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Biomedical subjects

C E Newman

Publications and source records attributed to C E Newman.

At least 19 recordsLinked to original sources

cis-platinum and ovarian carcinoma. In vitro chemosensitivity of cultured tumour cells from patients receiving high dose cis-platinum as first line treatment.

A study on the in vitro sensitivity of tumour cells from patients with ovarian cancer has been carried out in parallel with a clinical study designed to evaluate the role of high-dose cis-platinum (CIS) as first-line chemotherapy. A total of 50 samples from 102 patients have been successfully cultured and screened for in vitro chemosensitivity to 7 drugs, including CIS. The malignant nature of cells growing in culture was confirmed using a combination of karyology, morphology and immunohistochemical staining with HMFG2. Tumours were graded as sensitive (less than 40% of control 3H-leucine incorporation), intermediate (41-60% of control) or resistant (greater than 61% of control) to CIS. Correlation of in vitro sensitivity to cis-platinum with clinical response to cis-platinum assessed using CT scan and second-look laparotomy, showed positive correlation in 9/11 (89%) patients (8 = S/S; 1 = R/R); positive correlation between in vitro sensitivity to phosphoramide mustard and clinical response was also found in 4/6 patients receiving cyclophosphamide (3 = S/S; 1 = R/R). All patients with sensitive tumours showed a clinical response to cis-platinum. Comparison of cis-platinum sensitivity with sensitivity to phosphoramide mustard and melphalan showed that some tumours were sensitive only to cis-platinum; resistance to cis-platinum and sensitivity to phosphoramide mustard/melphalan was an infrequent occurrence. Some tumours which were resistant to cis-platinum showed sensitivity to adriamycin and bleomycin, particularly those from untreated patients. Sensitivity to 5-fluorouracil and resistance to cis-platinum was found in approximately equal proportions of tumours in both the treated and untreated groups.

Antineoplastic Combined Chemotherapy Protocols

Retinoblastoma, eosinophilic granuloma, and malignant melanoma: a case report.

The case history of a patient treated for unilateral hereditary retinoblastoma who subsequently developed malignant melanoma and eosinophilic granuloma is presented. Although the association between retinoblastoma and second malignancies including malignant melanoma is established, we have found no reports of third malignancies occurring in such individuals.

Adult

A comparison of three assays used for the in vitro chemosensitivity testing of human tumours.

In this study cell lines have been used to determine the level of correlation between three assays which are in use for in vitro prediction of human tumour chemosensitivity. The methods which were compared included a clonogenic assay, a monolayer assay and a short-term biochemical assay. The results indicated that the monolayer and clonogenic assays were either directly comparable or could be made comparable by reducing the drug exposure time in the monolayer assay. The biochemical assay also gave comparable results for 3 of the 5 drugs tested. It was concluded that although the 3 assays did not produce identical dose-response curves, the assays were equally valid when used for predictive testing because selection of cut-off points which were based on retrospective correlations between in vitro sensitivity data and response data, as established by other authors, compensated for differences in sensitivity between the assays.

Animals

Localisation and toxicity study of a vindesine-anti-CEA conjugate in patients with advanced cancer.

Safety of administration of a vindesine (VDS)-anti-CEA conjugate and its ability to localise after radiolabelling were investigated in patients with advanced metastatic carcinoma (4 colorectal and 4 ovarian). For imaging, patients received between 230 and 520 micrograms of 131I labelled antibody. In 5, localisation of conjugate was demonstrated, in another it was equivocal and in 2 patients, undetectable. For assessment of safety each patient also received a single dose of conjugate increasing from 1.2 to 42 mg antibody linked to 24 to 1800 micrograms VDS. The in vitro activity of the anti-CEA antibody and its ability to localise in vivo were preserved after conjugation. There was no obvious toxicity or hypersensitivity attributable to either the radiolocalisation or escalated doses of conjugate in any of the patients. The feasibility of the preparation and administration to patients of a vindesine-antibody conjugate has been demonstrated.

Antibodies, Neoplasm

HLA frequency and prognosis in lung cancer.

In 100 patients with lung cancer we have found no significant abnormality in overall HLA antigen frequency when compared to a control sample of 151 random health individuals from the same region, though there was a high relative risk of being HLA-BW22-positive and having lung cancer. There was an increased frequency of HLA-B5 in small-(oat-)cell anaplastic carcinomas (P less than 0.05); HLA-B15 in anaplastic tumours (P less than 0.05); HLA-B40 in Stage III patients (P = 0.05) and a decreased frequency of HLA-B12 in adenocarcinomas (P less than 0.05). In 86 patients followed up for 2 1/2-5 3/4 years after surgery we have been unable to confirm the significant association of HLA-AW19 and/or HLA-B5 with good prognosis as reported by others. The most striking observation was that the frequency of HLA-BW22 was significantly higher in patients alive at least 2 1/2 years after surgery when compared to the control groups (P less than 0.05) and 83% of patients HLA-BW22-positive are alive compared to only 52.5% of lung cancer patients lacking this antigen. However, all the P values become nonsignificant when multiplied by the number of antigens studied, and these observations need further investigation in a large, prospective study.

Adenocarcinoma

Intravascular haemolysis and renal impairment after blood transfusion in two patients on long-term 5-fluorouracil and mitomycin-C.

In a multicentre trial of adjuvant chemotherapy in gastric adenocarcinoma, a number of patients developed chronic haemolysis and renal failure following long-term treatment with 5-fluorouracil and mitomycin-C. This was exacerbated by blood transfusion, leading to an acute intravascular haemolytic state accompanied by rapid decline in renal function. One patient investigated extensively was treated with antiplatelet drugs, steroids, and fresh frozen plasma without success. At necropsy this patient and another had renal changes typical of the haemolytic-uraemic syndrome and no evidence of tumour recurrence. Long-term treatment with this drug combination is potentially dangerous, and routine monitoring of renal function is recommended.

Adenocarcinoma

The effect of cryopreservation of lymphocytes on E rosetting ability: a study in lung cancer patients and controls.

Two methods of measuring total T cell percentages have been used to assess the effect of freezing and storage on the ability of lymphocytes to form rosettes in blood transfusion donors, laboratory staff, patients awaiting surgery for non-malignant conditions and 48 preoperative lung cancer patients. A significant reduction in rosetting ability after freezing was found for the surgical patients group but not for the other groups. With frozen lymphocytes we have found the same significant decrease in the percentage of T cells seen with fresh lymphocytes when lung cancer patients are compared with the blood donor group. A significant difference in the percentage of T cells detected by the two assays with frozen lymphocytes was found in the control groups.

Blood Preservation

Preparation and characterization of an antiserum to cultured human oat-cell carcinoma cells.

Viable cultured oat-cell carcinoma cells were used to immunize a goat. The resulting antiserum contained high titres of anti-normal activity and antibodies to CEA. It was also shown, by indirect immunofluorescence, using fluorescein-conjugated rabbit anti-goat Ig, to localize at high titres on the surface membranes of human lung cancer cells of 4 different histological types. Booster immunizations produced a maximum secondary response one week after 2 weekly injections. The course of each immunization has been monitored for activity against normal human tissues, and the final sera have been absorbed with human spleen cells to remove anti-normal activity. Cross-reactivity with the lung-cancer-cell panel and antibodies to CEA persisted in high titre after absorption of anti-normal antibodies, and were present in the ammonium-sulphate-precipitated globulin fraction. The cells used for immunization did not produce detectable amounts of CEA in culture, and were not known to contain CEA prior to this experiment. Removal of anti-CEA antibodies by absorption with purified CEA has not reduced the cross-reactivity of the absorbed antiserum with the panel of human lung-cancer cells.

Antibodies, Neoplasm