Clinical results of bone marrow transplantation in aplasia. Report of Westminster Hospital bone marrow transplant team [proceedings].
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Anemia, Aplastic↗
Biomedical subjects
S Retsas
Publications and source records attributed to S Retsas.
Symptom relief with levamisole in stage IV Hodgkin's disease.
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Adult↗
Successful bone marrow transplant for Fanconi's anaemia.
A 15-year-old boy with Fanconi's anaemia, who required four units of blood each month, received a bone marrow graft from his 9-year-old brother, who has HLA identical and compatible on mixed lymphocyte reaction. Considerable immunosuppression was used and bacterial infection was prevented by vigorous decontamination in a Vickers-Trexler isolator. After the graft the patient's blood counts remained satisfactory for nine months, but it took six months before qualitative immune function was normal.
Adolescent↗
Effect of the position of the cyano-group of cyanopregnenolones on their drug metabolic inducing activity.
The effect of the position of the cyano-group of several cyanopregnenolones on the body's resistance to drugs and on drug metabolism was investigated. Female rats were pretreated with 2 alpha-, 6-, 16 alpha-, 17 alpha-cyano- or 16 alpha-cyanomethyl-pregnenolone or with pregnenolone, and the (in vivo) resistance to zoxazolamine, digitoxin and indomethacin, as well as the in vitro drug metabolism (post mitochondrial fraction) of zoxazolamine and ethylmorphine were determined. It was found that the 16-derivative was the most active in this respect, the 2- and 17-cyanopregnenolones were less active but significantly potent compared to controls, while the 6-cyano, the 16-cyanomethyl derivatives and pregnenolone were essentially inactive. These differences were explained in terms of an effective or poor fit of the steroids to their receptor. The poor performance of pregnenolone-16 alpha-acetonitrile was attributed to electronic effects. A hypothesis of some structural features of the receptor site for its interaction with the cyanopregnenolone inducers was presented.
Acetonitriles↗
Melanoma involving the gastrointestinal tract.
We studied 19 patients, 12 males and 7 females of a median age of 49 years (range 26-76) with clinical manifestations of gastro-intestinal (GI) involvement from malignant melanoma. Their records were available from an electronic database of 2163 patients registered between 1977 and 1998 with the Melanoma Unit initially at Westminster and currently at Charing Cross Hospital. Time interval from initial presentation of melanoma to the development of GI involvement ranged from 6 to 183 months (median 44 months). Twelve patients had a laparotomy and in eight of these resection of metastatic sites was complete. Ten patients received systemic treatment. Median survival from GI involvement for patients who had resection of metastases was 21.5 months (range 1 to 253 months). Enterectomy, especially in the presence of solitary intestinal metastases, can palliate and may prolong survival. The role of adjuvant chemotherapy is less well defined but is worthy of consideration.
Adult↗
Activity of platinum drugs against melanoma cell lines: is it modulated in vitro in the presence of tamoxifen?
Cisplatin and carboplatin have been used against human malignant melanoma as single agents and in combination. Tamoxifen is used in the treatment of breast cancer, but has no significant activity against human malignant melanoma. Tamoxifen, however, has been promoted as a modulator in some drug regimens. The addition of tamoxifen to cisplatin or carboplatin has been reported to enhance their activity against the human melanoma cell line T-289. We investigated whether tamoxifen potentiates, in vitro, the activity of cisplatin and carboplatin against C32, G361 and StMl11a melanoma cell lines. Tamoxifen alone at clinically achievable concentrations of 0.1 and 1.0 microM (168 hrs exposure) had no significant effect on growth. No chemopotentiation of the activity of cisplatin or carboplatin was observed with the addition of tamoxifen (0.1 and 1.0 microM). The platinum drugs were added for 1 hr (serially diluted from 100.0 microM). Against the G361 line there was a trend towards chemopotentiation of cisplatin by 0.1 microM of tamoxifen. However, this did not reach statistical significance. Tamoxifen (5.0 and 10.0 microM) produced some inhibitory activity, and a trend towards synergy with cisplatin was observed. However, these concentrations are not clinically feasible. Previous reports detecting synergistic interaction between tamoxifen (0.1 and 1.0 microM), and the platinum compounds against the T-289 melanoma cell line cannot be supported in our in vitro system.
Carboplatin↗
Growth inhibitory activity of S12363, a novel vinca alkaloid derivative on human melanoma cell lines.
The growth inhibitory activity of S12363, a new antineoplastic agent which belongs to the vinca alkaloid group incorporating an amino-phosphonate (bioester of valine), was studied on six human melanoma cell lines with different phenotypic characteristics and in vitro growth rates. S12363 was compared with vinblastine (VBL), vincristine (VCR) and vindesine (VDS) using the MTT assay. Inhibition was time- and dose-dependent. Overall, IC50 values ranged from 24-6770nM and 4.6-11.6 nM for the reference drugs and for S12363 respectively, after exposure for 1 hr. All the vinca alkaloids were more active when cells were exposed continuously for 72 hrs, inhibition by S12363 was greater than the reference drugs (p < 0.05 in 15/18 comparisons). The activities of VDS and S12363 were also compared using the clonogenic assay. IC50 values ranged from 45-500 nM and 17-75 nM respectively. On a molar basis, S12363 was significantly more active than VDS (ANOVA p < 0.0001). The shape of the cell survival curve obtained with S12363 was exponential, whereas that of VDS was of the exponential-plateau type. Furthermore, survival with higher concentrations of S12363 was inversely related to cells seeded. Cell cycle analysis showed these compounds to block cells in G2+M after exposure to their respective IC50 concentrations for 1 hr. This effect was obtained using a lower S12363 concentration. In summary, S12363 proved to be 18-83 times more active than the reference drugs in the MTT and 3-11 times more active than VDS in the clonogenic assay. Its high potency and dissimilar cell survival profile indicate that this compound possesses different biological properties, and therefore merits further in vivo evaluation.
Antineoplastic Agents, Phytogenic↗
Evaluation of S12363, a novel vinca alkaloid drug in the treatment of advanced malignant melanoma. A phase II study.
We conducted a phase II study with the new vinca alkaloid derivative S12363 in ten patients with metastatic malignant melanoma. Six patients had been pre-treated with other cytotoxic agents and all had received Vindesine. Four patients had no prior systemic treatment before entry into the study. S12363 was well tolerated subjectively, the main toxicity being haematological. Despite encouraging in vitro observations, no objective responses to S12363 have been documented in these patients with the doses and schedule used in this study. S12363 appears to have no clinically useful activity in metastatic malignant melanoma.
Adult↗