A clinical assessment of fluorescence polarisation changes in lymphocytes stimulated by phytohaemagglutinin (PHA) in malignant and benign diseases.

The modified double-zone SCM technique, developed in these laboratories as an in vitro test for cancer, is based on the differential response to PHA of lymphocytes harvested from two regions of a Ficoll-Triosil gradient. Lymphocyte responses are measured by changes in intracellular fluorescein fluorescence polarisation. We report its continued clinical evaluation in patients hospitalised with malignant and non-malignant diseases, including a blind trial of 78 patients with disorders of the gastrointestinal tract, breast and lung. Overall "false' negative and "false' positive rates from 336 blood samples were 1.8 and 3.3% respectively.

Comparison of radiotherapy alone and radiotherapy with chemotherapy using adriamycin and 5-fluorouracil in bronchogenic carcinoma.

Eighty-two patients with histologically confirmed lung cancer were randomly allocated to receive either radiotherapy alone (2400-3200 rads, depending upon cell type) or the same dose of radiotherapy followed by four cycles of adriamycin and 5-fluorouracil. Eighty-one patients were evaluated and for the group as a whole survival was better in the undifferentiated group assigned to receive adjuvant chemotherapy but survival in the patients with squamous tumours was not significantly prolonged. The chemotherapy was not unduly toxic.

Immunological state of patients with carcinoma of the bronchus before and after radiotherapy.

The immunological state of 30 patients with carcinoma of the bronchus was assessed before and after radiotherapy by lymphocyte response to PHA and E and EAC rosette formation. The results were compared with those from age-matched patients with benign chest disease and a group of healthy control subjects. Differences were found between the three groups and decreased immunological responses were found to correlate with shorter survival times for patients with cancer of the bronchus. These differences were not associated with the extent of the disease, or with the smoking habits of the patients. Significant differences in percentage EAC cell rosetting were demonstrated between lymphocytes from patients with malignant disease (31.3 +/- 2.0) and those for control groups (21.5 +/- 1.9 and 24.0 +/- 2.2). Cancer patients and benign chest disease patients both had significantly decreased mean E rosetting values (59.3% and 55.6%) compared with healthy control subjects (69.7%). The group of cancer patients with a normal percentage of T lymphocytes and total number of lymphocytes after radiotherapy, or those with low percentage EAC cell rosettes, had a greater than 80% survival after seven months compared with less than 50% for the rest of the patients with carcinoma of the bronchus.

Cancer-specific density changes in lymphocytes after stimulation with phytohaemagglutinin.

A fluorescence polarisation technique ("S.C.M. test") for detecting responses to phytohaemagglutinin revealed that the responsive lymphocytes from patients with malignant disease had an abnormal distribution after centrifugation through lymphocyte separation medium. In a small blind series the technique accurately distinguished patients with histologically proven malignancies from those with nonmalignant disease and normal people.

The macrophage electrophoretic mobility (MEM) test--an investigation of its value as a routine laboratory test in the detection of malignant disease.

A previous study of the MOD-MEM test showed promising results. We have attempted to repeat the study using a blind coded series of 210 blood samples from normal subjects and patients with either benign or malignant disease. Using standard criteria the false negative rate for cancer patients averaged 43% and the false positive rate for non-cancer patients averaged 34%. The results indicate that the test at the present time, under routine laboratory conditions, is not reliably reproducible and does not have the ability to effectively discriminate between benign and malignant disease. It is suggested that blind coded studies be used more frequently in assessment of tests with cancer detection potential.

Clinical improvement of patients with emphysema after radiotherapy.

In advanced emphysema the reduced lung retractive force permits dynamic compression of the airways during expiration; this gives rise to breathlessness which is often refractory to conventional remedies. Radiotherapy causes shrinkage of lung tissue and has therefore been given as treatment to 10 patients with emphysema. They have been followed for two years, during which time three have died from various causes, but no adverse effect of radiotherapy has been observed. All the patients at some time experienced a reduction in breathlessness on exertion and an increase in the range of their daily activities; the distensibility of their lungs was on average reduced but the response to test exercise was not altered. The possibility that the clinical improvement may have been a placebo effect is now being investigated.

The lymphocyte response and prognosis in cancer of the lung.

One hundred and twenty cases of cancer of the lung have been tested for their lymphocyte transformation to phytohaemagglutinin (PHA) before and after treatment by radical radiotherapy. The average response of these patients was lower than that of the controls. The fall in the lymphocyte response during treatment was calculated. The pre-treatment lymphocyte response with PHA was not related to survival after treatment. The fall in the lymphocyte response during treatment was related to the survival of the patients after treatment.

The lymphocyte response in Hodgkin's disease.

Fifty cases of Hodgkin's disease have been investigated using the lymphocyte transformation response to phytohaemagglutinin (PHA) as a mesure of their immunological reaction. The average response of all the cases was lower than that of the controls and lower than that of cases of carcinoma from all sites. Cases of Hodgkin's disease which had been treated previously with radiotherapy and/or chemotherapy had a markedly lower response than that of the untreated cases. There was no definite correlation between the stage of the disease and the lymphocyte response with PHA. Seven cases were also tested with pokeweek mitogen (PWM) and the response of the lymphocytes to PWM was found to parallel that of the PHA.