In Vitro Studies of Taxol as a Radiation Sensitizer in Human Tumor Cells

Liebmann, James; Cook, John A.; Fisher, Joyce M.; Teague, Diane; Mitchell, James B.

doi:10.1093/jnci/86.6.441

Cited by 242 publications

(104 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There are reports suggesting, that supraadditive interaction could be seen without mitotic arrest; 4,5 furthermore, even if mitotic arrest occurs, the enhancement in radioresponse is not necessarily the result of this. 6,9 When malignant tumors are exposed to paclitaxel followed by radiation, the resulting growth inhibition or delay is achieved by several mechanisms on both cellular and molecular levels. When paclitaxel is combined with radiation, the growth inhibition is expected to be potentiated at least by paclitaxel-induced inhibition of sublethal repair and repopulation, as well as the apoptosis-enabled reoxygenation when in vivo models are used.…”

Section: Discussionmentioning

confidence: 99%

“…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%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

View full text Add to dashboard Cite

show abstract

“…In the literature, it was demonstrated that vincristine-resistant RPMI-8226 and U-266 MM cells did not show any cross-resistance when exposed to ␥-radiation and vincristine-resistant sublines were radiosensitive (Mutlu et al, 2011). In addition, the results of other studies showed that paclitaxel enhanced tumor radio response (Choy et al, 1993;Klappe et al, 2004;Liebmann et al, 1994;Milas et al, 1994). Both vincristine and paclitaxel are chemotherapeutic agents that stabilize microtubule activity and arrest cells in G 2 -M phase.…”

Section: Cross-resistance To Radiationmentioning

confidence: 98%

An update on molecular biology and drug resistance mechanisms of multiple myeloma

Mutlu

Kiraz

Gündüz

et al. 2015

Critical Reviews in Oncology/Hematology

View full text Add to dashboard Cite

Multiple myeloma (MM), a neoplasm of plasma cells, is the second most common hematological malignancy. Incidance rates increase after age 40. MM is most commonly seen in men and African-American population. There are several factors to this, such as obesity, environmental factors, family history, genetic factors and monoclonal gammopathies of undetermined significance (MGUS) that have been implicated as potentially etiologic. Development of MM involves a series of complex molecular events, including chromosomal abnormalities, oncogene activation and growth factor dysregulation. Chemotherapy is the most commonly used treatment strategy in MM. However, MM is a difficult disease to treat because of its marked resistance to chemotherapy. MM has been shown to be commonly multidrug resistance (MDR)-negative at diagnosis and associated with a high incidence of MDR expression at relapse. This review deals with the molecular aspects of MM, drug resistance mechanisms during treatment and also possible new applications for overcoming drug resistance. © 2015 Elsevier Ireland Ltd

show abstract

“…As mitotic cells with double strand breaks will lose genetic material following cell division, irradiation of MSA-treated, transiently arrested late G2-/M-phasecells will result in genomic instability and eventually mitotic catastrophe. (35,(41)(42)(43)(44)(45) This implies that the therapeutic efficacy of the combined treatment modality strongly depends on the innate cellular drug sensitivity and in particular on the combination scheduling. Indeed, effects ranging from supra-additive interactions (Figure 3 A similar effect has also been described for synchronized HeLa cells, in which docetaxel resulted in a S-phase specific (and hence radioresistant) cell killing.…”

Section: Rationale For the Combined Use Of Irradiation And Cytotoxic mentioning

confidence: 99%

Microtubule stabilising agents and ionising radiation: Multiple exploitable mechanisms for combined treatment

Bley

Furmanova

Orlowski

et al. 2013

European Journal of Cancer

View full text Add to dashboard Cite

Combined radiochemotherapy treatment modalities are in use for many indications and therefore of high interest. Even though a combined modality in clinical use is often driven by prag-matic aspects, mechanistic preclinical-based concepts of interaction are of importance in order to translate and implement an optimal combination and scheduling of two modalities into the clinics. The use of microtubule stabilizing agents is a promising strategy for anti-cancer therapy as a part of combined treatment modality with ionizing radiation. Traditionally, microtubule targeting agents are classified as cytotoxic chemotherapeutics and are mostly used in a maxi-mally tolerated dose regimen. Apart from direct cytotoxicity and similar to mechanisms of mo-lecular targeting agents, microtubule stabilizing agents interfere with multiple cellular process-es, which can be exploited as part of combined treatment modalities. Recent preclinical investi-gations on the combination of ionizing radiation and microtubule stabilizing agents reveal new mechanistic interactions on the cellular and tumor level and elucidate the supra-additive tumor response observed particularly in vivo. The major focus on the mechanism of interaction was primarily based on radiosensitization due to cell cycle arrest in the most radiosensitive G2/M-phase of the cell cycle. However, other mechanisms of interaction such as reoxygenation and direct as well as indirect endothelial damage have also been identified. In this review we sum-marize and allocate additive and synergistic effects induced by the combined treatment of clini-cally relevant microtubule stabilizing agents and ionizing radiation along a described radiobio-logical framework encompassing distinct mechanisms relevant for exploiting the combination of drugs and ionizing radiation. primarily based on radiosensitization due to cell cycle arrest in the most radiosensitive G2/Mphase of the cell cycle. However, other mechanisms of interaction such as reoxygenation and direct as well as indirect endothelial damage have also been identified. In this review we summarize and allocate additive and synergistic effects induced by the combined treatment of clinically relevant microtubule stabilizing agents and ionizing radiation along a described radiobiological framework encompassing distinct mechanisms relevant for exploiting the combination of drugs and ionizing radiation.

show abstract

In Vitro Studies of Taxol as a Radiation Sensitizer in Human Tumor Cells

Abstract: Paclitaxel can radiosensitize to a modest degree some, but not all, human cell lines by a mechanism that requires the production of a G2/M cell cycle block. Additional studies are needed to define more clearly the mechanism by which paclitaxel radiosensitizes cells.

Cited by 242 publications

References 0 publications

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

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

An update on molecular biology and drug resistance mechanisms of multiple myeloma

Microtubule stabilising agents and ionising radiation: Multiple exploitable mechanisms for combined treatment

Contact Info

Product

Resources

About