ORCID Profile
0000-0003-1852-2969
Current Organisations
University of Ulm
,
Université de Bourgogne
,
Centre Georges-François Leclerc
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Publisher: Informa UK Limited
Date: 02-09-2014
Publisher: Springer Science and Business Media LLC
Date: 31-01-2022
DOI: 10.1038/S41590-021-01120-Y
Abstract: Tumors poorly infiltrated by T cells are more resistant to immunogenic chemotherapies and checkpoint inhibition than highly infiltrated tumors. Using murine models, we found that CCR6
Publisher: Wiley
Date: 29-04-2020
Abstract: We report on triethylene glycol‐based orthoformate cryptands, which adapt their bridgehead configurations in response to metal templates and intramolecular hydrogen bonding in a complex manner. In contrast to smaller 1.1.1 ‐orthoformate cryptands, the inversion from out,out ‐2.2.2 to in,in ‐2.2.2 occurs spontaneously by thermal homeomorphic isomerization, i. e., without bond breakage. The global thermodynamic minimum of the entire network, which includes an unprecedented third isomer ( in,out ‐2.2.2 ), could only be reached under conditions that facilitate dynamic covalent exchange. Both inversion processes were studied in detail, including DFT calculations and MD simulations, which were particularly helpful for explaining differences between equilibrium compositions in solvents chloroform and acetonitrile. Unexpectedly, the system could be driven to the in,out ‐2.2.2 state by using a metal template with a size mismatch with respect to the out,out ‐2.2.2 cage.
Publisher: Elsevier BV
Date: 10-2014
Publisher: Oxford University Press (OUP)
Date: 28-09-2018
DOI: 10.1634/THEONCOLOGIST.2018-0290
Abstract: We assessed the efficacy and safety of bevacizumab (BEV) through multiple lines in patients with recurrent glioblastoma who had progressed after first-line treatment with radiotherapy, temozolomide, and BEV. TAMIGA (NCT01860638) was a phase II, randomized, double-blind, placebo-controlled, multicenter trial in adult patients with glioblastoma. Following surgery, patients with newly diagnosed glioblastoma received first-line treatment consisting of radiotherapy plus temozolomide and BEV, followed by six cycles of temozolomide and BEV, then BEV monotherapy until disease progression (PD1). Randomization occurred at PD1 (second line), and patients received lomustine (CCNU) plus BEV (CCNU + BEV) or CCNU plus placebo (CCNU + placebo) until further disease progression (PD2). At PD2 (third line), patients continued BEV or placebo with chemotherapy (investigator's choice). The primary endpoint was survival from randomization. Secondary endpoints were progression-free survival in the second and third lines (PFS2 and PFS3) and safety. Of the 296 patients enrolled, 123 were randomized at PD1 (CCNU + BEV, n = 61 CCNU + placebo, n = 62). The study was terminated prematurely because of the high drop-out rate during first-line treatment, implying underpowered inferential testing. The proportion of patients receiving corticosteroids at randomization was similar (BEV 33%, placebo 31%). For the CCNU + BEV and CCNU + placebo groups, respectively, median survival from randomization was 6.4 versus 5.5 months (stratified hazard ratio [HR], 1.04 95% confidence interval [CI], 0.69–1.59), median PFS2 was 2.3 versus 1.8 months (stratified HR, 0.70 95% CI, 0.48–1.00), median PFS3 was 2.0 versus 2.2 months (stratified HR, 0.70 95% CI, 0.37–1.33), and median time from randomization to a deterioration in health-related quality of life was 1.4 versus 1.3 months (stratified HR, 0.76 95% CI, 0.52–1.12). The incidence of treatment-related grade 3 to 4 adverse events was 19% (CCNU + BEV) versus 15% (CCNU + placebo). There was no survival benefit and no detriment observed with continuing BEV through multiple lines in patients with recurrent glioblastoma. Previous research suggested that there may be value in continuing bevacizumab (BEV) beyond progression through multiple lines of therapy. No survival benefit was observed with the use of BEV through multiple lines in patients with glioblastoma who had progressed after first-line treatment (radiotherapy + temozolomide + BEV). No new safety concerns arose from the use of BEV through multiple lines of therapy.
Publisher: Springer Science and Business Media LLC
Date: 10-06-2010
DOI: 10.1007/S10637-010-9461-Z
Abstract: Platinum(II) metallointercalators represent a new class of DNA-damaging antitumor complexes active in cisplatin- and oxaliplatin-resistant cell lines. In the first part of our work, we have screened in vitro a serie of 18 metallointercalators with the structure [Pt(A(L))(I(L))](2+) where A(L) = ethylenediamine (EN) or diaminocyclohexane in R,R- (RR) or S,S- (SS) configuration and I(L) = 1,10-phenanthroline with different degree of methylation : no methylation (PHEN), mono-methylated in position 4 (4ME) or 5 (5ME), or di-methylated in positions 4 and 7 (47ME) or in positions 5 and 6 (56ME) or tetramethylated in positions 3,4,7 and 8 (3478ME). Eight compounds: PHENEN, 56MEEN, 47MERR, 56MERR, 4MESS, 5MESS, 47MESS and 56MESS exhibited significant cytotoxic effect, equivalent or higher than cisplatin, oxaliplatin or carboplatin in the human HCT8 colon and IGROV1 ovarian cancer cell lines for both 1 and 24 h incubation time. The high cytotoxicity of the most active compound, the 56MESS, could be related to the hydrophobicity of the phenanthroline ligand that increases cellular uptake in human HCT8, HT29 (colon) and IGROV1 (ovarian) as well as in rat PROb colon cell lines. Unfortunately, intravenous or intraperitoneal administration of 56MESS had no antitumoral activity in BD-IX rats with peritoneal carcinomatosis induced by an intraperitoneal PROb cells inoculation. Moreover, 56MESS displayed nephrotoxicity at pharmacological dose. Thus, these data query the in vivo/in vitro correlation and reconsider the place of the in vivo screening to select adequate candidate drug for further preclinical and clinical developments.
Location: United Kingdom of Great Britain and Northern Ireland
Location: No location found
No related grants have been discovered for Max von Delius.