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Journal articles on the topic "ZD6474"
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Heymach, J. V., B. E. Johnson, D. Prager, E. Csada, J. Roubec, M. Pesek, I. Spasova, J. Hou, S. Kennedy, and R. S. Herbst. "A phase II trial of ZD6474 plus docetaxel in patients with previously treated NSCLC: Follow-up results." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 7016. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.7016.
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7016 Background: ZD6474, a once-daily oral agent, targets key signaling pathways in cancer by inhibiting VEGF, EGF and RET receptor tyrosine kinases. ZD6474 in combination with docetaxel (Doc) was assessed in patients (pts) with refractory non-small-cell lung cancer (NSCLC). Methods: Pts eligible for this randomized, double-blind study had locally advanced or metastatic (stage IIIB/IV) NSCLC after failure of 1st-line platinum-based chemotherapy. The primary objective was to determine whether once-daily oral ZD6474 (100 or 300 mg) + Doc (75 mg/m2 i.v. infusion every 21 days) prolonged progression-free survival (PFS) vs Doc alone (80% power to detect 50% prolongation at P<0.2). Overall survival was a secondary objective. Results: A total of 127 pts (73 male/54 female; median age 59 yrs, range 29–82) received ZD6474 100 mg + Doc (n=42), ZD6474 300 mg + Doc (n=44) or Doc (n=41). The study met its primary objective of PFS prolongation with the addition of ZD6474: median PFS was 19 wks for ZD6474 100 mg + Doc (HR=0.64; P=0.074); 17 wks for ZD6474 300 mg + Doc (HR=0.83; P=0.461); and 12 wks for Doc. A total of 64 pts (50%) presented with histology other than adenocarcinoma, including 37 with squamous, and 13 pts (10%) entered with CNS metastases. Exploratory subgroup analyses suggest advantages in PFS for ZD6474 + Doc vs Doc both for adenocarcinoma and for other lung cancer histologies. Common adverse events (AEs) included diarrhea, rash and asymptomatic QTc prolongation, all responded to standard management or dose interruption/reduction. Four pts with squamous experienced hemoptysis (ZD6474 100 mg + Doc, n=2 CTC grade 1/2; Doc, n=2 CTC grade 3/4). No fatal episodes of hemoptysis or any CNS hemorrhage AEs were reported in pts receiving ZD6474. Overall survival data were immature at the time of PFS analysis, and a mature survival analysis will be conducted at ∼75% of deaths (anticipated April 2006, and will be presented at the meeting). As of December 2005, 40/127 (31%) pts were alive, 5 of whom continue to receive ZD6474. The minimum follow-up of pts still alive was 17 months. Conclusions: ZD6474 + Doc prolonged PFS vs Doc alone, and these promising data have led to the initiation of Phase III evaluation of ZD6474 + Doc in 2nd-line NSCLC. [Table: see text]
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Natale, R. B., D. Bodkin, R. Govindan, B. Sleckman, N. Rizvi, A. Capo, P. Germonpré, P. Stockman, S. Kennedy, and M. Ranson. "ZD6474 versus gefitinib in patients with advanced NSCLC: Final results from a two-part, double-blind, randomized phase II trial." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 7000. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.7000.
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7000 Background: ZD6474 is a once-daily oral agent that targets key signaling pathways in cancer by inhibiting VEGF, EGF and RET receptor tyrosine kinase activity. The efficacy and safety of ZD6474 was compared with that of gefitinib, an EGFR tyrosine kinase inhibitor. Methods: Patients with locally advanced or metastatic (stage IIIB/IV) non-small-cell lung cancer (NSCLC), after failure of 1st-line ± 2nd-line platinum-based chemotherapy because of toxicity or tumor progression, received daily oral doses of ZD6474 (300 mg) or gefitinib (250 mg) until disease progression or evidence of toxicity (Part A). After a washout period of 4 weeks, eligible patients had the option to switch to the alternative treatment, which continued until a withdrawal criterion was met (Part B). The dual primary objectives in Part A were assessments of progression-free survival (PFS) and safety/tolerability. All adverse events were assessed using Common Toxicity Criteria (CTC) version 2.0. Results: A total of 168 patients received initial treatment with ZD6474 (n=83) or gefitinib (n=85). In Part A, median PFS was 11.0 weeks for ZD6474 and 8.1 weeks for gefitinib (hazard ratio [95% CI] = 0.69 [0.50–0.96], P=0.025); disease control >8 weeks was achieved in 37/83 (45%) patients receiving ZD6474 and in 29/85 (34%) receiving gefitinib. The adverse event profile of ZD6474 in Part A was similar to that seen in previous trials, and included diarrhea (CTC grade 3/4, 8.4%), rash (CTC grade 3/4, 4.8%) and asymptomatic QTc prolongation (all CTC grade 1, 20.5%). There were no unexpected safety findings with gefitinib-treated patients. In Part B, disease control >8 weeks was achieved in 16/37 patients who switched to ZD6474 (from gefitinib) and in 7/29 who switched to gefitinib (from ZD6474). Overall survival was not significantly different between patients initially randomized to either ZD6474 or gefitinib (median 6.1 and 7.4 months, respectively). Conclusions: This study achieved its primary efficacy objective, with ZD6474 demonstrating a significant prolongation of PFS versus gefitinib. These data support further confirmatory trials of ZD6474 in patients with advanced NSCLC. [Table: see text]
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Carlomagno, Francesca, Teresa Guida, Suresh Anaganti, Livia Provitera, Svend Kjaer, Neil Q. McDonald, Anderson J. Ryan, and Massimo Santoro. "Identification of tyrosine 806 as a molecular determinant of RET kinase sensitivity to ZD6474." Endocrine-Related Cancer 16, no. 1 (March 2009): 233–41. http://dx.doi.org/10.1677/erc-08-0213.
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ZD6474 (vandetanib, Zactima, Astra Zeneca) is an anilinoquinazoline used to target the receptor tyrosine kinase RET in familial and sporadic thyroid carcinoma (IC50: 100 nM). The aim of this study was to identify molecular determinants of RET sensitivity to ZD6474. Here, we show that mutation of RET tyrosine 806 to cysteine (Y806C) induced RET kinase resistance to ZD6474 (IC50: 933 nM). Y806 maps close to the gate-keeper position at the RET kinase nucleotide-binding pocket. Although tyrosine 806 is a RET auto-phosphorylation site, its substitution to phenylalanine (Y806F) did not markedly affect RET susceptibility to ZD6474 (IC50: 87 nM), suggesting that phosphorylation of Y806 is not required for compound binding. Accordingly, the introduction of a phosphomimetic residue (Y806E) also caused resistance to ZD6474, albeit of a lesser degree (IC50: 512 nM) than the cysteine mutation. Y806C/E RET mutants were also resistant to ZD6474 with respect to intracellular signalling and activation of an AP1-responsive promoter. We conclude that Y806 is a molecular determinant of RET sensitivity to ZD6474. Y806C is a natural RET mutation identified in a patient affected by multiple endocrine neoplasia type 2B. Based on its rare occurrence, it is unlikely that Y806C will be a frequent cause of refractoriness to ZD6474; however, it may be envisaged that mutations at this site can mediate secondary resistance formation in patients treated with the compound.
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Wells, S., Y. N. You, V. Lakhani, J. Hou, P. Langmuir, D. Headley, M. Skinner, M. Morse, W. Burch, and M. Schlumberger. "A phase II trial of ZD6474 in patients with hereditary metastatic medullary thyroid cancer." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 5533. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.5533.
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5533 Background: Medullary thyroid carcinoma (MTC) is the most common cause of death in patients with hereditary syndromes caused by specific mutations in the RET protooncogene. RET activation is the oncogenic event, which results in intrinsic RET receptor tyrosine kinase activity, but other pathways, such as VEGFR- and EGFR-dependent signaling, also participate in tumor growth and development. ZD6474 is a once-daily oral agent that selectively targets RET, VEGFR and EGFR tyrosine kinases. The clinical activity of ZD6474 was evaluated in patients with hereditary MTC. Methods: In this open-label Phase II study, patients with unresectable, measurable, locally advanced or metastatic hereditary MTC and a RET germline mutation received once-daily oral doses of ZD6474 300 mg. The primary objective was to assess the objective tumor response (RECIST). Secondary objectives included assessments of biochemical response (determined by changes in plasma levels of calcitonin [CTN]) and safety/tolerability of ZD6474. An exploratory objective was to measure plasma levels of carcinoembryonic antigen (CEA). Results: As of 30 November 2005, 16 patients (6 male/10 female; median age 50 years, range 22–77) had entered the study and received initial treatment with ZD6474 300mg. The median duration of treatment was 136 days (range 16–353). Fifteen patients were evaluable for tumor response, CTN, and CEA. Objective tumor assessments have demonstrated partial responses in 3 patients (n = 2 confirmed; n = 1 unconfirmed), stable disease in 10 patients (n = 8, ≥8 and <24 weeks; n = 2, ≥24 weeks) and progressive disease in 2 patients. A >50% decrease from baseline in plasma CTN levels has been maintained for at least 4 weeks in 12/15 patients; a decrease in plasma CEA levels of the same magnitude and duration has been observed in 6/15 patients. Common adverse events (AEs) were diarrhea (n = 12) and nausea, rash and fatigue (each n = 11). CTC grade 3 AEs attributable to ZD6474 were QTc interval prolongation (n = 3), and diarrhea, skin rash and hypertension (each n = 2). Conclusions: ZD6474 shows promising evidence of clinical activity in patients with hereditary MTC. These are preliminary data and patients are still being recruited to this ongoing study. [Table: see text]
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Morelli, M. P., T. Cascone, T. Troiani, C. Tuccillo, R. Bianco, M. Romano, S. G. Eckhardt, S. De Pacido, G. Tortora, and F. Ciardiello. "Antitumor activity of the combination of cetuximab, an anti-EGFR blocking monoclonal antibody and ZD6474, an inhibitor of VEGFR and EGFR tyrosine kinases." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 13170. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.13170.
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13170 Background: The epidermal growth factor receptor (EGFR) autocrine pathway plays an important role in cancer cell growth. Vascular endothelial growth factor A (VEGF-A) is a key regulator of tumor-induced endothelial cell proliferation and vascular permeability. ZD6474 (ZACTIMA™) is an orally available, small molecule inhibitor of VEGF receptor-2 (VEGFR-2), EGFR and RET tyrosine kinase activity. We investigated the activity of ZD6474 in combination with cetuximab, an anti-EGFR blocking monoclonal antibody, to determine the antitumor activity of EGFR blockade through the combined use of two agents targeting the receptor at different molecular sites in cancer cells and of VEGFR-2 blockade in endothelial cells. Methods: The antitumor activity in vitro and in vivo of ZD6474 and/or cetuximab was tested in human cancer cell lines with a functional EGFR autocrine pathway. Results: In vitro, the combination of ZD6474 and cetuximab produced synergistic growth inhibition in all cancer cell lines tested as assessed by the Chou and Talalay method. In vivo, 4 weeks of treatment with ZD6474 (75 mg/kg p.o., days 1–5 each week) or cetuximab (1 mg i.p., days 2 and 5 each week) produced a tumor growth delay of 21–28 days (P < 0.001) in nude mice bearing established human colon carcinoma (GEO) or lung adenocarcinoma (A549) cancer xenografts compared with untreated controls. Combination treatment with ZD6474 and cetuximab for 4 weeks resulted in a more marked tumor growth delay of 120–140 days compared with controls, and this was significantly greater than with either single agent therapy (P < 0.001). Following combination treatment, 3/10 A549 xenograft-bearing mice and 4/10 GEO xenograft-bearing mice had no histologic evidence of tumor at the end of the experiment. Immunohistochemical analysis of tumor samples obtained from mice treated with the two drugs in combination demonstrated a cooperative inhibition of cancer cell proliferation and an almost complete suppression of tumor angiogenesis. Conclusions: This study provides a rationale for evaluating in a clinical setting the double blockade of EGFR in combination with inhibition of VEGFR-2 signaling as cancer therapy. [Table: see text]
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Troiani, T., O. Lockerbie, M. Morrow, F. Ciardiello, and S. G. Eckhardt. "ZD6474, an inhibitor of VEGFR and EGFR tyrosine kinases, blocks VEGF-C-induced activation of VEGFR-3 and cell proliferation in human colon cancer cell lines." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 13171. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.13171.
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13171 Background: Vascular endothelial growth factor receptors 1, 2 and 3 (VEGFR-1, -2 and -3) have a key role in activation and proliferation of endothelial cells, with expression of VEGFR-3 largely restricted to lymphatic endothelial cells. Although high expression of VEGFR-3 and its specific ligands, VEGF-C and VEGF-D, has been associated with an increased incidence of lymph node metastasis and a poor prognosis in different human malignancies, little is known about the role of this signaling pathway in tumor cells. This study investigated VEGFR-3 and its specific ligands in human colon cancer cells, and the antiproliferative activity of ZD6474, an inhibitor of VEGFR, epidermal growth factor receptor (EGFR) and RET tyrosine kinases, and of the EGFR inhibitors gefitinib and cetuximab. Methods: The expression of VEGFRs and EGFR was determined by RT-PCR, immunoblotting, flow cytometry and immunohistochemistry in four human colon cancer cell lines (HCT-116, HT-29, HCT-15 and SW480). Secretion of transforming growth factor-α (TGF-α), VEGF-A and VEGF-C by cancer cells was determined by ELISA. The in vitro antiproliferative effects of ZD6474, gefitinib and cetuximab were determined using an MTT assay. Results: All four human colon cancer cell lines expressed functional EGFR and secreted high levels of TGF-α. All four cell lines expressed VEGFR-1 and VEGFR-3, but not VEGFR-2, and secreted both VEGF-A and VEGF-C. Treatment with ZD6474 resulted in a dose-dependent cell growth inhibition (IC50 3–5 μM), whereas treatment with gefitinib or with cetuximab produced little growth inhibition under the same culture conditions. Addition of VEGF-C induced a 2-fold increase in cell growth in vitro in all four colon cancer cell lines. Treatment with ZD6474 blocked both basal and VEGF-C-induced phosphorylation of VEGFR-3, as well as VEGF-C-induced cell proliferation. Conclusions: Human colon cancer cell lines express VEGFR-1 and VEGFR-3, and secrete VEGF-A and VEGF-C. A potential VEGF-C/VEGFR-3 autocrine loop has been identified in human colon cancer cells, which can be inhibited by ZD6474, suggesting that ZD6474 may have direct antitumor activity through inhibition of VEGFR signaling. [Table: see text]
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Nakagawa, K., K. Kiura, T. Shinkai, K. Eguchi, Y. Ohe, N. Yamamoto, M. Tsuboi, S. Yokota, M. Fukuoka, and H. Jiang. "A randomized double-blind phase IIa dose-finding study of ZD6474 in Japanese patients with NSCLC." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 7067. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.7067.
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7067 Background: ZD6474 is a once-daily oral therapy that selectively inhibits key signaling pathways in cancer by targeting vascular endothelial growth factor receptor (VEGFR)-dependent tumor angiogenesis, and epidermal growth factor receptor (EGFR)- and RET-dependent cancer cell proliferation and survival. ZD6474 was evaluated as monotherapy in an ongoing randomized, double-blind, parallel-group, Phase IIa, dose-finding, multicenter study in Japan. Methods: Patients with locally advanced or metastatic (stage IIIB/IV) or recurrent non-small-cell lung cancer (NSCLC), after failure of one or two platinum-based chemotherapy regimens, were eligible for this study. Patients were randomized to receive ZD6474 100, 200 or 300 mg/day in a 1:1:1 ratio, with stratification according to sex, histology (adenocarcinoma vs other histology) and smoking status (smoker vs non-smoker). Tumor response was assessed every 4 weeks for the first 24 weeks of treatment and then every 8 weeks until progressive disease (PD) or withdrawal due to any reasons other than PD. The primary objective was the objective response rate, as evaluated by RECIST. Secondary objectives included disease control rate, tolerability and safety. Adverse events (AEs) were assessed using CTC version 3.0. Results: A total of 53 patients (34 males/19 females, median age 60 years [range 30–78], 35 adenocarcinomas and 33 smokers) with a WHO PS status of 0 (n = 20) or 1 (n = 33) were recruited from eight centers between December 2004 and September 2005. Among 53 patients, 6 partial responses (PR; 11%, 2 males/4 females, 6 adenocarcinomas, 2 smokers/4 non-smokers) have been confirmed and disease control (PR or stable disease≥ 8 weeks) has been observed in 27 patients (51%). The most common AEs were rash and diarrhea, and asymptomatic QTc prolongation was also observed. One patient died due to drug-related interstitial lung disease. Conclusions: In this ongoing trial, ZD6474 has demonstrated antitumor activity as monotherapy in patients with refractory NSCLC, with 11% experiencing a PR and 51% having disease control. The tolerability profile of ZD6474 was consistent with that seen previously. [Table: see text]
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Kovacs, Michael J., Donna E. Reece, Deborah Marcellus, Ralph M. Meyer, Sarah Matthews, Rui-Ping Dong, and Elizabeth Eisenhauer. "A Phase II Study of ZD6474, a Vascular Endothelial Growth Factor Receptor (VEGFR) and Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) in Patients with Relapsed Multiple Myeloma (MM)." Blood 104, no. 11 (November 16, 2004): 3464. http://dx.doi.org/10.1182/blood.v104.11.3464.3464.
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Abstract ZD6474 targets angiogenesis by inhibiting VEGFR TK and also affects EGFR signaling by inhibiting EGFR TK activity. This oral agent showed dose-related tumor growth inhibition in a broad range of in vivo xenograft models. In Phase I studies, drug- and dose-related adverse events included rash, diarrhea, hypertension, and asymptomatic QT/QTc prolongation. Four patients with NSCLC included in the phase I studies exhibited partial responses. Because MM is a disease in which angiogenesis is postulated to be a relevant target for therapy, we conducted a phase II trial of ZD6474 100 mg p.o. daily in patients with MM who had relapsed following either high-dose chemotherapy and stem cell transplantation, or following non-high-dose chemotherapy. Although a higher dose was recommended for solid tumour trials, a dose of 100 mg p.o. daily produced plasma levels in phase I in excess of the IC50 for in vitro inhibition of VEGF-stimulated HUVEC proliferation and seemed well tolerated. For the study reported here, patients all had a measurable M protein in the serum or urine and were required to have an ECOG PS of 0, 1 or 2. Patients were excluded if they had any of: AGC <1.0x109/L or platelet count <50x109/L; bilirubin, AST and/or ALT >1.5xUNL; creatinine >2xUNL; K+ <4.0mmol/L; abnormal Ca2+ or Mg2+ levels, prior thalidomide treatment or pre-existing cardiac dysfunction. The primary efficacy endpoint was objective response as assessed by reduction in M protein. Following written, informed consent, 18 patients were entered into the study from five centers (9 male/9 female; mean age 64 yrs [35– 81]). Fourteen patients had relapsed following high-dose chemotherapy with stem cell transplant. One patient was ineligible due to elevated baseline calcium and one was not evaluable (off study due to non drug-related infection with < 14 days of therapy) . Patients were treated for 3.0– 29.4 weeks (mean 9.8 weeks). Overall, ZD6474 was well tolerated with only three patients missing doses of ZD6474. The most common drug-related adverse events were nausea, vomiting, fatigue, rash, pruritis, headache, diarrhea, dizziness, and sensory neuropathy, all of which were Grade I – II in severity. There were no drug-related serious adverse events. Laboratory adverse events were infrequent: one patient had Grade III anemia, and there were no Grade III changes in biochemistry. No significant QTc interval changes were seen. Fifteen patients had plasma samples obtained for at least 4 weeks after starting treatment. Trough levels of ZD6474 achieved or exceeded the IC50 for inhibition of VEGF-stimulated HUVEC proliferation in 13 of the 15 patients by day 28. There were no responses in M protein levels. In conclusion, ZD6474 was well tolerated at a dose of 100 mg per day and achieved plasma levels predicted to inhibit VEGF signaling. However, this was not reflected in clinical benefit since none of the patients had a reduction in M protein. ZD6474 development in solid tumors is continuing in a series of Phase II trials.
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Heymach, J. V. "ZD6474 – clinical experience to date." British Journal of Cancer 92, S1 (June 2005): S14—S20. http://dx.doi.org/10.1038/sj.bjc.6602604.
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Nair, Binoj C., and Ratna K. Vadlamudi. "ZD6474 coerces breast cancer for an apoptotic journey." Cancer Biology & Therapy 9, no. 8 (April 15, 2010): 604–6. http://dx.doi.org/10.4161/cbt.9.8.11318.
Full textDissertations / Theses on the topic "ZD6474"
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Sandström, Maria. "Experimental therapies of malignant glioma : with emphasis on angiogenesis inhibition." Doctoral thesis, Umeå universitet, Institutionen för strålningsvetenskaper, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1955.
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Malignant glioma consists of a group of diseases where the localisation and the nature of the disease makes treatment an extreme challenge. Two important biological features of malignant glioma cells are their infiltrative growth and their ability to induce angiogenesis. Glioma cells migrate extensively behind the blood-brain barrier and infiltrate the surrounding brain making radical treatment with surgery and radiotherapy almost impossible. The aims of this thesis were to investigate factors of importance for glioma cell migration and angiogenesis and to evaluate if an anti-angiogenesis approach alone or in combination with current treatment modalities could inhibit glioma growth. For this purpose we used the BT4C orthotopic rat glioma model and investigated treatment effects of the vascular endothelial growth factor (VEGF) receptor-2 and epidermal growth factor (EGF) receptor tyrosine kinase inhibitor ZD6474 alone or in combination with temozolomide or radiotherapy. Altered protein expression pattern after anti-angiogenesis treatment was measured using a mass-spectrometric proteomic method, followed by multivariate data-analysis. The tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), and VEGF showed altered temporal and spatial mRNA expression during glioma progression. In early stages of tumour progression the expression was found throughout the tumour while in later stages, the expression was more predominant in the invasive tumour border. ZD6474 in monotherapy significantly inhibited tumour growth in the BT4C glioma model. The effect was further enhanced when combined with radiotherapy or temozolomide. Using mass-spectrometric methods an altered protein expression pattern after ZD6474 treatment was observed implicating the possibility to use proteomic methods for finding predictive biomarkers for anti-angiogenesis treatment. In conclusion, this thesis demonstrates a co-expression of factors important for glioma growth and angiogenesis and that treatment with an angiogenesis inhibitor has additive effects on glioma growth when combined with radiotherapy and chemotherapy. Finally, an altered protein expression pattern after anti-angiogenesis treatment is evident and detectable. Hopefully this work will contribute to and encourage further research to reach a better understanding of how to combine and evaluate different treatment approaches in malignant glioma.
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Wiegand, Ulrich. "Antiangiogenetische Therapie des humanen Pankreaskarzinoms durch ZD6474, ein neuartiger Inhibitor des vaskulären endothelialen Wachstumsfaktorrezeptor VEGF-R2 (KDR/FLK-1) Tyrosinkinase, nach orthotoper Implantation in die Nacktmaus." Diss., lmu, 2009. http://nbn-resolving.de/urn:nbn:de:bvb:19-98926.
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Ma, Hong [Verfasser]. "Target therapy against VEGFR and EGFR with ZD6474 enhances the therapeutic efficacy of irradiation in tumor-bearing nude mice / vorgelegt von Hong Ma." 2008. http://d-nb.info/996162283/34.
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Wiegand, Ulrich [Verfasser]. "Antiangiogenetische Therapie des humanen Pankreaskarzinoms durch ZD6474, ein neuartiger Inhibitor des vaskulären endothelialen Wachstumsfaktorrezeptor VEGF-R2 (KDR/FLK-1) Tyrosinkinase, nach orthotoper Implantation in die Nacktmaus / vorgelegt von Ulrich Wiegand." 2009. http://d-nb.info/993679471/34.
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Chen, Yu-hsin, and 陳郁心. "Francis Poulenc Petites Voix''s Music Analysis and Interpretation." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/zd6x7x.
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碩士國立中山大學
音樂學系研究所
95
Francis Poulenc ( 1899-1963 ) is one of the most important French composers in the early 20th -century. Influenced by Neo-classicism, Poulenc developed his own personal musical language which is light, humorous, and sagacious. He wrote in many different musical genres during his life, including ballet, opera, piano, vocal, choral, and chamber music. In 1936, after his good friend Pierre-Octave Ferroud’ sudden death in a car accident and religious experience in Rocamadour, Poulenc started to compose choral music, including Petites Voix. Petites Voix, completed in 1936, includes five short pieces for three-part treble voices. Poulenc chose five lovely poems as the text from Madeleina Ley’s poetry Petites Voix, and created five short choral songs. La Petite Fille Sage ( The Good Little Girl ) describes a substantial day of a little girl. Le Chien Perdu ( The Lost Dog ) is a conversation between a kid and a dog. En Renreant de L’école ( On the Way Home from School ) describes the surprising things that happened on the way home from school. Le Petit Garçon Malade ( The Little Sick Boy ) describes a sick boy whose mind is full of feelings of helplessness. Le Hérisson ( The Hedgehog ) talks about a father who brings a Hedgehog home and some funny things happen in the family. Each song describes a little story happening in daily life from a child’s point of view, and Poulenc has put these texts to music with excellent technique to express childlike innocence. This master report consists of seven parts. The first part is an introduction. It is followed by background of early 20th-century french music, a biographic sketch of Poulenc life, characteristics of Poulenc secular choral works, a biographic sketch of Madeleina Ley life, analysis of Petites Voix, and interpretation of Petites Voix. The last part is the conclusion. There are three appendices at the end of this paper. Appendix A contains the phonetic alphabets and the general rules of French diction. Appendix B offers the translation and a French pronunciation guide for the lyrics of these five pieces. Appendix C is a list of Poulenc choral works
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Hong, Wei-Huang, and 洪唯晃. "A Study of Teachers’ Perception and Acceptance of Electronic Textbooks at Junior High School in Kaohsiung City." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/zd6a54.
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碩士義守大學
資訊管理學系
105
This study is based on the technology acceptance model that Davis (1989) proposed. The primary purpose of this study is to explore junior high school teachers'' behavior pattern of using electronic textbooks; mainly the relationships among the external variables, perceived usefulness, perceived ease of use, and intention to use.This study used random sampling questionnaire survey method targeted at junior high school teachers in Kaoshiung City. Statistic methods included average, standard deviation, t-test, ANOVA and pearson product-moment correlation coefficient were used to analyze the 426 valid samples. The results are as followed:System quality has a moderate positive correlation to perceived usefulness.Perceived risk has a low negative correlation to perceived usefulness.Envirnmental factor has a moderate positive correlation to perceived usefulness.System quality has a moderate positive correlation to perceived ease of use.Perceived risk has a low negative correlation to perceived ease of use.Envirnmental factor has a moderate positive correlation to perceived ease of use. The perceived usefulness of junior high school teachers using electronic textbooks has a moderate positive correlation to perceived ease of use .The perceived usefulness of junior high school teachers using electronic textbooks has a moderate positive correlation to behavioral intention to use .The perceived ease of use of junior high school teachers using electronic textbooks has a moderate positive correlation to behavioral intention to use.
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Mason, William Lowell. "Feeling Machines: Immersion, Expression, and Technological Embodiment in Electroacoustic Music of the French Spectral School." Thesis, 2019. https://doi.org/10.7916/d8-k4nh-zd64.
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This dissertation considers the music and technical practice of composers affiliated with French spectralism, including Hugues Dufourt, Gérard Grisey, Tristan Murail, Jean-Claude Risset, and Kaija Saariaho. They regularly described their work, which was attuned to the transformative experiences that technologies of electronic sound production and reproduction could inspire in listeners, using metaphoric appeals to construction: to designing new sounds or exploring new illusory aural phenomena. To navigate a nascent but fast-expanding world of electronic and computer music, the spectralists appealed to physical musical attributes including gesture, space, and source-cause identification. Fascinated by gradual timbral transformations, they structured some of their pieces to invite speculative causal listening even while seeking to push it to expressive extremes.
I hypothesize that, much as the immersive technology of the cinema can create the illusory feeling of flight in viewers, electronic music can inspire listeners to have experiences in excess of their physical capabilities. Those feelings are possible because listening can be understood as empathetic and embodied, drawing on a listener’s embodied and ecological sensorimotor knowledge and musical imagery alongside referential, semiotic, and cultural aspects of music. One way that listeners can engage with sounds is by imagining how they would create them: what objects would be used, what kind of gestures would they perform, how much exertion would be required, what space would they inhabit. I cite recent research in psychoacoustics to argue that timbre indexes material, gesture, and affect in music listening. Technologies of sound production and reproduction allow for the manipulation of these tendencies by enabling composers to craft timbres that mimic, stretch, or subvert the timbres of real objects. Those electronic technologies also suggest manipulations to composers, by virtue of their design affordances, and perform an epistemological broadening by providing insight into the malleability of human perceptual modes. I illustrate these claims with analytic examples from Murail’s Ethers (1978), Saariaho’s Verblendungen (1984), and Grisey’s Les Chants de l’Amour (1984), relating an embodied and corporeal account of my hearing and linking it to compositional and technological features of spectral music.
Conference papers on the topic "ZD6474"
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Kim, Yoo-shin, and Brian E. O'Neill. "Abstract A18: Modified ZD6474 (Vandetanib) derivatives with VEGFR2 and non-peptide integrin antagonist (IA) slows tumor growth." In Abstracts: AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; March 5-8, 2015; Orlando, FL. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-8514.tumang15-a18.
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