PECAM-1 modulates liver damage induced by synergistic effects of TNF-α and irradiation.

The mechanisms of radiation-induced liver damage are poorly understood. We investigated if tumour necrosis factor (TNF)-α acts synergistically with irradiation, and how its activity is influenced by platelet endothelial cell adhesion molecule-1 (PECAM-1). We studied murine models of selective single-dose (25 Gy) liver irradiation with and without TNF-α application (2 μg/mouse; i.

Role of PECAM-1 in radiation-induced liver inflammation.

Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) is known to play an important role in hepatic inflammation. Therefore, we investigated the role of PECAM-1 in wild-type (WT) and knock-out (KO)-mice after single-dose liver irradiation (25 Gy). Both, at mRNA and protein level, a time-dependent decrease in hepatic PECAM-1, corresponding to an increase in intercellular cell adhesion molecule-1 (ICAM-1) (6 hrs) was detected in WT-mice after irradiation.

Hepatic fat accumulation and regulation of FAT/CD36: an effect of hepatic irradiation.

Irradiation is known to induce inflammation and affect fat metabolic pathways. The current study investigates hepatic fat accumulation and fatty acid transportation in a rat model of single dose liver irradiation (25-Gy). Rat livers were selectively irradiated in-vivo (25-Gy), sham-irradiated rats served as controls.

Gender affects acute organ toxicity during radiochemotherapy for rectal cancer: long-term results of the German CAO/ARO/AIO-94 phase III trial.

Introduction: The CAO/ARO/AIO-94 phase-III-trial demonstrated a significant improvement of preoperative chemoradiotherapy (CRT) versus postoperative CRT on local control for UICC stage II/III rectal cancer patients, but no effect on long-term survival. In this add-on evaluation, we investigated the association of gender and age with acute toxicity and outcome.

Patients And Methods: According to actual treatment analyses, 654 of 799 patients had received pre- (n=406) or postoperative CRT (n=248); in 145 patients postoperative CRT was not applied.

Rat model of fractionated (2 Gy/day) 60 Gy irradiation of the liver: long-term effects.

The liver is considered a radiosensitive organ. However, in rats, high single-dose irradiation (HDI) showed only mild effects. Consequences of fractionated irradiation (FI) in such an animal model have not been studied so far.

Differential regulation of ferritin subunits and iron transport proteins: an effect of targeted hepatic X-irradiation.

The current study aimed to investigate radiation-induced regulation of iron proteins including ferritin subunits in rats. Rat livers were selectively irradiated in vivo at 25 Gy. This dose can be used to model radiation effects to the liver without inducing overt radiation-induced liver disease.

Irradiation with protons for the individualized treatment of patients with locally advanced rectal cancer: a planning study with clinical implications.

Background And Purpose: Ongoing clinical trials aim to improve local control and overall survival rates by intensification of therapy regimen for patients with locally advanced rectal cancer. It is well known that whenever treatment is intensified, risk of therapy-related toxicity rises. An irradiation with protons could possibly present an approach to solve this dilemma by lowering the exposure to the organs-at-risk (OAR) without compromising tumor response.

Acute toxicity of radiochemotherapy in rectal cancer patients: a risk particularly for carriers of the TGFB1 Pro25 variant.

Purpose: Transforming growth factor-beta1 is related to adverse events in radiochemotherapy. We investigated TGFB1 genetic variability in relation to quality of life-impairing acute organ toxicity (QAOT) of neoadjuvant radiochemotherapy under clinical trial conditions.

Methods And Materials: Two independent patient cohorts (n = 88 and n = 75) diagnosed with International Union Against Cancer stage II/III rectal cancer received neoadjuvant radiation doses of 50.

Comparison of the micronucleus and chromosome aberration techniques for the documentation of cytogenetic damage in radiochemotherapy-treated patients with rectal cancer.

Purpose: The goal of the interdisciplinary Clinical Research Unit KFO179 (Biological Basis of Individual Tumor Response in Patients with Rectal Cancer) is to develop an individual Response and Toxicity Score for patients with locally advanced rectal cancer treated with neoadjuvant radiochemotherapy. The aim of the present study was to find a reliable and sensitive method with easy scoring criteria and high numbers of cell counts in a short period of time in order to analyze DNA damage in peripheral blood lymphocytes. Thus, the cytokinesis-block micronucleus (CBMN) assay and the chromosome aberration technique (CAT) were tested.

High-grade acute organ toxicity as a positive prognostic factor in primary radiochemotherapy for anal carcinoma.

Purpose: To test for a possible correlation between high-grade acute organ toxicity during primary radiochemotherapy and treatment outcome for patients with anal carcinoma.

Methods And Materials: From 1991 to 2009, 72 patients with anal carcinoma were treated at our department (10 patients had stage I, 28 patients had stage II, 11 patients had stage IIIA, and 13 patients had stage IIIB cancer [Union Internationale Contre le Cancer criteria]). All patients received normofractionated (1.

Single-dose gamma-irradiation induces up-regulation of chemokine gene expression and recruitment of granulocytes into the portal area but not into other regions of rat hepatic tissue.

Liver damage is a serious clinical complication of gamma-irradiation. We therefore exposed rats to single-dose gamma-irradiation (25 Gy) that was focused on the liver. Three to six hours after irradiation, an increased number of neutrophils (but not mononuclear phagocytes) was observed by immunohistochemistry to be attached to portal vessels between and around the portal (myo)fibroblasts (smooth muscle actin and Thy-1(+) cells).

High-grade acute organ toxicity during preoperative radiochemotherapy as positive predictor for complete histopathologic tumor regression in multimodal treatment of locally advanced rectal cancer.

Purpose: To test for a possible correlation between high-grade acute organ toxicity during preoperative radiochemotherapy and complete tumor regression after total mesorectal excision in multimodal treatment of locally advanced rectal cancer.

Patients And Methods: From 2001 to 2008, 120 patients were treated. Preoperative treatment consisted of normofractionated radiotherapy at a total dose of 50.

Effect of irradiation on gene expression of rat liver adhesion molecules: in vivo and in vitro studies.

Background And Purpose: Migration of leukocytes into tissue is a key element of innate and adaptive immunity. An animal study showed that liver irradiation, in spite of induction of chemokine gene expression, does not lead to recruitment of leukocytes into the parenchyma. The aim of this study was to analyze gene expression of adhesion molecules, which mediate leukocyte recruitment into organs, in irradiated rat liver in vivo and rat hepatocytes in vitro.

The impact of prostate volume changes during external-beam irradiation in consequence of HDR brachytherapy in prostate cancer treatment.

Purpose: To evaluate prostate volume changes during external-beam irradiation in consequence of high-dose-rate (HDR) brachytherapy in prostate cancer treatment.

Patients And Methods: 20 patients who underwent radiotherapy for prostate cancer were included in this prospective evaluation. All patients had a computed tomography (CT) scan for planning of the external-beam irradiation and additional scans after each HDR brachytherapy.

Noninvasive imaging of liver repopulation following hepatocyte transplantation.

Near infrared fluorescence (NIRF) optical imaging is a technique particularly powerful when studying in vivo processes at the molecular level in preclinical animal models. We recently demonstrated liver irradiation under the additional stimulus of partial hepatectomy as being an effective primer in the rat liver repopulation model based on hepatocyte transplantation. The purpose of this study was to assess optical imaging and the feasibility of donor cell expansion tracking in vivo using a fluorescent probe.

In vivo dosimetry in the urethra using alanine/ESR during (192)Ir HDR brachytherapy of prostate cancer--a phantom study.

A phantom study for dosimetry in the urethra using alanine/ESR during (192)Ir HDR brachytherapy of prostate cancer is presented. The measurement method of the secondary standard of the Physikalisch-Technische Bundesanstalt had to be slightly modified in order to be able to measure inside a Foley catheter. The absorbed dose to water response of the alanine dosimetry system to (192)Ir was determined with a reproducibility of 1.

The delineation of target volumes for radiotherapy of lung cancer patients.

Purpose: Differences in the delineation of the gross target volume (GTV) and planning target volume (PTV) in patients with non-small-cell lung cancer are considerable. The focus of this work is on the analysis of observer-related reasons while controlling for other variables.

Methods: In three consecutive patients, eighteen physicians from fourteen different departments delineated the GTV and PTV in CT-slices using a detailed instruction for target delineation.

Gold markers for tumor localization and target volume delineation in radiotherapy for rectal cancer.

Background And Purpose: In locally advanced rectal cancer, neoadjuvant radiochemotherapy is indicated. To improve target volume definition for radiotherapy planning, the potential of implanted gold markers in the tumor region was evaluated.

Patients And Methods: In nine consecutive patients, two to three gold markers were implanted in the tumor region during rigid rectoscopy.

Effect of tumour necrosis factor-alpha and irradiation alone or in combination on the viability of hepatocellular and biliary adenocarcinoma cell lines in vitro.

Background: Tumour necrosis factor alpha (TNF-alpha) may exhibit antitumoral activity and can influence the reaction of both tumour and normal tissue to radiation.

Aims: To test the effect of TNF-alpha and/or irradiation on hepatocellular (HepG2, Hep3B, Sk-Hep1, HuH7) and cholangiocellular (Sk-chA1, Mz-chA1) tumour cell lines.

Methods: Colony formation, apoptosis analysis and trypan blue exclusion were used to assess cell viability.

An easy irradiation technique (partial half-beam) to reduce renal dose in radiotherapy of cervical cancer including paraaortic lymph nodes.

Purpose: : For radiation treatment of patients with cervical cancer and a high risk for paraaortic lymph node involvement, an easy three-dimensional (3-D) conformal irradiation technique (partial half-beam [PHB]) for protection of organs at risk, especially of renal tissue, was developed.

Patients And Methods: : In five consecutive female patients a computed tomography scan was performed. Dose-volume histograms of the renal tissue and other organs at risk were analyzed for PHB, three other 3-D conformal techniques, and an intensitymodulated radiotherapy (IMRT) technique.

In vivo alanine/electron spin resonance (ESR) dosimetry in radiotherapy of prostate cancer: a feasibility study.

Purpose: We have developed a device to evaluate the potential of alanine/electron spin resonance (ESR) dosimetry for quality assurance in 3D conformal radiotherapy for prostate cancer. It consists of a rectal balloon carrying eight alanine dosimeter probes and two metal markers to document the exact position of the balloon. We measured the effects of an air-filled rectal balloon on the dose at the rectal wall and compared these results with the applied dose distribution of the treatment planning system.

Effect of radiation on gene expression of rat liver chemokines: in vivo and in vitro studies.

The aim of the study was to analyze the effect of a single irradiation on chemokine gene expression in the rat liver and in isolated rat hepatocytes. RNA extracted from livers and from hepatocytes within the first 48 h after irradiation was analyzed by real-time PCR and the Northern blot assay. The chemokine concentrations in the serum of irradiated rats were measured quantitatively by ELISA.