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Biomedical subjects

G J Rustin

Publications and source records attributed to G J Rustin.

156 records · Page 9Linked to original sources

Chemotherapy of advanced malignant teratomas.

Between 1977 and November 1979 we have treated 53 patients with malignant teratomas (43 males, 10 females). Thirty (70%) out of the 43 male patients had advanced and bulky disease at the time of presentation. Using different drug combinations in a sequential manner as described below, results are as follows: of the initial 33 male patients, 22 (67%) have discontinued treatment (mean 9.5 months). Nineteen have responded completely and 3 have static computed tomography (CT) nodules. Life-table analysis projects a survival of 66% (analysis at 1 December 1979). Nine out of 10 ovarian teratoma patients are alive. Adverse prognostic factors at the start of treatment were recognized in 9/10 male patients and the 1 female patient who have died. Although the survival of patients with malignant teratomas has improved dramatically, there are still problems with drug resistance in patients with very advanced disease. Patients with these tumours should continue to be treated in centres specializing in managing what has now become a potentially curable disease in most cases.

Adolescent↗

Studies on the subcellular organelles of neutrophils in chronic granulocytic leukaemia with special reference to alkaline phosphatase.

The organelle pathology of neutrophils in chronic granulocytic leukaemia (CGL) was investigated by analytical subcellular fractionation. There were minor reductions in activity of some granule enzymes with an abnormal distribution in sucrose density gradients of the specific granules. There was a marked reduction of 5'-nucleotidase activity but this is probably related to the relative reduction of the mononuclear cell contamination of the neutrophils isolated from leukaemic patients compared with controls. Another plasma membrane enzyme, NADH-nitroblue tetrazolium reductase, which has a microbicidal role, had increased activity. Neutrophils from patients with CGL had 13% the alkaline phosphatase activity of controls and were compared with neutrophils from women in the third trimester of pregnancy when the activity was increased to 8 times the control level. The latent activity, per cent inhibition by Levamisole, kinetic constants and subcellular distribution of alkaline phosphatase were similar in the three groups. It is suggested that the properties and intracellular localization of alkaline phosphatase are normal in CGL and that there is a quantitative lack of enzyme.

Alkaline Phosphatase↗

Studies on the subcellular localization of human neutrophil alkaline phosphatase.

The intracellular localization of alkaline phosphatase has been determined in human neutrophils with analytical subcellular fractionation by density gradient centrifugation and EM cytochemistry. Centrifugation on sucrose gradients containing 1 mM DETA and 5 units/ml of heparin showed that alkaline phosphatase was associated with a membranous component distinct from plasma membrane, mitochondria, specific granules and azurophil granules. There was no resolution from the endoplasmic reticulum. Density gradient centrifugation on a sucrose-imidazole-heparin gradient showed a clear resolution of the alkaline phosphatase-containing membranes from the Golgi and endoplasmic reticulum. Density gradient centrifugation of neutrophils that had been disrupted in the presenceof 0.12 mmol/l. digitonin clearly separated alkaline phosphatase-containing membranes from the endoplasmic reticulum. Part of the gamma-glutamyl transferase has a similar localization to that of alkaline phosphatase. EM cytochemistry of neutrophils, neutrophil homogenates and of the density gradient fractions identified alkaline phosphatase-containing granules as irregular-shaped, often tubular, structures. It is suggested that alkaline phosphatase and part of the gamma-glutamyl transferase activity are localized to a unique organelle in the human neutrophil.

Alkaline Phosphatase↗

Carcinoembryonic antigen levels in germ cell tumours.

Elevated serum carcinoembryonic antigen (CEA) prior to specific treatment was noted in 3% (7/258) of assessable patients with testicular, extragonadal or ovarian germ cell tumours (GCT). In addition, persistently raised CEA was documented in 7% (26/385) of patients during or after cisplatin-based chemotherapy for metastatic GCT. Raised CEA did not appear associated with adverse prognosis. Among patients undergoing resection of residual tumour masses post-chemotherapy, 8 of 36 with mature differentiated teratoma excised had raised CEA compared with only one of 39 patients where no mature teratoma was found. However, CEA levels remained elevated in 6 of the 8 cases despite apparent complete resection of mature teratoma. Elevated CEA in treated GCT patients may be caused by hepatotoxicity from chemotherapy, intercurrent diseases, or other unknown factors. History of cisplatin-based chemotherapy may be a confounding factor in interpreting raised CEA levels. CEA measurements do not help in the management of patients with germ cell tumours.

Adolescent↗

Circulating tumour markers in ovarian tumours.

Many circulating tumour markers are in clinical or experimental use for the management of ovarian tumours. The only marker to have an established role in the diagnosis, monitoring treatment, and detection of relapse of epithelial ovarian cancer (OC) is cancer antigen-125 (CA-125). The place of markers in predicting prognosis, in follow-up, and in screening for OC, is less well defined. This review concentrates on epithelial cancer of the ovary, and on CA-125, the most commonly-used OC marker. Other markers in epithelial OC are also discussed, as well as markers used in the management of germ cell tumours of the ovary, mixed Mullerian tumours, and stromal ovarian tumours.

Biomarkers, Tumor↗

Impact of tumour marker measurements upon management of patients with carcinoma of the ovary.

The clinical value of serum CA 125 in the management of patients with ovarian carcinoma has now been proven. Its role in screening for early potentially curable disease remains unproven due to its low sensitivity for early disease and requires further study in clinical trials. Its use in diagnosis of malignant pelvic lesions could lead to a more appropriate operation. Its most useful present application is to indicate which patients are no longer responding to chemotherapy and to prevent them being given unnecessary unpleasant treatment and also to avoid other investigations such as CT scans which give less information. Definitions for response to a specific therapy and also progression according to CA 125 criteria are given and require prospective testing.

Adenocarcinoma↗