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Biomedical subjects

K Sikora

Publications and source records attributed to K Sikora.

At least 145 records · Page 8Linked to original sources
PubMed1984

The selection of monoclonal antibodies for tumour localization in patients with colorectal carcinoma.

We have investigated the ability of various predictive studies to assess which monoclonal antibody (MCA) will be most useful in the immunoscintigraphic localization of metastatic colorectal carcinoma. A set of MCAs was obtained by fusing splenic lymphocytes from rats immunized with membrane preparations from fresh human colorectal cancer. Supernatants from 17 cloned hybridomas were found to bind strongly to colon carcinoma lines by indirect radioimmunoassay. Immunofluorescence using these MCAs on sections of fresh frozen colon carcinoma and normal tissue revealed different staining patterns. Nine MCAs were purified and labelled with 131I. Groups of mice bearing human colorectal tumour xenografts were given radiolabelled MCA and scanned. Six out of the nine MCAs showed tumour localization as determined by rectilinear scanning. Three MCAs which gave good tumour images in mice were selected for clinical evaluation in patients with advanced colorectal cancer. One gave good tumour images, another targeted to bone marrow and the third bound almost exclusively to normal liver. Clinical evaluation is clearly essential in the selection of MCAs for tumour localization.

Animals↗
PubMed1984

The increasing incidence of testicular cancer in East Anglia.

We have studied the age-related incidence of testicular cancer in the East Anglian region. The incidence for both teratoma and seminoma has almost doubled since 1960. Teratoma incidence, stable from 1960-1969 at 0.9 per 10(5) of the male population, increased between 1970 and 1975 to 1.7. This rise was the result of increased occurrence among younger men. Seminoma incidence also rose from 1.5 to 2.5 per 10(5), most rapidly between 1975 and 1980. Causes for the rising incidences have been suggested.

Adolescent↗
PubMed1984

Recombinant interferon in advanced breast cancer.

Fifteen patients with locally advanced refractory breast cancer have been treated with recombinant leucocyte interferon ( rIFN -alpha A) for up to 12 weeks. Toxicity was considerable with the initial dosage schedule employed but became acceptable after reducing the starting dose by 50%. Minor side effects occurred in all patients and major CNS toxicity in six. Nine patients showed some evidence of tumour regression at 4 weeks. Only two of these were still responding at 12 weeks. Response was unrelated to the length of previous history, oestrogen receptor status or previous responsiveness to cytotoxic or hormone therapy.

Adult↗
PubMed1984

The characterisation of gliomas using human monoclonal antibodies. Minireview on cancer research.

Malignant gliomas contain large numbers of invading lymphocytes. The function of these lymphocytes is unknown. It is likely that they are involved in host defence against the developing tumour. By isolating these cells and fusing them with a suitable myeloma system, hybrids can be established and their antibody activity analysed. Human monoclonal antibodies reactive to glioma cells have now been isolated and their specificity has been determined by radioimmunoassay, binding assays and immunoprecipitation. Furthermore, such antibodies can be radiolabelled with 131I and administered intravenously to localise tumours in patients. These antibodies have therapeutic potential as selective targeting agents for chemotherapy and other cytotoxic agents.

Antibodies, Monoclonal↗
PubMed1984

Cancer genes.

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Chromosome Aberrations↗
PubMed1983

Oncogenes.

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Cell Transformation, Viral↗
PubMed1983

Neurological effects of recombinant human interferon.

Ten women with advanced locally recurrent breast cancer who had failed to respond to radiation and hormonal and cytotoxic agents were given up to 12 weeks of recombinant leucocyte interferon 20 X 10(6) U/m2 daily or 50 X 10(6) U/m2 three times a week. Within one hour of administration influenza-like symptoms began, which one week later were superseded by lethargy, anorexia, and nausea, with a consequent loss of weight in most patients. Other side effects included profound somnolence, confusion, paraesthesia, and (in one patient) signs of an upper motor neurone lesion in the legs. All these effects together with increased slow wave activity in electroencephalograms from all patients during treatment disappeared when interferon was withdrawn and did not recur on reintroducing the drug at a lower dosage. Studies are continuing to determine the mechanisms of these effects.

Adult↗
PubMed1983

Subcutaneous culture chamber for continuous infusion of monoclonal antibodies.

Monoclonal antibodies allow the precise definition of molecular components present on tumour cell surfaces. Some human monoclonal antibodies prepared by fusing intratumoral lymphocytes from patients undergoing craniotomy for malignant glioma with cells from a specially derived human lymphoid line (LICR-LON-HMy2) bind to glioma surface components. To study the feasibility of continuous administration of human monoclonal antibodies directed against glioma we designed a chamber which enables hybridoma cells to be cultured in the subcutaneous tissue. This chamber allows antibodies to diffuse out, and nutrients and oxygen necessary for continued cell viability to diffuse in. Cells are unable to traverse the membrane pores of the device, so there is no risk that malignant cells put in the chamber can metastasise. The chamber has now been inserted in one patient with recurrent glioma, in whom the kinetics of internally labelled antibody release has been monitored.

Antibodies, Monoclonal↗
PubMed1983

Human hybridomas from patients with malignant disease.

Lymphocytes from 180 patients with a variety of malignant diseases were collected and fused with a human myeloma-derived line, LON-LICR-HMy2/CAM1. A total of 162 hybridomas was obtained. Only B lymphocyte markers were found on the surface of the fusion products. Flow cytometric analysis revealed a stably increased DNA content in the hybridoma cells. Some hybridoma supernatants were found to contain new Ig chains. Anti-tumour binding activity was found in 12 supernatants.

Antibodies, Monoclonal↗
PubMed1983

Localisation of metastatic carcinoma by a radiolabelled monoclonal antibody.

Rat monoclonal antibodies were prepared by immunising rats with human colorectal carcinoma cell membranes and fusing splenic lymphocytes with a rat myeloma. Hybridoma supernatants were screened by binding assays on membranes prepared from colorectal carcinoma tissue. One hybridoma supernatant, containing a monoclonal antibody with high binding activity on malignant compared to normal colon sections, was grown in large quantities in serum-free medium. After ammonium sulphate precipitation the antibody was purified by ion-exchange chromatography and labelled with 131I. Radiolabelled antibody was administered i.v. to 27 patients with colonic and other tumours. Scintigrams were obtained at 48 h. Computerised subtraction of the blood pool image revealed localised areas of uptake corresponding with areas of known disease in 13/16 patients with colorectal carcinoma and 3/4 patients with breast cancer.

Adult↗
PubMed1983

Localisation of malignant glioma by a radiolabelled human monoclonal antibody.

Human monoclonal antibodies were produced by fusing intratumoral lymphocytes from patients with malignant gliomas with a human myeloma line. One antibody was selected for further study after screening for binding activity to glioma cell lines. The patient from whom it was derived developed recurrent glioma. 1 mg of antibody was purified, radiolabelled with 131I, and administered intravenously. The distribution of antibody was determined in the blood, CSF and tumour cyst fluid and compared with that of a control human monoclonal immunoglobulin. Antibody localisation in the tumour was observed and confirmed by external scintiscanning.

Adult↗