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Biomedical subjects

K Sikora

Publications and source records attributed to K Sikora.

At least 109 records · Page 6Linked to original sources
PubMed1987

Expression of c-myc oncogene in coeliac disease.

A monoclonal antibody, produced by peptide immunisation was used to detect the distribution of p62c/myc by immunohistology in normal and coeliac small intestinal mucosa. The effect of gluten in four treated coeliac patients was investigated by taking serial jejunal biopsy specimens for six hours after a 10 g oral gluten challenge. There was a progressive increase in p62c/myc staining intensity in the villus enterocytes extending to the crypts, which accompanied the classical morphological changes occurring in the mucosa.

Antibodies, Monoclonal↗
PubMed1987

The potential of oncogene products as tumour markers.

This paper discusses the possibilities of using the altered expression of oncogenes and their products in neoplastic tissues as markers for the diagnosis, prognosis and monitoring of human malignant disease. Results from our studies of the c-myc oncogene and its product in human solid tumours, using DNA and RNA hybridization and a set of monoclonal antibodies (MCAs) raised against synthetic peptides, are presented. These illustrate three important principles. Firstly, the level of expression of the gene correlates closely with histological grading. Secondly, the increased expression of an oncogene in a tumour can be used as a marker for imaging with radiolabelled MCA. Thirdly, the detection of a 40,000 dalton serum protein, which is immunologically related to the p62c-myc oncoprotein, and its quantitative analysis in patients with cancer and normal controls, suggests that oncogene-related serum proteins may provide novel markers for monitoring tumour activity. These data support the view that the detailed analysis of oncogene expression has the potential to predict a tumour's behaviour and response to different therapeutic modalities.

Antibodies, Monoclonal↗
PubMed1986

Mortality in patients with testicular cancer: report of the Anglia and Trent testicular tumour groups.

The overall prognosis of patients with testicular cancer has improved dramatically over the past decade. Most patients are now treated in regional oncology centres in general hospitals. The cause of death was determined in 52 patients in the East Anglian and Trent regions who presented between 1980 and 1984. The overall mortality was 10.8%. Thirty four patients died with progressive disease, 12 of treatment related problems, two suddenly at home in between chemotherapy courses, and four of incidental causes. Reasons for treatment failure and for the deaths related to treatment were analysed and several recommendations made to reduce the death rate in this highly curable disease predominantly of young men.

Adult↗
PubMed1986

Monoclonal immunoscintigraphy for the detection of primary colorectal cancers: a prospective study.

A prospective study to investigate the value of monoclonal antibody (McAb) immunoscintigraphy for the detection of primary tumours of the colon and rectum has been undertaken. Twelve patients received 1 mg 131I-labelled McAb YPC 2/12.1, an antibody raised to a human colonic carcinoma membrane preparation. Imaging of the blood pool was achieved using 99mTc-labelled red cells. After surgery specimens were scanned and samples of normal and malignant tissue excised to obtain antibody binding ratios. In only one patient was the primary tumour visualized pre-operatively. Images of the resected specimens revealed the primary tumour in ten cases but this appeared to be a function of increased blood pool within the tumour rather than specific antibody localization. The mean tumour/normal tissue count ratio was 1.27:1 (range 0.63:1-1.93:1). It is concluded that the McAb YPC 2/12.1 is unlikely to be of use clinically. Furthermore when selecting McAbs for the purposes of immunoscintigraphy the results of in vitro binding to malignant cell lines, immunohistological studies and xenograft experiments may be misleading and careful clinical evaluation is necessary.

Antibodies, Monoclonal↗
PubMed1986

Monoclonal antibodies from mice bearing human colorectal carcinoma xenografts.

We have examined the serological response in immunosuppressed mice bearing xenografts of the human colorectal carcinoma line HT29. The sera of such animals contain antibodies which bind to HT29 cell membrane components. This antibody activity was not completely absorbed by either human lymphocytes or red blood cells suggesting that at least part of this activity is directed against tumour-associated antigens. By fusing the spleens from tumour-bearing animals to an established myeloma line we were able to produce 34 monoclonal antibodies which bound to HT29 cells. The specificity of these antibodies in binding assays against membrane preparations from a variety of normal and malignant tissues and cell lines was determined. Twenty-seven bound to components present on both normal and malignant human cell membranes; 4 to tumour membranes only, whilst 3 bound specifically to membranes prepared from colorectal carcinoma tissue or cell lines. Thus despite immunosuppression the xenograft-bearing mouse was able to recognise a number of antigens present on the tumour surface.

Animals↗
PubMed1986

Computed tomography of testicular tumours: distribution of abdominal lymphadenopathy.

The distribution of intra-abdominal nodal involvement was assessed in 145 patients presenting with testicular tumours referred for staging by computed tomography (CT). Of the 55 patients with definite evidence of nodal enlargement on CT, 33 had tumours of the left testicle, and 22 of the right. Nodal involvement was predominant in the left para-aortic chain in all 33 patients with a left testicular lesion and confined to the left in 31 (93%). Amongst the 22 patients with a right-sided lesion, nodal involvement was predominantly right-sided in 19 (86%) and confined to the right side in 15 (68%). In no patient were the contralateral nodes larger than the ipsilateral nodes. In all 15 patients in this series with early nodal involvement (8 left testicle, 7 right), disease appeared confined to the ipsilateral side. Although crossover of disease does occur, it was only seen in patients with more advanced disease and subsequent to ipsilateral nodal involvement. Knowledge of these findings, which correlate well with data from anatomical, surgical and direct lymphographic studies, should assist in the CT interpretation of equivocal nodal enlargement and aid decisions on the optimal interval for CT follow-up during surveillance.

Abdominal Neoplasms↗
PubMed1986

Cancer genes: their clinical potential.

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 oncogenes 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 have been constructed and used to produce monoclonal antibodies to oncogene products. Such antibodies have demonstrated the intracellular localisation of oncogene products and their cell cycle regulatory role. A battery of antibodies against the different oncogene products can be used to aid diagnosis and prognosis. Immunohistology and other methods permit the geographical and quantitative analysis of oncoprotein function in normal and neoplastic tissues. New tumour marker systems have been uncovered. Furthermore, by purification and biochemical analysis the molecular basis for the action of these proteins 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↗
PubMed1986

Monoclonal antibodies in oncology.

Monoclonal antibodies (MCAs) can be used to differentiate between normal and neoplastic cells and thus exploited for diagnostic and, ultimately, therapeutic gain. The evidence for the existence of human tumour antigens is reviewed. Several areas of diagnosis are already benefiting from the application of the monoclonal technology. Immunohistology can help the pathologist with difficult diagnostic problems. New classifications of lymphoma and leukaemia can be based on specific surface molecules. Similarly, the detection of shed tumour antigens is already established as part of the routine assessment of many patients with common solid tumours. Isotopically labelled monoclonal antibodies have been used to localise primary and metastatic tumours. The use of antibodies in this way is not only a promising diagnostic tool but also the first step in studying the possibility of arming antibodies to provide therapeutic agents. Such trials are currently in progress.

Animals↗
PubMed1986

Primary hepatocellular carcinoma localised by a radiolabelled monoclonal antibody.

A rat monoclonal antibody, YPC2/38.8, was selected from a panel of antibodies derived by immunising rats with fresh human colorectal carcinoma. It was found to bind to a 30 000 dalton protein present on the cell surface of normal colon and liver. This protein was increased 10-fold on primary hepatocellular carcinoma (PHC) cells. After labelling with 131I, YPC2/38.8 was shown to localise human PHCs grown as xenografts in immunosuppressed mice. Sixteen patients with PHC were given 1 mg of purified antibody labelled with 1 mCi of 131I by slow intravenous injection. In 8 out of 9 patients with PHC arising in non-cirrhotic livers, good tumour images were obtained on gamma camera or rectilinear scans, but in 7 patients who had developed PHC on the background of established hepatic cirrhosis, no tumour images were seen. Subsequent studies revealed that the 30K antigen recognised by this antibody was present in increased quantity on PHC cells and the regenerating liver cells in cirrhosis. We conclude that YPC2/38.8 may have potential for diagnostic localisation and possibly thence for the selective targeting of drugs or toxins in patients with PHC arising in a liver unaffected by significant parenchymal disease.

Adolescent↗
PubMed1986

Detection of the c-myc oncogene product in colonic polyps and carcinomas.

The c-myc oncogene has been implicated in the processes of normal cell proliferation and differentiation. Elevated levels of c-myc mRNA and its gene product (p62c-myc), have been detected in a variety of solid tumours and cultured cel lines. Its precise role in normal cell function and in neoplastic transformation and progression has yet to be elucidated. We have used a monoclonal antibody, raised by peptide immunisation, to determine the distribution by immunoperoxidase staining of the c-myc oncogene product in archival specimens of colonic polyps and carcinomas. Samples from 42 patients with colon carcinoma, 24 with benign polyps and 15 normal colon biopsies were examined. Normal colon revealed maximum staining in the mid-zone of the crypts, corresponding to the zone of differentiation and maturation. The staining was predominantly cytoplasmic. Adenomatous polyps revealed the most intense pattern of staining in areas of dysplastic change. Colonic tumours showed a wide range of staining. Well differentiated tumours contained more cytoplasmic p62c-myc than poorly differentiated tumours. These findings suggest that the c-myc oncogene product may play an important role in the evolution of colonic neoplasia.

Adenoma↗
PubMed1986

Localisation of lung cancer by a radiolabelled monoclonal antibody against the c-myc oncogene product.

A set of mouse nonoclonal antibodies against the c-myc oncogene product, a 62,000 dalton nuclear binding protein involved in cell cycle control, has been constructed by immunisation with synthetic peptide fragments. One such antibody, CT14, was radiolabelled with 131I and administered to 20 patients with different malignant diseases. Good tumour localisation was observed in 12 out of 14 patients with primary bronchial carcinoma but not in patients with pulmonary metastases from primary tumours elsewhere. Successfully localised tumours were all 3 cm or more in diameter. Monoclonal antibodies against oncogene products may provide novel selective tools for the diagnosis and therapy of cancer.

Adult↗
PubMed1986

The clinical significance of flow cytometric c-myc oncoprotein quantitation in testicular cancer.

A sensitive flow cytometric assay has been developed using a monoclonal antibody, Myc 1-6E10, to quantitate c-myc oncoprotein levels in nuclei isolated from wax embedded testicular tumours. The oncoprotein (p62c-myc) level increased significantly with increasing teratoma differentiation. Patients with intermediate and undifferentiated tumours who developed recurrence had lower p62c-myc levels than those who were disease free since their initial treatment. Such quantitative biochemical methods may provide new prognostic indices for cancer patients.

Antibodies, Monoclonal↗
PubMed1986

Advances in the management of testicular cancer.

Dramatic advances have been made over the last decade in the management of testicular cancer. There are three identifiable reasons for this. The first is the widespread availability of tumour markers to assess the state of disease and its response to therapy. The second is CT scanning, which has revolutionized our ability to locate with fine anatomical detail the location of metastases. The third is the development of effective, intensive chemotherapy together with the understanding of its side-effects and optimum usage. Problems still remain in patients who fail to respond completely to existing therapy. In addition, the profound side-effects of chemotherapy mean that much effort is being invested in the development of less toxic but equally effective forms of treatment.

Antineoplastic Combined Chemotherapy Protocols↗