Use of verapamil to enhance the antiproliferative activity of BCNU in human glioma cells: an in vitro and in vivo study

Bowles, Alfred P.; Pantazis, Cooley G.; Wansley, William

doi:10.3171/jns.1990.73.2.0248

Cited by 26 publications

(9 citation statements)

References 8 publications

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“…Cell cultures of human brain tumors are an established and valuable tool in the ongoing brain research [10,17,29,30]. There is as well a good support from the literature [31,32] and our own experience [11,12], that the MTT assay seems to be a promising method for antiproliferative studies in vitro.…”

Section: Discussionmentioning

confidence: 95%

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

et al. 1992

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In this study we assessed the influence of patient- and drug-specific parameters in the short-term MTT-chemosensitivity assay in 150 primary cell cultures derived from human brain tumors. In 45 patients the MTT assay was directly compared with the CFA (Colony Forming Assay). Resistance was 10-20% higher in the MTT assay than in the CFA, but there was a good agreement in both assays, that more malignant gliomas had a higher in vitro chemosensitivity against ACNU and BCNU. Overall the results demonstrate, that there is no uniform correlation between the in vitro chemosensitivity and the histopathological classification of the tumors, which corresponds well to the clinical situation. On the basis of this study we suggest prospective clinical trials with the MTT assay in human brain tumors.

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Section: Discussionmentioning

confidence: 95%

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

et al. 1992

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“…Tumor volume was recorded weekly by an individual blinded to the treatment strategy. A group receiving only BCNU was not included in this study for humane reasons, as the effect of BCNU alone on tumors is well established in the literature (20). Moreover, the aim of this study was to compare mice receiving H-ferritin siRNA with mice receiving the NS siRNA in order to determine whether there is a difference in efficacy between these 2 groups.…”

Section: Chemotherapeutic Efficacy In Vivomentioning

confidence: 99%

“…Throughout the course of the C-liposomes:siRNA administration, both groups received 12.5 mg/kg of BCNU weekly through intraperitonel injection. This concentration of BCNU is less than 50% of the reported effective dose (20) and was chosen on the basis of the decreased LD 50 observed in the human cell culture. The study was terminated at week 7 because the tumor growth was too large to continue in the control group.…”

Section: H-ferritin Sirna Enhanced Chemotherapeutic Sensitivity In Vivomentioning

confidence: 99%

Heavy Chain Ferritin siRNA Delivered by Cationic Liposomes Increases Sensitivity of Cancer Cells to Chemotherapeutic Agents

et al. 2011

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Approximately half of all gliomas are resistant to chemotherapy, and new therapeutic strategies are urgently needed to treat this cancer. We hypothesized that disrupting iron homeostasis in glioma cells could block tumor growth, based on an acute requirement for high levels of iron to meet energy requirements associated with their rapid growth. Ferritin is best known as an intracellular iron storage protein, but it also localizes to tumor cell nuclei where it seems to protect DNA from oxidative damage and to promote transcription. In this study, we hypothesize that silencing the H-ferritin (heavy chain ferritin) gene could increase tumor sensitivity to chemotoxins. To test this hypothesis, H-ferritin siRNA was delivered to several human cancer cell lines by using cationic liposomes (C-liposome). H-ferritin siRNA decreased protein expression by 80% within 48 hours, and this decrease was associated with more than 50% decrease in the LD 50 for DNA-alkylating agent carmustine (BCNU), which is commonly used to treat glioma in clinic. In a subcutaneous mouse model of human glioma, intratumoral injections of liposomes containing H-ferritin siRNA reduced the effective dose of BCNU needed for tumor suppression by more than 50%. A plasmid supercoil relaxation assay showed that H-ferritin specifically and directly protected DNA from BCNU treatment. H-ferritin siRNA additionally seemed to increase apoptosis in glioma cells in vitro upon H-ferritin knockdown. Overall, our results illustrate how silencing H-ferritin can effectively sensitize tumors to chemotherapy and also show the ability of C-liposomes to serve as a novel in vivo delivery tool for siRNAs. Cancer Res; 71(6); 2240-9. Ó2011 AACR.

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“…NIM is one of Ca 2+ antagonists. In recent years, Ca 2+ antagonists have been confirmed to show synergistic effect on the chemotherapeutics and could reverse the drug resistance of tumor cells for chemotherapeutics [7,8] . The combined use of MTX, CBP, Vm-26 and NIM seems reasonable, but there were little reported literatures.…”

Section: Discussionmentioning

confidence: 99%

In vitro Study of Interstitial Combination Chemotherapy in the Treatment of Glioma

Zhang

Wang

Chen

2005

Chinese-German J Clin Oncol

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Objective: To investigate the inhibitory effects of combination chemotherapy of Carboplatin (CBP), Teniposide (Vm-26), Methasquin (MTX), and Nimodipine (NIM) on glioma, and to explore the sensitivity of glioma cells to different treatment regimens so as to provide some clues for clinical usage of interstitial combination chemotherapy. Methods: MTT assay and 3 H-TdR incorporation assay were performed to evaluate the inhibitory effects upon the proliferation of glioma cells, and to compare the sensitivity of glioma cells to administration of CBP, Vm-26, MTX, and NIM with that of the administration of CBP+NIM, Vm-26+NIM, MTX+NIM, CBP+Vm-26+MTX, or CBP+Vm-26+MTX+NIM, respectively. Results: The inhibition rate of CBP+Vm-26+MTX+NIM combination administration against glioma cells was 96.64%, higher than that of CBP+NIM (69.03%), Vm-26+NIM (71.53%), MTX+NIM (52.75%), CBP+Vm-26+MTX (78.59%) (P <0.01), and the dosage of CBP, Vm-26, and MTX was declined to 1/10-1/100 that of respective use of CBP, Vm-26, and MTX. Conclusion: The curative effect of combination administration of CBP, Vm-26, MTX, and NIM was much better than that of respective administration, suggesting a higher inhibition rate and a lower dosage use.Glioblastoma is one of the most common malignant brain tumors in adults. Even if 99% of glioblastoma mass is removed during surgery, the tumor cells can still resume to the original figure after 8 weeks, and the recurrent rate is extremely high. Eliminating the residual cells and preventing recurrence had thereafter become the main treatment strategy. However, 30 years of studies have not clearly demonstrated a survival advantage for adjuvant chemotherapy regimens, and even though the results of meta-analysis are positive, the very modest increase in survival is still disappointing. New drugs and new treatment strategies are urgently needed to objectively change the still dismal fate of glioma patients. The purpose of this research is to in vitro evaluate the effects of combination chemotherapy of four commonly used chemotherapeutic drugs on glioma to provide information for clinical usage. Materials and methods Clinical materialsForty patients (32 initial patients and 8 recurrence patients) were diagnosed as having glioma in Tongji Hospital, including 27 men and 13 women, with age ranging

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Use of verapamil to enhance the antiproliferative activity of BCNU in human glioma cells: an in vitro and in vivo study

Cited by 26 publications

References 8 publications

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

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

Heavy Chain Ferritin siRNA Delivered by Cationic Liposomes Increases Sensitivity of Cancer Cells to Chemotherapeutic Agents

In vitro Study of Interstitial Combination Chemotherapy in the Treatment of Glioma

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