<i>In vitro</i> determination of tumour chemosensitivity in haematological malignancies

Bird, Martin C.; Bosanquet, AG; Gilby, Edward D.

doi:10.1002/hon.2900030102

Cited by 57 publications

(29 citation statements)

References 12 publications

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“…The chemosensitivity of tumour cells taken from different biopsy sites in haematological tumours has, however, not been similarly investigated. We have, therefore, studied the chemosensitivity of leukocytes taken simultaneously from peripheral blood and bone marrow of patients with chronic lymphocytic leukaemia (CLL), acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML), using a short-term differential staining cytotoxicity (DiSC) assay previously reported by us and others (Bird et al, 1985(Bird et al, , 1986Bosanquet et al, 1983;Weisenthal et al, 1984).…”

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confidence: 99%

“…Samples were diluted 1:1 (v/v) with PBS, and the leukocyte population (always >98% viable) was obtained by centrifugation over Ficoll-hypaque as described previously (Bird et al, 1985).…”

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confidence: 99%

“…The DiSC or micro-DiSC assay was performed as previously described (Bird et al, 1985(Bird et al, , 1986. Briefly, drugs were diluted to the required concentration range with PBS, and incubated with cells (lxl05ml-1 or 5x105 ml-1 in RPMI 1640 medium containing 10% foetal calf serum and 24mM NaHCO3 (RPMI-FCS)) under 5% CO2 at 37°C for 4 days.…”

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confidence: 99%

“…Single tubes were set up for each drug concentration and six control tubes received PBS in place of the drug. (With this system, the standard deviation on the results has been variously estimated at 12% and 20% (Bird et al, 1985(Bird et al, , 1986). Following this, cells were stained with nigrosin-fast green stain, containing a known number of permanently fixed duck red blood cells (DRBC), and cytocentrifuged onto collagen-coated slides.…”

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The influence of sample source and cell concentration on the in vitro chemosensitivity of haematological tumours

Bird¹,

Forskitt²,

Gilby³

et al. 1986

Br J Cancer

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Summary The Differential Staining Cytotoxicity (DiSC) assay has been used to study the effects of sample source and cell concentration on the in vitro chemosensitivity of haematological malignancies.The chemosensitivity of blood and bone marrow samples was significantly associated (P<0.001) in 12 cases where both were tested simultaneously. In 8 of the cases, where the in vitro result could be compared with clinical response, the in vitro and in vivo chemosensitivity was in agreement in 7, for both blood and bone marrow samples.The in vitro chemosensitivity of chronic lymphocytic leukaemia blood lymphocytes was dependent on the cell concentration for 4 out of 5 drugs tested. A five fold reduction in cell number resulted in a significantly greater cell kill with 4-hydroperoxycyclophosphamide, a greater cell kill (not significant) with chlorambucil and adriamycin, and a significantly lower cell kill with prednisolone. The cell concentration did not affect vincristine cytotoxicity.These results suggest that sample source is not an important consideration for the in vitro chemosensitivity of leukaemias, but that the cell concentration tested should not be varied from assay to assay if the results are to be used for comparative purposes.

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confidence: 99%

“…Samples were diluted 1:1 (v/v) with PBS, and the leukocyte population (always >98% viable) was obtained by centrifugation over Ficoll-hypaque as described previously (Bird et al, 1985).…”

mentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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The influence of sample source and cell concentration on the in vitro chemosensitivity of haematological tumours

Bird¹,

Forskitt²,

Gilby³

et al. 1986

Br J Cancer

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“…Two hundred cells were counted on each slide. In preliminary experiments this technique compared well in sensitivity to trypan blue exclusion and had the advantage that the morphology of viable cells could be assessed (Bird et al, 1985).…”

Section: Effects Of Cytokinesmentioning

confidence: 99%

Cytotoxic effects of tumour necrosis factor and gamma-interferon on acute myeloid leukaemia blasts

Price¹,

Brenner²,

Prentice³

et al. 1987

Br J Cancer

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Summary We have studied the cytotoxic effects of recombinant tumour necrosis factor and recombinant gamma interferon on primary cultures of leukaemia cells. The agents were added alone or in a combination to cells from 17 patients. Eleven had acute myeloblastic leukaemia (6 at presentation, 5 at relapse), 4 had acute lymphoblastic leukaemia, one had hairy cell leukaemia, and 2 had chronic myeloid leukaemia -one of whom was in myeloid blast transformation. Cells from patients with lymphoid malignancies or from the patient with chronic phase CML were not affected by either agent in any dose combination. In contrast, reduction of viability of myeloid blasts was weakly accelerated by TNF and y-interferon individually. Combination of the agents invariably produced enhanced killing and additive or synergistic effects were seen when 20-500 IU ml-I of each cytokine was present. This sensitivity was also shown by blast cells from 5 patients with relapsed AML. We therefore suggest that trials of such combination therapy may be indicated in drug resistant or relapsed AML.

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Long-term comparison of results of a drug sensitivity assayin vitro with patient response in lymphatic neoplasms

Bird

Bosanquet

Forskitt

et al. 1988

Cancer

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A short-term differential staining cytotoxicity (DiSC) assay was used to assess the sensitivity of tumor cells in vitro from patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma to various cytotoxic drugs. The results have been correlated with drug sensitivities of the tumors in vivo. The chemosensitivity in vitro of eight patients with CLL was observed for 12 to 42 months. In 44 cases the assay correctly predicted seven sensitive and 30 resistant tumors (84% positive correlations). There were six false predictions of sensitivity and one false prediction of resistance. Repeated testing of patients receiving treatment revealed significant and progressive development of drug resistance, while serial tests on untreated patients with CLL gave unaltered results. The development of cross-resistance to structurally related drugs was observed after treatment and many samples showed a high level of cross-resistance. However, teniposide showed greater activity than etoposide, and mitoxantrone showed greater activity than the anthracyclines. The high level of agreement between laboratory and clinical results suggests that the DiSC assay may have a useful place (1) in guiding the clinician in the selection of drugs for chemotherapy and (2) in giving an added indication of prognosis for an individual with a lymphatic neoplasm.

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In vitro determination of tumour chemosensitivity in haematological malignancies

Cited by 57 publications

References 12 publications

The influence of sample source and cell concentration on the in vitro chemosensitivity of haematological tumours

The influence of sample source and cell concentration on the in vitro chemosensitivity of haematological tumours

Cytotoxic effects of tumour necrosis factor and gamma-interferon on acute myeloid leukaemia blasts

Long-term comparison of results of a drug sensitivity assayin vitro with patient response in lymphatic neoplasms

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