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  • 1
    Abstract: Immunotherapy is a promising area of therapy in patients with neuro-oncological malignancies. However, early-phase studies show unique challenges associated with the assessment of radiological changes in response to immunotherapy reflecting delayed responses or therapy-induced inflammation. Clinical benefit, including long-term survival and tumour regression, can still occur after initial disease progression or after the appearance of new lesions. Refinement of the response assessment criteria for patients with neuro-oncological malignancies undergoing immunotherapy is therefore warranted. Herein, a multinational and multidisciplinary panel of neuro-oncology immunotherapy experts describe immunotherapy Response Assessment for Neuro-Oncology (iRANO) criteria based on guidance for the determination of tumour progression outlined by the immune-related response criteria and the RANO working group. Among patients who demonstrate imaging findings meeting RANO criteria for progressive disease within 6 months of initiating immunotherapy, including the development of new lesions, confirmation of radiographic progression on follow-up imaging is recommended provided that the patient is not significantly worse clinically. The proposed criteria also include guidelines for the use of corticosteroids. We review the role of advanced imaging techniques and the role of measurement of clinical benefit endpoints including neurological and immunological functions. The iRANO guidelines put forth in this Review will evolve successively to improve their usefulness as further experience from immunotherapy trials in neuro-oncology accumulate.
    Type of Publication: Journal article published
    PubMed ID: 26545842
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  • 2
    Publication Date: 2018-08-16
    Description: Purpose: Dendritic cells (DC) initiate adaptive immune responses through the uptake and presentation of antigenic material. In preclinical studies, intratumorally injected activated DCs (aDCs; DCVax-Direct) were superior to immature DCs in rejecting tumors from mice. Experimental Design: This single-arm, open-label phase I clinical trial evaluated the safety and efficacy of aDCs, administered intratumorally, in patients with solid tumors. Three dose levels (2 million, 6 million, and 15 million aDCs per injection) were tested using a standard 3 + 3 dose-escalation trial design. Feasibility, immunogenicity, changes to the tumor microenvironment after direct injection, and survival were evaluated. We also investigated cytokine production of aDCs prior to injection. Results: In total, 39 of the 40 enrolled patients were evaluable. The injections of aDCs were well tolerated with no dose-limiting toxicities. Increased lymphocyte infiltration was observed in 54% of assessed patients. Stable disease (SD; best response) at week 8 was associated with increased overall survival. Increased secretion of interleukin (IL)-8 and IL12p40 by aDCs was significantly associated with survival ( P = 0.023 and 0.024, respectively). Increased TNFα levels correlated positively with SD at week 8 ( P 〈 0.01). Conclusions: Intratumoral aDC injections were feasible and safe. Increased production of specific cytokines was correlated with SD and prolonged survival, demonstrating a link between the functional profile of aDCs prior to injection and patient outcomes. Clin Cancer Res; 24(16); 3845–56. ©2018 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Catalysis letters 14 (1992), S. 279-288 
    ISSN: 1572-879X
    Keywords: Lanthana-promoted Rh/SiO2 catalyst ; EXAFS ; H2 chemisorption ; CO chemisorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract EXAFS investigations at the Rh K edge of lanthana-promoted Rh/SiO2 catalysts showed that the local environment of the Rh ions in the oxidic catalyst precursor state did not depend on the La2O3 content and resembled that of Rh2O3. No LaRhO3 formation could be detected. In the reduced state, EXAFS as well as H2 and CO chemisorption demonstrated that La2O3 increased the Rh dispersion. Covering of the Rh metal particles by La2O3 was minor, because during catalyst preparation, La was impregnated prior to Rh.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Catalysis letters 14 (1992), S. 221-231 
    ISSN: 1572-879X
    Keywords: EXAFS ; titanium silicalite ; TS-1 ; [Ti]ZSM-5 ; [Li, Ti]Y
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Fluorescence X-ray absorption experiments were carried out on titanium containing zeolites. The edge- and EXAFS-regions proved that the coordination of the Ti-sites of TS-1 and [Ti]ZSM-5 are similar, although no quantitative data could be obtained for the coordination numbers. EXAFS analysis of a [Li, Ti]Y zeolite, containing 12% Ti, showed that most of the titanium has a rutile-like coordination and therefore is not likely to be present as part of the framework.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1572-879X
    Keywords: methanol synthesis ; Rh catalysts ; Pd catalysts ; impurity-free SiO2 support ; metal oxide additives ; formate intermediate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Catalysts were prepared from ultra pure SiO2, Pd and Rh nitrates and chlorides, and by doping with Al, Fe, Na, K or Ca nitrate. The activities and selectivities of the Pd and Rh catalysts were investigated at 553 K, H2/CO=2 or 3 and 2.5 or 4 MPa respectively. Additives had a strong influence on the catalytic properties. The doping with alkali and alkaline earth oxides led to a strong suppression of the CO dissociation. Particularly basic additives, such as Ca, had a strong promoting effect on the methanol production. This may confirm that the formation of methanol occurs through formate intermediates.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1572-879X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Pd-based catalysts prepared from ultra-pure SiO2 and doped with 5000 ppm Li, Ca and La were subjected to CO hydrogenation(H2/CO=2, p=9 bar, T=553 K) in a flow reactor directly attached to an ultra-high vacuum chamber with facilities for X-ray photoelectron spectroscopy (XPS) and secondary ion mass spectrometry (SIMS). The catalysts exhibited high selectivity (usually above 99%) for methanol synthesis and their activities were found to increase in the order Li〈Ca〈La. Subsequent analysis by SIMS revealed the presence of surface formate and methoxy on the silica support. No such species were found to be bound to the Pd particle surface. These conclusions are based on the detection of COO(H) and SiOCH3 ions while respective Pd-based species were absent from the mass spectra. This indicates a mechanism to be in operation in which hydrogen is activated on Pd metal and subsequently spilled over to the support in order to react with formate to methanol. XPS studies of SiO2 samples containing 10 wt% of Ca, in the absence of Pd metal, demonstrated Si 2p and O1s line shifts to lower binding energies as compared to pure SiO2.The spectra bear strong similarities with those of wollastonite,“CaSiO3”. A comparable behavior was found for Mg-dopedSiO2 but not for K- or Cs-doped SiO2, which show low activity in methanol formation.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1572-879X
    Keywords: hydrodenitrogenation ; catalytic sites ; competitive adsorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The inhibitive effect of nitrogen-containing compounds on hydrodenitrogenation was studied over NiMo(P)/Al2O3 catalysts. From the differences in the adsorption constants it is concluded that at least four distinct catalytic sites are involved in the elementary hydrodenitrogenation steps. The catalytic site for the cleavage of aliphatic C(sp3)-N bonds is acidic and most probably an SH species on a surface Mo or Ni site. The catalytic site for the hydrogenation of a phenyl group is different from that for alkene hydrogenation, the former being more coordinately unsaturated than the latter, with two or three sulphur vacancies. A fourth site is responsible for the hydrogenolysis of the C(sp2)-N bond of anilines. It is characterised by a more reduced environment of Mo and by phosphorus promotion.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1572-9028
    Keywords: hydrodenitrogenation ; toluidine ; methylcyclohexylamine ; kinetics ; nickel-promoted molybdenum sulphide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The hydrodenitrogenation (HDN) of o-toluidine and its reaction intermediates was studied over a NiMo/γ-Al2O3 catalyst. The kinetics of the HDN of methylcyclohexylamine and of the hydrogenation of cyclohexene were also studied. Hydrogenation of o-toluidine alone produces methylcyclohexene and methylcyclohexane. When a sufficient quantity of cyclohexene is added during the HDN of toluidine, methylcyclohexylamine, the first intermediate in the hydrogenation of toluidine, becomes detectable. Because of its strong adsorption constant and high rate constant for reacting further to methylcyclohexene and methylcyclohexane, methylcyclohexylamine is not observed in the HDN of toluidine. Adding cyclohexene decreases the adsorption of methylcyclohexylamine, thus enabling its detection. The rate and adsorption constants of methylcyclohexylamine and cyclohexene in the HDN of methylcyclohexylamine were calculated by fitting the kinetic data to a Langmuir–Hinshelwood equation. A two-site model was used to describe the surface reactions, with one site for the methylcyclohexylamine reactions and the other for the cyclohexene reaction.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Antonie van Leeuwenhoek 45 (1979), S. 339-345 
    ISSN: 1572-9699
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-2242
    Keywords: Key words Lr19 translocation ; Thinopyrum ; Ph-induced recombinants ; Physical mapping
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  Following the induction of allosyndetic pairing between the Thinopyrum-derived Lr19 translocation in ‘Indis’ wheat and homoeologous wheat chromatin, eight suspected recombinants for the Lr19 region were recovered. These selections were characterised for marker loci that were previously used to construct a physical map of the Lr19 segment. At the same time near-isogenic lines were developed for some of the selected segments and tested for seedling leaf-rust resistance in order to confirm the presence of Lr19. It appeared that three of the four white-endosperm selections do not possess Lr19 and only one, 88M22-149, is a true Lr19 recombinant. The resistance gene in the three non-Lr19 selections resides on chromosome 6B, appears to derive from ‘Indis’, and was selected unintentionally during backcrossing. The pedigree of ‘Indis’ is suspect and it is believed that the Lr19 translocation in ‘Indis’ is in reality the Th. ponticum-derived (T4) segment rather than being of Th. distichum origin as was believed earlier. The white-endosperm recombinant, 88M22-149, retained the complete Lr19 resistance and was apparently re-located to chromosome arm 7BL in a double-crossover event. 88M22-149 has lost the Sd1 gene and often shows strong self-elimination in translocation heterozygotes. This effect may result from additional gametocidal loci or from an altered chromosome structure following re-location of the segment. 88M22-149 in fact contains a duplicated region involving the Wsp-B1 locus. Three selections had partially white endosperms and expressed Lr19 and other Thinopyrum marker alleles. Polymorphisms for the available markers confirmed that the translocated segment in at least one of them had been shortened through recombination with chromosome arm 7DL. Further markers need to be studied in order to determine whether the translocation in the remaining two partially white recombinants had also undergone recombination with wheat. The eighth selection has yellow endosperm and appears to self-eliminate in certain translocation heterozygotes. No evidence of recombination could be found with the markers used. If the latter selections are in fact recombinants they may prove useful in attempts to unravel the complex segregation distortion mechanism.
    Type of Medium: Electronic Resource
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