Biomedical subjects

Barbara Kaser-Hotz

Publications and source records attributed to Barbara Kaser-Hotz.

At least 19 recordsLinked to original sources

PubMed2006

The influence of fractionated radiation therapy on plasma vascular endothelial growth factor (VEGF) concentration in dogs with spontaneous tumors and its impact on outcome.

BACKGROUND AND PURPOSE: Vascular endothelial growth factor (VEGF), a specific pro-angiogenic factor is proposed to be involved in cancer progression and resistance to radiation therapy by promoting angiogenesis and by protecting endothelial cells from radiation induced apoptosis. The aim of this study, was first to assess the influence of ionizing radiation on plasma VEGF concentration in spontaneous canine tumors during fractionated radiation therapy with curative or palliative intent and second to analyze plasma VEGF concentration as predictor for treatment outcome. PATIENTS AND METHODS: For plasma VEGF analysis a human VEGF enzyme linked immunosorbent assay was used. Sixty dogs with various tumor types were included in this study. Dogs were irradiated with either low dose per fx (3-3.5 Gy per fraction, total dose: 42-49 Gy, group A: curative intent) or high dose per fx (6-8 Gy per fraction, total dose: 24-30 Gy, group B: palliative intent). Blood samples were taken before and after dose application at certain time points during therapy. Follow-up evaluation was performed for analysis of time to treatment failure and survival. RESULTS: Repeated measures analysis showed no increase of plasma VEGF in dogs treated with fractionated radiation therapy (group A and B). Dichotomizing baseline plasma VEGF into two groups with high and low plasma VEGF, resulted in shorter time to treatment failure in dogs with high plasma VEGF levels (TTF, group A: P=0.038, group B: P=0.041). CONCLUSIONS: This study demonstrated that dogs with a plasma VEGF level higher than 5 pg/ml had a poorer outcome after radiation therapy. It is therefore, suggested, to use plasma VEGF as predictor for treatment outcome in radiation therapy.

Animals↗

PubMed2006

Is the risk for secondary cancers after proton therapy enhanced distal to the Planning Target Volume? A two-case report with possible explanations.

It is often assumed that radiation-induced secondary cancer after proton therapy forms preferentially close to the distal fall-off of the spread-out Bragg peak because of an increased relative biological effectiveness (RBE) with regard to cancer induction of low-energy protons. In this study we analyze to what extent dose gradients distal to the Planning Target Volume (PTV) may, independently from the RBE, contribute to enhanced radiation carcinogenesis. The study is based on two dogs which, out of 30 dogs treated with proton therapy at the Paul Scherrer Institute (PSI), developed a secondary cancer. Both dogs were originally diagnosed and treated for a fibrosarcoma and developed an osteosarcoma 48 and almost 60 months, respectively, after radiotherapy. From the dose distributions of the initial radiotherapy for both dogs three-dimensional maps of secondary cancer complication probability (SCCP) were computed. The SCCP maps were analyzed in the regions where the dogs developed a secondary cancer. The SCCP maps showed an enhanced risk in the regions of the femur where the secondary cancers were detected, as compared to the SCCP of the total femur. Excess risk of radiation-induced cancer at the distal part of proton radiation fields can thus be explained using SCCP calculations on the basis of the physical dose distributions. Therefore, the occurrence of secondary cancer close to the distal dose gradients of proton therapy is not necessarily due to an increased RBE of low-energy protons. More extensive studies based on more patients will be necessary to further elucidate the factors influencing the development of secondary tumors.

Animals↗

PubMed2006

Changes in vascularity and blood volume as a result of photodynamic therapy can be assessed with power Doppler ultrasonography.

BACKGROUND AND OBJECTIVES: One principal mechanism of photodynamic therapy (PDT) in tumors is destruction of tumor-associated vasculature. In the present study, the vascular effects of PDT in tumors were investigated with power Doppler ultrasonography. MATERIALS AND METHODS: Seven cutaneous squamous cell carcinomas in cats were treated. Tumors were examined via power Doppler ultrasonography before, 5 minutes, 1 hour, and 24 hours after PDT. Images were digitized for computer-aided assessment of vascularity and blood volume. RESULTS: Mean baseline tumor vascularity and blood volume were moderate. During PDT, a significant decrease in vascularity and blood volume was noted. Lowest values were found 24 hours after PDT. CONCLUSIONS: Power Doppler ultrasonography represents a non-invasive modality to successfully monitor the vascular effects and thus, treatment efficacy, of PDT.

Animals↗

PubMed2006

Influence of pretreatment polarographically measured oxygenation levels in spontaneous canine tumors treated with radiation therapy.

BACKGROUND AND PURPOSE: The level of hypoxia in primary tumors has been described to influence response to treatment. The aim of the present study was to investigate the impact of pretreatment oxygen level measurements in spontaneous canine tumors on treatment outcome. MATERIALS AND METHODS: Data of pretreatment tumor oxygenation status and local tumor response after primary radiation therapy in a group of spontaneously occurring tumors in dogs (n=52) was collected. Radiation therapy was given with curative (14-17x3-3.5 Gy) or palliative intent (3x8 Gy or 4-5x6 Gy). Progression-free interval and overall survival were correlated to polarographically measured tumor oxygenation status. RESULTS: In the curatively irradiated group, tumors with median pO2 values<or=10 mmHg tended to have shorter median progression- free interval compared to better oxygenated tumors (246 vs. 739 days). The same trend could be shown for overall survival (330 vs. 745 days), indicating a cutoff value in this region. In the group treated with lower doses of radiation, the level of oxygen was no longer found to be of prognostic value; however, in this group hemoglobin had a significant impact on outcome. CONCLUSION: In curatively irradiated spontaneous canine tumors, tumor hypoxia was found to be a prognostic indicator, independent of tumor histologies and volume.

Age Factors↗

PubMed2006

The impact of IMRT and proton radiotherapy on secondary cancer incidence.

BACKGROUND AND PURPOSE: There is concern about the increase of radiation-induced malignancies with the application of modern radiation treatment techniques such as intensity-modulated radiotherapy (IMRT) and proton radiotherapy. Therefore, X-ray scatter and neutron radiation as well as the impact of the primary dose distribution on secondary cancer incidence are analyzed. MATERIAL AND METHODS: The organ equivalent dose (OED) concept with a linear-exponential and a plateau dose-response curve was applied to dose distributions of 30 patients who received radiation therapy of prostate cancer. Three-dimensional conformal radiotherapy was used in eleven patients, another eleven patients received IMRT with 6-MV photons, and eight patients were treated with spot-scanned protons. The treatment plans were recalculated with 15-MV and 18-MV photons. Secondary cancer risk was estimated based on the OED for the different treatment techniques. RESULTS: A modest increase of 15% radiation-induced cancer results from IMRT using low energies (6 MV), compared to conventional four-field planning with 15-MV photons (plateau dose-response: 1%). The probability to develop a secondary cancer increases with IMRT of higher energies by 20% and 60% for 15 MV and 18 MV, respectively (plateau dose-response: 2% and 30%). The use of spot-scanned protons can reduce secondary cancer incidence as much as 50% (independent of dose-response). CONCLUSION: By including the primary dose distribution into the analysis of radiation-induced cancer incidence, the resulting increase in risk for secondary cancer using modern treatment techniques such as IMRT is not as dramatic as expected from earlier studies. By using 6-MV photons, only a moderate risk increase is expected. Spot-scanned protons are the treatment of choice in regard to secondary cancer incidence.

Dose-Response Relationship, Radiation↗

PubMed2005

Radiation risk estimates after radiotherapy: application of the organ equivalent dose concept to plateau dose-response relationships.

Estimates of secondary cancer risk after radiotherapy are becoming more important for comparative treatment planning. Modern treatment planning systems provide accurate three-dimensional (3D) dose distributions for each individual patient. The dose distributions can be converted into organ equivalent doses to describe radiation-induced cancer after radiotherapy (OED(rad-ther)) in the irradiated organs. The OED(rad-ther) concept assumes that any two dose distributions in an organ are equivalent if they cause the same radiation-induced cancer risk. In this work, this concept is applied to dose-response relationships, which are leveling off at high dose. The organ-dependent operational parameter of this dose-response relationship was estimated by analyzing secondary cancer incidence data of patients with Hodgkin's disease. The dose distributions of a typical radiotherapy treatment plan for treating Hodgkin's disease was reconstructed. Dose distributions were calculated in individual organs from which cancer incidence data were available. The model parameter was obtained by comparing dose and cancer incidence rates for the individual organs.

Body Burden↗

PubMed2005

Optimizing photodynamic therapy: in vivo pharmacokinetics of liposomal meta-(tetrahydroxyphenyl)chlorin in feline squamous cell carcinoma.

PURPOSE: The aim of the present study was to optimize and simplify photodynamic therapy using a new liposomal formulation of the photosensitizer meta-(tetrahydroxyphenyl)chlorin [m-THPC (Foscan); liposomal m-THPC (Fospeg)] and to reduce systemic reactions to the photosensitizer. EXPERIMENTAL DESIGN: To examine the pharmacokinetics of liposomal m-THPC, we determined tissue and plasma variables in feline patients with spontaneous squamous cell carcinoma. In vivo fluorescence intensity measurements of tumor and skin were done with a fiber spectrophotometer after i.v. injection of m-THPC or liposomal m-THPC in 10 cats. Blood samples, drawn at several time points after photosensitizer administration, were analyzed by high-performance liquid chromatography. RESULTS: None of the liposomal m-THPC-treated cats showed side effects during or after drug injection. Fluorescence intensities, fluorescence ratios (tumor fluorescence divided by skin fluorescence), and bioavailability in the tumor were 2 to 4 times higher with liposomal m-THPC compared with m-THPC. Liposomal m-THPC concentration in the tumor increased constantly to reach a maximum at 4 hours after injection. Plasma concentration and bioavailability were approximately 3 times higher with liposomal m-THPC compared with m-THPC measured at the time points of highest plasma concentration. The distribution half-life was shorter with liposomal m-THPC, resulting in maximal tumor accumulation up to 5.5 times earlier. Maximal tumor accumulation and maximal fluorescence ratio with liposomal m-THPC occurred at the same time point, indicating maximal selectivity. In both groups, all cats responded to therapy. CONCLUSIONS: Liposomal m-THPC was well tolerated by all cats and seems to have superior pharmacokinetic properties compared with m-THPC. The efficacy of the drug warrants further study.

Animals↗

PubMed2005

Estimation of radiation-induced cancer from three-dimensional dose distributions: Concept of organ equivalent dose.

PURPOSE: Estimates of secondary cancer risk after radiotherapy are becoming more important for comparative treatment planning. Modern treatment planning systems provide accurate three-dimensional dose distributions for each individual patient. These data open up new possibilities for more precise estimates of secondary cancer incidence rates in the irradiated organs. We report a new method to estimate organ-specific radiation-induced cancer incidence rates. The concept of an organ equivalent dose (OED) for radiation-induced cancer assumes that any two dose distributions in an organ are equivalent if they cause the same radiation-induced cancer incidence. METHODS AND MATERIALS: The two operational parameters of the OED concept are the organ-specific cancer incidence rate at low doses, which is taken from the data of the atomic bomb survivors, and cell sterilization at higher doses. The effect of cell sterilization in various organs was estimated by analyzing the secondary cancer incidence data of patients with Hodgkin's disease who were treated with radiotherapy in between 1962 and 1993. The radiotherapy plans used at the time the patients had been treated were reconstructed on a fully segmented whole body CT scan. The dose distributions were calculated in individual organs for which cancer incidence data were available. The model parameter that described cell sterilization was obtained by analyzing the dose and cancer incidence rates for the individual organs. RESULTS: We found organ-specific cell radiosensitivities that varied from 0.017 for the mouth and pharynx up to 1.592 for the bladder. Using the two model parameters (organ-specific cancer incidence rate and the parameter characterizing cell sterilization), the OED concept can be applied to any three-dimensional dose distribution to analyze cancer incidence. CONCLUSION: We believe that the concept of OED presented in this investigation represents a first step in assessing the potential risk of secondary cancer induction after the clinical application of radiotherapy.

Dose-Response Relationship, Radiation↗

PubMed2005

A simple dose-response relationship for modeling secondary cancer incidence after radiotherapy.

Estimates of secondary cancer risk after radiotherapy are becoming more important for comparative treatment planning. There is great uncertainty concerning the dose-response relationship for radiation-induced carcinogenesis at doses higher than 4 Gy. The purpose of this report is to determine a simple dose-response relationship for secondary cancer incidence after radiotherapy treatment which can be used for comparative treatment planning. In this report a simple one-parameter model to estimate the complication probability of secondary cancer was fitted to literature data on secondary cancer incidence after radiotherapy. The results showed a linear dose-response relationship in the low-dose part and an exponentially decreasing one after a maximum at around 10 Gy. The observed dose-response relationship and the literature data used to fit the dose-response indicate that cell death effects are important for the explanation of secondary cancer incidence. Even using a dose and dose-rate effectiveness factor (DDREF) of two (instead of one), a cancer incidence maximum is observed at around 10 Gy, with decreasing incidence at higher doses.

Dose-Response Relationship, Radiation↗

PubMed2005

Patient specific optimization of the relation between CT-hounsfield units and proton stopping power with proton radiography.

The purpose of this work is to show the feasibility of using in vivo proton radiography of a radiotherapy patient for the patient individual optimization of the calibration from CT-Hounsfield units to relative proton stopping power. Water equivalent tissue (WET) calibrated proton radiographs of a dog patient treated for a nasal tumor were used as baseline in comparison with integrated proton stopping power through the calibrated CT of the dog. In an optimization procedure starting with a stoichiometric calibration curve, the calibration was modified randomly. The result of this iteration is an optimized calibration curve which was used to recalculate the dose distribution of the patient. One result of this experiment was that the mean value of the deviations between WET calculations based on the stoichiometric calibration curve and the measurements was shifted systematically away from zero. The calibration produced by the optimization procedure reduced this shift to around 0.4 mm. Another result was that the precision of the calibration, reflected as the standard deviation of the normally distributed deviations between WET calculation and measurement, could be reduced from 7.9 to 6.7 mm with the optimized calibration. The dose distributions based on the two calibration curves showed major deviations at the distal end of the target volume.

Animals↗

PubMed2005

Evaluation of quantified contrast-enhanced color and power Doppler ultrasonography for the assessment of vascularity and perfusion of naturally occurring tumors in dogs.

OBJECTIVE: To investigate subjective and computerized methods of evaluation of color Doppler (CD) and power Doppler (PD) ultrasonographic images (obtained before and after administration of contrast medium) for quantitative assessment of vascularity and perfusion of various naturally occurring tumors in dogs. SAMPLE POPULATION: 34 tumors in 34 dogs. PROCEDURE: Tumors in dogs were examined via CD and PD ultrasonography before and after i.v. injection of a microbubble contrast agent (pre- and postcontrast examinations, respectively). Images were digitized for subjective assessment of vessel density and vascular pattern and computer-aided assessment of parameters of vascularity (fractional area [FA]) and perfusion (color-weighted FA [CWFA] and mean color-weighted FA [CWFA] and mean color level). RESULTS: With both analysis methods, more vessels were identified in precontrast PD ultrasonographic images than in precontrast CD ultrasonographic images. Moreover, compared with values for precontrast PD ultrasonography, FA, CWFA, and mean color level were higher for postcontrast PD ultrasonography. In postcontrast images, there was a significant association between vessel densities determined through subjective and computerized assessments. Although sample size was small, vascularity of squamous cell carcinomas was significantly greater than that of other tumor types. Ten of the 19 softer than issue that sarcomas had low vessel density with minor contrast enhancement. With increasing gross tumor volume, FA and CWFA decreased for all Doppler ultrasonographic methods. CONCLUSIONS AND CLINICAL RELEVANCE: Higher values of the ultrasonographic parameters representing vascularity and perfusion of tumors in dogs were determined via PD ultrasonography after administration of contrast medium than via PD or CD ultrasonography without administration of contrast medium.

Animals↗

PubMed2004

Oxygenation of spontaneous canine tumors during fractionated radiation therapy.

BACKGROUND AND PURPOSE: Tumor oxygenation predicts treatment outcome, and reoxygenation is considered important in the efficacy of fractionated radiation therapy. Therefore, the purpose of this study was to document the changes of the oxygenation status in spontaneous canine tumors during fractionated radiation therapy using polarographic needle electrodes. MATERIAL AND METHODS: Tumor oxygen partial pressure (pO(2)) measurements were performed with the Eppendorf-pO(2)-Histograph. The measurements were done under general anesthesia, and probe tracks were guided with ultrasound. pO(2) was measured before radiation therapy in all dogs. In patients treated with curative intent, measurements were done sequentially up to eight times (total dose: 45-59.5 Gy). Oxygenation status of the palliative patient group was examined before each fraction of radiation therapy up to five times (total dose: 24-30 Gy). RESULTS: 15/26 tumors had a pretreatment median pO(2) < or = 10 mmHg. The pO(2) values appeared to be quite variable in individual tumors during fractionated radiation therapy. The pO(2) of initially hypoxic tumors (pretreatment median pO(2) < or = 10 mmHg) remained unchanged during fractionated radiotherapy, whereas in initially normoxic tumors the pO(2) decreased. CONCLUSION: Hypoxia is common in spontaneous canine tumors, as 57.7% of the recorded values were < or = 10 mmHg. The data of this study showed that initially hypoxic tumors remained hypoxic, whereas normoxic tumors became more hypoxic.

Animals↗

PubMed2004

Combining magnetic and optical tracking for computer aided therapy.

A fast and accurate magnetic tracking system was developed for applications in real-time tumor tracking, computer-aided surgery, and endoscopy. The tracking is based on the application of miniaturized sensors. Once implanted in the patient, the sensors receive signals from an external field generator. The fast evaluation of the signals allows the online determination of position and orientation of each sensor. With the help of optical tracking, the sensor coordinates are transformed in the reference system used by the clinician. The effects of eddy currents in nearby electrically-conducting objects are taken into account using special computational methods. The present paper presents the results of a first experiment in a canine model.

Electromagnetic Fields↗

PubMed2004

First proton radiography of an animal patient.

The purpose of this work is to show the feasibility of proton radiography in terms of radiation dose, imaging speed, image quality (density and spatial resolution), and image content under clinical conditions. Protons with 214 MeV energy can penetrate through most patients and were used for imaging. The measured residual range (or energy) of the protons behind the patient was subtracted from the range without an object in the beam path and used to create a projected image. The image content is therefore proportional to the range that protons have lost in the patient. We took proton images of the head of a dog after it received proton radiotherapy treatment of a nasal tumor. The spatial resolution by measuring for each proton separately its coordinate in front of and behind the patient was approximately 1 mm. The acquisition time was on the order of several seconds and was limited by the patient table movement. The range sensitivity of the images was approximately 0.6 mm, which is good enough to use the images for therapy range verification. The dose that the dog received during exposure was 0.03 mGy, which is approximately a factor 50-100 smaller than for a comparable x-ray image. The potential to obtain quantitative images of proton ranges with satisfying spatial and range resolution and low dose to the patient suggests that proton radiography should be applied to patients who are under proton radiotherapy treatment.

Animals↗

PubMed2004

Uptake of 18F-fluorocholine, 18F-fluoroethyl-L-tyrosine, and 18F-FDG in acute cerebral radiation injury in the rat: implications for separation of radiation necrosis from tumor recurrence.

UNLABELLED: Differentiation between posttherapy radiation necrosis and recurrent tumor in humans with brain tumor is still a difficult diagnostic task. The new PET tracers (18)F-fluoro-ethyl-l-tyrosine (FET) and (18)F-fluorocholine (N,N-dimethyl-N-(18)F-fluoromethyl-2-hydroxyethylammonium [FCH]) have shown promise for improving diagnostic accuracy. This study assessed uptake of these tracers in experimental radiation injury. METHODS: In a first model, circumscribed lesions were induced in the cortex of 35 rats using proton irradiation of 150 or 250 Gy. After radiation injury developed, uptake of (18)F-FET, (18)F-FCH, and (18)F-FDG was measured using autoradiography and correlated with histology and disruption of the blood-brain barrier as determined with Evans blue. In a second model, uptake of the tracers was assessed in acute cryolesions, which are characterized by the absence of inflammatory cells. RESULTS: Mean (18)F-FET, (18)F-FCH, and (18)F-FDG standardized uptake values in the most active part of the radiation lesion and the contralateral normal cortex (in parentheses) were 2.27 +/- 0.46 (1.42 +/- 0.23), 2.52 +/- 0.42 (0.61 +/- 0.12), and 6.21 +/- 1.19 (4.35 +/- 0.47). The degree of uptake of (18)F-FCH and (18)F-FDG correlated with the density of macrophages. In cryolesions, (18)F-FET uptake was similar to that in radiation lesions, and (18)F-FCH uptake was significantly reduced. CONCLUSION: Comparison of tracer accumulation in cryolesions and radiation injuries demonstrates that (18)F-FET uptake is most likely due to a disruption of the blood-brain barrier alone, whereas (18)F-FCH is additionally trapped by macrophages. Uptake of both tracers in the radiation injuries is generally lower than the published uptake in tumors, suggesting that (18)F-FET and (18)F-FCH are promising tracers for separating radiation necrosis from tumor recurrence. However, the comparability of our data with the literature is limited by factors such as different species and acquisition protocols and modalities. Thus, more studies are needed to settle this issue. Nevertheless, (18)F-FCH and (18)F-FET seem superior to (18)F-FDG for this purpose.

Acute Disease↗

PubMed2003

Apoptotic response of irradiated T-lymphocytes. An epidemiologic study in canine radiotherapy patients.

BACKGROUND: Evaluation of radiation-induced apoptosis in T-lymphocytes was developed for human medicine in order to predict the sensitivity of individual patients to radiation therapy and has regular use in cases of suspected hypersensitivity. A major goal of the present study was to evaluate the usefulness of the apoptosis assay in veterinary medicine for application in radiation sensitivity testing. The main goal was to examine potential changes in sensitivity of T-lymphocytes to radiation-induced apoptosis during the course of radiation treatment. This is a clear example of the advantageous use of spontaneous canine tumors to augment human cancer research. MATERIAL AND METHODS: Blood was collected in heparin tubes, diluted 1 : 10 in RPMI medium, irradiated with X-rays and incubated for 48 h. T-lymphocytes were labeled using FITC-conjugated antibodies, erythrocytes were lysed, and DNA stained with propidium iodide. For cell analysis, a Becton Dickinson FACScan flow cytometer was used. Radiation-induced apoptosis in T-lymphocytes was quantified. Blood samples from tumor-bearing dogs were taken before the first fraction and at the end of radiation therapy. RESULTS: Apoptosis in lymphocytes is dependent on donor age and donor weight. Tumor-bearing dogs when compared with healthy dogs showed no significant differences in levels of induced apoptosis. No significant changes were seen in the levels of radiation-induced apoptosis in blood taken before, during, or after radiation therapy. CONCLUSION: The leukocyte apoptosis assay can be successfully applied to canine patients, and a wide spectrum of sensitivities to radiation-induced apoptosis is observed. The sensitivity of a patient's peripheral blood T-lymphocytes to radiation-induced apoptosis does not change as a result of the trauma of radiotherapy during the course of tumor treatment.

Age Factors↗

PubMed2002

Rescue of hypoxia-inducible factor-1alpha-deficient tumor growth by wild-type cells is independent of vascular endothelial growth factor.

In tumors, rapid cell proliferation associated with deficient vascularization leads to areas of hypoxia. Tumor hypoxia has direct consequences on clinical and prognostic parameters and is a potential therapeutic target. The hypoxic response depends critically on hypoxia-inducible factor-1alpha (HIF-1alpha) in pathological (e.g., tumorigenesis) as well as physiological (e.g., development and wound healing) processes. By s.c. injection of HIF-1alpha(-/-) embryonic stem (ES) cells in nude mice, we were able to demonstrate the role of HIF-1alpha in cell differentiation of teratocarcinomas. HIF-1alpha(+/+) tumors grow fast and preferentially form neuronal tissue, whereas HIF-1alpha(-/-) tumors show delayed growth and favorably form mesenchyme-derived tissue. Mixing wild-type and HIF-1alpha(-/-) ES cells in the same tumor at a ratio as low as 1:100, we showed that HIF-1alpha(+/+) cells can rescue the growth of mixed tumors although these tumors are not significantly different phenotypically or genotypically from the original HIF-1alpha(-/-) tumors. Interestingly, these results are not restricted to teratocarcinomas: they were confirmed with mixtures of Hepa1/Hepa1C4 cells (where HIF-1beta is mutated), demonstrating that growth changes are not related to differences in differentiation observed within teratocarcinomas. We also showed that despite lower mRNA expression, vascular endothelial growth factor protein status in HIF-1alpha(-/-) and mixed tumors does not significantly differ from the HIF-1alpha(+/+) tumors. Moreover, we demonstrated that tumor vascularization remains proportional to vascular endothelial growth factor protein levels, but that hypoxic up-regulation of this growth factor is not the decisive factor influencing tumor growth. Differences in levels of apoptosis are not responsible for alteration in growth because poly(ADP-ribose) polymerase cleavage, a hallmark of the apoptotic process, was similar in HIF-1alpha(+/+), HIF-1alpha(-/-), and mixed tumors. Our data demonstrate that the HIF-1alpha-dependent response of a few cells is capable of sustaining the growth of the whole tumor, probably through the secretion of factors up-regulated under low oxygen conditions.

Animals↗

PubMedDate not supplied

A comparison of normal tissue complication probability of brain for proton and photon therapy of canine nasal tumors.

This study compared the calculated normal tissue complication probability of brain in dogs with a nasal tumor, which had both photon and proton treatment planning. Nine dogs diagnosed with a variety of histologies, but all with large, caudally located nasal tumors were studied. Three-dimensional (3-D) photon dose distribution, and a proton dose distribution was calculated for each dog. To calculate the normal tissue complication probability (NTCP) for brain, the partial brain volume irradiated with the prescribed dose was determined, then a mathematic model relating complications to partial volume and radiation dose was used. The NTCP was always smaller for proton plans as compared to photon plans, indicating conformation of the dose to the target allows a higher dose to be given. If a 5% NTCP were accepted, the mean applicable dose for this group of dogs was 50.2 Gy for photons, but 58.3 Gy for protons. Not all dogs would benefit the same from proton irradiation. If a large partial brain volume has to be irradiated, the advantage becomes minimal. There is also a minimal advantage if the planning target volume (PTV) includes a small, superficial brain volume. However, for a complex PTV shape the degree of conformation is clearly superior for protons and results in smaller calculated NTCPs.

Animals↗