Purpose: Radiotherapy exerts direct antivascular effects in tumors and also induces a proangiogenic stress response in tumor cells via the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (mTOR) pathway. Therefore, the combination of radiotherapy and antiangiogenic therapy with mTOR inhibitor RAD001 (Everolimus) might exert additive/synergistic effects on tumor growth. Experimental Design: Effects of radiation combined with mTOR inhibitor RAD001were studied on proliferation of murine colon cancer CT-26, human pancreatic cancer L3.6pl, and human umbilical vascular endothelial cells in vitro. In vivo tumor growth of subcutaneous colon cancer CT 26 and orthotopic pancreatic cancer L3.6pl was assessed after fractionated radiotherapy (5 Â 2 or 5 Â 4 Gy) with or without the addition of the mTOR inhibitor RAD001. RAD001 (1.5 mg/kg/d) was administered until the end of experiments beginning before or after radiotherapy.Results: A single dose of 2 Gy reduced in vitro proliferation of L3.6pl (-16%), CT-26 (-70%), and human umbilical vascular endothelial cells (HUVEC; -72%). The mTOR inhibitor RAD001 (10 ng/mL) suppressed proliferation of HUVEC (-83 %), L3.6pl (-8%), and CT-26 (-82 %). Combination of even low concentrations of 0.01 ng/mL RAD001 and 0.25 Gy radiation significantly reduced proliferation of HUVECs (-57%), whereas additive effects of RAD001 and radiation on tumor cells were seen only at the highest concentrations tested. In vivo, RAD001 introduced before radiotherapy (5 Â 2 Gy) improved tumor growth control in mice (L3.6pl: 326 mm 3 versus 1144 mm 3 ; CT-26: 210 mm 3 versus 636 mm 3 ; P < 0.05 versus control).RAD001turned out to possess a dose-modifying effect on radiotherapy. Conclusion: Endothelial cells seem to be most sensitive to combination of mTOR inhibition and radiotherapy. Additive tumor growth delay using the mTOR inhibitor RAD001 and radiotherapy in vivo therefore might rely on combined antiangiogenic and antivascular effects.
Due to an aging population the incidence
of both cardiac and tumor-related illnesses is increasing.
A problem may arise if radiotherapy is necessary in close
anatomic proximity to an implantable cardioverter-defibrillator
(ICD). These highly precise devices may respond
to ionizing radiation with a loss of function or uncontrolled
stimulation, with both effects being potentially life
threatening. Available guidelines recommend the dose
maximum to a pacemaker to be cumulative below 2 Gy.
For most patients undergoing radiation therapy of the
neck or of the chest this limit is exceeded, thus making a
removal of the device and an implantation of an external
ICD necessary. Case Report: A patient with severe cardiac
problems underwent an implantation of an ICD.
However, a recurrence of a laryngeal cancer was diagnosed.
The irradiation dose after resection was 60 Gy to
the tumor region and 50 Gy to the lymph nodes. Irradiation
peakload to the ICD was calculated to be 2.5 Gy. This
dose was verified with thermoluminescence measurements.
The ICD was externally deactivated during the
sessions of irradiation. Device checks demonstrated no
malfunction. Conclusion: Even though the dose limits of
the ICD of 2 Gy were exceeded, the device demonstrated
a regular function during and after radiotherapy.
Deep and superficial body temperatures were measured by in vitro and in vivo experiments, using a fluoroptic procedure and a variety of magnetic and electromagnetic fields, in the course of magnetic resonance imaging (0.35 T; 1.5 T). In vitro experiments were performed to select and check the appropriate temperature method. Temperature measurements in the human body were carried out centrally (esophageal and rectal measurements). In vivo experiments in 30 volunteers showed no significant changes (p = 0.05) in central or peripheral temperatures resulting from the application of static or dynamic fields or radiofrequency.
The current induced in the outer circuit of a fast response ionization chamber exposed to pulsed radiation consists of two components, a fast one induced by free electrons and a slow one induced by ions. The fast electron component may be used for the representation of the shape of the ionizing pulse. In order to avoid interference with the slow ion current, the latter has to be removed from the signal. This is achieved by deriving a voltage course from the chamber signal which fits the shape of the ion component and subtracting this from the entire signal. The function of the electronic circuit used for this purpose is described. Some considerations about the time resolution of the chamber gas are to be found in the appendix.
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