Comparison of cancer chemotherapeutic agents in asynchronous and synchronous 9L cells

Henderson, Sheri D.; Kimler, B. F.; Barnes, Mary L.

doi:10.1007/bf00203539

Cited by 3 publications

(2 citation statements)

References 18 publications

(31 reference statements)

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“…The correlation between high S-phase and high sensitivity to ADR is in accordance with the findings of Barranco [14]. Although more refined assays exist [15], the results suggest that simple variations of cell line growth conditions before clonogenic assay can be used to study the specificity of new drugs for cell kill in different cell cycle phases.…”

Section: Discussionsupporting

confidence: 75%

Reduced variation in the clonogenic assay obtained by standardization of the cell culture conditions prior to drug testing on human small cell lung cancer cell lines

Jensen¹,

Roed²,

Vindeløv³

et al. 1989

Invest New Drugs

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An advantage of established tumor cell lines compared to fresh human tumor specimens used in sensitivity assessments is the possibility of repeated experiments. Ultimately a database of sensitivity profiles on a panel of cell lines can be made and the sensitivity to new drugs compared with historical data. A prerequisite of this strategy is a minimal interexperimental variation. The sensitivity of eight human small cell lung cancer cell lines to adriamycin, daunomycin, aclacinomycin A, and mitoxantrone was tested in the clonogenic assay. A covariation in the sensitivity to the drugs emphasized the importance of simultaneous drug testing on the same batch of cells. On one cell line (NCI-N592) the interexperimental variation was further evaluated and a significant correlation was found between preexposure culture conditions, size of S-phase, and sensitivity to adriamycin, daunomycin, and mitoxantrone. Rigorous standardization of the growth conditions prior to clonogenic assay reduced the variation in the sensitivity to adriamycin from a factor of five to only 10-15%. It is concluded that simultaneous experiments on the same batch of cells in drug comparisons should be used if possible. Specification and standardization of culture conditions are necessary in the comparison of drugs tested in different experiments. Inclusion of the same reference drug in all experiments may further increase the validity of comparisons in different experiments.

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Section: Discussionsupporting

confidence: 75%

Reduced variation in the clonogenic assay obtained by standardization of the cell culture conditions prior to drug testing on human small cell lung cancer cell lines

Jensen¹,

Roed²,

Vindeløv³

et al. 1989

Invest New Drugs

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show abstract

“…In experimental brain tumors, this drug has demonstrated definite cytotoxicity in tissue cultures of both rat [34] and human glioma cell lines [35], and antitumor activity in rat and mouse brain tumor models [28,35,36]. The response have also been observed in recurrent or progressive primary brain tumors after failure of radiation therapy when the drug was administered intraarterially or intravenously [15,38].…”

Section: Discussionmentioning

confidence: 99%

Intracerebral chemotherapy in the 9L rat brain tumor model

et al. 1992

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We have used the 9L rat brain tumor model to search for effective chemotherapeutic approaches to the management of brain tumors. Several antineoplastic agents which have been proposed or are currently being used for human brain tumors, including 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU), bleomycin, aziridinylbenzoquinone (AZQ), cis-Platinum, and acivicin, were administered intravenously (iv), intraperitoneally (ip), or intracerebrally (ic) to rats burdened with the intracranial 9L gliosarcoma. The results confirm that BCNU is the most effective systemic agent among the chemotherapeutic agents tested as indicated by its ability to significantly increase the median survival time (MST) and life span of the tumor-burdened animals. Bleomycin is an effective agent against the intracranial 9L tumor when administered ic. While neither systemic single iv dose AZQ (0.5-2.5 mg/kg) nor multiple ip treatments (0.5-1.0 mg/kg x 5, q 6 h) were effective in prolonging the survival, single ic dose AZQ (5-50 micrograms/rat) treatment significantly increased the MST of the treated animals (P< 0.05). Systemic AZQ treatments using higher doses produced a hematological toxicity, resulting in a decrease in MST of the treated animals. Cis-Platinum, either administered ip or ic, produced only a marginal effect on survival, although acute neurologic toxicity limited the dose of cis-Platinum that could be administered ic. Acivicin, either administered ip or ic, produced no effect on the survival of treated animals. Our results suggest that local treatment with certain antineoplastic agents may be an efficient therapy in the management of brain tumors.

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The 9L rat brain tumor model for pre-clinical investigation of radiation-chemotherapy interactions

Kimler

1994

J Neuro-Oncol

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The rat 9L gliosarcoma brain tumor model has been used for more than thirty years to investigate a variety of potential therapeutic agents, combinations, schedules, and approaches that might be applicable to the management of high-grade malignant brain tumors in man. When tumor cells are implanted intracerebrally, a solid tumor grows until its mass results in the death of the animal, typically between 20 and 30 days postinoculation. Radiation therapy (either single or fractionated doses) is effective at prolonging survival in a dose-dependent manner. Numerous cancer chemotherapeutic agents, by a variety of doses, schedules, and routes of delivery, have demonstrated therapeutic efficacy in the 9L model. The combination of radiation and agents such as AZQ, BCNU, bleomycin, and cis-platinum has resulted in prolongation of survival that is significantly better than either agent used alone, without exceeding the tolerance of critical normal tissues. These pre-clinical data suggest that combining standard fractionated radiation therapy with appropriate concomitant cytotoxic chemotherapeutic agents might benefit patients with high-grade brain tumors.

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Comparison of cancer chemotherapeutic agents in asynchronous and synchronous 9L cells

Cited by 3 publications

References 18 publications

Reduced variation in the clonogenic assay obtained by standardization of the cell culture conditions prior to drug testing on human small cell lung cancer cell lines

Reduced variation in the clonogenic assay obtained by standardization of the cell culture conditions prior to drug testing on human small cell lung cancer cell lines

Intracerebral chemotherapy in the 9L rat brain tumor model

The 9L rat brain tumor model for pre-clinical investigation of radiation-chemotherapy interactions

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