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Biomedical subjects

K Sikora

Publications and source records attributed to K Sikora.

At least 127 records · Page 7Linked to original sources

A simultaneous flow cytometric assay for c-myc oncoprotein and DNA in nuclei from paraffin embedded material.

A simultaneous flow cytometric assay for the c-myc oncoprotein and DNA in nuclei extracted from archival paraffin wax embedded clinical biopsies is presented. The nuclei were extracted by pepsin digestion after dewaxing 20 micron sections. The c-myc oncoprotein was probed with a mouse monoclonal antibody. This was raised against a synthetic peptide corresponding to a hydrophilic region of the protein predicted from the amino acid sequence. The technique is illustrated with biopsies from patients with testicular cancer and with benign and malignant neoplasms of the colon.

Antibodies, Monoclonal↗

Tumour localisation by human monoclonal antibodies.

We have derived sets of human monoclonal antibodies by fusing lymphocytes from cancer patients with a human lymphoid line, LICR-LON/HMy2. Two antibodies, LGL1.1D6 and LLU6.3A4, derived from patients with glioma and bronchial carcinoma respectively, were selected for clinical study on the basis of binding patterns in radioimmunoassays with tumour cell lines and localisation of human tumour xenografts. Highly purified monoclonal antibodies were prepared using bulk supernatants from hybridomas grown in serum free medium. After radiolabelling with 131I, 1 mg antibody was injected intravenously into patients with advanced glioma and carcinoma of the bronchus. Good localisation was obtained in five out of eight patients with glioma and five out of seven patients with carcinoma of the bronchus. Despite the technical difficulties inherent in the production of human monoclonal antibodies this study demonstrates their potential for the clinical localisation of solid tumours.

Animals↗

Detection of the c-myc oncogene product in testicular cancer.

A set of monoclonal antibodies was constructed by immunising mice with peptide fragments of the c-myc oncogene product. One such antibody, Myc 1-6E10 was shown to bind to a 62,000 dalton protein identifiable with the c-myc product (p62c-myc). The antigen recognised was not destroyed by paraffin wax embedding. Myc 1-6E10 was used to characterise the distribution of p62c-myc in archival testicular tumour material. Normal testes expressed only small amounts of p62c-myc. Seminomas showed increased nuclear and cytoplasmic staining. Undifferentiated teratoma showed little activity, whereas p62c-myc was abundant in the nuclei of differentiating epithelial structures, yolk sacs and embryoid bodies. Only small amounts of p62c-myc were seen in the tumours of 5 patients who subsequently died from their disease.

Antibodies, Monoclonal↗

Abdominal pain as a presenting symptom of male germ cell tumour.

Twenty-three patients who presented with abdominal pain and were found to have germ cell tumours have been reviewed. The overall survival of these patients was no different from the survival of those presenting with testicular swellings. Intra-abdominal germ cell tumour remains an important differential diagnosis of abdominal pain in men.

Abdomen↗

Age as a prognostic factor in epithelial ovarian carcinoma.

One prognostic factor in epithelial ovarian cancer appears to be the patient's age at presentation. We have retrospectively analysed data from 2305 patients with this tumour in East Anglia during the period 1960-1980. The influence of age as a factor in survival was studied by comparing outcome in young patients between the ages of 15 and 35 (3.1% of all cases) with the outcome in the women over 35. The prognosis was significantly better in young patients, even when age correction is applied. This has implications for the management of patients with this common tumour.

Adolescent↗

Breast lumps and lymphoma.

We report two cases of young women in whom a breast lump was the first symptom of disseminated lymphoma. They were managed by wide excision of the affected segments of breast. Histological diagnosis was aided by immunoperoxidase stains for immunoglobulin chains. Further investigations demonstrated the wide spread nature of the disease, with involvement of bone marrow, bone cortex, lymph nodes and lung. Both patients received systemic chemotherapy, which achieved complete remission in one.

Adult↗

Bleomycin lung: computed tomographic observations.

Changes characteristic of bleomycin lung were seen in 15 out of 18 patients whose lungs were examined by computed tomography following standard chemotherapy for testicular cancers. These changes affected mainly the posterior aspects of the lungs and were predominantly subpleural in nature. The total dose of bleomycin given did not appear to correlate with the grade of bleomycin damage. Amongst six patients with adequate follow-up studies there has been improvement in the CT appearance of three.

Bleomycin↗

Oncogenes.

The central problem in cancer therapy is the poor selectivity of current systemic agents against the common solid tumours. The demonstration that unique segments of DNA, constant in location and conserved in evolution are involved in growth control opens new avenues for basic and clinical research. The functions of the products of these genes need to be elucidated. Examples of growth control functions include homology to growth factors, surface receptors, protein kinases and cell cycle control proteins. From DNA sequence data peptides predicted to be exposed within intact molecules can be constructed and used to produce monoclonal antibodies to oncogene products. Such antibodies have now been successfully used to demonstrate the intracellular localisation of gene products as well as the cell cycle regulatory role of the c-myc protein. By having a battery of antibodies against the different gene products their direct clinical application for diagnosis and prognosis has become a reality. Immunohistology and flow cytometry permit the geographical and quantitative analysis of function in normal and neoplastic tissues. Furthermore, by purification and biochemical analysis the molecular basis for their action can be elucidated. It is likely that by the end of the decade new drugs that inhibit oncoprotein function will be available for clinical trial.

Animals↗