Background : Anti-apoptotic proteins may be involved in tumor development, progression and the response to treatment, Bcl-2 is by far the most studied anti-apoptotic protein. A novel inhibitor of apoptosis, designated survivin, and the heat shock proteins (HSPs) have recently been found in many human cancers. Immunohistochemical methods were used to determine the expression level of survivin, HSP70 and bcl-2 in non-small cell lung cancer (NSCLC) to evaluate their clinical significance. Materials and Methods : Tissue array slides were obtained from 99 surgically resected NSCLCs. Immunohistochemical staining was performed by an immuno-peroxidase technique using an avidin-biotinylated horseradish peroxidase complex. Anti-survivin rabbit polyclonal antibodies, anti-HSP70 mouse monoclonal antibodies and anti-bcl-2 mouse monoclonal antibodies were used as the primary antibodies. Results : Positive staining of survivin was detected in 33.3% of the cases. Survivin positivity is associated with to females and recurrence. A nonstatistically significant trend toward increased survivin expression was observed in non-smokers, and its expression inversely correlated with the number of cigarettes smoked in smokers. HSP70 was detected in 84.8% but this did not correlated with the clinicopathologic characteristics. Bcl-2 was detected in 18.2% and its expression correlated to tumor recurrence. No significant difference in the median survival time was noted in a comparison of all cases with survivin expression and those without. There was no association between HSP70 or bcl-2 expression and survival. Conclusion : Survivin expression was significantly associated with females and tumor recurrence. In addition its expression was inversely associated with the number of cigarettes smoked. However, HSP70 and bcl-2 expression were not associated with the clinical parameters or survival. This suggests that measuring the survivin levels may be useful in identifying patients at high risk for disease recurrence. Therefore, survivin might be a new diagnostic/therapeutic target in cancer.
Oh, Se An;Kang, Min Kyu;Kim, Sung Kyu;Yea, Ji Woon
Progress in Medical Physics
/
v.24
no.3
/
pp.145-153
/
2013
Stereotactic body radiation therapy (SBRT) is increasingly used to treat spinal metastases. To achieve the highest steep dose gradients and conformal dose distributions of target tumors, intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) techniques are essential to spine radiosurgery. The purpose of the study was to qualitatively compare IMRT and VMAT techniques with International Spine Radiosurgery Consortium (ISRC) contoured consensus guidelines for target volume definition. Planning target volume (PTV) was categorized as TB, $T_{BPT}$ and $T_{ST}$ depending on sectors involved; $T_B$ (vertebral body only), $T_{BPT}$ (vertebral body+pedicle+transverse process), and $T_{ST}$ (spinous process+transverse process). Three patients treated for spinal tumor in the cervical, thoracic, and lumbar region were selected. Eacg tumor was contoured by the definition from the ISRC guideline. Maximum spinal cord dose were 12.46 Gy, 12.17 Gy and 11.36 Gy for $T_B$, $T_{BPT}$ and $T_{ST}$ sites, and 11.81 Gy, 12.19 Gy and 11.99 Gy for the IMRT, RA1 and RA2 techniques, respectively. Average fall-off dose distance from 90% to 50% isodose line for $T_B$, $T_{BPT}$, and $T_{ST}$ sites were 3.5 mm, 3.3 mm and 3.9 mm and 3.7 mm, 3.7 mm and 3.3 mm for the IMRT, RA1 and RA2 techniques, respectively. For the most complicated target $T_{BPT}$ sites in the cervical, thoracic and lumbar regions, the conformity index of the IMRT, RA1 and RA2 is 0.621, 0.761 and 0.817 and 0.755, 0.796 and 0.824 for rDHI. Both IMRT and VMAT techniques delivered high conformal dose distributions in spine stereotactic radiosurgery. However, if the target volume includes the vertebral body, pedicle, and transverse process, IMRT planning resulted in insufficient conformity index, compared to VMAT planning. Nevertheless, IMRT technique was more effective in reducing the maximum spinal cord dose compared to RA1 and RA2 techniques at most sites.
Ryu, Jung Kyu;Oh, Jang-Hoon;Kim, Hyug-Gi;Rhee, Sun Jung;Seo, Mirinae;Jahng, Geon-Ho
Investigative Magnetic Resonance Imaging
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v.18
no.1
/
pp.1-6
/
2014
Purpose : $T_2{^*}$ relaxation time which includes susceptibility information represents unique feature of tissue. The objective of this study was to investigate $T_2{^*}$ relaxation times of the normal glandular tissue and fat of breast using a 3T MRI system. Materials and Methods: Seven-echo MR Images were acquired from 52 female subjects (age $49{\pm}12 $years; range, 25 to 75) using a three-dimensional (3D) gradient-echo sequence. Echo times were between 2.28 ms to 25.72 ms in 3.91 ms steps. Voxel-based $T_2{^*}$ relaxation times and $R_2{^*}$ relaxation rate maps were calculated by using the linear curve fitting for each subject. The 3D regions-of-interest (ROI) of the normal glandular tissue and fat were drawn on the longest echo-time image to obtain $T_2{^*}$ and $R_2{^*}$ values. Mean values of those parameters were calculated over all subjects. Results: The 3D ROI sizes were $4818{\pm}4679$ voxels and $1455{\pm}785$ voxels for the normal glandular tissue and fat, respectively. The mean $T_2{^*}$ values were $22.40{\pm}5.61ms$ and $36.36{\pm}8.77ms$ for normal glandular tissue and fat, respectively. The mean $R_2{^*}$ values were $0.0524{\pm}0.0134/ms$ and $0.0297{\pm}0.0069/ms$ for the normal glandular tissue and fat, respectively. Conclusion: $T_2{^*}$ and $R_2{^*}$ values were measured from human breast tissues. $T_2{^*}$ of the normal glandular tissue was shorter than that of fat. Measurement of $T_2{^*}$ relaxation time could be important to understand susceptibility effects in the breast cancer and the normal tissue.
It is generally regarded a design system in post-industrial society, which products designed by in-house designers or design consultancy are manufactured in factory and distributed in market for the consumer. Although it is treated an old design system in traditional society, the traces of vernacular design has been remaining in the state of adopted to the periodical needs in these days, also proving the attribute of design culture to constitute human's material environment as well as existing design systems. There were discovered various design artifacts in daily surroundings vary from the established design in several manners, user modifications or manufactures in everyday lives formalized them. It was approached a case study that analyze the changes of artifact configuration and designer/user context and creation process of the non-professional design artifacts, Creativity Template Theory and ACM(Artifact Context Model) have been utilized for the analysis model. From the analysis result, It assume that the everyday artifacts may be ordinary but extra-ordinary including particular ideas and identity represented by everyday designers or users. Beside these characteristics induce the potentiality that reflect on creative motives for the designers or a complementary artifact generator filling up with drawbacks in established design system. The everyday design domain, various explorations and alternatives are made, is seems to be another design practice domain dissimilar to the one in the industry-based design. Moreover it provides an more easily accessability for the approaching user-friendly design, user customization because they conduct the reliable modeling of consumer and end-user. Finally, based on the exploratory study regarding interpretation of context and configuration in the everyday artifacts, new approach for the design process and design education through more detailed cognitive modeling of everyday designers will be a further study.
A series of 25 patients with residual, recurrent, and unresectable gastric cancer received various combination of surgery, radiotherapy (RT), chemotherapy (CT), and hyperthermia (HT). They were placed into 7 categories; 1) CT and HT-14 patients; 2) RT and HT-15 patients; 3) surgery, RT and HT-2 patients; 4) surgery, RT, HT and CT-1 patient; 5) RT, HT and CT -1 patient; 6) RT and CT-1 patient; 7) RT alone-1 patient. Three patients had curative resection. 21 patients received irradiation with tightly contoured portals to spare as much small bowel, kidney and marrow as possible. Hyperthermia was applied regionally once or twice a week for 23 patients using 8 MHz radiofrequency capacitive heating device (Thermotron RF-8). HT was given approximately 30 min after RT 7 patients were treated with CT: 4 patients received HT and concomitant Mitomycin-C; 3 patients received HT and sequential 5-FU+Adriamycin+Mitomycin-C. There was not any treatment related deaths. There was also no evidence of treatment related problems with liver, kidney, stomach, or spinal cord except only one case of transient diabetic ketoacidosis. The tumor response was evaluable in 22 patients. None achieved complete remission.11 ($50\%$) achieved partial remission. The response rate was correlated with total radiation dose and achieved maximum temperature. 9 of 14 ($64\%$) received more than 4000 cGy showed partial remission; especially, all 3 patients received more than 5500 cGy achieved partial response.8 of the 12 patients ($67\%$) who achieved maximal temperature more than $41^{\circ}C$ showed partial response in comparing with $25\%$ (2 of 8 patients, below $41^{\circ}C$). The numbers of HT, however, was not correlated with the response. 3 of the 25 patients ($12\%$) remain alive. The one who was surgically unresectable and underwent irradiation alone is in progression of the disease with distant metastases. The remaining two patients with curative resection are alive with free of disease, 24 and 35 months, respectively. The median survival by response are 11.5 months in responders and 4.6 months in non-responders.
Intensity-modulated radiotherapy(IMRT) have the ability to provide better dose conformity and sparing of critical normal tissues than three-dimensional radiotherapy(3DCRT). Especially, with the benefit of health insurance in 2011, its use now increasingly in many modern radiotherapy departments. Also the use of linear accelerator with high-energy photon beams over 10 MV is increasing. As is well known, these linacs have the capacity to produce photonueutrons due to photonuclear reactions in materials with a large atomic number such as the target, flattening filters, collimators, and multi-leaf collimators(MLC). MLC-based IMRT treatments increase the monitor units and the probability of production of photoneutrons from photon-induced nuclear reactions. The purpose of this study is to quantitatively evaluate the dose of photoneutrons produced from 3DCRT and IMRT technique for Rando phantom in cervical cancer. We performed the treatment plans with 3DCRT and IMRT technique using Rando phantom for treatment of cervical cancer. An Rando phantom placed on the couch in the supine position was irradiated using 15 MV photon beams. Optically stimulated luminescence dosimeters(OSLD) were attached to 4 different locations (abdomen, chest, head and neck, eyes) and from center of field size and measured 5 times each of locations. Measured neutron dose from IMRT technique increased by 9.0, 8.6, 8.8, and 14 times than 3DCRT technique for abdomen, chest, head and neck, and eyes, respectively. When using IMRT with 15 MV photonbeams, the photoneutrons contributed a significant portion on out-of-field. It is difficult to prevent high energy photon beams to produce the phtoneutrons due to physical properties, if necessary, It is difficult to prevent high energy photon beams to produce the phtoneutrons due to physical properties, if necessary, it is need to provide the additional safe shielding on a linear accelerator and should therefore reduce the out-of-field dose.
Purpose: This study was designed to investigate the cellular uptake of various tumor imaging radiopharmaceuticals in human breast cancer cells before and after paclitaxel exposure considering viable cell number. Materials and Methods: F-18-fluorodeoxyglucose, C-11-methionine, Tl-201, Tc-99m-MIBI, and Tc-99m-tetrofosmin were used to evaluate the cellular uptake in MCF-7 cells. MCF-7 cells were cultured in multi-well plates. Wells were divided into DMSO exposure control group, and paclitaxel exposure group. The exposure durations of paclitaxel with 10 nM or 100 nM were 2 h, 6 h, 12 h, 24 h, and 48 h. Results: Viable cell fraction was reduced as the concentration and exposure time of paclitaxel increased. After 10 nM paclitaxel exposure, the cellular uptake of all 5 radiopharmaceuticals was not reduced significantly, irrespective of exposure time and viable cell fraction. After 100 nM paclitaxel exposure, the cellular uptake of all 5 radiopharmaceuticals was enhanced significantly irrespective of viable cell fraction. The peak uptake was observed in experimental groups with paclitaxel exposure for 6 to 48 h according the type of radiopharmaceutical. When the cellular uptake was adjusted for the viable cell fraction and cell count, the peak cellular uptake was observed in experimental groups with paclitaxel exposure for 48 h, irrespective of the type of radiopharmaceutical. Conclusion: The cellular uptake of F-18-fluorodeoxyglucose, C-11-methionine, Tl-201, Tc-99m-MIBI, and Tc-99m-tetrofosmin did not reflect viable cell number in MCF-7 cells after paclitaxel exposure for up to 48 h.
Kim Young Ae;Lim Sun-Young;Ko Woo Shin;Choi Byung Tae;Lee Yong Tae;Rhee Sook-Hee;Park Kun-Young;Lee Won-Ho;Choi Yung Hyun
Journal of Life Science
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v.15
no.2
s.69
/
pp.169-175
/
2005
Resveratrol (3,4',5-trihydroxy-trans-stilbene), a phytoalexin found in grape skins, peanuts, and red wine, has been reported to have a wide range of biological and pharmacological properties. $Amyloid-\beta$ deposition and senile plaque-associated astrocytes are common neuropathological features of Alzheimer's disease. In this study, we have explored the effects of resveratrol on $amyloid-\beta-peptide-mediated$ cytotoxicity in vitro and modulation of cell growth-regulatory gene products in astroglioma C6 cells to elucidate its possible mechanism for anti-cytotoxicity. Exposure of C6 cells to $Amyloid-\beta$ resulted in dose-dependent growth inhibition and morphological changes of C6 cells, which were recovered by pre-treatment with resveratrol. The anti-proliferative effect of $amyloid-\beta$ was associated with the induction of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21 (WAF1/CIP1) expression assessed by RT-PCR and Western blot analysis in time-dependent manner in C6 cells. In addition, the pro-apoptotic Bax expression was also up-regulated in $amyloid-\beta-treated$ C6 cells without alteration of anti-apoptotic Bcl-2 and $Bcl-X_L$ expression. However, pre-treatment of resveratrol significantly inhibited $amyloid-\beta-induced$ p53, p21 and Bax levels, suggesting that the modulation of p53, p21 and Bax levels could be one of the possible pathways by which resveratrol functions as anti-cytotoxic agent. Our results demonstrate that resveratrol may enhance the protection against $amyloid-\beta-induced$ cytotoxicity by promoting the survival of glial cells.
The granites in the southern Gimcheon area can be divided into two parts, marginal hornblende biotite granodiorite (Mgd) and central biotite granodiorite to granite (Cgd). Mgd and Cgd are gray in color and display gradational contact relations and are mainly composed of coarse-grained and medium-grained rocks, respectively. Mgd has more frequent and larger mafic enclaves than Cgd, and the two granites partly show parallel foliation at thire contact with gneisses. From representative samples of the granites, K-Ar biotite ages of 197∼207 Ma were obtained. Considering the blocking temperature of biotite, it is suggested that the emplacement age of the granitic magma was probably late Triassic. The anorthite contents of plagioclases in Mgd display less variation than those of Cgd, indicating that Mgd crystallized within a narrow range of temperatures. In the Al$\_$total/-Mg diagram, the biotites from the granites plot within the subalkaline field, and the smooth slope indicates differentiation from a single magma. All amphiboles from the granites belong to magnesio-hornblende. The linear trends of major oxides, AFM and Ba-Sr-Rb indicate that Mgd and Cgd were fractionally differentiated from a single granitic magma body crystallizing from the margin inwards. The relations of modal (Qz+Af) vs. Op, K$_2$O vs. Na$_2$O, Fe$_2$$O_3$ vs. FeO, Fe$\^$+3/(Fe$\^$+3/+Fe$\^$+2/) and K/Rb vs. Rb/Sr show that they belong to I-type and magnetite-series granitic rocks developed by the progressive melting products of fixed sources. REE data, normalized to chondrite value, have trends of enriched LREE and depleted HREE together with weakly negative Eu anomalies.
Purpose : To elucidate the effects of pentoxifylline and diltiazem on the late response of the salivary glands of the rat after irradiation. Materials and Methods : Sixteen Sprague-Dawley rats were divided into 4 groups : (a) irradiation alone (b) irradiation with pentixifylline (PTX) (c) irradiation with diltiazem (DTZ) (d) irradiation with both PTX and DTZ. Irradiation was given in a single fraction of 16 Gy using 4 MV photon energy through an anterior port encompassing the left side of the salivary gland leaving the right side of salivary gland as a control. PTX, 20 mg/kg and/or DTZ, 50 mg/kg were infused intraperitoneally before irradiation, Two rats from each group were sacrificed on the 10th week and the rest was sacrificed on the 16th week after irradiation. Histopathologic examinations were undertaken for each section and the proportion of vacuolated cells out of the total number of cells under light microscopic fields was calculated. The statistical significance in the difference of the proportion of the vacuolated cells among the experimental groups was evaluated by a $x^2$-test. Results : Irradiated salivary glands of the 10th week group revealed markedly increased number of vacuolated cells compared to those of unirradiated control. The proportion of vacuolated cells was significantly reduced in both the PTX group (p value=0.001) and the combined PTX and DTX group compared to those of irradiation alone group. The DTZ alone group did not reveal the significant reduction of vacuolated cells compared to those of irradiation alone group (p value, >0.05). The 16th week groups revealed similar findings to those of the 10th week group, but the degree of chronic inflammatory cell infiltrates and interstitial fibrosis was increased and the number of acinar cells was reduced compared to those of the 10th week group. Conclusions : PTX significantly reduced the late radiation response of salivary glands, but DTZ did not reduce the same degree as PTX did. Taking the positive results of this study into consideration, it seems reasonable to apply PTX into the clinical trial for the head and neck irradiation to reduce the late radiation sequelae of salivary glands in the near future. At the same time the further experiment to clarify the subcellar mechni는 involved in PTX should be preceded.
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