Temozolomide in Patients with High Grade Gliomas

Brandes, Alba Ariela; Pasetto, Lara Maria; Vastola, Francesca; Monfardini, S.

doi:10.1159/000012158

Cited by 24 publications

(20 citation statements)

References 22 publications

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“…2 TMZ inhibits IK Ca channels in humans at these low concentrations because it is highly lipophilic and crosses the blood-brain barrier [1,5,28,29]. Because of TMZ's high potency, our findings might be important in determining TMZ's in vivo mechanism.…”

Section: Discussionmentioning

confidence: 80%

Evidence for the Inhibition by Temozolomide, an Imidazotetrazine Family Alkylator, of Intermediate-Conductance Ca2+-Activated K+ Channels in Glioma Cells

Yeh

Hung

et al. 2016

Cell Physiol Biochem

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Background: Temozolomide (TMZ), an oral alkylator of the imidazotetrazine family, is used to treat glioma. Whether this drug has any ionic effects in glioma cells remains largely unclear. Methods: With the aid of patch-clamp technology, we investigated the effects of TMZ on the ionic currents in U373 glioma cells. The mRNA expression of KCNN4 (K_Ca3.1) in U373 glioma cells and TMZ's effect on K⁺ currents in these KCNN4 siRNA-transfected U373 cells were investigated. Results: In whole-cell recordings, TMZ decreased the amplitude of voltage-dependent K⁺ currents (I_K) in U373 cells. TMZ-induced I_K inhibition was reversed by ionomycin or 1-ethyl-2-benzimidazolinone (1-EBIO). In cell-attached configuration, TMZ concentration-dependently reduced the activity of intermediate-conductance Ca²⁺-activated K⁺ (IK_Ca) channels with an IC₅₀ value of 9.2 µM. Chlorzoxazone or 1-EBIO counteracted the TMZ-induced inhibition of IK_Ca channels. Although TMZ was unable to modify single-channel conductance, its inhibition of IK_Ca channels was weakly voltage-dependent and accompanied by a significant prolongation in the slow component of mean closed time. However, neitherlarge-conductance Ca²⁺-activated (BK_Ca) nor inwardly rectifying K⁺ (Kir) channels were affected by TMZ. In current-clamp mode, TMZ depolarized the cell membrane and 1-EBIO reversed TMZ-induced depolarization. TMZ had no effect on I_K in KCNN4 siRNA-transfected U373 cells. Conclusion: In addition to the DNA damage it does, its inhibitory effect on IK_Ca channels accompanied by membrane depolarization could be an important mechanism underlying TMZ-induced antineoplastic actions.

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Section: Discussionmentioning

confidence: 80%

Evidence for the Inhibition by Temozolomide, an Imidazotetrazine Family Alkylator, of Intermediate-Conductance Ca2+-Activated K+ Channels in Glioma Cells

Yeh

Hung

et al. 2016

Cell Physiol Biochem

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“…Nitrosoureas are the most active drugs, while procarbazine and platinum compounds make up the secondline treatment [3,4]. Nonetheless, in recent years new drugs have been tested, and some, such as temozolomide (TMZ), are promising [5].…”

Section: Introductionmentioning

confidence: 99%

Temozolomide in Patients with Glioblastoma at Second Relapse after First Line Nitrosourea-Procarbazine Failure: A Phase II Study

Brandes¹,

Ermani

Basso³

et al. 2002

Oncology

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Objectives: To investigate the efficacy of temozolomide (TMZ) in relationship to progression free survival at 6 months (PFS-6), median time to progression (TTP), response rate and toxicity, a phase II study was conducted in patients with recurrent glioblastoma multiforme (GBM) following surgery plus radiotherapy and a first-line regimen based on nitrosourea, procarbazine and vincristine. Methods: Forty-two patients with GBM were administered TMZ at the dose of 150 mg/m²/daily for 5 days every 4 weeks. Results: The PFS-6 and at 12 months (PFS-12) was 24% (95% Confidence Interval [CI] = 14–42%) and 8% (CI = 2–27%), respectively, with a median TTP of 11.7 weeks (CI = 9–22 weeks). The response was assessed in all 42 patients; we observed 2 complete responses (CR) (4.7%), 6 partial responses (PR) (14.3%), and 9 stable disease (SD) (21.4%), with CR+PR = 19% (CI = 7–31%). Conclusion: TMZ as a second line regimen is a valid option in patients with heavily pretreated GBM.

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“…Some studies report that initial chemotherapeutic treatment with temozolomide (TMZ) or PCV (procarbazine, lomustine and vincristine) is effective for some cases of GC [15][16][17]. TMZ is an oral prodrug that is currently used for the management of malignant gliomas [18]. According to Mattox, et al, patients with GC, who demonstrated a positive response to treatment, were treated by TMZ (temozolomide) (26.2%), followed by RT alone (26.2%), concomitant TMZ and RT (20%), and RT with other agents (PCV, ACNU (Nimustine), vincristine, or cisplatin) (21.3%) [4].…”

Section: Treatmentmentioning

confidence: 99%

CASE REPORT: An Indolent Presentation of Gliomatosis Cerebri in an Elderly Patient: Posterior Fossa Decompression Prior to Treatment

Kang¹,

Raval²,

Black³

et al. 2014

Cureus

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Temozolomide in Patients with High Grade Gliomas

Cited by 24 publications

References 22 publications

Evidence for the Inhibition by Temozolomide, an Imidazotetrazine Family Alkylator, of Intermediate-Conductance Ca2+-Activated K+ Channels in Glioma Cells

Evidence for the Inhibition by Temozolomide, an Imidazotetrazine Family Alkylator, of Intermediate-Conductance Ca2+-Activated K+ Channels in Glioma Cells

Temozolomide in Patients with Glioblastoma at Second Relapse after First Line Nitrosourea-Procarbazine Failure: A Phase II Study

CASE REPORT: An Indolent Presentation of Gliomatosis Cerebri in an Elderly Patient: Posterior Fossa Decompression Prior to Treatment

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