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505 results on '"Lewensohn, R."'

4. 18F-FDG-PET guided vs whole tumour radiotherapy dose escalation in patients with locally advanced non-small cell lung cancer (PET-Boost): Results from a randomised clinical trial

Author

Cooke, S.A., de Ruysscher, D., Reymen, B., Lambrecht, M., Persson, G.F., Faivre-Finn, C., Dieleman, E.M.T., Lewensohn, R., Diessen, J.N.A.V., Sikorska, K., Lalezari, F., Vogel, W., van Elmpt, W., Damen, E.M.F., Sonke, J.J., Belderbos, J.S.A., Cooke, S.A., de Ruysscher, D., Reymen, B., Lambrecht, M., Persson, G.F., Faivre-Finn, C., Dieleman, E.M.T., Lewensohn, R., Diessen, J.N.A.V., Sikorska, K., Lalezari, F., Vogel, W., van Elmpt, W., Damen, E.M.F., Sonke, J.J., and Belderbos, J.S.A.

Abstract

Background and purpose: We aimed to assess if radiation dose escalation to either the whole primary tumour, or to an 18F-FDG-PET defined subvolume within the primary tumour known to be at high risk of local relapse, could improve local control in patients with locally advanced non-small-cell lung cancer. Materials and methods: Patients with inoperable, stage II-III NSCLC were randomised (1:1) to receive dose-escalated radiotherapy to the whole primary tumour or a PET-defined subvolume, in 24 fractions. The primary endpoint was freedom from local failure (FFLF), assessed by central review of CT-imaging. A phase II ‘pick-the-winner’ design (alpha = 0.05; beta = 0.80) was applied to detect a 15 % increase in FFLF at 1-year. ClinicalTrials.gov:NCT01024829. Results: 150 patients were enrolled. 54 patients were randomised to the whole tumour group and 53 to the PET-subvolume group. The trial was closed early due to slow accrual. Median dose/fraction to the boosted volume was 3.30 Gy in the whole tumour group, and 3.50 Gy in the PET-subvolume group. The 1-year FFLF rate was 97 % (95 %CI 91–100) in whole tumour group, and 91 % (95 %CI 82–100) in the PET-subvolume group. Acute grade ≥ 3 adverse events occurred in 23 (43 %) and 20 (38 %) patients, and late grade ≥ 3 in 12 (22 %) and 17 (32 %), respectively. Grade 5 events occurred in 19 (18 %) patients in total, of which before disease progression in 4 (7 %) in the whole tumour group, and 5 (9 %) in the PET-subvolume group. Conclusion: Both strategies met the primary objective to improve local control with 1-year rates. However, both strategies led to unexpected high rates of grade 5 toxicity. Dose differentiation, improved patient selection and better sparing of central structures are proposed to improve dose-escalation strategies.

Published
2023

5. P2.13-03 Plasma Profiling Unveils Transcriptional Signatures Associated with Resistance to Osimertinib in Non-Small Cell Lung Cancer

Author

Alexeyenko, A., primary, Brustugun, O.T., additional, Eide, I.J. Zwicky, additional, Gencheva, R., additional, Kosibaty, Z., additional, Lai, Y., additional, de Petris, L., additional, Tsakonas, G., additional, Grundberg, O., additional, Franzen, B., additional, Viktorsson, K., additional, Lewensohn, R., additional, Hydbring, P., additional, and Ekman, S., additional

Published
2022
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10. FP16.04 A Nationwide Population-Based Mapping of Mutations and Gene Fusions in Lung Cancer Among Never-Smokers

Author

Salomonsson, A., primary, Jönsson, M., additional, Behndig, A., additional, Bergman, B., additional, Botling, J., additional, Brandén, E., additional, Koyi, H., additional, Brunnström, H., additional, De Petris, L., additional, Helenius, G., additional, Hussein, A., additional, Johansson, M., additional, Kentson, M., additional, Lamberg, K., additional, Lewensohn, R., additional, Mager, U., additional, Monsef, N., additional, Ortiz-Villalon, C., additional, Patthey, A., additional, Sundh, J., additional, Vikström, A., additional, Wagenius, G., additional, Staaf, J., additional, and Planck, M., additional

Published
2021
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12. A Nationwide Population-Based Mapping of Mutations and Gene Fusions in Lung Cancer Among Never-Smokers

Author

Salomonsson, A., Jönsson, M., Behndig, A., Bergman, B., Botling, J., Brandén, E., Koyi, H., Brunnström, H., De Petris, L., Helenius, Gisela, Hussein, A., Johansson, M., Kentson, M., Lamberg, K., Lewensohn, R., Mager, U., Monsef, N., Ortiz-Villalon, C., Patthey, A., Sundh, Josefin, Vikström, A., Wagenius, G., Staaf, J., Planck, M., Salomonsson, A., Jönsson, M., Behndig, A., Bergman, B., Botling, J., Brandén, E., Koyi, H., Brunnström, H., De Petris, L., Helenius, Gisela, Hussein, A., Johansson, M., Kentson, M., Lamberg, K., Lewensohn, R., Mager, U., Monsef, N., Ortiz-Villalon, C., Patthey, A., Sundh, Josefin, Vikström, A., Wagenius, G., Staaf, J., and Planck, M.

Published
2021
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15. OC-0609: The PET-boost trial: isotoxic homogeneous or FDG-directed dose escalation in stage II-III NSCLC

Author

Cooke, S., primary, De Ruysscher, D., additional, Reymen, B., additional, Lambrecht, M., additional, Persson, G. Fredberg, additional, Faivre-Finn, C., additional, Dieleman, E., additional, Lewensohn, R., additional, Van Diessen, J., additional, Sikorska, K., additional, Lalezari, F., additional, Sonke, J., additional, and Belderbos, J., additional

Published
2020
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16. Genes and variants in hematopoiesis-related pathways are associated with gemcitabine/carboplatin-induced thrombocytopenia

Author

Björn, N., Sigurgeirsson, Benjamin, Svedberg, A., Pradhananga, Sailendra, Brandén, E., Koyi, H., Lewensohn, R., de Petris, L., Apellániz-Ruiz, M., Rodríguez-Antona, C., Lundeberg, Joakim, Gréen, Henrik, Björn, N., Sigurgeirsson, Benjamin, Svedberg, A., Pradhananga, Sailendra, Brandén, E., Koyi, H., Lewensohn, R., de Petris, L., Apellániz-Ruiz, M., Rodríguez-Antona, C., Lundeberg, Joakim, and Gréen, Henrik

Abstract

Chemotherapy-induced myelosuppression, including thrombocytopenia, is a recurrent problem during cancer treatments that may require dose alterations or cessations that could affect the antitumor effect of the treatment. To identify genetic markers associated with treatment-induced thrombocytopenia, we whole-exome sequenced 215 non-small cell lung cancer patients homogeneously treated with gemcitabine/carboplatin. The decrease in platelets (defined as nadir/baseline) was used to assess treatment-induced thrombocytopenia. Association between germline genetic variants and thrombocytopenia was analyzed at single-nucleotide variant (SNV) (based on the optimal false discovery rate, the severity of predicted consequence, and effect), gene, and pathway levels. These analyses identified 130 SNVs/INDELs and 25 genes associated with thrombocytopenia (P-value < 0.002). Twenty-three SNVs were validated in an independent genome-wide association study (GWAS). The top associations include rs34491125 in JMJD1C (P-value = 9.07 × 10−5), the validated variants rs10491684 in DOCK8 (P-value = 1.95 × 10−4), rs6118 in SERPINA5 (P-value = 5.83 × 10−4), and rs5877 in SERPINC1 (P-value = 1.07 × 10−3), and the genes CAPZA2 (P-value = 4.03 × 10−4) and SERPINC1 (P-value = 1.55 × 10−3). The SNVs in the top-scoring pathway “Factors involved in megakaryocyte development and platelet production” (P-value = 3.34 × 10−4) were used to construct weighted genetic risk score (wGRS) and logistic regression models that predict thrombocytopenia. The wGRS predict which patients are at high or low toxicity risk levels, for CTCAE (odds ratio (OR) = 22.35, P-value = 1.55 × 10−8), and decrease (OR = 66.82, P-value = 5.92 × 10−9). The logistic regression models predict CTCAE grades 3–4 (receiver operator characteristics (ROC) area under the curve (AUC) = 0.79), and large decrease (ROC AUC = 0.86). We identified and validated genetic variations within hematopoiesis-related pathways that provide a solid foundatio, QC 20220412

Published
2020
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17. P2.14-33 An Open-Label PET-MRI Study to Determine Brain Exposure of Osimertinib in Patients with EGFR Mutant NSCLC and CNS Metastases

Author

Ekman, S., primary, Varrone, A., additional, Jucaite, A., additional, Vishwanathan, K., additional, Brown, A., additional, Cselényi, Z., additional, Martin, H., additional, Lewensohn, R., additional, Schou, M., additional, Laus, G., additional, Van Der Aart, J., additional, Johnström, P., additional, Singh, N., additional, and Farde, L., additional

Published
2019
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18. P2.10-01 Analysis of Human Papilloma Viruses (HPV) and Human Polyoma Viruses (HPyV) in Lung Cancer from Swedish Never-Smokers

Author

Ramqvist, T., primary, Ortiz-Villalón, C., additional, Brandén, E., additional, Koyi, H., additional, De Petris, L., additional, Wagenius, G., additional, Brodin, O., additional, Reuterswärd, C., additional, Dalianis, T., additional, Jönsson, M., additional, Staaf, J., additional, Lewensohn, R., additional, and Planck, M., additional

Published
2019
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20. P1.14-37 Lung Cancer in Never-Smokers: A Nationwide Population Based Mapping of Targetable Alterations

Author

Salomonsson, A., primary, Jönsson, M., additional, Reuterswärd, C., additional, Behndig, A., additional, Bergman, B., additional, Botling, J., additional, Brandén, E., additional, Brunnström, H., additional, De Petris, L., additional, Hussein, A., additional, Johansson, M., additional, Koyi, H., additional, Lundström, K. Lamberg, additional, Lewensohn, R., additional, Monsef, N., additional, Ortiz-Villalón, C., additional, Patthey, A., additional, Vikström, A., additional, Wagenius, G., additional, Staaf, J., additional, and Planck, M., additional

Published
2019
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29. P1.01-074 Exosomal RNA-Profiling of Lung Pleural Effusions Identifies Adenocarcinoma Patients through Elevated miR-200 Expression

Author

Hydbring, P., primary, De Petris, L., additional, Branden, E., additional, Koyi, H., additional, Novak, M., additional, Kanter, L., additional, Hååg, P., additional, Hurley, J., additional, Tadigotla, V., additional, Skog, J., additional, Viktorsson, K., additional, Ekman, S., additional, and Lewensohn, R., additional

Published
2017
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35. Creating a data exchange strategy for radiotherapy research: Towards federated databases and anonymised public datasets

Author

Skripcak, T., Belka, C., Bosch, W., Brink, C. Van den, Brunner, T., Budach, V., Buttner, D., Debus, J., Dekker, A., Grau, C., Gulliford, S., Hurkmans, C., Just, U., Krause, M., Lambin, P., Langendijk, J.A., Lewensohn, R., Luhr, A., Maingon, P., Masucci, M., Niyazi, M., Poortmans, P.M.P., Simon, M., Schmidberger, H., Spezi, E., Stuschke, M., Valentini, V., Verheij, M., Whitfield, G., Zackrisson, B., Zips, D., Baumann, M., Skripcak, T., Belka, C., Bosch, W., Brink, C. Van den, Brunner, T., Budach, V., Buttner, D., Debus, J., Dekker, A., Grau, C., Gulliford, S., Hurkmans, C., Just, U., Krause, M., Lambin, P., Langendijk, J.A., Lewensohn, R., Luhr, A., Maingon, P., Masucci, M., Niyazi, M., Poortmans, P.M.P., Simon, M., Schmidberger, H., Spezi, E., Stuschke, M., Valentini, V., Verheij, M., Whitfield, G., Zackrisson, B., Zips, D., and Baumann, M.

Abstract

Contains fulltext : 136235.pdf (publisher's version ) (Open Access), Disconnected cancer research data management and lack of information exchange about planned and ongoing research are complicating the utilisation of internationally collected medical information for improving cancer patient care. Rapidly collecting/pooling data can accelerate translational research in radiation therapy and oncology. The exchange of study data is one of the fundamental principles behind data aggregation and data mining. The possibilities of reproducing the original study results, performing further analyses on existing research data to generate new hypotheses or developing computational models to support medical decisions (e.g. risk/benefit analysis of treatment options) represent just a fraction of the potential benefits of medical data-pooling. Distributed machine learning and knowledge exchange from federated databases can be considered as one beyond other attractive approaches for knowledge generation within "Big Data". Data interoperability between research institutions should be the major concern behind a wider collaboration. Information captured in electronic patient records (EPRs) and study case report forms (eCRFs), linked together with medical imaging and treatment planning data, are deemed to be fundamental elements for large multi-centre studies in the field of radiation therapy and oncology. To fully utilise the captured medical information, the study data have to be more than just an electronic version of a traditional (un-modifiable) paper CRF. Challenges that have to be addressed are data interoperability, utilisation of standards, data quality and privacy concerns, data ownership, rights to publish, data pooling architecture and storage. This paper discusses a framework for conceptual packages of ideas focused on a strategic development for international research data exchange in the field of radiation therapy and oncology.

Published
2014

41. Human papilloma virus (HPV) and p53 immunostaining in advanced tonsillar carcinoma--relation to radiotherapy response and survival

Author

Signe Friesland, Mellin H, Munck-Wikland E, Nilsson A, Lindholm J, Dalianis T, and Lewensohn R

Subjects
Papillomavirus Infections, Remission Induction, Tonsillar Neoplasms, Genes, p53, Prognosis, Radiation Tolerance, Survival Analysis, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, Immunoenzyme Techniques, Radiotherapy, High-Energy, Tumor Virus Infections, Treatment Outcome, Biomarkers, Tumor, Carcinoma, Squamous Cell, Humans, Life Tables, Tumor Suppressor Protein p53, Papillomaviridae, Follow-Up Studies, Neoplasm Staging, Retrospective Studies
Abstract

Human papilloma virus (HPV), which is frequently present in tonsillar carcinoma seems to be a prognostically favourable factor for patient survival and also for low risk of relapse. Since HPV may abrogate the function of wild type p53 and hence influence radiosensitivity we attempted to analyse if HPV and p53 status in tonsillar carcinoma affected tumour response to radiotherapy (RT) and patient survival.Pre-treatment primary tonsillar carcinoma specimens were obtained retrospectively from 40 patients, 21 complete responders (CR) and 19 non-complete responders (non-CR) of which 38/40 were stage III and IV tumours. The paraffin-embedded biopsies were analysed for presence of HPV DNA, by general and type specific PCR, and for p53 overexpression by immunohistochemical staining with the murine Mab DO-1.It was possible to analyse HPV in 34 and p53 in 39 patients. Presence of HPV DNA (HPV+) and p53 immunostaining (p53+) were not correlated with response to RT, since 8/18 CR patients and 6/16 non-CR patients were HPV+ and 11/21 CR patients and 8/18 non-CR patients were p53+. A tendency towards a survival benefit in patients with HPV+ tumours was observed and this tendency was significant for patients with stage IV HPV + tumours (p = .0431), and in particular HPV+/p53- cancers (p = .0195). A difference in survival between patients with p53+ cancer as compared to patients with p53- lesions was not demonstrated. In conclusion, although presence of HPV and p53 immunoreactivity in tonsillar carcinoma could not be related to RT response, determination of HPV and p53 status may still prove useful as predictive/prognostic markers.

Published
2001

43. miRNA-214 modulates radiotherapy response of non-small cell lung cancer cells through regulation of p38MAPK, apoptosis and senescence.

Author

Salim H, Akbar NS, Zong D, Vaculova AH, Lewensohn R, Moshfegh A, Viktorsson K, Zhivotovsky B, Salim, H, Akbar, N S, Zong, D, Vaculova, A H, Lewensohn, R, Moshfegh, A, Viktorsson, K, and Zhivotovsky, B

Abstract

Background: Radio- and chemotherapy (RT/CT) resistance hampers success in combating small and non-small cell lung cancers (SCLC/NSCLC). The underlying molecular mechanisms of RT/CT resistance of LCs are multifactorial and have been understood in part hitherto. miRNAs, key regulators of mRNAs, are well-recognised oncomirs; however, their role in regulating RT response remains poorly understood.Methods: Six human NSCLC and five SCLC cell lines with different SF2 values were investigated. Using microarray we examined whether expression of miRNAs is linked to the RT resistance of NSCLCs or SCLCs. Obtained data were validated by quantitative real-time PCR. Apoptosis and senescence were analysed using siRNA transfection, western blot and flow cytometry.Results: miRNA-21, miRNA-1827, miRNA-214, miRNA-339-5p, miRNA-625, miRNA-768-3p, miRNA-523-3p, miRNA-1227, miRNA-324-5p, miRNA-423-3p, miRNA-1301 and miRNA-1249 are differentially expressed in LC cells. miRNA-214 is upregulated in RT-resistant NSCLC cells relative to radiosensitive counterparts. Considering miRNA-214 as a putative regulator of RT resistance, we demonstrate that knockdown of miRNA-214 in radioresistant NSCLCs sensitised them to RT by stimulation of senescence. Consistently, overexpression of miRNA-214 in radiosensitive NSCLCs protected against RT-induced apoptosis. Protection was mediated by p38MAPK, as downregulation of this kinase could reverse the miRNA-214 overexpression-induced resistance of NSCLC cells.Conclusion: miRNA profiling of LC revealed putative RT resistance signalling circuits, which might help in sensitisation of LC to RT. [ABSTRACT FROM AUTHOR]

Published
2012
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45. An autocrine VEGF/VEGFR2 and p38 signaling loop confers resistance to 4-hydroxytamoxifen in MCF-7 breast cancer cells

Author

Aesoy, R., Sanchez, B.C., Norum, J.H., Lewensohn, R., Viktorsson, K., Linderholm, Barbro, Aesoy, R., Sanchez, B.C., Norum, J.H., Lewensohn, R., Viktorsson, K., and Linderholm, Barbro

Abstract

Tamoxifen, a partial estrogen receptor antagonist, is part of the standard treatment of both primary and advanced breast cancers. However, significant proportions of breast cancers are either de novo resistant or develop tamoxifen resistance during the course of treatment through mechanisms which have been only partly characterized. We have previously found that high vascular endothelial growth factor (VEGF) or VEGF receptor 2 (VEGFR2) expression and concomitant high p38 mitogen-activated protein kinase activity within breast cancers predict a poor outcome for tamoxifen-treated patients. Here, we have molecularly dissected how VEGF/VEGFR2 and p38 are linked, and contribute to tamoxifen resistance within breast cancer using a MCF-7 BC cell model with different 4-hydroxytamoxifen (4-OHT) responsiveness. We report that MCF-7 breast cancer cell lines with tamoxifen resistance have increased secretion of VEGF and increased signaling through VEGFR2 compared with parental MCF-7 cells. 4-OHT treatment caused the ablation of VEGF secretion in parental MCF-7 cells, whereas in the tamoxifen-resistant subline, a VEGF/ VEGFR2 signaling loop was still evident upon treatment. Increased basal levels of total and phosphorylated p38 were observed in tamoxifen-resistant cells. Pharmacologic inhibition of p38 reduced the proliferation of both tamoxifen-responsive and tamoxifen-resistant cells and showed an additive growth-inhibitory effect in combination with 4-OHT. A connection between VEGF/ VEGFR2 and p38 signaling was identified by VEGF and VEGFR2 knockdown, which equally reduced both the total and the active forms of p38 in tamoxifen-resistant cells. Taken together, our results suggest that decreased sensitivityto 4-OHT is caused by a death-protecting VEGF/VEGFR2 and p38 growth factor loop in breast cancer cells. Inhibition of these signaling pathways may be beneficial to overcome tamoxifen resistance. Copyright © 2008 American Association for Cancer Research.

Published
2008
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46. Stereotactic body radiotherapy for medically inoperable patients with stage I non-small cell lung cancer - A first report of toxicity related to COPD/CVD in a non-randomized prospective phase II study

Author

Baumann, P., Nyman, J., Hoyer, M., Gagliardi, G., Lax, I., Wennberg, B., Drugge, N., Ekberg, L., Friesland, S., Johansson, K.-A., Lund, J.-A., Morhed, E., Nilsson, K., Levin, N., Paludan, M., Sederholm, Christer, Traberg, A., Wittgren, L., Lewensohn, R., Baumann, P., Nyman, J., Hoyer, M., Gagliardi, G., Lax, I., Wennberg, B., Drugge, N., Ekberg, L., Friesland, S., Johansson, K.-A., Lund, J.-A., Morhed, E., Nilsson, K., Levin, N., Paludan, M., Sederholm, Christer, Traberg, A., Wittgren, L., and Lewensohn, R.

Abstract

Background and Aims: In a retrospective study using stereotactic body radiotherapy (SBRT) in medically inoperable patients with stage I NSCLC we previously reported a local control rate of 88% utilizing a median dose of 15 Gy × 3. This report records the toxicity encountered in a prospective phase II trial, and its relation to coexisting chronic obstructive pulmonary disease (COPD) and cardio vascular disease (CVD). Material and methods: Sixty patients were entered in the study between August 2003 and September 2005. Fifty-seven patients (T1 65%, T2 35%) with a median age of 75 years (59-87 years) were evaluable. The baseline mean FEV1% was 64% and median Karnofsky index was 80. A total dose of 45 Gy was delivered in three fractions at the 67% isodose of the PTV. Clinical, pulmonary and radiological evaluations were made at 6 weeks, 3, 6, 9, 12, 18, and 36 months post-SBRT. Toxicity was graded according to CTC v2.0 and performance status was graded according to the Karnofsky scale. Results: At a median follow-up of 23 months, 2 patients had relapsed locally. No grade 4 or 5 toxicity was reported. Grade 3 toxicity was seen in 12 patients (21%). There was no significant decline of FEV1% during follow-up. Low grade pneumonitis developed to the same extent in the CVD 3/17 (18%) and COPD 7/40 (18%) groups. The incidence of fibrosis was 9/17 (53%) and pleural effusions was 8/17 (47%) in the CVD group compared with 13/40 (33%) and 5/40 (13%) in the COPD group. Conclusion: SBRT for stage I NSCLC patients who are medically inoperable because of COPD and CVD results in a favourable local control rate with a low incidence of grade 3 and no grade 4 or 5 toxicity. © 2008 Elsevier Ireland Ltd. All rights reserved.

Published
2008
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47. EXPERIMENTAL THERAPEUTICS AND PHARMACOLOGY

Author

Aaberg-Jessen, C., primary, Fogh, L., additional, Halle, B., additional, Jensen, V., additional, Brunner, N., additional, Kristensen, B. W., additional, Abe, T., additional, Momii, Y., additional, Watanabe, J., additional, Morisaki, I., additional, Natsume, A., additional, Wakabayashi, T., additional, Fujiki, M., additional, Aldaz, B., additional, Fabius, A. W. M., additional, Silber, J., additional, Harinath, G., additional, Chan, T. A., additional, Huse, J. T., additional, Anai, S., additional, Hide, T., additional, Nakamura, H., additional, Makino, K., additional, Yano, S., additional, Kuratsu, J.-i., additional, Balyasnikova, I. V., additional, Prasol, M. S., additional, Kanoija, D. K., additional, Aboody, K. S., additional, Lesniak, M. S., additional, Barone, T., additional, Burkhart, C., additional, Purmal, A., additional, Gudkov, A., additional, Gurova, K., additional, Plunkett, R., additional, Barton, K., additional, Misuraca, K., additional, Cordero, F., additional, Dobrikova, E., additional, Min, H., additional, Gromeier, M., additional, Kirsch, D., additional, Becher, O., additional, Pont, L. B., additional, Kloezeman, J., additional, van den Bent, M., additional, Kanaar, R., additional, Kremer, A., additional, Swagemakers, S., additional, French, P., additional, Dirven, C., additional, Lamfers, M., additional, Leenstra, S., additional, Balvers, R., additional, Kleijn, A., additional, Lawler, S., additional, Gong, X., additional, Andres, A., additional, Hanson, J., additional, Delashaw, J., additional, Bota, D., additional, Chen, C.-C., additional, Yao, N.-W., additional, Chuang, W.-J., additional, Chang, C., additional, Chen, P.-Y., additional, Huang, C.-Y., additional, Wei, K.-C., additional, Cheng, Y., additional, Dai, Q., additional, Morshed, R., additional, Han, Y., additional, Auffinger, B., additional, Wainwright, D., additional, Zhang, L., additional, Tobias, A., additional, Rincon, E., additional, Thaci, B., additional, Ahmed, A., additional, He, C., additional, Lesniak, M., additional, Choi, Y. A., additional, Pandya, H., additional, Gibo, D. M., additional, Fokt, I., additional, Priebe, W., additional, Debinski, W., additional, Chornenkyy, Y., additional, Agnihotri, S., additional, Buczkowicz, P., additional, Rakopoulos, P., additional, Morrison, A., additional, Barszczyk, M., additional, Hawkins, C., additional, Chung, S., additional, Decollogne, S., additional, Luk, P., additional, Shen, H., additional, Ha, W., additional, Day, B., additional, Stringer, B., additional, Hogg, P., additional, Dilda, P., additional, McDonald, K., additional, Moore, S., additional, Hayden-Gephart, M., additional, Bergen, J., additional, Su, Y., additional, Rayburn, H., additional, Edwards, M., additional, Scott, M., additional, Cochran, J., additional, Das, A., additional, Varma, A. K., additional, Wallace, G. C., additional, Dixon-Mah, Y. N., additional, Vandergrift, W. A., additional, Giglio, P., additional, Ray, S. K., additional, Patel, S. J., additional, Banik, N. L., additional, Dasgupta, T., additional, Olow, A., additional, Yang, X., additional, Mueller, S., additional, Prados, M., additional, James, C. D., additional, Haas-Kogan, D., additional, Dave, N. D., additional, Desai, P. B., additional, Gudelsky, G. A., additional, Chow, L. M. L., additional, LaSance, K., additional, Qi, X., additional, Driscoll, J., additional, Ebsworth, K., additional, Walters, M. J., additional, Ertl, L. S., additional, Wang, Y., additional, Berahovic, R. D., additional, McMahon, J., additional, Powers, J. P., additional, Jaen, J. C., additional, Schall, T. J., additional, Eroglu, Z., additional, Portnow, J., additional, Sacramento, A., additional, Garcia, E., additional, Raubitschek, A., additional, Synold, T., additional, Esaki, S., additional, Rabkin, S., additional, Martuza, R., additional, Wakimoto, H., additional, Ferluga, S., additional, Tome, C. L., additional, Forde, H. E., additional, Netland, I. A., additional, Sleire, L., additional, Skeie, B., additional, Enger, P. O., additional, Goplen, D., additional, Giladi, M., additional, Tichon, A., additional, Schneiderman, R., additional, Porat, Y., additional, Munster, M., additional, Dishon, M., additional, Weinberg, U., additional, Kirson, E., additional, Wasserman, Y., additional, Palti, Y., additional, Gramatzki, D., additional, Staudinger, M., additional, Frei, K., additional, Peipp, M., additional, Weller, M., additional, Grasso, C., additional, Liu, L., additional, Berlow, N., additional, Davis, L., additional, Fouladi, M., additional, Gajjar, A., additional, Huang, E., additional, Hulleman, E., additional, Hutt, M., additional, Keller, C., additional, Li, X.-N., additional, Meltzer, P., additional, Quezado, M., additional, Quist, M., additional, Raabe, E., additional, Spellman, P., additional, Truffaux, N., additional, van Vurden, D., additional, Wang, N., additional, Warren, K., additional, Pal, R., additional, Grill, J., additional, Monje, M., additional, Green, A. L., additional, Ramkissoon, S., additional, McCauley, D., additional, Jones, K., additional, Perry, J. A., additional, Ramkissoon, L., additional, Maire, C., additional, Shacham, S., additional, Ligon, K. L., additional, Kung, A. L., additional, Zielinska-Chomej, K., additional, Grozman, V., additional, Tu, J., additional, Viktorsson, K., additional, Lewensohn, R., additional, Gupta, S., additional, Mladek, A., additional, Bakken, K., additional, Carlson, B., additional, Boakye-Agyeman, F., additional, Kizilbash, S., additional, Schroeder, M., additional, Reid, J., additional, Sarkaria, J., additional, Hadaczek, P., additional, Ozawa, T., additional, Soroceanu, L., additional, Yoshida, Y., additional, Matlaf, L., additional, Singer, E., additional, Fiallos, E., additional, Cobbs, C. S., additional, Hashizume, R., additional, Tom, M., additional, Ihara, Y., additional, Santos, R., additional, Torre, J. D. L., additional, Lepe, E., additional, Waldman, T., additional, James, D., additional, Huang, X., additional, Yu-Jen, L., additional, Gupta, N., additional, Solomon, D., additional, Zhang, Z., additional, Hayashi, T., additional, Adachi, K., additional, Nagahisa, S., additional, Hasegawa, M., additional, Hirose, Y., additional, Gephart, M. H., additional, Su, Y. S., additional, Hingtgen, S., additional, Kasmieh, R., additional, Nesterenko, I., additional, Figueiredo, J.-L., additional, Dash, R., additional, Sarkar, D., additional, Fisher, P., additional, Shah, K., additional, Horne, E., additional, Diaz, P., additional, Stella, N., additional, Huang, C., additional, Yang, H., additional, Wei, K., additional, Huang, T., additional, Hlavaty, J., additional, Ostertag, D., additional, Espinoza, F. L., additional, Martin, B., additional, Petznek, H., additional, Rodriguez-Aguirre, M., additional, Ibanez, C., additional, Kasahara, N., additional, Gunzburg, W., additional, Gruber, H., additional, Pertschuk, D., additional, Jolly, D., additional, Robbins, J., additional, Hurwitz, B., additional, Yoo, J. Y., additional, Bolyard, C., additional, Yu, J.-G., additional, Wojton, J., additional, Zhang, J., additional, Bailey, Z., additional, Eaves, D., additional, Cripe, T., additional, Old, M., additional, Kaur, B., additional, Serwer, L., additional, Le Moan, N., additional, Ng, S., additional, Butowski, N., additional, Krtolica, A., additional, Cary, S. P. L., additional, Johns, T., additional, Greenall, S., additional, Donoghue, J., additional, Adams, T., additional, Karpel-Massler, G., additional, Westhoff, M.-A., additional, Kast, R. E., additional, Dwucet, A., additional, Wirtz, C. R., additional, Debatin, K.-M., additional, Halatsch, M.-E., additional, Merkur, N., additional, Kievit, F., additional, Stephen, Z., additional, Wang, K., additional, Kolstoe, D., additional, Ellenbogen, R., additional, Zhang, M., additional, Kitange, G., additional, Haefner, E., additional, Knubel, K., additional, Pernu, B. M., additional, Sufit, A., additional, Pierce, A. M., additional, Nelson, S. K., additional, Keating, A. K., additional, Jensen, S. S., additional, Lachowicz, J., additional, Demeule, M., additional, Regina, A., additional, Tripathy, S., additional, Curry, J.-C., additional, Nguyen, T., additional, Castaigne, J.-P., additional, Davis, T., additional, Davis, A., additional, Tanaka, K., additional, Keating, T., additional, Getz, J., additional, Kapp, G. T., additional, Romero, J. M., additional, Lee, S., additional, Ramisetti, S., additional, Slagle-Webb, B., additional, Sharma, A., additional, Connor, J., additional, Lee, W.-S., additional, Kluk, M., additional, Aster, J. C., additional, Ligon, K., additional, Sun, S., additional, Lee, D., additional, Ho, A. S. W., additional, Pu, J. K. S., additional, Zhang, Z.-q., additional, Lee, N. P., additional, Day, P. J. R., additional, Leung, G. K. K., additional, Liu, Z., additional, Liu, X., additional, Madhankumar, A. B., additional, Miller, P., additional, Webb, B., additional, Connor, J. R., additional, Yang, Q. X., additional, Lobo, M., additional, Green, S., additional, Schabel, M., additional, Gillespie, Y., additional, Woltjer, R., additional, Pike, M., additional, Lu, Y.-J., additional, Luchman, H. A., additional, Stechishin, O., additional, Nguyen, S., additional, Cairncross, J. G., additional, Weiss, S., additional, Lun, X., additional, Wells, J. C., additional, Hao, X., additional, Grinshtein, N., additional, Kaplan, D., additional, Luchman, A., additional, Senger, D., additional, Robbins, S., additional, Madhankumar, A., additional, Rizk, E., additional, Payne, R., additional, Park, A., additional, Pang, M., additional, Harbaugh, K., additional, Wilisch-Neumann, A., additional, Pachow, D., additional, Kirches, E., additional, Mawrin, C., additional, McDonell, S., additional, Liang, J., additional, Piao, Y., additional, Nguyen, N., additional, Yung, A., additional, Verhaak, R., additional, Sulman, E., additional, Stephan, C., additional, Lang, F., additional, de Groot, J., additional, Mizobuchi, Y., additional, Okazaki, T., additional, Kageji, T., additional, Kuwayama, K., additional, Kitazato, K. T., additional, Mure, H., additional, Hara, K., additional, Morigaki, R., additional, Matsuzaki, K., additional, Nakajima, K., additional, Nagahiro, S., additional, Kumala, S., additional, Heravi, M., additional, Devic, S., additional, Muanza, T., additional, Knubel, K. H., additional, Neuwelt, A., additional, Wu, Y. J., additional, Donson, A., additional, Vibhakar, R., additional, Venkatamaran, S., additional, Amani, V., additional, Neuwelt, E., additional, Rapkin, L., additional, Foreman, N., additional, Ibrahim, F., additional, New, P., additional, Cui, K., additional, Zhao, H., additional, Chow, D., additional, Stephen, W., additional, Nozue-Okada, K., additional, Nagane, M., additional, McDonald, K. L., additional, Ogawa, D., additional, Chiocca, E., additional, Godlewski, J., additional, Patel, A., additional, Pasupuleti, N., additional, Gorin, F., additional, Valenzuela, A., additional, Leon, L., additional, Carraway, K., additional, Ramachandran, C., additional, Nair, S., additional, Quirrin, K.-W., additional, Khatib, Z., additional, Escalon, E., additional, Melnick, S., additional, Phillips, A., additional, Boghaert, E., additional, Vaidya, K., additional, Ansell, P., additional, Shalinsky, D., additional, Zhang, Y., additional, Voorbach, M., additional, Mudd, S., additional, Holen, K., additional, Humerickhouse, R., additional, Reilly, E., additional, Parab, S., additional, Diago, O., additional, Ryken, T., additional, Agarwal, S., additional, Al-Keilani, M., additional, Alqudah, M., additional, Sibenaller, Z., additional, Assemolt, M., additional, Sai, K., additional, Li, W.-y., additional, Li, W.-p., additional, Chen, Z.-p., additional, Saito, R., additional, Sonoda, Y., additional, Kanamori, M., additional, Yamashita, Y., additional, Kumabe, T., additional, Tominaga, T., additional, Sarkar, G., additional, Curran, G., additional, Jenkins, R., additional, Scharnweber, R., additional, Kato, Y., additional, Lin, J., additional, Everson, R., additional, Soto, H., additional, Kruse, C., additional, Liau, L., additional, Prins, R., additional, Semenkow, S., additional, Chu, Q., additional, Eberhart, C., additional, Sengupta, R., additional, Marassa, J., additional, Piwnica-Worms, D., additional, Rubin, J., additional, Shai, R., additional, Pismenyuk, T., additional, Moshe, I., additional, Fisher, T., additional, Freedman, S., additional, Simon, A., additional, Amariglio, N., additional, Rechavi, G., additional, Toren, A., additional, Yalon, M., additional, Shimazu, Y., additional, Kurozumi, K., additional, Ichikawa, T., additional, Fujii, K., additional, Onishi, M., additional, Ishida, J., additional, Oka, T., additional, Watanabe, M., additional, Nasu, Y., additional, Kumon, H., additional, Date, I., additional, Sirianni, R. W., additional, McCall, R. L., additional, Spoor, J., additional, van der Kaaij, M., additional, Geurtjens, M., additional, Veiseh, O., additional, Fang, C., additional, Leung, M., additional, Strohbehn, G., additional, Atsina, K.-K., additional, Patel, T., additional, Piepmeier, J., additional, Zhou, J., additional, Saltzman, W. M., additional, Takahashi, M., additional, Valdes, G., additional, Inagaki, A., additional, Kamijima, S., additional, Hiraoka, K., additional, Micewicz, E., additional, McBride, W. H., additional, Iwamoto, K. S., additional, Gruber, H. E., additional, Robbins, J. M., additional, Jolly, D. J., additional, McCully, C., additional, Bacher, J., additional, Thomas, T., additional, Murphy, R., additional, Steffen-Smith, E., additional, McAllister, R., additional, Pastakia, D., additional, Widemann, B., additional, Chen, P., additional, Hua, M., additional, Liu, H., additional, Woolf, E. C., additional, Abdelwahab, M. G., additional, Fenton, K. E., additional, Liu, Q., additional, Turner, G., additional, Preul, M. C., additional, Scheck, A. C., additional, Shen, W., additional, Brown, D., additional, Pedersen, H., additional, Hariono, S., additional, Yao, T.-W., additional, Sidhu, A., additional, Weiss, W. A., additional, Nicolaides, T. P., additional, and Olusanya, T., additional

Published
2013
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48. The novel melphalan prodrug J1 inhibits neuroblastoma growth in vitro and in vivo

Author

Wickstrom, M., Johnsen, J.I., Ponthan, F., Segerstrom, L., Sveinbjornsson, B., Lindskog, M., Lovborg, Henrik, Viktorsson, K., Lewensohn, R., Kogner, P., Larsson, R., Gullbo, J., Wickstrom, M., Johnsen, J.I., Ponthan, F., Segerstrom, L., Sveinbjornsson, B., Lindskog, M., Lovborg, Henrik, Viktorsson, K., Lewensohn, R., Kogner, P., Larsson, R., and Gullbo, J.

Abstract

Neuroblastoma is the most common extracranial solid tumor of childhood. The activity of J1 (L-melphalanyl-p-L-fluorophenylalanine ethyl ester), an enzymatically activated melphalan prodrug, was evaluated in neuroblastoma models in vitro and in vivo. Seven neuroblastoma cell lines with various levels of drug resistance were screened for cytotoxicity of J1 alone or in combination with standard cytotoxic drugs, using a fluorometric cytotoxicity assay. J1 displayed high cytotoxic activity in vitro against all neuroblastoma cell lines, with IC50 values in the submicromolar range, significantly more potent than melphalan. The cytotoxicity of J1, but not melphalan, could be significantly inhibited by the aminopeptidase inhibitor bestatin. J1 induced caspase-3 cleavage and apoptotic morphology, had additive effects in combination with doxorubicin, cyclophosphamide, carboplatin, and vincristine, and synergistically killed otherwise drug-resistant cells when combined with etoposide. Athymic rats and mice carrying neuroblastoma xenografts [SHSY5Y, SK-N-BE(2)] were treated with equimolar doses of melphalan, J1, or no drug, and effects on tumor growth and tissue morphology were analyzed. Tumor growth in vivo was significantly inhibited by J1 compared with untreated controls. Compared with melphalan, J1 more effectively inhibited the growth of mice with SH-SY5Y xenografts, was associated with higher caspase-3 activation, fewer proliferating tumor cells, and significantly decreased mean vascular density. In conclusion, the melphalan prodrug J1 is highly active in models of neuroblastoma in vitro and in vivo, encouraging further clinical development in this patient group. Copyright © 2007 American Association for Cancer Research.

Published
2007
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49. Expression of DNA damage response proteins and complete remission after radiotherapy of stage IB-IIA of cervical cancer.

Author

Beskow, C, Kanter, L, Holgersson, A, Nilsson, B, Frankendal, B, Åvall-Lundqvist, Elisabeth, Lewensohn, R, Beskow, C, Kanter, L, Holgersson, A, Nilsson, B, Frankendal, B, Åvall-Lundqvist, Elisabeth, and Lewensohn, R

Abstract

The primary aim of this study was to investigate if the expression of the DNA damage identifying protein DNA-PKcs known to be involved in DNA repair after treatment with ionising radiation can be used as a predictive marker for radiotherapy (RT) response in cervical cancer. Formalin-fixed primary tumour biopsies from 109 patients with cervical cancer, FIGO-stage IB-IIA, treated with preoperative brachytherapy followed by radical surgery were analysed by immunohistochemistry. In addition, correlation studies between early pathological tumour response to radiation and expression of Ku86, Ku70, Mdm-2, p53 and p21 in primary tumours were also performed. We found that tumour-transformed tissue shows positive immunostaining of DNA-PKcs, Ku86 and Ku70, while non-neoplastic squamous epithelium and tumour-free cervix glands show negative immunoreactivity. Expression of DNA-PKcs positively correlated with both Ku86 and Ku70, and a statistically significant correlation between the Ku subunits was also found. After RT, 85 patients demonstrated pathologic complete remission (pCR), whereas 24 patients had residual tumour in the surgical specimen (non-pCR). The main finding of our study is that there was no correlation between the outcome of RT and the expression of DNA-PK subunits. Positive p53 tumours were significantly more common among non-pCR cases than in patients with pCR (P=0.031). Expression of p21 and Mdm-2 did not correlate with the outcome of RT.

Published
2006
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