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Biomedical subjects

F J Cleton

Publications and source records attributed to F J Cleton.

At least 55 records · Page 3Linked to original sources

ras oncogene activation in human ovarian carcinoma.

Samples of 37 fresh human ovarian tumor biopsies were screened to detect proto-oncogene amplification and ras mutations. Three samples showed c-K-ras2 amplification; none of the other oncogenes tested revealed any gene amplification. 5-, 25-, and 120-fold amplifications were assessed by dilution experiments and soft laser densitometry. Corresponding elevated levels of c-K-ras2 mRNA and p21 ras protein were found in the three tumors. Analysis by the polymerase chain reaction method to detect point mutations of codon 12 or codon 61 of Harvey-, Kirsten-, or N-ras showed only the wildtype sequence in all specimens. No correlation was found between ras activation and degree of tumor progression or histological subtype. DNA from one of the tumors with c-K-ras2 amplification proved to have high transforming activity in the NIH 3T3 tumorigenicity assay, but the transforming gene was not c-K-ras2.

Carcinoma↗

Reduced morbidity from skeletal metastases in breast cancer patients during long-term bisphosphonate (APD) treatment.

131 patients with osteolytic metastases from breast cancer were randomised to receive long-term oral treatment with aminohydroxy-propylidene-bisphosphonate (APD), 300 mg daily (n = 70), or to act as controls (n = 61) in a multicentre trial. Specific antitumour therapy was at the discretion of the clinician and variable. An interim analysis was made after a median follow-up of 13 months in the APD group and 14 months in the controls. There was a significant reduction in pathological fractures and severe bone pain in the APD group, and hypercalcaemia was prevented. Consequently the necessity for radiotherapy for skeletal complications was more than halved; the number of systemic therapy changes was also reduced. Gastrointestinal side-effects of APD led to a drop-out of 8% of patients. Oral supportive APD therapy is simple and convenient, and significantly reduced skeletal morbidity in advanced breast cancer.

Adult↗

Osteolytic bone metastases in breast carcinoma pathogenesis, morbidity and bisphosphonate treatment.

In this review different aspects of osteolytic bone metastasis of breast carcinoma including morbidity, pathogenesis, accompanying hypercalcaemia and treatment, are discussed. Bone metastases occur in many patients with breast cancer (percentages of up to 85% have been reported); although patients seldom die of bone metastases morbidity is pronounced. Literature data point out that humoral factors, such as prostaglandins and the recently described growth factors are of importance beside cell interactions between monocytes, lymphocytes, osteoclasts and tumour cells. Nowadays, no significance is attributed to parathyroid hormone (PTH) overproduction in this respect. The differential diagnosis between primary hyperparathyroidism and tumour-induced hypercalcaemia is not always easy biochemically; combinations of both do occur less frequently than has been assumed in the past. A new and promising line of investigations involves the growth factors, which can increase osteolytic bone resorption and may bind to epidermal growth factor (EGF) or PTH receptors, thus inducing some of the biological effects of PTH (including hypercalcaemia). Until recently it was exceedingly difficult to treat tumour-induced hypercalcaemia (TIH) (the acute condition). Since the availability of the bisphosphonates dichloromethylidene bisphosphonate (Cl2MDP) and 3-amino-1-hydroxypropylidene-1, l-bisphosphonate (APD) this treatment has become very simple. Preliminary results, derived from the literature, point out that bisphosphonate treatment might also be effective in providing long-term control.

Bone Neoplasms↗

Chemotherapy in advanced ovarian cancer.

The chemotherapy of advanced ovarian cancer is reviewed. Treatment with single agents results in low remission rates and few complete remissions. The results have been improved with modern combination chemotherapy, which includes cisplatin, although a longer follow up is needed for definite conclusions to be made concerning survival. Toxicity and drug resistance remain important problems. The future prospects of treatment with emphasis on intraperitoneal chemotherapy are discussed.

Alkylating Agents↗

Radiolabelled monoclonal antibodies: a new diagnostic tool in nuclear medicine.

This review describes the state of the art for scintigraphic tumour detection using radiolabelled very pure (monoclonal) antibodies. In vivo imaging by scintigraphy may be useful for visualisation of cancer sites and treatment monitoring in oncologic patients. Imaging includes the computer-assisted processing of the scintigrams to remove background and non-target radioactivity. The clinical use of this method ("radioimmunoscintigraphy") depends, however, on the availability of the desired antibodies. Developments in the field of antibody labelling and emission tomography in the upcoming years are crucial for the usefulness of radioimmunoscintigraphy in daily practice.

Antibodies, Monoclonal↗

Immunological characterization of non-Hodgkin's lymphoma: enrichment of neoplastic cells from lymphoid tissues and blood.

Cell suspensions prepared from lymph nodes, spleen or peripheral blood of patients with non-Hodgkin's lymphoma (NHL) often contain a high percentage of residual nonmalignant cellular elements. By E-rosette sedimentation, it was possible to enrich such suspensions from patients with various types of lymphoma for malignant cells. In patients with a B- or non-B/non-T-cell lymphoma, the neoplastic cells were found in the non-T fraction. The capacity to respond to stimulation by various stimuli was then confined to the T-cell fraction, which contained the residual normal T-cells. In patients with T-cell lymphomas, in which the malignant cells had retained the capacity to form E-rosettes, lymphoma cells were found in the T fraction. These cells usually did not respond to mitogenic stimuli. Using this separation method, small proportions of neoplastic cells could be identified in mixed cell populations. Thus, in the blood from nine out of 23 lymphoma patients without abnormalities in routine blood tests, a population of abnormal cells was detected after cell separation. This included a monoclonal B-cell population in the blood of four patients, a questionably monoclonal B-cell population in the blood of two patients and in increased non-B/non-T cell population in the blood of three patients.

B-Lymphocytes↗

Significance of plasma fibrinopeptide A (fpA) in patients with malignancy.

In 124 patients with various types of malignancy, fpA and delta fpA were measured. In 35 of these patients the effect of heparin injection on fpA and delta fpA was studied. All patients were ambulant without clinical signs of venous thromboembolism or DIC and had not received cytostatic, anticoagulant, or radiotherapy recently. In about 75% of these patients, fpA was elevated, whereas in the blood of one third of the patients, both elevated fpA levels and accelerated delta fpA were detected. Eight of the 45 patients with accelerated delta fpA (and elevated fpA) presented laboratory signs of low-grade DIC. In the patients taken at random for heparin administration, delta fpA normalized upon heparin injection, whereas in the majority of patients, irrespective of the fpA-generation rate, fpA levels were not affected by "adequate" heparinization. These results indicate that (1) about 30% of the (selected) patients admitted to our cancer clinic present with evidence of intravascular thrombin activity and (2) in 70% of these patients fpA is generated, at least in part, at a site not accessible to heparin. In addition 95% of patients with active metastatic disease showed an elevated fpA, whereas 90% of cancer patients in remission and 80% of patients without metastasis had a normal fpA, indicating that fpA can potentially be used to estimate the spread and the activity of the malignant process.

Adolescent↗

[Developments in research on and treatment of cancer (author's transl)].

The epidemiology of cancer is reviewed with particular emphasis on the geographic variations in the incidence of certain types of cancer. Several new developments in the prevention and treatment of cancer are discussed. The main advance in the results of treatment is due to chemotherapy, preferably in conjunction with radiotherapy and surgery. Much is expected of this procedure for the future.

Animals↗

Early responses to chemotherapy detected by pulse cytophotometry.

DNA/cell distributions were recorded by automated cytofluorometry (=pulse cytophotometry) in bone-marrow aspirates of leukaemia and lymphosarcoma patients subjected to chemotherapy. In most cases, early perturbations in DNA/cell histographs were observed, characteristically reflecting the known mode of action of the drugs. These changes in general preceded the clinical observation of drug response. In a series of 23 measurements in 19 patients, a positive correlation between early cytophotometric changes and clinical effects of chemotherapy was observed in 17 patients. Five patients were negative for both cytophotometric and clinical reactions and one patient was probably false-positive. The validity of the assay for early detection of drug resistance in acute leukaemia and related diseases is discussed.

Adult↗