Chemosensitivity of glioma cells in vitro: a meta analysis

Wolff, Johannes; Trilling, T.; Mölenkamp, Gabriele; Egeler, R. Maarten; Jürgens, Heribert

doi:10.1007/s004320050305

Cited by 129 publications

(72 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Based on in vivo and in vitro studies, brain tumors might be expected to be sensitive to chemotherapy agents, as anthracyclines [3,4]. Yet, most patients fail to achieve adequate disease control due to insufficient cytoreduction of unresectable tumors, or develop tumor relapse despite apparent gross-total resection and/or irradiation [2].…”

Section: Introductionmentioning

confidence: 99%

Detection of doxorubicin hydrochloride accumulation in the rat brain after morphine treatment by mass spectrometry

Sardi

Marca

Giovannini

et al. 2010

Cancer Chemother Pharmacol

View full text Add to dashboard Cite

Keywords: blood-brain barrier, doxorubicin, morphine, rodent model, mass spectrometry 2 ABSTRACT Purpose: The blood brain barrier discriminates the access of several molecules into the brain. This hampers the use of some drugs, as doxorubicin, potentially active for treatment of brain tumors. We explored the feasibility of active modification of the blood brain barrier protection, by using morphine pretreatment, to allow doxorubicin accumulation into the brain in an animal model. Methods:Rats were pretreated with different doses of intraperitoneal morphine before injection of doxorubicin (12 mg/kg). Quantitative analysis of doxorubicin was performed by mass spectrometry.Acute hearth and kidney damage was analyzed by measuring doxorubicin accumulation, LDH activity and malondialdehyde plasma levels. Results: The concentration of doxorubicin was significantly higher in all brain areas of rats pretreated with morphine than in control tissues (P <0.001). This was evident only at therapeutic morphine dose (10 mg/kg, three times over 24 hours), while lower doses (2.5 and 5 mg/kg) were not associated with doxorubicin accumulation.Pretreatment with morphine did not induce an elevation of LDH activity or of lipid peroxidation compared to controls. Conclusion: Our data suggest that morphine pre-treatment is able to allow doxorubicin penetration inside the brain, by modulating the blood-brain barrier. This is not associated with acute cardiac or renal toxicity. These preliminary results will enable us to generate novel therapeutic approaches to refractory or recurrent brain tumors, and might be useful in other human diseases of the central nervous system in which molecules usually stopped by the blood brain barrier may have a therapeutic impact.3

show abstract

Section: Introductionmentioning

confidence: 99%

Detection of doxorubicin hydrochloride accumulation in the rat brain after morphine treatment by mass spectrometry

Sardi

Marca

Giovannini

et al. 2010

Cancer Chemother Pharmacol

View full text Add to dashboard Cite

show abstract

“…Often, the in vitro sensitivity of cancer cells does not correlate well with in vivo response. Especially, cell cultures have been long questioned to represent glioma biology due to changes under standard culture conditions (Wolff et al, 1999;Voskoglou-Nomikos et al, 2003;Lee et al, 2006). Therefore, short-term primary cell cultures (with less than 10 trypsinization passages) and particularly three-dimensional spheroid models were considered to reflect the tumor biology better (Sutherland, 1988;Bjerkvig et al, 1990).…”

mentioning

confidence: 99%

The genomic profile of human malignant glioma is altered early in primary cell culture and preserved in spheroids

et al. 2007

View full text Add to dashboard Cite

Screening of therapeutics relies on representative cancer models. The representation of human glioblastoma by in vitro cell culture models is questionable. We obtained genomic profiles by array comparative genomic hybridization of both short-and long-term primary cell and spheroid cultures, derived from seven glioblastomas and one anaplastic oligodendroglioma. Chromosomal copy numbers were compared between cell cultures and spheroids and related to the parental gliomas using unsupervised hierarchical clustering and correlation coefficient. In seven out of eight short-term cell cultures, the genomic profiles clustered further apart from their parental tumors than spheroid cultures. In four out of eight samples, the genetic changes in cell culture were substantial. The average correlation coefficient between parental tumors and spheroid profiles was 0.89 (range: 0.79-0.97), whereas that between parental tumors and cell cultures was 0.62 (range: 0.10-0.96). In two out of three long-term cell cultures progressive genetic changes had developed, whereas the spheroid cultures were genetically stable. It is concluded that genomic profiles of primary cell cultures from glioblastoma are frequently deviant from parental tumor profiles, whereas spheroids are genetically more representative of the glioblastoma. This implies that glioma cell culture data have to be handled with the highest caution.

show abstract

“…It has effects with a strong dose -response relationship in malignant glioma cells cultured in vitro and there is substantial evidence that carboplatin is one of the most potent cytotoxic agents against human gliomas in vitro (Doz et al, 1991;Wolff et al, 1999). Etoposide is a semisynthetic podophillotoxin that acts against topoisomerase II with demonstrated activity against gliomas and other brain tumours (Fulton et al, 1996); furthermore, carboplatin and etoposide cross the blood -brain barrier (Postmus et al, 1984;Kiya et al, 1992) and have been detected in cerebrospinal fluid.…”

mentioning

confidence: 99%

Phase II trial of carboplatin and etoposide for patients with recurrent high-grade glioma

et al. 2004

View full text Add to dashboard Cite

We present the results of a phase II trial of carboplatin and etoposide (CE) combination as first-line chemotherapy in patients with recurrent glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA) after surgery and radiotherapy. We assess the activity and the tolerability of this combination. 30 patients with GBM (25) and AA (5) were treated with VP-16 (etoposide) 120 mg m À2 and CBCDA (carboplatin) 100 mg m À2 for 3 days every 4 weeks. Moreover, we performed a retrospective analysis of topoisomerase IIa gene status using chromogenic in situ hybridisation. The median age was 54 years (21 -73 years); Eastern Cooperative Oncology Group performance score was 0-1 in 25 patients and 2 in five patients. All patients had been previously treated with surgical resection (21 radical resections) followed by radiation therapy (40 -60 Gy). We observed six (20%) complete responses, three (10%) partial responses and 12 (40%) stable diseases, with a response rate of 30%. The median time to progression was 4 months, while progression-free survival at 6 months was 33.3%. The median survival time was 10 months. Neutropenia occurred in 9 patients: four patients had grade 4, two patients grade 3 and three patients grade 2. In the conclusion of this clinical trial, the CE combination has shown activity in recurrent GBM and AA, with a good toxicity profile. Alterations in the copy number of topoisomerase IIa gene seem to be a rare event and in our series do not influence response to the CE combination.

show abstract

Chemosensitivity of glioma cells in vitro: a meta analysis

Abstract: The efficacy of nitrosourea in vitro is low.

Cited by 129 publications

References 28 publications

Detection of doxorubicin hydrochloride accumulation in the rat brain after morphine treatment by mass spectrometry

Detection of doxorubicin hydrochloride accumulation in the rat brain after morphine treatment by mass spectrometry

The genomic profile of human malignant glioma is altered early in primary cell culture and preserved in spheroids

Phase II trial of carboplatin and etoposide for patients with recurrent high-grade glioma

Contact Info

Product

Resources

About