| 31. |
- Philchenkov, A., et al.
(author)
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Caspases and cancer : Mechanisms of inactivation and new treatment modalities
- 2004
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In: Experimental Oncology. - 0204-3564. ; 26:2, s. 82-97
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Journal article (peer-reviewed)abstract
- Elimination of superfluous or mutated somatic cells is provided by various mechanisms including apoptosis. Deregulation of apoptotic signaling pathways may contribute to oncogenesis. Aspartate specific cysteine proteases, termed caspases are the key effector molecules in apoptosis. The aim of this review is to summarize the various defects in caspase-dependent cell death machinery identified in the neoplastic cells. These include not only mutations, but also alterations of gene methylation, and altered mRNA stability. Among the molecules that we discuss are elements of the extrinsic death pathway like CD95 (APO-1/Fas), FADD, FLIPs, FLICE, other apical caspases, components of the intrinsic apoptotic pathway like Apaf-1, caspase-9, and modulators of apoptotic pathways like IAPs, Smac/DIABLO, OMI/HtrA2, and other apoptosis regulating proteins. We also discuss recent data on cancer-specific agents that target effector mechanisms of apoptosis. Particular emphasis is given to the prospects for combining cell suicide-activating approaches with classical cancer therapies.
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| 32. |
- Rahpeymai, Neda, et al.
(author)
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Microarray-based diagnosis of breast cancer using decision trees
- 2003
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Conference paper (peer-reviewed)abstract
- We apply the decision tree algorithm C4.5 to gene expression data in order to induce decision trees for identification of breast cancer patients. Using expression data from 108 known breast cancer-related genes for 75 patients with various diseases of the breast, we are able to induce decision trees with 89% accuracy in separating cancer from non-cancer patients in a cross-validation test. We also show that by inducing a separate decision tree for each cancer-related gene, and using the expression level of the individual gene as the decision variable, it is possible to obtain decision trees which aid the understanding of signaling pathways involved in breast cancer. In addition, we also show that the C4.5 algorithm is able to identify key breast cancer genes when decision trees are induced on expression data sets containing randomly selected genes. This result indicates that it is possible to make biological discoveries when applying decision tree algorithms to large sets of gene expression data in diseases where the genetic basis is not well characterised.
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| 33. |
- Brédart, A., et al.
(author)
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A comprehensive assessment of satisfaction with care : preliminary psychometric analysis in French, Polish, Swedish and Italian oncology patients
- 2001
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In: Patient Education and Counseling. - 0738-3991 .- 1873-5134. ; 43:3, s. 243-252
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Journal article (peer-reviewed)abstract
- Satisfaction with care may be closely related to quality of life in cancer patients. This evaluation is especially relevant when quality of care is considered. The present study assessed whether equivalent scaling properties could be found in a comprehensive assessment of satisfaction with care (CASC) administered in cancer patients from French, Polish and Swedish oncology settings, in comparison to the scaling properties previously evidenced in the CASC with an Italian sample. A total of 140, 186 and 133 oncology patients were approached in France, Poland and Sweden, respectively. Specific items in the CASC were identified as consistently omitted across country samples. Multitrait scaling analysis on an item-grouping adapted for the French, Polish, Swedish and Italian samples provided excellent internal consistencies and convergent validity estimates. Discriminant validity proved less satisfactory, evidencing overlap between hypothesised care dimensions across country samples. The identification of omitted or overlapping items will lead to the design of a revised CASC version to further test in larger cross-cultural samples.
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| 34. |
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| 35. |
- Smeland, S, et al.
(author)
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Scandinavian Sarcoma Group Osteosarcoma Study SSG VIII: prognostic factors for outcome and the role of replacement salvage chemotherapy for poor histological responders
- 2003
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In: European Journal of Cancer. - 1879-0852. ; 39:4, s. 488-494
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Journal article (peer-reviewed)abstract
- From 1990 to 1997, 113 eligible patients with classical osteosarcoma received neo-adjuvant chemotherapy consisting of high-dose methotrexate, cisplatin and doxorubicin. Good histological responders continued to receive the same therapy postoperatively, while poor responders received salvage therapy with an etoposide/ifosfamide combination. With a median follow-up of 83 months, the projected metastasis-free and overall survival rates at 5 years are 63 and 74%, respectively. Independent favourable prognostic factors for outcome were tumour volume < 190 ml, 24-h serum methotrexate > 4.5 muM and female gender. The etoposide/ifosfamide replacement combination did not improve outcome in the poor histological responders. In conclusion, this intensive multi-agent chemotherapy results in > 70% of patients with classical osteosarcoma surviving for 5 years. The data obtained from this non-randomised study do not support discontinuation and exchange of all drugs used preoperatively in histological poor responders. As observed in previous Scandinavian osteosarcoma studies, female gender appears to be a strong predictor of a favourable outcome. (C) 2003 Elsevier Science Ltd. All rights reserved.
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| 36. |
- Johnsson, Stefan
(author)
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Development and evaluation of an independent system for absorbed dose calculations in radiotherapy
- 2003
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Doctoral thesis (other academic/artistic)abstract
- The aim of this work was to develop, implement and evaluate an independent system with which to calculate the absorbed dose, delivered by high-energy X-ray beams, to the prescription point and the depth of dose maximum. The introduction of such a system in the clinical routine may help ensure high-quality treatment and avoidance of errors which may jeopardise the clinical outcome of the treatment (i.e. under- or overdose). A set of equations for calculating the absorbed dose to the prescription point was compiled in a software application (“HandCalc”), which is completely independent of the treatment planning system (TPS). For instance, HandCalc includes models to calculate the absorbed dose from photons scattered in the patient, the transmission of the primary kerma in the patient, the variation of the primary kerma in air with collimator setting (i.e. head scatter), and corrections for heterogeneities in the patient. A new expression for the transmission of the primary kerma in the patient was derived in which the coefficients are strictly defined (and given a physical interpretation) by the first two moments of the spectral distribution of the incident beam. Further investigations also revealed that these moments can be used to determine water-to-air stopping power ratios more accurately than other beam quality indices. In practice, the moments are derived from “in-air equivalent”, narrow-beam measurements using a mini-phantom. The degree of in-air equivalence was investigated with Monte Carlo simulations, which showed that the optimum measurement depth in a mini-phantom is somewhat below the depth of dose maximum. Based upon comparisons with measurements and the TPS, a clinical action level of +/- 4% was chosen for HandCalc. Deviations greater than this are, with all probability, due to erroneous handling of the patient dataset during the preparation phase. An “entrance dose factor” was added in order to correct the dose calculations at the depth of dose maximum where electron equilibrium has not been established. The entrance dose factor was found to vary with beam quality and collimator setting, while no variation was detected with the presence of an acrylic tray (for block support) or with the source-surface distance (SSD). HandCalc was implemented in a hand-held PC which makes dose calculations inside the treatment room at the time of administration of the first fraction possible. An important feature of HandCalc is the built-in report function, which logs results from the calculation for later evaluation. In a study including 700 patients, deviations greater than the action level were found to be due either to limitations in HandCalc or to a systematic deviation between the planned and measured SSD. HandCalc has proven to be a fast and accurate tool for independent dose calculations inside the treatment room and it requires only a limited amount of extra time for the user to perform the calculations. Thus, it can easily be incorporated as part of the daily clinical quality control programme in order to prevent errors which may jeopardise the clinical outcome of the treatment.
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| 37. |
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| 38. |
- Brun, Eva, et al.
(author)
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FDG PET studies during treatment: Prediction of therapy outcome in head and neck squamous cell carcinoma.
- 2002
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In: Head and Neck. - : Wiley. - 1043-3074. ; 24:2, s. 127-135
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Journal article (peer-reviewed)abstract
- BACKGROUND: Positron emission tomography (PET) provides metabolic information of tissues in vivo. The purpose of this study was to assess the value of PET with 2-[(18) F] fluoro-2-deoxy-D-glucose (FDG) in prediction of therapy outcome (tumor response, survival, and locoregional control) in locally advanced HNSCC. METHODS: Between 1993 and 1999 47 patients underwent PET before (PET(1)) and after (PET(2)) 1 to 3 weeks of radical treatment with evaluation of metabolic rate (MR) and standardized uptake value (SUV) of FDG. All patients received radiotherapy, and 10 also received neoadjuvant chemotherapy. Median follow-up time was 3.3 years. RESULTS: Low and high MR FDG at PET(2), with median value as cutoff, was associated with complete remission in 96% and 62% (p =.007), with 5-year overall survival in 72% and 35% (p =.0042) and with local control in 96% and 55% (p =.002), respectively. CONCLUSIONS: FDG PET in the early phase of treatment of HNSCC is associated with tumor response, survival, and local control. Copyright 2002 John Wiley & Sons, Inc.
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| 39. |
- Dewyngaert, J. Keith, et al.
(author)
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Procedure for unmasking localization information from ProstaScint scans for prostate radiation therapy treatment planning
- 2004
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In: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016 .- 1879-355X. ; 60:2, s. 654-662
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Journal article (peer-reviewed)abstract
- Purpose: To demonstrate a method to extract the meaningful biologic information from In-111-radiolabeled capromab pendetide (ProstaScint) SPECT scans for use in radiation therapy treatment planning by removing that component of the In-111 SPECT images associated with normal structures. Methods and Materials: We examined 20 of more than 80 patients who underwent simultaneous Tc-99m/In-111 SPECT scans, which were subsequently registered to the corresponding CT/MRI scans. A thresholding algorithm was used to identify Tc-99m uptake associated with blood vessels and CT electron density associated with bone marrow. Corresponding voxels were removed from the In-111 image set. Results: No single threshold value was found to be associated with the Tc-99m uptake that corresponded to the blood vessels. Intensity values were normalized to a global maximum and, as such, were dependent upon the quantity of Tc-99m pooled in the bladder. The reduced ProstaScint volume sets were segmented by use of a thresholding feature of the planning system and superimposed on the CT/MRI scans. Conclusions: ProstaScint images are now closer to becoming a biologically and therapeutically useful and accurate image set. After known sources of normal intensity are stripped away, the remaining areas that demonstrate uptake may be segmented and superimposed on the treatment-planning CT/MRI volume.
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| 40. |
- Höglund, Johanna, 0070-
(author)
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On the Use of 76Br-labelled Monoclonal Antibodies for PET : Preclinical Evaluation of Halogenated Antibodies for Diagnosis and Treatment of Cancer
- 2002
-
Doctoral thesis (other academic/artistic)abstract
- Radioactive substances are used in vivo to localize and characterize malignant tumours, generally by scintigraphic methods. In this context positron emission tomography (PET) in combination with radiolabelled monoclonal antibodies (mAbs) may provide a sensitive and specific method for detection of cancer. Individual dose calculations, based on such PET measurements, may be carried out to predict the possible use of mAbs labelled with therapeutic nuclides. The positron emitter 76Br, with a half-life of 16 h, is a well-suited candidate for radiolabelling and PET imaging. One drawback of radiobromine is that bromide, the ultimate catabolite after degradation of brominated mAb, is only tardily excreted from the body and is evenly distributed throughout the extracellular space, thereby increasing the background radioactivity. The aim of this work was to produce 76Br-mAb preparations with high accumulation and retention in tumour tissue together with a quick clearance of 76Br-labelled catabolites. Furthermore, the possibility to use brominated or iodinated mAbs in combination with PET to predict 211At-mAb dosimetry was evaluated.Monoclonal Abs directed against colorectal cancer were labelled with 76Br using the direct Chloramine-T-method or indirectly by labelling the precursor molecule N-succinimidyl para-(tri-methylstannyl) benzoate with 76Br, which was subsequently conjugated to the mAbs. Monoclonal Ab A33 labelled with 76Br using the two labelling protocols was characterized in vitro and in vivo in a rat tumour xenograft model. The mAb A33 was also labelled with 125I for comparison. In addition, mAb A33 was labelled with 211At, 125I and 76Br using the indirect labelling protocol and the mAb pharmacokinetics was studied in normal rats in order to estimate if data from brominated or iodinated mAb could be used for dosimetry of 211At in healthy organs and tissue.In conclusion, both direct and indirect labelling resulted in high yields and mAbs with preserved immunoreactivity. In vivo characterization of 76Br-brominated mAb A33 showed that the indirect labelling method makes 76Br-brominated mAb A33 a promising candidate for tumour imaging with PET due to the faster excretion of radiolabelled catabolites compared with direct bromination. Finally, mAb A33 labelled with 76Br and 124/125I can be used to predict the 211At dose of astatinated mAb A33 in most organs given that a correction factor is applied for organs with varying uptake.
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