BCNU stability as a function of ethanol concentration and temperature

Tepe, Paul; Hassenbusch, Samuel J.; Benoit, Ronald; Anderson, James H.

doi:10.1007/bf00146872

Cited by 7 publications

(4 citation statements)

References 13 publications

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“…BCNU (M r 214.06; Bristol-Myers Pharmaceuticals) was prepared by dissolving 100 mg of BCNU in 30 mL of 10% ethanol and was stored at À70jC to ensure drug stability (21). Subsequently, BCNU stock solution was added to culture medium or was injected i.p.…”

Section: Methodsmentioning

confidence: 99%

Noninvasive Assessment of E2F-1–Mediated Transcriptional Regulation In vivo

et al. 2008

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Targeted therapies directed against individual cancer-specific molecular alterations offer the development of diseasespecific and individualized treatment strategies. Activation of the transcription factor E2F-1 via alteration of the p16-cyclinD-Rb pathway is one of the key molecular events in the development of gliomas. E2F-1 binds to and activates the E2F-1 promoter in an autoregulatory manner. The human E2F-1 promoter has been shown to be selectively activated in tumor cells with a defect in the pRb pathway. Paradoxically, E2F-1 also carries tumor suppressor function. Our investigations focused on analyzing the dynamics of the activity of the E2F-1 responsive element under basal conditions and certain stimuli such as chemotherapy using molecular imaging technology. We constructed a retrovirus bearing the Cis-E2F-TA-LITG reporter system to noninvasively assess E2F-1-dependent transcriptional regulation in culture and in vivo. We show that our reporter system is sensitive to monitor various changes in cellular E2F-1 levels and its transcriptional control of our reporter system to follow the state of the Rb/E2F pathway and the DNA damage-induced up-regulation of E2F-1 activity in vivo. Exposure to 1,3-bis(2-chloroethyl)-1-nitrosourea leads to increased E2F-1 expression levels in a dose-and time-dependent manner, which can be quantified by imaging in vivo, leading to an alteration of cell cycle progression and caspase 3/7 activity. In summary, noninvasive imaging of E2F-1 as a common downstream regulator of cell cycle progression using the Cis-E2F-TA-LUC-IRES-TKGFP reporter system is highly attractive for evaluating the kinetics of cell cycle regulation and the effects of novel cell cycle targeting anticancer agents in vivo. [Cancer Res 2008;68(14):5932-40]

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Section: Methodsmentioning

confidence: 99%

Noninvasive Assessment of E2F-1–Mediated Transcriptional Regulation In vivo

et al. 2008

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“…The maximal effect of BCNU may occur within the first 24 hours after administration (Personal communication, Frank A. Bambarola, Oncology Division, Bristol-Myers, Evansville, IN), and the half-life of BCNU at 37 ~ C is approximately 6-8 hours [6]. After 96 hours, a false negative may occur due to the surviving cells continuing to divide and replacing those cells which may have been killed by BCNU.…”

Section: B Bcnu Stabilitymentioning

confidence: 98%

To the editor: Following is our response to the comments by Tonnet al

et al. 1993

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“…BCNU was dissolved in ethanol (ETOH) to a final concentration of 10%. In addition, a separate sample of BCNU was dissolved in 100% D5W (5% dextrose in water) [Baxter Healthcare Corp, Deerfield, IL] as described by Tepe et al [47] and Levin et al [48]. The latter authors reported that BCNU recovery rates were higher (approximately 96%) when dissolved in 100% D5W than in ETOH (approximately 90%).…”

Section: Drugsmentioning

confidence: 99%

Test for chemotherapeutic sensitivity of cerebral gliomas: use of colorimetric MTT assay

et al. 1992

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This study was undertaken to evaluate the colorimetric MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide] assay as a means of testing the sensitivity of gliomas to chemotherapeutic agents in vitro. Eight human glioma established cell lines were plated in 96-well tissue culture plates and incubated for 4 days with 10 different anti-cancer agents; 5 different concentrations of each drug were tested. The MTT dye was then added to the wells, and the resulting formazan precipitate was solubilized with dimethylsulfoxide (DMSO). The spectrophotometric absorbance (measured at 570 nm) of control and experimental wells was used to calculate the cytotoxicity index (CI). Values with a CI greater than 50% growth inhibition indicated cytotoxic efficacy (sensitivity to the chemotherapeutic drug). Six of the seven (85.7%) glioma cell lines were highly sensitive at varying concentrations to mitomycin C, cisplatin, and doxorubicin. Four of the seven (57.1%) cell lines demonstrated intermediate sensitivity to mitoxantrone and vinblastine. Five of the seven (71.4%) cell lines exhibited resistance to etoposide, bleomycin, cosmegen, and BCNU. One of the cell lines tested, U-138MG, failed to produce the MTT formazan precipitate, so that the sensitivity of this cell line to the panel chemotherapeutic drugs could not be determined. The variability of the results indicates the need for an in vitro screening method to evaluate the effectiveness of clinical and experimental chemotherapeutic agents. The MTT assay provides a rapid method of screening antineoplastic agents against gliomas for cytotoxicity.

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BCNU stability as a function of ethanol concentration and temperature

Cited by 7 publications

References 13 publications

Noninvasive Assessment of E2F-1–Mediated Transcriptional Regulation In vivo

Noninvasive Assessment of E2F-1–Mediated Transcriptional Regulation In vivo

To the editor: Following is our response to the comments by Tonnet al

Test for chemotherapeutic sensitivity of cerebral gliomas: use of colorimetric MTT assay

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