Sensitivity of latent cancer to chemotherapy.

The paper is a review of some cancer patients who were treated successfully by surgery followed by chemotherapy. The cases suggest the hypothesis that early cancer growth following surgery is more sensitive to chemotherapy than the active cancer growth of the original tumor.

Intractable chronic lymphocytic leukemia and interferon.

The hypothesis that interferon may be useful for intractable chronic lymphocytic leukemia (CLL) is based on two incidental findings: first, the similarity in the in vitro radioresistance of the blood lymphocytes of intractable CLL and of hairy cells; secondly, the similarity of the incidence of intractable CLL patients and the incidence of CLL patients who respond to interferon treatment.

An animal model for intractable chronic lymphocytic leukemia.

Lymphomas developed in mice treated with X-irradiation. The radiosensitivity of cells of the lymphomas had a bimodal frequency distribution. The cells of 11 lymphomas had approximately the same radiosensitivity as normal murine lymphocytes; 6 lymphomas were highly radioresistant.

Differences between responsive and intractable chronic lymphocytic leukemia.

About 19-26% of patients with chronic lymphocytic leukemia (CLL) have intractable disease resistant to chemotherapy, have a relatively short median survival time and are responsive to splenectomy. Lymphocytes from patients with intractable CLL are resistant in vitro to X-irradiation and to colchicine. Responsive CLL is an accumulative disease while intractable CLL is a proliferative disease.

Essential in vitro test before treatment of patients with intractable chronic lymphocytic leukemia.

About 23% of all chronic lymphocytic leukemic (CLL) patients have intractable CLL (ICLL) which is resistant to conventional therapy and has a poor prognosis. The ICLL patients complicate the determination of the efficacy of new therapeutic agents. An in vitro test is needed for the diagnosis of ICLL patients during the first examination.

Pathogenesis of intractable chronic lymphocytic leukemia (ICLL).

About 23% of all patients with chronic lymphocytic leukemia (CLL) are resistant to chemotherapy and have intractable CLL. Recent work showed the usefulness of splenectomy for the treatment of ICLL patients. The peripheral blood lymphocytes of ICLL patients were radioresistant in vitro.

Chronic lymphocytic leukemic patients, resistant to chemotherapy.

In four reported studies, intensive chemotherapy of various types was administered to large groups of patients with chronic lymphocytic leukemia (CLL) in advanced stages. About half of the patients were non-responders to the therapy. Resistance to therapy was also found in 12% of patients with early CLL and in 19 CLL patients who had in vitro radioresistant lymphocytes before therapy.

Relationship between in vitro and in vivo radiosensitivity of lymphocytes in chronic lymphocytic leukemia.

A significant positive correlation was obtained between the in vitro radiosensitivity of the blood lymphocytes of patients with chronic lymphocytic leukemia (CLL) and the in vivo response of the total leukocyte count subsequent to radiation therapy. Four types of equations were used to represent and measure the effect of in vitro X-irradiation on lymphocytes from CLL patients and measure the response of patients to a course of radiotherapy. For the in vivo analysis we used data from 10 patients who were routinely treated with a total of 16 courses of radiation therapy.

Effects of alcohol and hyperthermia on normal and leukemic lymphocytes.

By the method of viable lymphocyte counts, ethanol was found (1) to have a cytocidal effect on normal and leukemic lymphocytes; (2) to be more toxic to leukemic than to normal lymphocytes; (3) to be synergistic with hyperthermia, and (4) to decrease the critical temperature of normal lymphocytes from 43 to 41.5 degree C.

Effects of hyperthermia on radiosensitivity of normal and leukaemic lymphocytes.

We measured the effects of X-irradiation plus incubation at elevated temperatures on peripheral blood lymphocytes from normal persons and from patients with chronic lymphocytic leukaemia. Counts of viable lymphocytes were based on morphological characteristics by phase microscopy. Dose-effect curves for X-irradiation were biphasic.

Cytology and colchicine sensitivity of viable cells from lymph nodes with malignant lymphoma.

Viable cell suspensions were prepared from 31 nodes diagnosed non-Hodgkin's malignant lymphoma, and from 30 non-malignant nodes. The cells were examined and counted by phase contrast microscopy. The suspensions were characterized by the percentage of large cells and by a colchicine-sensitivity index.

Chronic lymphocytic leukemia: correlation of clinical course and therapeutic response with in vitro testing and morphology of lymphocytes.

Forty-two patients with chronic lymphocytic leukemia (CLL) were studied for morphology of lymphocytes by light and electron microscopy (EM), in vitro responses of lymphocytes to a battery of physical and chemical agents, overall clinical status, immunologic status, course, and response to therapy. CLL lymphocytes could be classified by EM into four groups on the basis of cell size and nuclear contour and by light microscopy into two groups, small cells and large cells (lymphosarcoma cells). Patient survival did not vary with cell size or morphology as determined by light or electron microscopy.

A colchicine-sensitivity test for leukaemic lymphocytes.

Non-dividing lymphocytes from patients with chronic lymphocytic leukaemia were more sensitive than normal lymphocytes to reagents as prednisolone, cytarabine, vincristine and colchicine. The maximum difference was obtained when the cells were incubated with colchicine at 37 degrees C for 20 h. The sensitivity was measured by a 'sensitivity index' which was an estimate of the average percentage of lymphocytes killed by 1.

Inhibition by ionophore A23187 of the cytotoxicity of vincristine, colchicine and X-rays to leukemic lymphocytes.

The ionophore A23187 was tested for its effect on the sensitivity of normal and leukemic lymphocytes to colchicine, vincristine, and X-irradiation. The ionophore was used because it transfers divalent cations through biological membranes and causes the transformation of normal lymphocytes. The sensitivity of the cells was measured by incubation of lymphocyte suspensions with and without reagent at 37 degrees C for one to seven days and counting the number of viable lymphocytes before and after incubation.

Sensitivity of leukaemic lymphocytes to microtubular reagents.

Tests were make in this and in previous studies on the cytocidal action of cold (27 degrees), heat (43-50 degrees) anoxia, EDTA, colchicine and vincristine on non-dividing lymphocytes from normal individuals and from patients with chronic lymphocytic leukaemia. The reagents were selected for this work because they have been reported to have an effect on microtubules of various types of cells. All of the reagents were found to be more toxic to leukaemic than to normal lymphocytes.