Radiation up-regulates the expression of VEGF in a canine oral melanoma cell line

Irene Flickinger,Barbara C Rütgen,Wilhelm Gerner,Ivana Calice,Alexander Tichy,Armin Saalmüller,Miriam Kleiter 대한수의학회 2013 JOURNAL OF VETERINARY SCIENCE Vol.14 No.2

To evaluate radiosensitivity and the effects of radiation on the expression of vascular endothelial growth factor (VEGF) and VEGF receptors in the canine oral melanoma cell line, TLM 1,cells were irradiated with doses of 0, 2, 4, 6, 8 and 10 Gray (Gy). Survival rates were then determined by a MTT assay, while vascular endothelial growth factor receptor (VEGFR)-1 and -2expression was measured by flow cytometry and apoptotic cell death rates were investigated using an Annexin assay. Additionally, a commercially available canine VEGF ELISA kit was used to measure VEGF. Radiosensitivity was detected in TLM 1 cells, and mitotic and apoptotic cell death was found to occur in a radiation dose dependent manner. VEGF was secreted constitutively and significant up-regulation was observed in the 8 and 10 Gy irradiated cells. In addition, a minor portion of TLM 1 cells expressed vascular endothelial growth factor receptor (VEGFR)-1 intracellularly. VEGFR-2was detected in the cytoplasm and was down-regulated following radiation with increasing dosages. In TLM 1 cells,apoptosis plays an important role in radiation induced cell death. It has also been suggested that the significantly higher VEGF production in the 8 and 10 Gy group could lead to tumour resistance.

Stereotactic radiosurgery for arteriovenous malformations after embolization: a case-control study

Kano, Hideyuki,Kondziolka, Douglas,Flickinger, John C.,Park, Kyung-Jae,Iyer, Aditya,Yang, Huai-che,Liu, Xiaomin,Monaco, Edward A.,Niranjan, Ajay,Lunsford, L. Dade Journal of Neurosurgery Publishing Group 2012 Journal of Neurosurgery Vol.117 No.2

<B>Object</B><P>In this paper the authors' goal was to define the long-term benefits and risks of stereotactic radiosurgery (SRS) for patients with arteriovenous malformations (AVMs) who underwent prior embolization.</P><B>Methods</B><P>Between 1987 and 2006, the authors performed Gamma Knife surgery in 996 patients with brain AVMs; 120 patients underwent embolization followed by SRS. In this series, 64 patients (53%) had at least one prior hemorrhage. The median number of embolizations varied from 1 to 5. The median target volume was 6.6 cm<SUP>3</SUP> (range 0.2-26.3 cm<SUP>3</SUP>). The median margin dose was 18 Gy (range 13.5-25 Gy).</P><B>Results</B><P>After embolization, 25 patients (21%) developed symptomatic neurological deficits. The overall rates of total obliteration documented by either angiography or MRI were 35%, 53%, 55%, and 59% at 3, 4, 5, and 10 years, respectively. Factors associated with a higher rate of AVM obliteration were smaller target volume, smaller maximum diameter, higher margin dose, timing of embolization during the most recent 10-year period (1997-2006), and lower Pollock-Flickinger score. Nine patients (8%) had a hemorrhage during the latency period, and 7 patients died of hemorrhage. The actuarial rates of AVM hemorrhage after SRS were 0.8%, 3.5%, 5.4%, 7.7%, and 7.7% at 1, 2, 3, 5, and 10 years, respectively. The overall annual hemorrhage rate was 2.7%. Factors associated with a higher risk of hemorrhage after SRS were a larger target volume and a larger number of prior hemorrhages. Permanent neurological deficits due to adverse radiation effects (AREs) developed in 3 patients (2.5%) after SRS, and 1 patient had delayed cyst formation 210 months after SRS. No patient died of AREs. A larger 12-Gy volume was associated with higher risk of symptomatic AREs. Using a case-control matched approach, the authors found that patients who underwent embolization prior to SRS had a lower rate of total obliteration (p = 0.028) than patients who had not undergone embolization.</P><B>Conclusions</B><P>In this 20-year experience, the authors found that prior embolization reduced the rate of total obliteration after SRS, and that the risks of hemorrhage during the latency period were not affected by prior embolization. For patients who underwent embolization to volumes smaller than 8 cm<SUP>3</SUP>, success was significantly improved. A margin dose of 18 Gy or more also improved success. In the future, the role of embolization after SRS should be explored.</P>

Aneurysms increase the risk of rebleeding after stereotactic radiosurgery for hemorrhagic arteriovenous malformations.

Kano, Hideyuki,Kondziolka, Douglas,Flickinger, John C,Yang, Huai-che,Park, Kyung-Jae,Flannery, Thomas J,Liu, Xiaomin,Niranjan, Ajay,Lunsford, L Dade American Heart Association] 2012 Stroke Vol.43 No.10

<P>The purpose of this study was to define the risk of rebleeding after stereotactic radiosurgery (SRS) for hemorrhagic arteriovenous malformations with or without associated intracranial aneurysms.</P>

Maternal Age: A Major Factor Affecting the Outcome of in Vitro Fertilization

( Claudio A. Benodiva ),( Luis Blasco ),( Richard Tureck ),( Luigi Mastroianni ),( George L. Flickinger ),( Sun Haeng Kim ) 대한산부인과학회 1988 대한산부인과학회 학술대회 Vol.62 No.-

Salvage gamma knife stereotactic radiosurgery followed by bevacizumab for recurrent glioblastoma multiforme: a case-control study.

Park, Kyung-Jae,Kano, Hideyuki,Iyer, Aditya,Liu, Xiaomin,Niranjan, Ajay,Flickinger, John C,Lieberman, Frank S,Lunsford, L Dade,Kondziolka, Douglas M. Nijhoff ; Kluwer Academic Publishers 2012 Journal of neuro-oncology Vol.107 No.2

<P>We evaluated the efficacy and safety of gamma knife stereotactic radiosurgery (GKSR) followed by bevacizumab combined with chemotherapy in 11 patients with recurrent glioblastoma multiforme who experienced tumor progression despite aggressive initial multi-modality treatment. Our experience included eight male and three female patients. The median patient age at GKSR was 62 years (range 46-72 years). At the time of GKSR, seven patients had a first recurrence and four had two or more recurrences. The median interval from the initial diagnosis until GKSR was 17 months (range 5-34.5 months). The median tumor volume was 13.6 cm(3) (range 1.2-45.1 cm(3)) and the median margin dose of GKSR was 16 Gy (range 13-18 Gy). Following GKSR, bevacizumab was administrated with irinotecan in nine patients and with temozolomide in one patient. One patient was treated with bevacizumab monotherapy. The treatment outcomes were compared to 44 case-matched controls who underwent GKSR without additional bevacizumab. At a median of 13.7 months (range 4.6-28.3 months) after radiosurgery, tumor progression was evident in seven patients. The median progression-free survival (PFS) was 15 months (95% confidential interval (CI), 6.5-23.3 months). Six-month and 1-year PFS rates were 73 and 55%, respectively. The median overall survival (OS) from GKSR was 18 months (95% CI, 10.1-25.7 months) and 1-year OS rate was 73%. One patient (9%) experienced grade III toxicity and one patient (9%) had major adverse radiation effects. Compared with patients who did not receive bevacizumab, the patients who received bevacizumab had significantly prolonged PFS (15 months vs. 7 months, P = 0.035) and OS (18 months vs. 12 months, P = 0.005), and were less likely to develop an adverse radiation effect (9 vs. 46%, P = 0.037). The combination of salvage GKSR followed by bevacizumab added potential benefit and little additional risk in a small group of patients with progressive glioblastoma. Further experience is needed to define the efficacy and long-term toxicity with this strategy.</P>

Open Source Machine Translation with DELPH-IN

( Francis Bond ),( Stephan Oepen ),( Melanie Siegel ),( Ann Copestake ),( Dan Flickinger ) 경희대학교 언어연구소 2006 언어연구 Vol.23 No.2

The Deep Linguistic Processing with HPSG Initiative (DELPH-IN) provides the infrastructure needed to produce open-source semantic transfer-based machine translation systems. We have made available a prototype Japanese-English machine translation system built from existing resources include parsers, generators, bidirectional grammars and a transfer engine.

Effects of Dietary Flaxseed Lignan Extract on Symptoms of Benign Prostatic Hyperplasia

Wei Zhang,Xiaobing Wang,Yi Liu,Haimei Tian,Brent Flickinger,Mark W. Empie,Sam Z. Sun 한국식품영양과학회 2008 Journal of medicinal food Vol.11 No.2

A flaxseed lignan extract containing 33% secoisolariciresinol diglucoside (SDG) was evaluated for its abilityto alleviate lower urinary tract symptoms (LUTS) in 87 subjects with benign prostatic hyperplasia (BPH). A randomized, dou-ble-blind, placebo-controlled clinical trial with repeated measurements was conducted over a 4-month period using treatmentdosages of 0 (placebo), 300, or 600 mg/day SDG. After 4 months of treatment, 78 of the 87 subjects completed the study.For the 0, 300, and 600 mg/day SDG groups, respectively, the International Prostate Symptom Score (IPSS) decreased . 3.67.1.56, . 7.33. 1.18, and . 6.88. 1.43 (mean. SE, P. .100,. .001, and. .001 compared to baseline), the Quality of Lifescore (QOL score) improved by . 0.71. 0.23, . 1.48. 0.24, and . 1.75. 0.25 (mean. SE, P. .163 and .012 comparedto placebo and P. .103,. .001, and. .001 compared to baseline), and the number of subjects whose LUTS grade changedfrom “moderate/severe” to “mild” increased by three, six, and 10 (P. .188, .032, and .012 compared to baseline). Maximumurinary flows insignificantly increased 0.43. 1.57, 1.86. 1.08, and 2.7. 1.93 mL/second (mean. SE, no statistical sig-nificance reached), and postvoiding urine volume decreased insignificantly by . 29.4. 20.46, . 19.2. 16.91, and . 55.62.36.45 mL (mean. SE, no statistical significance reached). Plasma concentrations of secoisolariciresinol (SECO), enterodiol(ED), and enterolactone (EL) were significantly raised after the supplementation. The observed decreases in IPSS and QOLscore were correlated with the concentrations of plasma total lignans, SECO, ED, and EL. In conclusion, dietary flaxseed lig-nan extract appreciably improves LUTS in BPH subjects, and the therapeutic efficacy appeared comparable to that of com-monly used intervention agents of .1A-adrenoceptor blockers and 5.-reductase inhibitors.

Outcomes of Gamma Knife surgery for trigeminal neuralgia secondary to vertebrobasilar ectasia

Park, Kyung-Jae,Kondziolka, Douglas,Kano, Hideyuki,Berkowitz, Oren,Ahmed, Safee Faraz,Liu, Xiaomin,Niranjan, Ajay,Flickinger, John C.,Lunsford, L. Dade American Association of Neurological Surgeons 2012 Journal of Neurosurgery Vol.116 No.1

<B>Object</B><P>Vertebrobasilar ectasia (VBE) is an unusual cause of trigeminal neuralgia (TN). The surgical options for patients with medically refractory pain include percutaneous or microsurgical rhizotomy and microvascular decompression (MVD). All such procedures can be technically challenging. This report evaluates the response to a minimally invasive procedure, Gamma Knife surgery (GKS), in patients with TN associated with severe vascular compression caused by VBE.</P><B>Methods</B><P>Twenty patients underwent GKS for medically refractory TN associated with VBE. The median patient age was 74 years (range 48-95 years). Prior surgical procedures had failed in 11 patients (55%). In 9 patients (45%), GKS was the first procedure they had undergone. The median target dose for GKS was 80 Gy (range 75-85 Gy). The median follow-up was 29 months (range 8-123 months) after GKS. The treatment outcomes were compared with 80 case-matched controls who underwent GKS for TN not associated with VBE.</P><B>Results</B><P>Intraoperative MR imaging or CT scanning revealed VBE that deformed the brainstem in 50% of patients. The trigeminal nerve was displaced in cephalad or lateral planes in 60%. In 4 patients (20%), the authors could identify only the distal cisternal component of the trigeminal nerve as it entered into the Meckel cave.</P><P>After GKS, 15 patients (75%) achieved initial pain relief that was adequate or better, with or without medication (Barrow Neurological Institute [BNI] pain scale, Grades I-IIIb). The median time until pain relief was 5 weeks (range 1 day-6 months). Twelve patients (60%) with initial pain relief reported recurrent pain between 3 and 43 months after GKS (median 12 months). Pain relief was maintained in 53% at 1 year, 38% at 2 years, and 10% at 5 years. Some degree of facial sensory dysfunction occurred in 10% of patients. Eventually, 14 (70%) of the 20 patients underwent an additional surgical procedure including repeat GKS, percutaneous procedure, or MVD at a median of 14 months (range 5-50 months) after the initial GKS. At the last follow-up, 15 patients (75%) had satisfactory pain control (BNI Grades I-IIIb), but 5 patients (25%) continued to have unsatisfactory pain control (BNI Grade IV or V). Compared with patients without VBE, patients with VBE were much less likely to have initial (p = 0.025) or lasting (p = 0.006) pain relief.</P><B>Conclusions</B><P>Pain control rates of GKS in patients with TN associated with VBE were inferior to those of patients without VBE. Multimodality surgical or medical management strategies were required in most patients with VBE.</P>

Progress in High Power-particle Beams and Pulsed Power Applications at Karlsruhe Institute of Technology

G. Mueller,W. An,Th. Berghofer,M. DelGiacco,Ch. Eing,R. Fetzer,B. Flickinger,W. Frey,H. Giese,M. Gottel,Ch. Gusbeth,A. Heinzel,P. Hoppe,A. Jianu,F. Lang,K. Leber,M. Sack,G. Schuhmacher,J. Singer,R. St 한국물리학회 2011 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.59 No.61

In this paper, we review the progress that has been achieved at Karlsruhe Institute of Technology (KIT) for several industrial scale projects and in basic investigations based on intense particle beams and pulsed power technologies.