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Träfflista för sökning "AMNE:(MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology) srt2:(1995-1999);srt2:(1998)"

Sökning: AMNE:(MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology) > (1995-1999) > (1998)

  • Resultat 41-50 av 83
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41.
  • Bratt, O, et al. (författare)
  • Clinical course of early onset prostate cancer with special reference to family history as a prognostic factor
  • 1998
  • Ingår i: European Urology. - 0302-2838. ; 34:1, s. 19-24
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The aim of this study was to describe the clinical characteristics of early onset prostate cancer, with special reference to family history as a possible prognostic factor.MATERIAL AND METHODS: We identified all cases of prostate cancer diagnosed before the age of 51 in the Southern health care region in Sweden between 1958 and 1994. Clinical data were collected retrospectively from medical records. Data about family history of prostate cancer were also collected from the parish authorities and the Regional Cancer Registry.RESULTS: In all, 89 cases were included. The median time of follow-up was 17 years. During the time of follow-up, 65 patients died, 57 of whom died from prostate cancer. At diagnosis, 34% of the patients had localized, 22% had locally advanced, and 40% had metastatic tumours. The tumours were well differentiated in 30% of the cases, moderately differentiated in 38%, and poorly differentiated in 28%. Information on tumour grade and stage was missing in 3 cases. The cause-specific survival was 48% at 5 years and 29% at 10 years. The 18 patients with a family history of prostate cancer had a somewhat better prognosis than the patients with a negative family history, though the difference did not reach statistical significance (p = 0.08).CONCLUSIONS: Early onset prostate cancer is a serious disease with high mortality. The proportions of patients with poorly differentiated and metastatic tumours appeared to be larger than for cases diagnosed later in life, but this could be explained by selection bias since younger men may have a lower probability of having asymptomatic localized tumours diagnosed. Family history of prostate cancer was not significantly associated with prognosis.
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43.
  • Burnet, N G, et al. (författare)
  • Describing patients' normal tissue reactions: concerning the possibility of individualising radiotherapy dose prescriptions based on potential predictive assays of normal tissue radiosensitivity. Steering Committee of the BioMed2 European Union Concerted Action Programme on the Development of Predictive Tests of Normal Tissue Response to Radiation Therapy.
  • 1998
  • Ingår i: International journal of cancer. Journal international du cancer. - 0020-7136. ; 79:6, s. 606-13
  • Tidskriftsartikel (refereegranskat)abstract
    • Clinical radiotherapeutic doses are limited by the tolerance of normal tissues. Patients given a standard treatment exhibit a range of normal tissue reactions, and a better understanding of this individual variation might allow for individualisation of radiotherapeutic prescriptions, with consequent improvement in the therapeutic ratio. At present, there is no simple way to describe normal tissue reactions, which hampers communication between clinic and laboratory and between groups from different centres. There is also no method for comparing the severity of reactions in different normal tissues. This arises largely because there is no definition of a "normal" reaction, an "extreme" reaction or the particular term "over-reactor" (OR). This report proposes definitions for these terms, as well as a simple terminology for describing normal tissue reactions in patients having radiotherapy. The "normal" range represents the individual variation in normal tissue reactions amongst large numbers of patients treated in the same way which is within clinically acceptable limits. The term "OR" is applied to an individual whose reaction is more severe than the normal range but also implies that this forced a major change in the radiotherapeutic prescription or that the reactions were very severe or fatal. A "severe OR" would develop serious problems with a typical radical dose, while an "extreme OR" would have such difficulties at a much lower dose. To describe the normal range, a numerical scale is suggested, from 1 to 5, resistant to sensitive. The term "highly radiosensitive" (HR) is suggested for category 5. An "informal" relative scale, as suggested here, is quick and simple. It should allow comparison between different hospitals, compensate for differences in radiotherapeutic dose and technique and allow comparison of reactions between different anatomical sites. It should be adequate for discriminating patients at the extremes of the normal range from those at the centre. It is hoped that the definitions and terminology proposed here will aid communication in the field of predictive testing of normal tissue radiosensitivity.
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44.
  • Daşu, Alexandru, et al. (författare)
  • Liquid ionization chamber measurements of dose distributions in small 6 MV photon beams
  • 1998
  • Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 43:1, s. 21-36
  • Tidskriftsartikel (refereegranskat)abstract
    • A new liquid ionization chamber (LIC) design optimized for high spatial resolution was used for measurements of dose distributions in radiation fields intended for stereotactic radiosurgery (SRS). This work was mainly focused on the properties of this detector in radiation fields from linear accelerators for clinical radiotherapy (pulsed radiation with dose rates from approximately 0.5 to 5 Gy min-1 and beam diameters down to 8 mm). The narrow beams used in stereotactic radiosurgery require detectors with small sizes in order to provide a good spatial resolution. The LIC is investigated to see whether it can be used as a detector for dose measurements in beams currently used for stereotactic radiosurgery. Its properties are compared with those of silicon diodes. The comparisons include output factor (OF), depth dose and profile measurements in 6 MV photon fields of different sizes. For OF measurements, an NACP air ionization chamber was also used in the comparison. The dependence of the response on the detector orientation in the photon beam is also investigated for the diodes and the LIC. The results suggest that LICs can provide better properties than diodes for measuring dose distributions in narrow photon beams.
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45.
  • Daşu, Alexandru, et al. (författare)
  • New insights into factors influencing the clinically relevant oxygen enhancement ratio
  • 1998
  • Ingår i: Radiotherapy and Oncology. - 0167-8140 .- 1879-0887. ; 46:3, s. 269-277
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND PURPOSE: This paper deals with the variations in the oxygen enhancement ratios that could be observed (OER') when comparing oxic and hypoxic cells in different types of fractionated experiments as a consequence of the non-linearity of the underlying cell survival curves. Calculations have been made of the OER' that would be obtained for fractionated irradiations with a series of small doses to allow the comparison of isoeffective doses in oxic and hypoxic conditions. Two styles of fractionated experiment were modelled. In one, the dose per fraction was kept constant in the oxic and hypoxic arms of the experiment, necessitating more fractions in hypoxia to achieve the same level of cell kill. In the other the number of fractions was kept constant and the fraction size was varied to obtain equal levels of damage. The first is the relevant design for the clinic, whereas the second is the design most commonly used in animal studies. MATERIALS AND METHODS: Three models of the survival curve were used to simulate the response of cells to radiation injury, all based on the linear quadratic model, but with various added assumptions. A simple classical LQ model is compared with two models in which the concept of inducible repair is added. In one of these the induction dose for 'switching on' the more resistant response is assumed to be increased in hypoxia and in the other it is assumed to be independent of the oxygen tension. RESULTS: These calculations show a clear and previously unsuspected dependence of the measured OER' on the design of the fractionated experiment. The values obtained in the clinical and animal types of study differ considerably with all three models. The direction and magnitude of that difference depends critically on the assumptions about the fine structure of the survival curve shape. The authors suggest that the inducible repair version with an oxygen-dependent induction dose is probably the most relevant model. Using this, the measured OER' is reduced at doses around 2 Gy for the clinically relevant design of constant sized fractions to the oxic and hypoxic cells. It may even, in certain model assumptions, fall below unity resulting in an increased sensitivity, not resistance, from the hypoxia. CONCLUSIONS: These calculations indicate the urgent need for more knowledge about the fine structure of the low dose region of the survival curves for human tumour cells and especially for comparisons in the presence and absence of oxygen. The extent of the hypersensitivity at very low doses, the trigger dose needed to induce the repair and its oxygen modification may be dominant factors in determining the response of tumour cells to clinically relevant fractionation schedules.
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46.
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47.
  • Denekamp, Juliana, et al. (författare)
  • Hyperfractionation as an effective way of overcoming radioresistance
  • 1998
  • Ingår i: International Journal of Radiation Oncology, Biology, Physics. - 0360-3016 .- 1879-355X. ; 42:4, s. 705-709
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To model the influence of hypoxic radioprotection in fractionated treatments over a range of fraction sizes. To determine whether there is a "therapeutic window" of dose per fraction where hypoxic radioresistance could be reduced, and if so, where it occurs in different cell lines. MATERIALS AND METHODS: A mathematical model has been used to simulate the response of cells to low doses of radiation, in the region of clinical interest. We have used the inducible repair variant of the linear quadratic (LQ) equation, with a hypersensitive region (alphaS) at low doses that gradually transforms to the accepted "resistance" in the shoulder region (alphaR). It contains two new parameters, the ratio alphaS/alphaR, and D(C). We have accepted that the "induction dose" D(C) is modified by anoxia to the same extent as the other parameters. We have initially modeled using theoretical parameters and then checked the conclusions with 14 sets of published experimental data for cell lines investigated for inducible repair. RESULTS: We have computed the clinical hypoxic protection (OER') as a function of dose per fraction in simulations of clinical fractionated schedules. We have identified a therapeutic window in terms of dose per fraction at about 0.5 Gy, where the OER' is minimized, regardless of the precise cell survival curve parameters. The minimum OER' varies from one cell line to another, falling to about 1.0 if alphaS/alphaR = 6-10 and even far below 1.0 if alphaS/alphaR > or = 20. DISCUSSION: Hyperfractionation using 0.5 Gy fractions may therefore be more effective than oxygen mimetic chemical sensitizers, since it could even make some tumor cells more sensitive than oxic normal tissues. The tumor lines that benefit most from this type of sensitization are those with the highest intrinsic oxic radioresistance, i.e. those with high SF2 values.
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48.
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49.
  • Denekamp, Juliana, et al. (författare)
  • Vasculature and microenvironmental gradients: the missing links in novel approaches to cancer therapy?
  • 1998
  • Ingår i: Advances in Enzyme Regulation. - 0065-2571 .- 1873-2437. ; 38:1, s. 281-299
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper illustrates how the concept of the malignant cell per se as the prime and only target in cancer therapy may be erroneous. The micro-vasculature evoked to satisfy nutritional requirements of solid tumors, and the inadequacy of this nutrition for all tumor cells, provide novel targeting concepts. The vascular architecture and the microenvironmental gradients (VAMP) will differ from one tumor to another and may determine whether current therapies succeed or fail. Many agents have a different toxicity or mode of action at the pathophysiological oxygen tensions that prevail in solid tumors. This warrants more attention. The hypoxic cell or the immature proliferating endothelial cell may provide tumor specificity that is more general than, and greater than, that conferred by the process of malignant transformation. The poor vasculature of solid tumors is often regarded as a problem by the oncologist. It limits the access of cytotoxic drugs, monoclonal antibodies, cytokines, etc. It also leads to hypoxic radioresistance because of diffusion limited chronic hypoxia and perfusion limited intermittent hypoxia, resulting from transient vessel closure. However, it can also be seen as a potential target, since prolonged vessel occlusion can lead to an avalanche of cell death. Strategies to prevent further expansion of the vascular network (anti-angiogenesis) should stabilize tumors and prevent further growth. Vascular targeting, aiming to damage the microvascular function and cause occlusion, can lead to extensive cell death. The target may relate to the excessive proliferation of endothelial cells in tumors or to abnormal functional aspects, such as altered cell shape (influencing permeability) adhesiveness to leukocytes or steps in the coagulation cascade. These microvascular features and microenvironmental gradients, and the phenotypic consequences of them, have been relatively neglected. The altered milieu and inadequate neovasculature is a common feature of all types of solid tumor, whereas the genetic changes that can give rise to a malignancy are very variable, from tumor site to site and even within a site from individual to individual. It seems, therefore, that therapies that could be of widespread general applicability might more easily be found from the micro-environmental or anti-vascular approaches than from gene therapy targeted at specific oncogenes. This approach will require cross fertilisation between scientists from quite disparate backgrounds, whose paths seldom cross, and who may not read, or even scan, each other's literature. If the endothelium or the low oxygen tension in subsets of tumor cells are the key to successful cancer treatment in mice, there are considerable implications for screening methods in vitro and for predictive and prognostic tests made on homogenized tumor samples.
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