References of "Grigoriu, Bogdan"
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See detailSystematic qualitative review of randomised trials conducted in nonsmall cell lung cancer with a noninferiority or equivalence design
Paesmans, Marianne; Grigoriu, Bogdan; Ocak, Sebahat et al

in European Respiratory Journal (2015), 45(2), 511-524

The use of noninferiority randomised trials for patients with advanced non-small cell lung cancer has emerged during the past 10–15 years but has raised some issues related to their justification and ... [more ▼]

The use of noninferiority randomised trials for patients with advanced non-small cell lung cancer has emerged during the past 10–15 years but has raised some issues related to their justification and methodology. The present systematic review aimed to assess trial characteristics and methodological aspects. All randomised clinical trials with a hypothesis of noninferiority/equivalence, published in English, were identified. Several readers extracted a priori defined methodological information. A qualitative analysis was then performed. We identified 20 randomised clinical trials (three phase II and 17 phase III), 11 of them being conducted in strong collaboration with industry. We highlighted some deficiencies in the reports like the lack of justification for both the noninferiority assumption and the definition of the noninferiority margin, as well as inconsistencies between the results and the authors’ conclusions. CONSORT guidelines were better followed for general items than for specific items (p<0.001). Improvement in the reporting of the meth"odology of noninferiority/equivalence trials is needed to avoid misleading interpretation and to allow readers to be fully aware of the assumptions underlying the trial designs. They should be restricted to limited specific situations with a strong justification why a noninferiority hypothesis is acceptable. [less ▲]

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See detailValproate, in combination with pemetrexed and cisplatin, provides additional efficacy to the treatment of malignant mesothelioma.
Vandermeers, Fabian ULg; Hubert, Pascale ULg; Delvenne, Philippe ULg et al

in Clinical Cancer Research : An Official Journal of the American Association for Cancer Research (2009), 15(8), 2818-28

PURPOSE: Present chemotherapeutic regimens are marginally efficient in tumor cells being particularly resistant to radiotherapy and/or chemotherapy. We hypothesized that unresponsiveness of tumors to ... [more ▼]

PURPOSE: Present chemotherapeutic regimens are marginally efficient in tumor cells being particularly resistant to radiotherapy and/or chemotherapy. We hypothesized that unresponsiveness of tumors to conventional therapeutic agents might be due to inappropriate gene expression resulting from epigenetic modifications and leading to transcriptional silencing. The goal of this study was to evaluate the anticancer effect of a histone deacetylase inhibitor, valproate, on mesothelioma cells in combination with pemetrexed and cisplatin, the usual first-line regimen of chemotherapy for this tumor. Experimental Design and RESULTS: We show that valproate augments apoptosis induced by pemetrexed and cisplatin in mesothelioma cell lines and in tumor cells from patient's biopsies. Onset of apoptosis involves both extrinsic and intrinsic pathways requiring enzymatic activities of caspases 8 and 9, respectively. Valproate but not suberoylanilide hydroxamic acid efficiently stimulates the production of reactive oxygen species. The free radical scavenger N-acetylcysteine inhibits apoptosis, indicating that reactive oxygen species are major mediators of valproate activity. As expected, valproate alone or combined with pemetrexed and cisplatin triggers hyperacetylation of histone H3. Bid protein processing in truncated t-Bid and cytochrome c release from mitochondria are significantly increased in the presence of valproate, providing a mechanistic rationale for improvement of the proapoptotic efficacy of cisplatin and pemetrexed. Finally, valproate when combined with pemetrexed and cisplatin prevents tumor growth in mouse models of epithelioid mesothelioma. CONCLUSIONS: These observations support the potential additional efficacy of valproate in combination with pemetrexed and cisplatin for treatment of malignant mesothelioma. [less ▲]

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