Assay of anti-cancer drugs in tissue culture: Relationship of relapse free interval (RFI) and in vitro chemosensitivity in patients with malignant cerebral glioma

Abstract

Summary One hundred and seventeen patients with cerebral glioma (Kernohan grades III and IV) were treated with adjuvant chemotherapy using procarbazine (PCB), CCNU and vincristine (VCR) following whole head irradiation. Cell cultures were prepared from 40 patients in this series and their sensitivity to each cytotoxic drug was assessed in a mictotitration assay with 35 S-methionine incorporation as the end point. Twenty-two of forty (55%) patients responded to PCB and/or CCNU in vitro, and sensitivity to these drugs was linked with increased RFI, whilst sensitivity to VCR was not. The RFI of patients who had responded to PCB or CCNU in vitro was significantly longer than the RFI of patients whose tumours failed to respond in vitro or patients who had not been tested. There was no difference in sex ratio, extent of operation, radiation dose and degree of steroid cover between responders, non-responders and untested groups. Grade III tumours tended to be more sensitive in vitro than grade IV tumours. The age of patients also influenced in vitro chemosensitivity. Patients with chemosensitive tumours in vitro tended to be younger than patients with insensitive tumours in vitro. Further statistical analysis, taking into account these prognostic factors, indicated an association between chemosensitivity in vitro and RFI.

The MTT assay for chemosensitivity testing of human tumors of the central nervous system

“…If this is due to a biological phenomen like cell viability or proliferative capacity, which influences the results of the assays in different ways, or to the effect of different assay conditions, is presently unknown. Similar results to our findings in the MTT assay were reported by Bogdahn [15] and Thomas [40]. Nonsignificant was also the higher in vitro resistance in female patients, as in the series of Bogdahn [15].…”

Tissue transglutaminase 2 inhibition promotes cell death and chemosensitivity in glioblastomas

“…Chemosensitivity testing in vitro shows variable responses between individual cell lines and particular drugs agent tested. There has however been a general correlation between chemosensitivity testing in vitro compared with in vivo responses (32,33). Tumors resistant to chemotherapy have developed mechanisms that inhibit apoptotic pathways.…”

Glutathione levels and chemosensitizing effects of buthionine sulfoximine in human malignant glioma cells

“…The MTT assay was chosen as a rapid screening method of proliferative capacity for both the biopsy and cultured cells. Previous studies have established the validity of using proliferative assays as monitors of brain tumor cell drug sensitivities [20,21]. Both fresh biopsy material and cells which had been expanded by culture in vitro were used in the chemosensitivity testing.…”