Radiation and taxol effects on synchronized human cervical carcinoma cells

Geard, Charles R.; Jones, Jacqueline M.

doi:10.1016/0360-3016(94)90457-x

Cited by 60 publications

(21 citation statements)

References 15 publications

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“…Maximum toxicity of PAC is at mitosis, in agreement with the findings of others (Donaldson et al. 1994;Geard and Jones, 1994;Long and Fairchild, 1994), and consistent with the mitotic spindle apparatus forming the main target of PAC. This occurs irrespective of whether synchronisation of cells is achieved using serum stimulation of quiescent cells (Donaldson et al.…”

Section: Treatmentssupporting

confidence: 78%

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S-phase specificity of cell killing by docetaxel (Taxotere) in synchronised HeLa cells

Hennequin

Giocanti²,

Favaudon³

1995

Br J Cancer

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Summary Cell viability following short (1 h) contact with paclitaxel or docetaxel was assayed using synchronised HeLa cells. Docetaxel proved almost totally lethal against S-phase cells. Its toxicity was only partial against cells in mitosis. and declined to a minimum with progression to GI. For paclitaxel. cytotoxicity increased with progression through S and G,, peaked at the time of mitosis. and decreased thereafter. Maximum resistance to paclitaxel was in early S. Although lethal, brief exposure to docetaxel in S-phase did not delay progression through S and G2. (Extra et al., 1993; Rowimsky et al., 1992).The elucidation of the mode of action of taxoids is of great interest in consideration of their promising anti-tumour potential. PAC in the micromolar range is a promoter of tubulin polymenrsation, thus decreasing the critical concentration of tubulin required for the self-assembly of microtubules (Schiff et al., 1979) in the absence of microtubule-associated proteins and of GTP (Schiff and Horwitz, 1981 , promotes the reorganisation of the microtubule network into dense bundles or asters (De Brabander et al., 1981a;Roberts et al., 1989) and induces complex arrays of cross-bridged microtubules and intermediate filaments (Geuens et al.. 1983;Green and Goldman, 1983). DOC produces the same effects as PAC on the microtubule system, yet it appears more potent than PAC on a molar basis (Gueritte-Voegelein et al., 1991; Ringel and Horwitz, 1991;Horwitz, 1992;Diaz and Andreu, 1993). These effects have been proposed to play a major role in the antineoplastic activity of PAC (Rowinsky et al., 1988); however, they are not observed unless cells are exposed for extended lengths of time to supralethal amounts of drug (Amin-Hanjani et al., 1991). and attempts at identifying the mode of action of taxoids in living cells from studies in the test tube should take into consideration the capability of cells to accumulate these drugs in large excess over the medium (Jordan et al., 1993;Riou et al., 1994).Exposure of human cells to PAC brings about a sustained block at the metaphase-anaphase boundary. This again requires prolonged, continuous contact with lethal amounts of drug, and large differences in the efficiency of the mitotic block occur among cell lines (Gupta, 1985;Roberts et al.. 1990)

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Section: Treatmentssupporting

confidence: 78%

“…This occurs irrespective of whether synchronisation of cells is achieved using serum stimulation of quiescent cells (Donaldson et al. 1994), mitotic shake-off selection (Geard and Jones, 1994). nocodazole treatment (Long and Fairchild, 1994) or double thymidine block ( Figure 5).…”

Section: Treatmentsmentioning

confidence: 99%

S-phase specificity of cell killing by docetaxel (Taxotere) in synchronised HeLa cells

Hennequin

Giocanti²,

Favaudon³

1995

Br J Cancer

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“…The results obtained with this combined treatment modality in vitro seem to be somewhat less than has been expected. Both supraadditive [3][4][5][6] and additive [7][8][9][10] results have been reported in a variety of malignant cell lines, but subadditive interaction has also been demonstrated in vitro. 11,12 Contradictory outcomes in cytotoxic studies on the mechanism of action of paclitaxel have thrown doubt on the accumulation in G 2 /M being the main reason for the antitumor activity of paclitaxel.…”

mentioning

confidence: 99%

Paclitaxel combined with fractionated radiation in vitro: A study with vulvar squamous cell carcinoma cell lines

Raitanen

Rantanen

Kulmala

et al. 2001

Intl Journal of Cancer

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Concurrent paclitaxel and radiation has given promising results in the treatment of a variety of solid tumors. We wanted to test the efficacy of this combination for vulvar carcinoma, which currently has a poor outcome in advanced stages. The radiation sensitivity, sublethal damage repair (SLDR) capacity and effect of paclitaxel during fractionated radiation were assessed in our study on 7 vulvar inherently radioresistant squamous cell carcinoma (SCC) cell lines. The 96-well plate clonogenic assay was used. Survival data were fitted to the linear quadratic model. The area under the curve (AUC), equivalent to mean inactivation dose (D ), was obtained with numerical integration. AUC ratios between single-dose radiation and fractionated radiation with or without paclitaxel were used to determine the SLDR of the cell lines and the effect of paclitaxel on it. Seven currently tested vulvar SCC cell lines were found to have a limited capacity of repairing sublethal damage (SLD). Only 3 of them presented SLDR of significance. The effect of concurrent radiation and paclitaxel was clearly additive when the radiation dose was fractionated in most of the cell lines. In addition, 2 of the cell lines having SLDR exhibited a trend toward losing the repair capacity when paclitaxel was present during the irradiation. In addition, the survival curve of the UM-SCV-1A cell line gave the impression of a true paclitaxel effect on SLDR. Paclitaxel used concurrently with fractionated radiation showed effectiveness on vulvar carcinoma. The effect was at least additive and could even be expected to abrogate the SLDR during split-dose radiation.

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“…4 For this purpose, chemotherapeutic agents should have anti-cancer activity against cervical cancer cells and behave as a radiosensitizer. The rationales of using paclitaxel in combination with cisplatin in concurrent chemoradiation are that 1) paclitaxel acts as a radiosensitizer in vitro, 7,8 2) a phase I study with cisplatin plus paclitaxel has proved excellent overall response in patients with locally advanced cervical cancer, 9 and 3) cisplatin plus paclitaxel have activity against metastatic and recurrent cervical cancer. 10 Recently, several studies which used cisplatin plus paclitaxel with concurrent radiation have been reported.…”

Section: Introductionmentioning

confidence: 99%

Comparison of concurrent chemoradiotherapy with cisplatin plus 5-fluorouracil versus cisplatin plus paclitaxel in patients with locally advanced cervical carcinoma

et al. 2009

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Objective: The aim of this study was to compare survival outcomes and toxicities between concurrent radiotherapy with cisplatin plus 5-fluorouracil and that with cisplatin plus paclitaxel in patients with locally advanced cervical carcinoma. Methods:We retrospectively reviewed data from 93 locally advanced cervical carcinoma patients (stage IB to IVA) who had been treated by concurrent radiotherapy with cisplatin plus 5-fluorouracil (CF, n=45) vs. cisplatin plus paclitaxel (CP, n=48) as primary therapy. Toxicities and survival outcomes were compared. Results: In the CP group, there were higher frequencies of severe (grade 3 or 4) leukopenia (79.2%, as compared to 11.1% in the CF group), severe neutropenia (77.1%, as compared to 8.9% in the CF group) and severe peripheral neuropathy (12.5%, as compared to 2.2% in the CF group). In the CF group, there were higher frequencies of severe nausea (33.3%, as compared to 14.6% in the CP group) and severe hyponatremia (11.1%, as compared to 0% in the CP group). Five-year DFS of the CF and CP groups was 67.4% and 79.1%, respectively (p=NS). Five year OS of the CF and CP groups was 79.6% and 80.9%, respectively (p=NS). Conclusion: Concurrent radiotherapy with cisplatin plus paclitaxel showed increased leukopenia, neutropenia and peripheral neuropathy, but less gastrointestinal toxicity (nausea) than that with cisplatin plus 5-fluorouracil. Survival outcome between these two groups was not statistically different in this study. Large prospective randomized controlled studies will be needed to confirm this result.

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Radiation and taxol effects on synchronized human cervical carcinoma cells

Cited by 60 publications

References 15 publications

S-phase specificity of cell killing by docetaxel (Taxotere) in synchronised HeLa cells

S-phase specificity of cell killing by docetaxel (Taxotere) in synchronised HeLa cells

Paclitaxel combined with fractionated radiation in vitro: A study with vulvar squamous cell carcinoma cell lines

Comparison of concurrent chemoradiotherapy with cisplatin plus 5-fluorouracil versus cisplatin plus paclitaxel in patients with locally advanced cervical carcinoma

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