Aim of this study is to investigate the feasibility of 2D ion chamber array as a substitute of the water phantom system in a periodic Linac QA. For the feasibility study, a commercial ion chamber matrix was used as a substitute of the water phantom in the measurement for a routine QA beam properties. The device used in this study was the I'm RT MatriXX (Wellhofer Dosimetrie, Germany). The MatriXX consists of a 1,020 vented ion chamber array, arranged in $24{\times}24\;cm^2$ matrix. Each ion chamber has a volume of $0.08\;cm^3$, spacing of 0.762 cm. We investigated dosimetric parameters such as dose symmetry, energy ($TPR_{20,10}$), and absolute dose for comparing with the water phantom data with a Farmer-type ionization chamber (FC65G, Wellhofer Dosimetrie, Germany). For the MatriXX measurements, we used the white polystyrene phantom (${\rho}:\;1.18\;g/cm^3$) and also considered the intrinsic layer (${\rho}:\;1.06\;g/cm^3$, t: 0.36 cm) of MatriXX to be equivalent to water depth. In the preliminary study of geometrical QA using MatriXX, the rotation axis of collimator and half beam junction test were included and compared with film measurements. Regarding the dosimetrical QA, the MatriXX has shown good agreements within ${\pm}1%$ compared to the water phantom measurements. In the geometrical test, the data from MatriXX were comparable with those from the films. In conclusion, the MatriXX is a good substitute for water phantom system and film measurements. In addition, the results indicate that the MatriXX as a cost-effective novel QA tool to reduce time and personnel power.
[ $\underline{Purpose}$ ]: For the first time, a nationwide survey in the Republic of Korea was conducted to determine the basic parameters for the treatment of esophageal cancer and to offer a solid cooperative system for the Korean Pattern of Care Study database. $\underline{Materials\;and\;Methods}$: During $1998{\sim}1999$, biopsy-confirmed 246 esophageal cancer patients that received radiotherapy were enrolled from 23 different institutions in South Korea. Random sampling was based on power allocation method. Patient parameters and specific information regarding tumor characteristics and treatment methods were collected and registered through the web based PCS system. The data was analyzed by the use of the Chi-squared test. $\underline{Results}$: The median age of the collected patients was 62 years. The male to female ratio was about 91 to 9 with an absolute male predominance. The performance status ranged from ECOG 0 to 1 in 82.5% of the patients. Diagnostic procedures included an esophagogram (228 patients, 92.7%), endoscopy (226 patients, 91.9%), and a chest CT scan (238 patients, 96.7%). Squamous cell carcinoma was diagnosed in 96.3% of the patients; mid-thoracic esophageal cancer was most prevalent (110 patients, 44.7%) and 135 patients presented with clinical stage III disease. Fifty seven patients received radiotherapy alone and 37 patients received surgery with adjuvant postoperative radiotherapy. Half of the patients (123 patients) received chemotherapy together with RT and 70 patients (56.9%) received it as concurrent chemoradiotherapy. The most frequently used chemotherapeutic agent was a combination of cisplatin and 5-FU. Most patients received radiotherapy either with 6 MV (116 patients, 47.2%) or with 10 MV photons (87 patients, 35.4%). Radiotherapy was delivered through a conventional AP-PA field for 206 patients (83.7%) without using a CT plan and the median delivered dose was 3,600 cGy. The median total dose of postoperative radiotherapy was 5,040 cGy while for the non-operative patients the median total dose was 5,970 cGy. Thirty-four patients received intraluminal brachytherapy with high dose rate Iridium-192. Brachytherapy was delivered with a median dose of 300 cGy in each fraction and was typically delivered $3{\sim}4\;times$. The most frequently encountered complication during the radiotherapy treatment was esophagitis in 155 patients (63.0%). $\underline{Conclusion}$: For the evaluation and treatment of esophageal cancer patients at radiation facilities in Korea, this study will provide guidelines and benchmark data for the solid cooperative systems of the Korean PCS. Although some differences were noted between institutions, there was no major difference in the treatment modalities and RT techniques.
Objective : This study was tried to investigate the specific relationships among cognitve function, neurbehavioral symptoms, and daily living functions, as well as provide the guidline of more proper clinical approches for patients with subcortical cerebrovascular disease. Objects and Methods Subjects were 85 patients whose diagnosis was confirmed by brain CT or MRI and controls were 195 normal persons matched by educational level with the subjects. The cognitive functions were evaluated by BNA(Benton neuropsychiatric assessment), subjective neurobehavioral symptoms by SCL-90-R(Sympton Check List-90-Revised), objective neurobehavioral symptoms by NRS(Neurobehavioral Rating Scale), and daily living function symptoms by NRS(Neurobehavioral Rating Scale), and daily living function by GERRI(Geriatric Evaluation by Relative's Rating Instrument) and IADL(Instrumental Activities of Daily Living Scale). Results: 1) Subjects showed significantly lower cognitive functions than controls in all tests of BNA except Lt-Rt Orientation Test(p=0.09) and facial Recognition Test(p=0.186). 2) In subjective neurobehavioral symptoms, subjects showed significantly lower scores in all symptoms except anxiety(p=0.059), hostility(p=0.159), and phobic anxiety(p=0.849). But in objects neurobehavioral symptoms, subjects showed significantly higher in scores in psychoticism (p=0.000) and neuroticism(p=0.025) of NRS. 3) The score of social functioning of GERRI(p=0.000) and that of IADL(p=0.000) were significantly higher in subjects than in controls. 4) for correlation between cognitive and daily living functions, there were significant correlations between the scores of all items on BNA and the score of cognitive or social function of GERRI and the socre of MDL in corntrols, whereas in subjects, there were significant correlations only between the scores of BNA and the score of IADL. 5) for correlation between neuroehavioral symptoms and daily living functions, there were significant correlatons between the socre of subjective neurobehavioral symptoms and the scores of all subscales of GERRI and the score of MDL in controls. On the contrary, in subjects, there were significant correlations between the score of social function of GERRI and the score of objective neurobehavioral symptoms such as psychoticism, agitiation-hostility, and decrease d motivation-emotional withdrawl. Conclusion : Above results suggest that disturbances in specific function of brain may play a role as a predictor of impairments with specific daily living functions and also suggest that specific correlations among various functions may be useful as clinical parameters for setting of the treatment goal and for assessing the ongoing process in the treatment and rehavilitation of the patients with subcortical cerebrovascular disease.
Heat shock protein 90 (Hsp90) is ATPase-directed molecular chaperon and affects survival of cancer cell. Inhibitory effect of Hsp90 by inducing cell cycle arrest and apoptosis in the cancer cell was reported. However, its role during oocyte maturation and early embryo development is very insufficient. In this study, we traced the effects of Hsp90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), on meiotic maturation and early embryonic development in pigs. We also investigated several indicators of developmental potential, including structural integrity, gene expression (Hsp90-, cell cycle-, and apoptosis-related genes), and apoptosis, which are affected by 17-AAG. Then, we examined the roles of Hsp90 inhibitor on viability of primary cells in pigs. Porcine oocytes were cultured in the NCSU-23 medium with or without 17-AAG for 44 h. The proportion of GV arrested oocytes was significantly different between the 17-AAG treated and untreated group (78.2 vs 34.8%, p<0.05). After completion of meiotic maturation, the proportion of MII oocytes was lower in the 17-AAG treated group than in the control group (27.9 vs 71.0%, p<0.05). After IVF, the percentage of penetrated oocytes was significantly lower in the 17-AAG treated group (25.2%), resulting in lower normal pronucleus formation (2PN of 14.6%). Therefore, the inhibition of meiotic progression by Hsp90 inhibitor played a critical role in fertilization status. Porcine embryo were cultured in the PZM-3 medium with or without 17-AAG for 6 days. In result, significant differences in developmental potential were detected between the embryos that were cultured with or without 17-AAG. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) showed that the number of containing fragmented DNA at the blastocyst stage increased in the 17-AAG treated group compared with control (7.5 vs 4.4, respectively). Blastocysts that developed in the 17-AAG treated group had low structural integrity and high apoptotic nuclei than those of the untreated control, resulting in decrease the embryonic qualities of preimplantation porcine blastocysts. The mRNA expressions of cell cycle-related genes were down-regulated in the 17-AAG treated group compared with control. Also, the expression of the pro-apoptotic gene Bax increased in 17-AAG treated group, whereas expression of the anti-apoptotic gene Bel-XL decreased. However, the expression of ER stress-related genes did not changed by 17-AAG. Cultured pESF cells were treated with or without 17-AAG and used for MIT assay. The results showed that viability of pESF cells were decreased by treatment of 17-AAG ($2{\mu}M$) for 24 hr. These results indicated that 17-AAG decreased cell proliferation and increased cell death. Expression patterns Hsp90 complex genes (Hsp70 and p23), cell cycle-related genes (cdc2 and cdc25c) and apoptosis-related genes (Bax and Bcl-XL) were significantly changed by using RT-PCR analysis. The spliced form of pXbp-1 product (pXbp-1s) was detected in the tunicamycin (TM) treated cells, but it is not detected in 17-AAG treated cells. In conclusion, Hsp90 appears to play a direct role in porcine early embryo developmental competence including structural integrity of blastocysts. Also, these results indicate that Hsp90 is closely associated with cell cycle- and apoptosis-related genes expression in developing porcine embryos.
Purpose: It is well known from clinical experience that acute complications of chemoradiation therapy vary from patients to patients. However, there are no known factors to predict these acute complications before treatment starts. The human XRCC1 gene is known as a DNA base excision repair gene. We investigated the possibilities of XRCC1 gene polymorphisms as a predictor for the acute complications of chemoradiation therapy in colorectal cancer patients. Materials and Methods: From July 1997 to June 2003, 86 colorectal cancer patients (71 rectal cancer, 13 sigmoid colon cancer and 2 colon cancer patients) were treated with chemoradiation therapy at the Department of Radiation Oncology, Inha University Hospital. Twenty-two patients were in stage B, 50 were in stage C, 8 were in stage D and 6 patients were unresectable cases. External radiation therapy was delivered with 10MV X-ray at a 1.8 Gy fraction per day for a total dose of radiation of $30.6{\sim}59.4 Gy$ (median: 54 Gy). All the patients received 5-FU based chemotherapy regimen. We analyzed the acute complications of upper and lower gastrointestinal tract based on the RTOG complication scale. The initial and lowest WBC and platelet count were recorded during both the RT period and the whole treatment period. Allelic variants of the XRCC1 gene at codons 194, 280 and 399 were analyzed in the lymphocyte DNA by performing PCR-RFLP. Statistical analyses were carried out with the SAS (version 6.12) statistical package. Results: When all the variables were assessed on the multivariate analysis, recurrent disease revealed the factors that significantly correlated with upper gastrointestinal acute complications. Arg399Gln polymorph isms of the XRCC1 gene, the radiation dose and the frequencies of chemotherapy during radiation therapy were significantly correlated with lower gastrointestinal complications. Arg399Gln polymorph isms also affected the decrease of the WBC and platelet count during radiation therapy. Conclusion: Although the present sample size was too small for fully evaluating this hypothesis, this study suggests that Arg399Gln polymorph isms of the XRCC1 genes may be used as one of the predictors for acute complications of chemoradiation therapy in colorectal cancer patients.
Purpose: Cancer specific killing can be achieved by therapeutic gene activated by cancer specific promotor. Expression of sodium iodide symporter (NIS) gene causes transportation and concentration of iodide into the cell, therefore radioiodine treatment after NIS gene transfer to cancer cell could be a form of radionuclide gene therapy. luciferase (Luc) gene transfected cancer cell can be monitored by in vivo optical imaging after D-luciferin injection. Aims of the study are to make vector with both therapeutic NIS gene driven by AFP promoter and reporter Luc gene driven by CMV promoter, to perform hepatocellular carcinoma specific radiodiodine gene therapy by the vector, and assessment of the therapy effect by optical imaging using luciferase expression. Materials and Methods: A Vector with AFP promoter driven NIS gene and CMV promoter driven Luc gene (AFP-NIS-CMV-Luc) was constructed. Liver cancer cell (HepG2, Huh-7) and non liver cancer cell (HCT-15) were transfected with the vector using liposome. Expression of the NIS gene at mRNA level was elucidated by RT-PCR. Radioiodide uptake, perchlorate blockade, and washout tests were performed and bioluminescence also measured by luminometer in these cells. In vitro clonogenic assay with 1-131 was performed. In vivo nuclear imaging was obtained with gamma camera after 1-131 intraperitoneal injection. Results: A Vector with AFP-NIS-CMV-Luc was constructed and successfully transfected into HepG2, Huh-7 and HCT-15 cells. HepG2 and Huh-7 cells with AFP-NIS-CMV-Luc gene showed higher iodide uptake than non transfected cells and the higher iodide uptake was totally blocked by addition of perchlorate. HCT-15 cell did not showed any change of iodide uptake by the gene transfection. Transfected cells had higher light output than control cells. In vitro clonogenic assay, transfected HepG2 and Huh-7 cells showed lower colony count than non transfected HepG2 and Huh-7 cells, but transfected HCT-15 cell did not showed any difference than non transfected HCT-15 cell. Number of Huh-7 cells with AFP-NIS-CMV-Luc gene transfection was positively correlated with radioidine accumulation and luciferase activity. In vivo nuclear imaging with 1-131 was successful in AFP-NIS-CMV-Luc gene transfected Huh-7 cell xenograft on nude mouse. Conclusion: A Vector with AFP promoter driven NIS and CMV promoter driven Luc gene was constructed. Transfection of the vector showed liver cancer cell specific enhancement of 1-131 cytotoxicity by AFP promoter, and the effect of the radioiodine therapy can be successfully assessed by non-invasive luminescence measurement.
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