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1دورية أكاديمية
المؤلفون: Stockhammer, G, Brotchi, J, Leblanc, R, Bernstein, M, Schackert, G, Weber, F, Ostertag, C, Mulder, NH, Mellstedt, H, Seiler, R, Yonekawa, Y, Twerdy, K, Kostron, H, DeWitte, O, Lambermont, M, Velu, T, Laneuville, P, Villemure, JG, Rutka, JT, Warnke, P, Laseur, M, Mooij, JJA, Boethius, J, Mariani, L, Meyer, M, Brandli, C, Frei, K, Konu, D, GianellaBorradori, A
المصدر: Journal of molecular medicine (Berlin, Germany). 75(4):300-304
مصطلحات موضوعية: Medicin och hälsovetenskap
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2دورية أكاديمية
المؤلفون: Kusumanto, YH, Van Weel, V., Mulder, NH, Smit, AJ, Van den Dungen, JJAM, Hooymans, JMM, Sluiter, WJ, Tio, RA, Quax, PHA, Gans, ROB, Dullaart, RPF, Hospers, GAP
المصدر: Kusumanto , YH , Van Weel , V , Mulder , NH , Smit , AJ , Van den Dungen , JJAM , Hooymans , JMM , Sluiter , WJ , Tio , RA , Quax , PHA , Gans , ROB , Dullaart , RPF & Hospers , GAP 2006 , ' Treatment with intramuscular vascular endothelial growth factor gene compared with placebo for patients with diabetes mellitus and critical limb ischemia : A double-blind randomized trial ' , Human Gene Therapy , vol. 17 , no. 6 , pp. 683-691 . https://doi.org/10.1089/hum.2006.17.683Test
مصطلحات موضوعية: QUALITY-OF-LIFE, PERIPHERAL ARTERIAL-DISEASE, LOWER-EXTREMITY ISCHEMIA, CRITICAL LEG ISCHEMIA, THERAPEUTIC ANGIOGENESIS, PHASE-II, PHVEGF(165), AMPUTATIONS, STANDARDS
الوصف: Despite advances in revascularization techniques, limb salvage and relief of pain cannot be achieved in many diabetic patients with diffuse peripheral vascular disease. Our objective was to determine the effect of intramuscular administration of phVEGF(165) (vascular endothelial growth factor gene-carrying plasmid) on critical limb ischemia (CLI) compared with placebo (0.9% NaCl). A double-blind, placebo-controlled study was performed in 54 adult diabetic patients with CLI. The primary end point was the amputation rate at 100 days. Secondary end points were a 15% increase in pressure indices (ankle-to-brachial index and toe-to-brachial index), clinical improvement (skin, pain, and Quality of Life score), and safety. In patients (n = 27) treated with placebo versus phVEGF(165)-treated patients (n=27) the following results were found: 6 amputations versus 3 (p = not significant [NS]); hemodynamic improvement in 1 versus 7 (p = 0.05); improvement in skin ulcers, 0 versus 7 (p = 0.01); decrease in pain, 2 versus 5 (p = NS); and overall, 3 versus 14 responding patients (p = 0.003). No grade 3 or 4 adverse effects were seen in these patients. We conclude that this small, randomized gene therapy study failed to meet the primary objective of significant amputation reduction. However, significant and meaningful improvement was found in patients treated with a VEGF(165)-containing plasmid. There were no substantial adverse events.
وصف الملف: application/pdf
الإتاحة: https://doi.org/10.1089/hum.2006.17.683Test
https://hdl.handle.net/11370/a91065b0-2184-4f9e-857b-854e250542f9Test
https://research.rug.nl/en/publications/a91065b0-2184-4f9e-857b-854e250542f9Test
https://pure.rug.nl/ws/files/191076434/hum.2006.17.683.pdfTest -
3دورية أكاديمية
المؤلفون: Buursma, AR, de Vries, EFJ, Garssen, J, Kegler, D, van Waarde, A, Schirm, J, Hospers, GAP, Mulder, NH, Vaalburg, W, Klein, HC
المصدر: Buursma , AR , de Vries , EFJ , Garssen , J , Kegler , D , van Waarde , A , Schirm , J , Hospers , GAP , Mulder , NH , Vaalburg , W & Klein , HC 2005 , ' [F-18]FHPG positron emission tomography for detection of herpes simplex virus (HSV) in experimental HSV encephalitis ' , Journal of Virology , vol. 79 , no. 12 , pp. 7721-7727 . https://doi.org/10.1128/JVI.79.12.7721-7727.2005Test
مصطلحات موضوعية: VIRAL ENCEPHALITIS, ALZHEIMERS-DISEASE, GENE-THERAPY, BRAIN-EDEMA, INFECTION, SCHIZOPHRENIA, HERPES-SIMPLEX-VIRUS-1, INOCULATION, ACYCLOVIR, DIAGNOSIS
الوصف: Herpes simplex virus type 1 (HSV-1) is one of the most common causes of sporadic encephalitis. The initial clinical course of HSV encephalitis (HSE) is highly variable, and the infection may be rapidly fatal. For effective treatment with antiviral medication, an early diagnosis of HSE is crucial. Subtle brain infections with HSV may be causally related to neuropsychiatric disorders such as Alzheimer's dementia. We investigated the feasibility of a noninvasive positron emission tomography (PET) imaging technique using [F-18]FHPG as a tracer for the detection of HSE. For this purpose, rats received HSV-1 (infected group) or phosphate-buffered saline (control group) by intranasal application, and dynamic PET scans were acquired. In addition, the distribution of tracer accumulation in specific brain areas was studied with phosphor storage imaging. The PET images revealed that the overall brain uptake of [F-18] FHPG was significantly higher for the infected group than for control animals. Phosphor storage images showed an enhanced accumulation of [F-18]FHPG in regions known to be affected after intranasal infection with HSV. High-performance liquid chromatography metabolite analysis showed phosphorylated metabolite(s) of [F-18]FHPG in infected brains, proving that the increased [F-18]FHPG uptake in infected brains was due to HSV thymidine kinase-mediated trapping. Freeze lesion experiments showed that damage to the blood-brain barrier could in principle induce elevated [F-18] FHPG uptake, but this nonspecific tracer uptake could easily be discriminated from HSE-derived uptake by differences in the tracer kinetics. Our results show that [F-18]FHPG PET is a promising tool for the detection of HSV encephalitis.
وصف الملف: application/pdf
الإتاحة: https://doi.org/10.1128/JVI.79.12.7721-7727.2005Test
https://hdl.handle.net/11370/0f18058e-ee51-4bda-9eac-492706e7eb3bTest
https://research.rug.nl/en/publications/0f18058e-ee51-4bda-9eac-492706e7eb3bTest
https://pure.rug.nl/ws/files/16303431/Buursma2005.pdfTest -
4دورية أكاديمية
المؤلفون: Buursma, AR, van Dillen, IJ, van Waarde, A, Vaalburg, W, Hospers, GAP, Mulder, NH, de Vries, EFJ
المصدر: Buursma , AR , van Dillen , IJ , van Waarde , A , Vaalburg , W , Hospers , GAP , Mulder , NH & de Vries , EFJ 2004 , ' Monitoring HSVtk suicide gene therapy : the role of [F-18]FHPG membrane transport ' , British Jounal of Cancer , vol. 91 , no. 12 , pp. 2079-2085 . https://doi.org/10.1038/sj.bjc.6602216Test
مصطلحات موضوعية: positron emission tomography, gene therapy, herpes simplex virus thymidine kinase, ganciclovir, [F-18]FHPG, membrane transport, acyclovir, VIRUS THYMIDINE KINASE, HUMAN-ERYTHROCYTES, NUCLEOSIDE, CELLS, EXPRESSION, PET, PHOSPHORYLASE, METABOLISM, ANALOGS, TUMORS
الوصف: Favourable pharmacokinetics of the prodrug are essential for successful HSVtk/ganciclovir (GCV) suicide gene therapy. [F-18] FHPG PET might be a suitable technique to assess the pharmacokinetics of the prodrug GCV noninvasively, provided that [F-18] FHPG mimics the behaviour of GCV. Since membrane transport is an important aspect of the pharmacokinetics of the prodrug, we investigated the cellular uptake mechanism of [F-18] FHPG in an HSVtk expressing C6 rat glioma cell line and in tumour- bearing rats. The nucleoside transport inhibitors dipyridamol, NBMPR and 2- chloroadenosine did not significantly affect the [F-18] FHPG uptake in vitro. Thymidine and uridine significantly decreased [F-18] FHPG uptake by 84 and 58%, respectively, but an enzyme assay revealed that this decline was due to inhibition of the HSVtk enzyme rather than membrane transport. Nucleobase transport inhibitors, thymine and adenine, caused a 58 and 55% decline in tracer uptake, respectively. In vivo, the ratio of [F-18] FHPG uptake in C6tk and C6 tumours decreased from 3.070.5 to 1.070.2 after infusion of adenine. Thus, in our tumour model, [F-18] FHPG transport exclusively occurred via purine nucleobase transport. In this respect, FHPG does not resemble GCV, which is predominantly taken up via the nucleoside transporter, but rather acyclovir, which is also taken up via the purine nucleobase carrier.
وصف الملف: application/pdf
الإتاحة: https://doi.org/10.1038/sj.bjc.6602216Test
https://hdl.handle.net/11370/3d786975-068f-4efb-958d-b3885166c9caTest
https://research.rug.nl/en/publications/3d786975-068f-4efb-958d-b3885166c9caTest
https://pure.rug.nl/ws/files/62241486/Monitoring_HSVtk_suicide_gene_therapy.pdfTest -
5دورية أكاديمية
المؤلفون: Hofstra, LS, de Vries, EGE, van der Zee, AGJ, Beijnen, JH, Rosing, H, Mulder, NH, Aalders, JG, Willemse, PHB
المصدر: Hofstra , LS , de Vries , EGE , van der Zee , AGJ , Beijnen , JH , Rosing , H , Mulder , NH , Aalders , JG & Willemse , PHB 2001 , ' A phase I and pharmacokinetic study of intraperitoneal topotecan ' , British Jounal of Cancer , vol. 85 , no. 11 , pp. 1627-1633 .
مصطلحات موضوعية: intraperitoneal, topotecan, ovarian cancer, pharmacokinetics, phase I, EPITHELIAL OVARIAN-CANCER, CELL LUNG-CANCER, EVERY 21 DAYS, TOPOISOMERASE-I, INHIBITOR TOPOTECAN, CLINICAL-TRIALS, ACUTE-LEUKEMIA, CAMPTOTHECIN, DRUG, CHEMOTHERAPY
الوصف: Purpose: To evaluate the feasibility and pharmacology of intraperitoneal (IP) topotecan. Patients and methods: Fifteen patients with recurrent ovarian cancer in a phase I trial were treated with escalating IP topotecan doses (5-30 mg/m(2)) for pharmacokinetic analysis. Results: Dose limiting toxicity (DLT) was acute hypotension, chills and fever at the 30 mg/m(2) dose level. Haematological toxicity and abdominal pain were mild for all dose levels studied. Pharmacokinetics: Peak plasma levels of total topotecan were reached at 2.7 +/- 1.1 h after IP instillation. The apparent V-SS was 69.9 +/- 25.4 L/m(2), plasma clearance 13.4 +/- 2.5 L/h/m(2) and plasma T1/2 3.7 +/- 1.3 h. The plasma AUC was correlated with the dose (R = 0.95, P <0.01). The plasma AUC ratio of lactone versus total topotecan (lactone + carboxy-forms) increased with the dose from 16% to 55%, (R = 0.84, P <0.01). Peritoneal total topotecan was cleared from the peritoneal cavity at 0.4 +/- 0.3 L/h.m(2) with a T1/2 = 2.7 +/- 1.7 h. The mean peritoneal/plasma AUC ratio for total topotecan was 54 - 34. Conclusion: A substantial dose of topotecan can be delivered by the IP route, achieving cytotoxic plasma levels of topotecan, with acceptable toxicity. The recommended dose for further phase 11 trials is 20 mg/m(2) IP, which enables combination with active doses of other cytotoxic drugs, in view of its limited myelotoxicity when given by this route. (C) 2001 Cancer Research Campaign.
وصف الملف: application/pdf
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6دورية أكاديمية
المؤلفون: Schroder, CP, Wisman, GBA, de Jong, S, van der Graaf, WTA, Ruiters, MHJ, Mulder, NH, de Leij, LFMH, van der Zee, AGJ, de Vries, EGE
المصدر: Schroder , CP , Wisman , GBA , de Jong , S , van der Graaf , WTA , Ruiters , MHJ , Mulder , NH , de Leij , LFMH , van der Zee , AGJ & de Vries , EGE 2001 , ' Telomere length in breast cancer patients before and after chemotherapy with or without stem cell transplantation ' , British Jounal of Cancer , vol. 84 , no. 10 , pp. 1348-1353 . https://doi.org/10.1054/bjoc.2001.1803Test
مصطلحات موضوعية: breast cancer, telomere length, high-dose chemotherapy, autologous stem cell transplantation, HEMATOPOIETIC-CELLS, CARCINOMA, DYNAMICS, RECIPIENTS, STABILITY, CHILDREN, VIVO, DNA
الوصف: High-dose chemotherapy and peripheral blood stem cell transplantation (PBSCT) may accelerate telomere length loss in haematopoietic stem cells. As data including pre-and post-treatment samples are lacking, we studied leukocyte telomere length and telomerase activity before and after treatment in breast cancer patients randomized to receive 5 adjuvant courses FEC (5-FU, epirubicin and cyclophosphamide) (n = 17), or 4 x FEC followed by high-dose cyclophosphamide, thiotepa, carboplatin and autologous PBSCT (n = 16). Haemoglobin. MCV, leukocyte-and platelet numbers were assessed prior to (t(0)), 5 months after (t(1)) and 9 months after chemotherapy (t(2)); these parameters were decreased at t(1) and t(2) compared to t(0) (high-dose: all parameters; standard-dose: leukocytes and platelets), and all parameters were lower after high-dose than standard-dose treatment at t(1). Paired individual leukocyte samples of t(0) and t(1) showed telomere length change (determined by telomere restricted fragment (TRF) assay) ranging from (+)0.8 to -2.2 kb, with a decreased TRF length in 9 patients of both groups. Telomerase activity (determined by TRAP assay) was below detection limit in leukocyte samples of t(0) and t(1). Thus, standard-and high-dose chemotherapy negatively affect haematological reconstitution in this setting. In individual patients, telomere length can be remarkably changed following haematological proliferative stress after treatment. (C) 2001 Cancer Research Campaign.
وصف الملف: application/pdf
الإتاحة: https://doi.org/10.1054/bjoc.2001.1803Test
https://hdl.handle.net/11370/9fc654b7-ce91-4edf-8758-eaefaa17e639Test
https://research.rug.nl/en/publications/9fc654b7-ce91-4edf-8758-eaefaa17e639Test
https://pure.rug.nl/ws/files/62260684/Telomere_length_in_breast_cancer_patients.pdfTest -
7دورية أكاديمية
المؤلفون: Nieboer, P, de Vries, EGE, Mulder, NH, Sleijfer, DTh, Willemse, PHB, Hospers, GAP, Gietema, JA, Sluiter, WJ, van der Graaf, WTA
المصدر: Bone Marrow Transplantation ; volume 27, issue 9, page 959-966 ; ISSN 0268-3369 1476-5365
مصطلحات موضوعية: Transplantation, Hematology
الإتاحة: https://doi.org/10.1038/sj.bmt.1703030Test
https://www.nature.com/articles/1703030Test
https://www.nature.com/articles/1703030.pdfTest -
8دورية أكاديمية
المؤلفون: Calogero, A, Timmer-Bosscha, H, Tiebosch, ATMG, Mulder, NH, Hospers, GAP, Schraffordt Koops, H.
المصدر: Calogero , A , Timmer-Bosscha , H , Tiebosch , ATMG , Mulder , NH , Hospers , GAP & Schraffordt Koops , H 2000 , ' Limitations of the nested reverse transcriptase polymerase chain reaction on tyrosinase for the detection of malignant melanoma micrometastases in lymph nodes ' , British Jounal of Cancer , vol. 83 , no. 2 , pp. 184-187 . https://doi.org/10.1054/bjoc.2000.1282Test
مصطلحات موضوعية: tyrosinase, melanoma, lymph nodes, nested RT-PCR, PERIPHERAL-BLOOD, MESSENGER-RNA, RT-PCR, TUMOR PROGRESSION, SENTINEL NODES, CLINICAL STAGE, CELL-LINES, MARKER, IMMUNOHISTOCHEMISTRY, MART-1
الوصف: The specificity and sensitivity of the nested reverse transcriptase polymerase chain reaction (RT-PCR) on tyrosinase was studied, for the detection of micrometastases of malignant melanoma. The specificity was assessed in the blood of six healthy donors, four patients with non-melanoma cancers of which one patient was treated with granulocyte-colony stimulating factor. Lymph nodes of nine patients without malignant melanoma were tested and four cell lines of various other tumours. Six of the nine non-melanoma lymph nodes were positive in this assay. The sensitivity was tested in a spike experiment in vitro, using a melanoma cell line. The detection limit was ten melanoma cells per 10(7) peripheral blood lymphocytes. (C) 2000 Cancer Research Campaign.
وصف الملف: application/pdf
الإتاحة: https://doi.org/10.1054/bjoc.2000.1282Test
https://hdl.handle.net/11370/2050d491-5d1a-4260-a2d2-b0edb14f2fd4Test
https://research.rug.nl/en/publications/2050d491-5d1a-4260-a2d2-b0edb14f2fd4Test
https://pure.rug.nl/ws/files/62262803/Limitations_of_the_nested_reverse_transcriptase_polymerase_chain_reaction.pdfTest -
9دورية أكاديمية
المؤلفون: de Jong, RS, Mulder, NH, Uges, DRA, Sleijfer, DT, Hoppener, FJP, Groen, HJM, Willemse, PHB, van der Graaf, WTA, de Vries, EGE
المصدر: de Jong , RS , Mulder , NH , Uges , DRA , Sleijfer , DT , Hoppener , FJP , Groen , HJM , Willemse , PHB , van der Graaf , WTA & de Vries , EGE 1999 , ' Phase I and pharmacokinetic study of the topoisomerase II catalytic inhibitor fostriecin ' , British Jounal of Cancer , vol. 79 , no. 5-6 , pp. 882-887 . https://doi.org/10.1038/sj.bjc.6690141Test
مصطلحات موضوعية: fostriecin, topoisomerase II, phase I, pharmacokinetics, CARCINOMA CELL-LINE, ANTIBIOTIC CL-920, RESISTANCE, ASSAY
الوصف: We conducted a phase I and pharmacokinetic study of the topoisomerase II catalytic inhibitor fostriecin. Fostriecin was administered intravenously over 60 min on days 1-5 at 4-week intervals. Dose was escalated from 2 mg m(-2) day(-1) to 20 mg m(-2) day(-1) in 20 patients. Drug pharmacokinetics was analysed with high performance liquid chromatography with UV-detection, Plasma collected during drug administration was tested in vitro for growth inhibition of a teniposide-resistant small-cell lung cancer (SCLC) cell line. The predominant toxicities were elevated river transaminases (maximum common toxicity criteria (CTC) grade 4) and serum creatinine (maximum CTC grade 2). These showed only a limited increase with increasing doses, often recovered during drug administration and were fully reversible. Duration of elevated alanine-amino transferase (ALT) was dose-limiting in one patient at 20 mg m(-2), Other frequent toxicities were grade 1-2 nausea/vomiting, fever and mild fatigue. Mean fostriecin plasma half-life was 0.36 h (initial; 95% CI, 0-0.76 h) and 1.51 h (terminal; 95% GI, 0.41-2.61. hf. A metabolite, most probably dephosphorylated fostriecin, was detected in plasma and urine. No tumour responses were observed, but the plasma concentrations reached in the patients were insufficient to induce significant growth inhibition in vitro. The maximum tolerated dose (MTD) has not been reached, because drug supply was stopped at the 20 mg m-2 dose level. However, further escalation seems possible and is warranted to achieve potentially effective drug levels. Fostriecin has a short plasma half-life and longer duration of infusion should be considered.
وصف الملف: application/pdf
الإتاحة: https://doi.org/10.1038/sj.bjc.6690141Test
https://hdl.handle.net/11370/cbf9ea2f-55f8-40a2-87e0-48d62ac35150Test
https://research.rug.nl/en/publications/cbf9ea2f-55f8-40a2-87e0-48d62ac35150Test
https://pure.rug.nl/ws/files/62265499/Phase_I_and_pharmacokinetic_study_of_the.pdfTest -
10دورية أكاديمية
المؤلفون: Withoff, S, van der Zee, AGJ, de Jong, S, Hollema, H, Smit, EF, Mulder, NH, de Vries, EGE
المصدر: Withoff , S , van der Zee , AGJ , de Jong , S , Hollema , H , Smit , EF , Mulder , NH & de Vries , EGE 1999 , ' DNA topoisomerase II alpha and -beta expression in human ovarian cancer ' , British Jounal of Cancer , vol. 79 , no. 5-6 , bjoc.1998.0120 , pp. 748-753 . https://doi.org/10.1038/sj.bjc.6690120Test
مصطلحات موضوعية: DNA topoisomerase II alpha and -beta, ovarian cancer, CARCINOMA CELL-LINE, GENE-EXPRESSION, DRUG-RESISTANCE, DIFFERENTIAL EXPRESSION, RIBONUCLEIC-ACID, CHEMOTHERAPY, ADRIAMYCIN, TUMORS, LEUKEMIA, ENZYME
الوصف: To study DNA topoisomerase II alpha (Topo-II alpha) and -beta expression and regulation in human ovarian cancer, 15 ovarian tumour samples were investigated. To compare different levels of expression, the samples were screened for topo II alpha and -beta mRNA with Northern blotting and a quantitative reverse transcriptase polymerase chain reaction (RT-PCR) assay for Topo-II alpha mRNA. Additionally. protein levels were determined with Western blotting and topoisomerase II activity levels with the decatenation assay. The results obtained were compared with each other and with the tumour Volume index of the samples. In tumours with a tumour volume index greater than or equal to 50%, the mRNA levels (as determined by Northern blotting) and protein levels for each isozyme were in accordance. Additionally, correlations were found between Topo-II alpha RT-PCR data and Topo-II alpha Northern blot results, and between Topo-II alpha RT-PGR data and Topo-II alpha protein levels. interestingly, Topo-II beta protein levels correlated better with Topo-II activity than Topo-II alpha protein levels. In eight ovarian cystadenoma samples, no Topo-II alpha protein could be found. In only three out of eight of these cystadenomas, Topo-II beta protein could be detected. These findings suggest that Tapo-II alpha and Topo-II beta protein levels are upregulated in ovarian cancer and may indicate that Topo-II beta is an interesting target for chemotherapy in ovarian tumours.
وصف الملف: application/pdf
الإتاحة: https://doi.org/10.1038/sj.bjc.6690120Test
https://hdl.handle.net/11370/c19fe774-6cd8-4120-a9f4-81c5672b8c3fTest
https://research.rug.nl/en/publications/c19fe774-6cd8-4120-a9f4-81c5672b8c3fTest
https://pure.rug.nl/ws/files/62264611/DNA_topoisomerase_II_and_expression_in_human.pdfTest
