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Glioblastoma chemotherapy adjunct via potent serotonin receptor-7 inhibition using currently marketed high-affinity antipsychotic medicines.

ABSTRACT: Glioblastoma treatment as now constituted offers increased survival measured in months over untreated patients. Because glioblastomas are active in synthesizing a bewildering variety of growth factors, a systematic approach to inhibiting these is being undertaken as treatment adjunct. The serotonin 7 receptor is commonly overexpressed in glioblastoma. Research documentation showing agonists at serotonin receptor 7 cause increased extracellular regulated kinase 1/2 activation, increased interleukin-6 synthesis, increased signal transducer and activator of transcription-3 activation, increased resistance to apoptosis and other growth enhancing changes in glioblastoma is reviewed in this paper. Because three drugs in wide use to treat thought disorders - paliperidone, pimozide and risperidone - are also potent and well-tolerated inhibitors at serotonin receptor 7, these drugs should be studied for growth factor deprivation in an adjunctive role in glioblastoma treatment.

SUBMITTER: Kast RE

PROVIDER: S-EPMC2990148 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Glioblastoma chemotherapy adjunct via potent serotonin receptor-7 inhibition using currently marketed high-affinity antipsychotic medicines.

Kast R E RE

British journal of pharmacology 20101001 3

Glioblastoma treatment as now constituted offers increased survival measured in months over untreated patients. Because glioblastomas are active in synthesizing a bewildering variety of growth factors, a systematic approach to inhibiting these is being undertaken as treatment adjunct. The serotonin 7 receptor is commonly overexpressed in glioblastoma. Research documentation showing agonists at serotonin receptor 7 cause increased extracellular regulated kinase 1/2 activation, increased interleuk ...[more]

PMID: 20880389

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Project description:OBJECTIVES:This proof-of-principle, single-center, randomized, examiner-blind, crossover study compared two experimental polyvinyl acetate (PVA)-based denture adhesives (Test Adhesives 1 and 2) with a marketed reference polymethyl vinyl ether/maleic anhydride (PMV/MA)-based adhesive and no adhesive using incisal bite force area over baseline over 12 hr (AOB0-12 ) in participants with an at least moderately well-fitting complete maxillary denture. Previous in vitro studies suggested the experimental denture adhesives provided superior performance. MATERIALS AND METHODS:Participants were randomized to a treatment sequence such that each received each treatment once. Prior to treatment application (baseline) and at 0.5, 1, 3, 6, 9, and 12 hr following the application, participants bit on a force transducer until their maxillary denture dislodged. Between-treatment differences in AOB0-12 were analyzed using analysis of covariance. For study validity, the reference adhesive was compared with no adhesive. Participants were asked to rate sensory experiences and ease of denture removal. RESULTS:Twenty-three participants were included in the modified intent-to-treat population. Although Test Adhesives 1 and 2 had a higher mean AOB0-12 than no adhesive, differences were not statistically significant. No statistically significant difference was also found between the reference adhesive and no adhesive; hence, study validity was not attained. Participants did not report any clear differences between the test or reference adhesives in terms of taste or feel; however, dentures were easier to remove with the test adhesives versus reference. No treatment-related adverse events were reported. CONCLUSION:Neither the experimental PVA-based denture adhesives nor the PMV/MA-based reference product demonstrated a statistically significant difference in incisal bite force AOB0-12 compared with no adhesive. The reasons for these unexpected results is unclear; they suggest that findings of in vitro tests for denture adhesive performance are not always translated to in vivo performance (Clinicaltrials.gov: NCT02937870).

Dataset Information

Glioblastoma chemotherapy adjunct via potent serotonin receptor-7 inhibition using currently marketed high-affinity antipsychotic medicines.

Publications

Glioblastoma chemotherapy adjunct via potent serotonin receptor-7 inhibition using currently marketed high-affinity antipsychotic medicines.

Similar Datasets

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