Quantitation of chemosensitivity in acute myelocytic leukaemia

Lihou, Michelle G.; Smith, Peter J.

doi:10.1038/bjc.1983.229

Cited by 17 publications

(3 citation statements)

References 18 publications

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“…Since the broad scale use of chemotherapy for treating human cancers, individual drug susceptibility has been studied using various test systems. Not surprisingly, the first studies have been performed in leukaemia, where access to cancer cells is undemanding ( Bosanquet et al , 1983 ; Lihou and Smith, 1983 ; Park et al , 1983 ). For solid tumours, different test systems have been established, starting with clonogenic assays, which aimed at culturing isolated tumour cells in the presence of different cytotoxic drug concentrations in vitro in a manner much like bacterial antibiotic sensitivities.…”

Section: Discussionmentioning

confidence: 99%

Slice cultures from head and neck squamous cell carcinoma: a novel test system for drug susceptibility and mechanisms of resistance

et al. 2013

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Background:Human head and neck squamous cell carcinoma (HNSCC) fundamentally vary in their susceptibility to different cytotoxic drugs and treatment modalities. There is at present no clinically accepted test system to predict the most effective therapy for an individual patient.Methods:Therefore, we established tumour-derived slice cultures which can be kept in vitro for at least 6 days. Upon treatment with cisplatin, docetaxel and cetuximab, slices were fixed and paraffin sections were cut for histopathological analysis.Results:Apoptotic fragmentation, activation of caspase 3, and cell loss were observed in treated tumour slices. Counts of nuclei per field in untreated compared with treated slices deriving from the same tumour allowed estimation of the anti-neoplastic activity of individual drugs on an individual tumour.Conclusion:HNSCC-derived slice cultures survive well in vitro and may serve not only to improve personalised therapies but also to detect mechanisms of tumour resistance by harvesting surviving tumour cells after treatment.

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Section: Discussionmentioning

confidence: 99%

Slice cultures from head and neck squamous cell carcinoma: a novel test system for drug susceptibility and mechanisms of resistance

et al. 2013

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“…A reduction in survival, at clinically achievable drug levels, to 37% was adopted for classifying tumours into sensitive and resistant groups Moon et al, 1981;Lihou & Smith, 1983& 1985Kornblith et al, 1981;Rosenbloom et al, 1983;Kimmel et al, 1987). The pharmacokinetic parameter C x T (concentration time.product) (Mellett, 1974;Alberts et al, 1980) was used as the measure of clinically achievable drug exposure.…”

Section: Drug Testing Protocolmentioning

confidence: 99%

Comparison of in vitro activity of epipodophyllotoxins with other chemotherapeutic agents in human medulloblastomas

Tomlinson

Lihou²,

Smith³

1991

Br J Cancer

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Summary Surgical specimens from 15 medulloblastoma patients were used to establish early passage cultures. In vitro sensitivity to a battery of cytotoxic agents, including some in current medulloblastoma treatment protocols, was measured. Drug sensitivity was assessed at clinically relevant drug concentrations using the 3H-thymidine uptake method. Tumours were predicted to be sensitive if >37% were killed by exposure to drugs at clinically achievable levels. A poor response to vincristine (Vcr), cis-platin (CDDP), hydroxyurea (HU) Medulloblastoma is an important paediatric brain tumour because of its high incidence and malignant behaviour. The overall disease free survival at 5 years, in patients receiving surgery and craniospinal axis radiotherapy, is approximately 50%. This is considered to be the upper limit of curability by these treatment modalities. Chemotherapy has been shown to be advantageous in selected patient groups either as adjuvant therapy or as treatment of recurrent disease. The value of chemotherapy in the treatment of medulloblastoma will be dependent on the availability and identification of drugs active against this tumour. At present, protocols for chemotherapy usually include the lipophilic compounds carmustine (BCNU) or lomustine and procarbazine. Vincristine (Vcr), whilst poorly absorbed by cerebrospinal fluid and brain, is also commonly used (Bloom, 1986;Workman, 1986). Currently '8 in 1F therapy is being evaluated (Pendergrass et al., 1987).Cytotoxicity has been assessed by clonal assays in agar or on plastic, incorporation of 3H-thymidine into DNA, uptake of vital dyes and other methods with much the same results. Predictions of resistance are close to 100% correct; prediction of sensitivity, whilst less reliable, still has a success rate of around 70% Moon et al., 1981; Rosenbloom et al., 1983;Bogdahn, 1983;Kornblith et al., 1981;Kimmel et al., 1987). We have examined drug sensitivity in human medulloblastoma by using 14 early passage cultures. Our study provides data on the degree of heterogeneity of response between medulloblastomas obtained from a number of patients. Furthermore, the cells were from early passage cultures, and hence should give a better indication of chemosensitivity of the tumours in vivo. The epipodophyllotoxins teniposide (VM-26) and etoposide (VP16-213) were identified as potentially useful agents in this disease. We investigated the basis of primary clinical resistance to these drugs by quantitating intracellular steady-state drug concentrations, drug-induced protein-linked DNA strand breaks, and topoisomerase II expression and activity. Materials and methods Establishment of cell culturesAll studies were made on material collected at procedures performed for clinical reasons and remaining after sufficient tissue has been taken for clinical laboratory study. The histological diagnosis was confirmed by an independent neuropathologist (Professor B.W. Scheithauer). Over a period of 2 years, 16 medulloblastoma specimens were received from a total of 15 patients...

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“…Patients with leukaemia or lymphoma were excluded from this study. Results of studies on acute myelocytic leukaemia have been reported elsewhere (Lihou & Smith, 1983). All studies were made on material collected at operations performed for clinical reasons and remaining after sufficient tissue had been taken for clinical laboratory study.…”

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confidence: 99%

Limitations of the agar colony-forming assay for the assessment of paediatric tumours

Ablett¹,

Smith²,

Sheridan³

et al. 1984

Br J Cancer

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Quantitation of chemosensitivity in acute myelocytic leukaemia

Cited by 17 publications

References 18 publications

Slice cultures from head and neck squamous cell carcinoma: a novel test system for drug susceptibility and mechanisms of resistance

Slice cultures from head and neck squamous cell carcinoma: a novel test system for drug susceptibility and mechanisms of resistance

Comparison of in vitro activity of epipodophyllotoxins with other chemotherapeutic agents in human medulloblastomas

Limitations of the agar colony-forming assay for the assessment of paediatric tumours

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