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  • 1
    Online Resource
    Online Resource
    Imatinib Mesylate in Patients with WHO B3 Thymomas and Thymic Carcinomas
    Elsevier BV ; 2009
    In:  Journal of Thoracic Oncology Vol. 4, No. 10 ( 2009-10), p. 1270-1273
    Details
    In: Journal of Thoracic Oncology, Elsevier BV, Vol. 4, No. 10 ( 2009-10), p. 1270-1273
    Type of Medium: Online Resource
    ISSN: 1556-0864
    URL: Article
    DOI: 10.1097/JTO.0b013e3181b6be57
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2009
    detail.hit.zdb_id: 2223437-8
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  • 2
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    Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
    Springer Science and Business Media LLC ; 2017
    In:  Nature Communications Vol. 8, No. 1 ( 2017-04-26)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2017-04-26)
    Abstract: Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/ncomms14977
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2553671-0
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  • 3
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    Phase I Dose-Escalation Study of Once Weekly or Once Every Two Weeks Administration of High-Dose Sunitinib in Patients With Refractory Solid Tumors
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 5 ( 2019-02-10), p. 411-418
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 5 ( 2019-02-10), p. 411-418
    Abstract: Dose and schedule optimization of treatment with tyrosine kinase inhibitors is of utmost importance. On the basis of preclinical data, a phase I clinical trial of once weekly or once every 2 weeks administration of high-dose sunitinib in patients with refractory solid malignancies was conducted. PATIENTS AND METHODS Patients with advanced cancer refractory to standard treatment were eligible. With use of a standard 3 + 3 phase I design, patients received escalating doses of sunitinib, in 100 mg increments, starting at 200 mg once weekly. In both the once weekly and once every 2 weeks cohorts, 10 more patients were included at the maximum tolerated dose level. Primary end points were safety and tolerability. RESULTS Sixty-nine patients with advanced cancer, predominantly colorectal cancer (42%), were treated with this alternative dosing regimen. Maximum tolerated dose was established at 300 mg once weekly and 700 mg once every 2 weeks, resulting in nine- and 18-fold higher maximum plasma concentrations compared with standard dose, respectively. Treatment was well tolerated, with fatigue (81%), nausea (48%), and anorexia (33%) being the most frequent adverse events. The only grade 3 or 4 treatment-related adverse event in 5% or more of patients was fatigue (6%). Sixty-three percent of patients had significant clinical benefit, with a 30% progression-free survival of 5 months or more. CONCLUSION Sunitinib administered once weekly at 300 mg or once every 2 weeks at 700 mg is feasible, with comparable tolerability as daily administration. Administration of 700 mg once every 2 weeks can be considered as the most optimal schedule because of the highest maximum plasma concentration being reached. The promising preliminary antitumor activity of this alternative schedule in heavily pretreated patients warrants further clinical evaluation and might ultimately indicate a class characteristic of tyrosine kinase inhibitors.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.18.00725
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 4
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    A phase 1 study of weekly high dose sunitinib in patients with advanced solid tumors: Early signs of activity in non-RCC tumor types.
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 15_suppl ( 2015-05-20), p. e13550-e13550
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 15_suppl ( 2015-05-20), p. e13550-e13550
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2015.33.15_suppl.e13550
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
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  • 5
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    Dose-Finding and Pharmacokinetic Study of Cisplatin, Gemcitabine, and SU5416 in Patients With Solid Tumors
    American Society of Clinical Oncology (ASCO) ; 2002
    In:  Journal of Clinical Oncology Vol. 20, No. 6 ( 2002-03-15), p. 1657-1667
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 20, No. 6 ( 2002-03-15), p. 1657-1667
    Abstract: PURPOSE: To investigate the feasibility and pharmacokinetics of the combination cisplatin, gemcitabine, and SU5416. PATIENTS AND METHODS: Patients received cisplatin 80 mg/m 2 on day 1, gemcitabine 1,250 mg/m 2 on days 1 and 8, repeated every 3 weeks, and SU5416 (85 and 145 mg/m 2 ) intravenously twice weekly. Pharmacokinetics of all three agents, side effects, and antitumor response were investigated in patients with solid tumors amenable to therapy with cisplatin/gemcitabine. RESULTS: In the first cohort of three patients entered at the 85 mg/m 2 dose, no dose-limiting toxicities were observed. In the next cohort (145 mg/m 2 ), three patients developed a thromboembolic event. After entry was restricted to patients with low thromboembolic risk, three additional patients enrolled at 145 mg/m 2 developed a thromboembolic event. The dose was then reduced to 85 mg/m 2 in all patients still on the study, and three additional patients were entered on this dose level. In 19 treated patients, eight patients developed nine thromboembolic events (three transient ischemic attacks, two cerebrovascular accidents, and four deep venous thromboses). The most common toxicities observed were those previously reported for SU5416 alone (headache and phlebitis) and for this chemotherapy regimen (nausea, thrombocytopenia, and leucopenia). No significant pharmacologic interaction among the three drugs was observed. Response rates were similar to those expected in the patient population selected for this study. Analysis of variables of the coagulation cascade and of vessel wall activation was performed in three patients and showed significant increases in thrombin generation and endothelial cell perturbation in a treatment cycle–dependent manner. CONCLUSION: The incidence of thromboembolic events, possibly related to the particular regimen tested in this study, discourages further investigation of this regimen.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2002.20.6.1657
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2002
    detail.hit.zdb_id: 2005181-5
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  • 6
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    Randomized phase 2 study of gemcitabine and cisplatin with or without vitamin supplementation in patients with advanced esophagogastric cancer (AEGC).
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 15_suppl ( 2016-05-20), p. e15555-e15555
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. e15555-e15555
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2016.34.15_suppl.e15555
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
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  • 7
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    Selection of Protein Kinase Inhibitors Based on Tumor Tissue Kinase Activity Profiles in Patients with Refractory Solid Malignancies: An Interventional Molecular Profiling Study
    Oxford University Press (OUP) ; 2018
    In:  The Oncologist Vol. 23, No. 10 ( 2018-10-01), p. 1135-e118
    Details
    In: The Oncologist, Oxford University Press (OUP), Vol. 23, No. 10 ( 2018-10-01), p. 1135-e118
    Abstract: Clinically applicable tools are needed for treatment selection and repurposing of available protein kinase inhibitors (PKIs) in patients with advanced solid tumors refractory to standard treatment. Using a tyrosine kinase peptide substrate microarray, observed inhibitory activity in vitro could not sufficiently predict clinical benefit of treatment with the selected PKI. Background This exploratory molecular profiling study determined the feasibility and benefit of the selection of protein kinase inhibitors (PKIs) based on kinase activity profiling in patients with refractory solid malignancies. Methods Adult patients with biopsy-accessible refractory solid tumors were eligible. Per patient, the inhibitory potency of sunitinib, dasatinib, erlotinib, sorafenib, everolimus, and lapatinib was determined in tumor lysates from fresh biopsies using a tyrosine kinase peptide substrate microarray. The most active PKI in this in vitro assay was selected for treatment. Results Thirteen patients were enrolled in the feasibility part and underwent tumor biopsy. Of 12 patients in whom kinase activity profiling was performed, 11 started treatment with a selected PKI: dasatinib in 8, sunitinib in 2, and erlotinib in 1 patient(s). Eight patients were evaluable for response. One patient had stable disease (SD) & gt;4 months on sunitinib; one patient had SD at 6 weeks but progressive disease (PD) at 12 weeks. The remaining patients had PD after 6 weeks of treatment. Conclusion Kinase inhibition profiles of multiple PKIs can be reliably determined using fresh tumor biopsies from patients with refractory solid tumors. However, the current in vitro microarray selection approach insufficiently predicted clinical benefit of PKI treatment in these patients.
    Type of Medium: Online Resource
    ISSN: 1083-7159 , 1549-490X
    URL: Article
    DOI: 10.1634/theoncologist.2018-0263
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 2023829-0
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  • 8
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    Book Reviews
    Brill ; 1982
    In:  Bijdragen tot de taal-, land- en volkenkunde / Journal of the Humanities and Social Sciences of Southeast Asia Vol. 138, No. 1 ( 1982), p. 167-189
    Details
    In: Bijdragen tot de taal-, land- en volkenkunde / Journal of the Humanities and Social Sciences of Southeast Asia, Brill, Vol. 138, No. 1 ( 1982), p. 167-189
    Abstract: - Rita Bolland, Alfred Bühler, The patola of Gujarat. Double ikat in India. Krebs AG Basel, 1979. Vol. 1, 360 p. tekst, ill. Vol. 2, afb. in kleur en zwart/wit, krt. tab. noten, verkl. woorden. litl., Eberhard Fischer (eds.) - Raymond Buve, Hugo G. Nutini, Ritual kinship. The structure and historical development of the Compadrazgo system in rural Tlaxcala, Vol. I. Princeton University Press, N.J., 1980, XVI plus 494 pp., maps, tables, glossary and index., Betty Bell (eds.) - Benno Galjart, G.A. Banck, Jagen met een kat... Schaarse middelen en sociale relaties in de Braziliaanse staat Espirito Santo, CEDLA Incidentele publicaties no. 8, CEDLA, Amsterdam 1977. - R.A.L.H. Gunawardana, J. van Goor, Jan Kompanie as schoolmaster: Dutch education in Ceylon, 1690-1795, Historische Studies, Instituut voor Geschiedenis der Rijksuniversiteit te Utrecht, XXIV, Wolters-Noordhoff Groningen, 1978, 205 pp., 3 maps. - Ria Kloppenborg, R.A.L.H. Gunawardana, Robe and plough. Monasticism and economic interest in early medieval Sri Lanka. Association for Asian Studies, Monographs and Papers No. XXXV, University of Arixona Press, Tucson, Arizona, 1979; 377 pages, including bibliography and index. - Els Postel-Coster, Jan van Bremen, Romantropologie - Essays over antropologie en literatuur, Antropologisch-Sociologisch Centrum Universiteit van Amsterdam, 1979., Sjaak van der Geest, Jojada Verrips (eds.) - Arie de Ruijter, T. Lemaire, Over de waarde van kulturen. Een inleiding in de kultuurfilosofie. Ambo, Baarn 1976, herdruk 1980. 509 blz. - P. van de Velde, W. Arens, The man-eating myth. Oxford University Press, New York, 1979. XIV + 206 pp., 12 illustrations. - E.Ch.L. van der Vliet, Klaus E. Müller, Geschichte der antiken ethnographie und ethnologischen theoriebildung von den anfängen bis auf die byzantinischen historiographen, Teil II (Studien zur Kulturkunde 52), Wiesbaden: Franza Steiner Verlag, 1980. 563 pp. 11 figs. - J.J. de Wolf, P.T.W. Baxter, Age, generation and time: Some features of East African age organisations. C. Hurst and Co., London 1978., Uri Almagor (eds.) - J.J. de Wolf, Myrtle S. Langley, The Nandi of Kenya: Life crisis rituals in a period of change. C. Hurst and Co., London 1979.
    Type of Medium: Online Resource
    ISSN: 0006-2294 , 2213-4379
    URL: Article
    DOI: 10.1163/22134379-90003488
    Language: Unknown
    Publisher: Brill
    Publication Date: 1982
    detail.hit.zdb_id: 2484489-5
    SSG: 7,23
    SSG: 10
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  • 9
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    Dose-Finding Study of the Multitargeted Tyrosine Kinase Inhibitor SU6668 in Patients with Advanced Malignancies
    American Association for Cancer Research (AACR) ; 2005
    In:  Clinical Cancer Research Vol. 11, No. 17 ( 2005-09-01), p. 6240-6246
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 11, No. 17 ( 2005-09-01), p. 6240-6246
    Abstract: Purpose: SU6668 is a tyrosine kinase inhibitor which targets platelet-derived growth factor receptor-β, fibroblast growth factor receptor-1, vascular endothelial growth factor receptor-2, and KIT. We did a phase I study to define the maximum tolerated dose and to assess the pharmacokinetics of SU6668 administered orally thrice daily with food. Patients and Methods: Patients with histologically proven, advanced, and progressive solid tumors were included at a starting dose level of 400 mg/m2 thrice daily. The early onset of dose-limiting toxicities (DLT) required dose reductions to 100 and 200 mg/m2 thrice daily. Pharmacokinetics was done on days 1, 28, and 56. Results: Sixteen patients were included. Two of the first three patients developed DLTs, which consisted of grade 4 fatigue and grade 3 serositis-like pains. Six patients at dose level 100 mg/m2 thrice daily experienced no DLT. At dose level 200 mg/m2 thrice daily, two out of seven patients experienced DLTs consisting of grade 3 abdominal pain, grade 4 anorexia and grade 3 nausea/vomiting. Increasing doses resulted in a disproportional increase in area under the curve and Cmax (peak plasma concentration). Both variables, however, decreased significantly on days 28 and 56 compared with day 1 (P & lt; 0.05). No objective responses were observed. Acute phase response, probably mediated by interleukin-6, was observed in serial blood samples. Conclusions: The maximum tolerated dose of SU6668 given orally, thrice daily under fed conditions, is 100 mg/m2. Because of the low plasma levels reached at this dose level, the efficacy of SU6668 as a single agent is not to be expected.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-04-2466
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2005
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 10
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    A phase 1/2 study of intermittent, high dose sunitinib in patients with advanced solid tumors.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. 2591-2591
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 2591-2591
    Abstract: 2591 Background: Despite widespread clinical integration, refinement of treatment with sunitinib is actively pursued. Sub-therapeutic blood levels rather than true resistance and tumor adaptation through drug accumulation have been accounted as reasons for treatment failure. Based on our preclinical data with high dose sunitinib and prospective analyses supporting the concept of intermittent dosing, we designed a phase 1 trial to investigate the feasibility and tolerability of high dose, once weekly (1w) or once every two weeks (2w) sunitinib (NCT02058901). Methods: Eligible were patients (pts) with advanced solid tumors, refractory to standard treatment, measurable disease, WHO ≤ 1. Sunitinib was administered orally 1w or 2w. Starting dose was 200 mg, with cohorts escalating in 100 mg steps until maximum tolerated dose (MTD). Response was evaluated by RECIST 1.1. Treatment continued until progression or unacceptable toxicity. Dedicated PK sampling was performed. Sunitinib plasma concentration was measured by LC-MS. Results: 34 (w) and 24 (2w) pts were included, predominantly with mCRC [56% (1w) and 55% (2w)]. MTD was set at 300 mg (1w) and 700 mg (2w). Most common adverse events were fatigue (79%, one pt with G3), nausea (71%, all G1-2), anorexia (29%, all G1-2). Median PFS of evaluable pts was 2.7 mo (1w) and 2.6 mo (2w), while 39% pts (1w) and 25% pts (2w) had PFS 〉 5 mo. CT scans in pts with treatment benefit showed extensive tumor necrosis. Mean sunitinib plasma Cmax was 190 [300 mg (1w), range: 185-295] and 476 ng/mL [(700 mg (2w), range: 323-580] . Accumulation was minimal. Conclusions: Once weekly or once every two weeks, high dose sunitinib is feasible and clinically efficacious in heavily pretreated pts with advanced solid tumors, while toxicity remains well manageable. Importantly, no accumulation was recorded and sunitinib exposure was significantly increased, compared to the universal, flat dose. Since increased sunitinib exposure has been correlated to improved outcome, we consider this alternative scheduling as promising strategy to produce enduring clinical benefit in a wider patient population. Expansion cohorts are ongoing. Clinical trial information: NCT02058901.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.2591
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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