, the LDH assay may prove more appropriate in certain experimental settings.

Cell Survival↗