• Tuberculosis and Respiratory Diseases
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• v.47 no.3
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• pp.347-355
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• 1999

Background: Phospholipase C(PLC) plays a central role in cellular signal transduction and is important in cellular growth, differentiation and transformation. There are currently ten known mammalian isozymes of PLC reported to this date. Hydrolysis of phosphatidylinositol 4,5-bisphosphate($PIP_2$) by PLC produces two important second messengers, inositol 1,4,5-trisphosphate($IP_3$) and diacylglycerol. PLC-${\gamma}1$, previously, was known to be activated mainly through growth factor receptor tyrosine kinase. Other mechanisms of activating PLC-yl have been reported such as activation through tau protein in the presence of arachidonic acid in bovine brain and activation by $IP_3$, phosphatidic acid, etc. Very recently, another PLC-${\gamma}1$ activator protein such as tau has been found in bovine lung tissue, which now is considered to be AHNAK protein. But there has been no report concerning AHNAK and its associated disease to this date. In this study, we examined the expression of the PLC-${\gamma}1$ activator, AHNAK, in lung cancer specimens and their paired normal. Methods: From surgically resected human lung cancer tissues taken from twenty-eight patients and their paired normal counterparts, we evaluated expression level of AHNAK protein using immunoblot analysis of total tissue extract Immunohistochemical stain was performed with primary antibody against AHNAK protein. Results: Twenty-two among twenty-eight lung cancer tissues showed overexpression of AHNAK protein (eight of fourteen squamous cell lung cancers, all of fourteen adenocarcinomas). The resulting bands were multiple ranging from 70 to 200 kDa in molecular weight and each band was indistinct and formed a smear, reflecting mobility shift mainly due to proteolysis during extraction process. On immunohistochemistry, lung cancer tissues showed a very heavy, dense staining with anti-AHNAK protein antibody as compared to the surrounding normal lung tissue, coresponding well with the results of the western blot Conclusion: The overexpression of PLC-${\gamma}1$ activator protein, AHNAK in lung cancer may provide evidence that the AHNAK protein and PLC-${\gamma}1$ act in concerted manner in carcinogenesis.

• The Journal of Korean Society for Radiation Therapy
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• v.28 no.1
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• pp.35-46
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• 2016

Purpose : BoS(Base of Skull) Frame, the fixation tool which is used for the proton of brain cancer increases the lateral penumbra by increasing the airgap (the distance between patient and beam jet), due to the collision of the beam of the posterior oblique direction. Thus, we manufactured the fixation tool per se for improving the limits of BoS frame, and we'd like to evaluate the utility of the manufactured fixation tool throughout this study. Materials and Methods : We've selected the 3 patients of brain cancer who have received the proton therapy from our hospital, and also selected the 6 beam angles; for this, we've selected the beam angle of the posterior oblique direction. We' ve measured the planned BoS frame and the distance of Snout for each beam which are planned for the treatment of the patient using the BoS frame. After this, we've proceeded with the set-up that is above the location which was recommended by the manufacturer of the BoS frame, at the same beam angle of the same patient, by using our in-house Bos frame fixation tool. The set-up was above 21 cm toward the superior direction, compared to the situation when the BoS frame was only used with the basic couch. After that, we've stacked the snout to the BoS frame as much as possible, and measured the distance of snout. We've also measured the airgap, based on the gap of that snout distance; and we've proceeded the normalization based on each dose (100% of each dose), after that, we've conducted the comparative analysis of lateral penumbra. Moreover, we've established the treatment plan according to the changed airgap which has been transformed to the Raystation 5.0 proton therapy planning system, and we've conducted the comparative analysis of DVH(Dose Volume Histogram). Results : When comparing the result before using the in-house Bos frame fixation tool which was manufactured for each beam angle with the result after using the fixation tool, we could figure out that airgap than when not used in accordance with the use of the in-house Bos frame fixation tool was reduced by 5.4 cm ~ 15.4 cm, respectively angle. The reduced snout distance means the airgap. Lateral Penumbra could reduce left, right, 0.1 cm ~ 0.4 cm by an angle in accordance with decreasing the airgap while using each beam angle in-house Bos frame fixation tool. Due to the reduced lateral penumbra, Lt.eyeball, Lt.lens, Lt. hippocampus, Lt. cochlea, Rt. eyeball, Rt. lens, Rt. cochlea, Rt. hippocampus, stem that can be seen that the dose is decreased by 0 CGE ~ 4.4 CGE. Conclusion : It was possible to reduced the airgap by using our in-house Bos frame fixation tool for the proton therapy; as a result, it was possible to figure out that the lateral penumbra reduced. Moreover, it was also possible to check through the comparative analysis of the treatment plan that when we reduce the lateral penumbra, the reduction of the unnecessary irradiation for the normal tissues. Therefore, Using the posterior oblique the Brain cancer proton therapy should be preceded by decreasing the airgap, by using our in-house Bos frame fixation tool; also, the continuous efforts for reducing the airgap as much as possible for the proton therapy of other area will be necessary as well.

• The Korean Journal of Nuclear Medicine
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• v.33 no.3
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• pp.327-336
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• 1999

Purpose: To assess the quantitative accuracy and the clinical utility of 3D volumetric PET imaging with FDG in brain studies, 24 patients with various neurological disorders were studied. Materials and Methods: Each patient was injected with 370 MBq of 2-[$^{18}F$]fluoro-2-deoxy-D-glucose. After a 30 min uptake period, the patients were imaged for 30 min in 2 dimensional acquisition (2D) and subsequently for 10 min in 3 dimensional acquisition imaging (3D) using a GE $Advance^{TM}$ PET system, The scatter corrected 3D (3D SC) and non scatter-corrected 3D images were compared with 2D images by applying ROIs on gray and white matter, lesion and contralateral normal areas. Measured and calculated attenuation correction methods for emission images were compared to get the maximum advantage of high sensitivity of 3D acquisition. Results: When normalized to the contrast of 2D images, the contrasts of gray to white matter were $0.75{\pm}0.13$ (3D) and $0.95{\pm}0.12$ (3D SC). The contrasts of normal area to lesion were $0.83{\pm}0.05$ (3D) and $0.96{\pm}0.05$ (3D SC). Three nuclear medicine physicians judged 3D SC images to be superior to the 2D with regards to resolution and noise. Regional counts of calculated attenuation correction was not significantly different to that of measured attenuation correction. Conclusion: 3D PET images with the scatter correction in FDG brain studies provide quantitatively and qualitatively similar images to 2D and can be utilized in a routine clinical setting to reduce scanning time and patient motion artifacts.

• Bioinformatics and Biosystems
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• v.1 no.1
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• pp.67-72
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• 2006

The aim of this paper is to discuss the effect of missing values in detecting differentially expressed genes in a cDNA microarray experiment in the context of a one sample problem. We conducted a cDNA micro array experiment to detect differentially expressed genes for the metastasis of colorectal cancer based on twenty patients who underwent liver resection due to liver metastasis from colorectal cancer. Total RNAs from metastatic liver tumor and adjacent normal liver tissue from a single patient were labeled with cy5 and cy3, respectively, and competitively hybridized to a cDNA microarray with 7775 human genes. We used $M=log_2(R/G)$ for the signal evaluation, where Rand G denoted the fluorescent intensities of Cy5 and Cy3 dyes, respectively. The statistical problem comprises a one sample test of testing E(M)=0 for each gene and involves multiple tests. The twenty cDNA microarray data would comprise a matrix of dimension 7775 by 20, if there were no missing values. However, missing values occur for various reasons. For each gene, the no missing proportion (NMP) was defined to be the proportion of non-missing values out of twenty. In detecting differentially expressed (DE) genes, we used the genes whose NMP is greater than or equal to 0.4 and then sequentially increased NMP by 0.1 for investigating its effect on the detection of DE genes. For each fixed NMP, we imputed the missing values with K-nearest neighbor method (K=10) and applied the nonparametric t-test of Dudoit et al. (2002), SAM by Tusher et al. (2001) and empirical Bayes procedure by $L\ddot{o}nnstedt$ and Speed (2002) to find out the effect of missing values in the final outcome. These three procedures yielded substantially agreeable result in detecting DE genes. Of these three procedures we used SAM for exploring the acceptable NMP level. The result showed that the optimum no missing proportion (NMP) found in this data set turned out to be 80%. It is more desirable to find the optimum level of NMP for each data set by applying the method described in this note, when the plot of (NMP, Number of overlapping genes) shows a turning point.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6781-6785
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• 2014

Purpose: This study used receiver operating characteristic curves to analyze Surveillance, Epidemiology and End Results (SEER) medulloblastoma (MB) and primitive neuroectodermal tumor (PNET) outcome data. The aim of this study was to identify and optimize predictive outcome models. Materials and Methods: Patients diagnosed from 1973 to 2009 were selected for analysis of socio-economic, staging and treatment factors available in the SEER database for MB and PNET. For the risk modeling, each factor was fitted by a generalized linear model to predict the outcome (brain cancer specific death, yes/no). The area under the receiver operating characteristic curve (ROC) was computed. Similar strata were combined to construct the most parsimonious models. A Monte Carlo algorithm was used to estimate the modeling errors. Results: There were 3,702 patients included in this study. The mean follow up time (S.D.) was 73.7 (86.2) months. Some 40% of the patients were female and the mean (S.D.) age was 16.5 (16.6) years. There were more adult MB/PNET patients listed from SEER data than pediatric and young adult patients. Only 12% of patients were staged. The SEER staging has the highest ROC (S.D.) area of 0.55 (0.05) among the factors tested. We simplified the 3-layered risk levels (local, regional, distant) to a simpler non-metastatic (I and II) versus metastatic (III) model. The ROC area (S.D.) of the 2-tiered model was 0.57 (0.04). Conclusions: ROC analysis optimized the most predictive SEER staging model. The high under staging rate may have prevented patients from selecting definitive radiotherapy after surgery.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5957-5960
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• 2013

Background: Gliomas are the most common type of primary brain tumor in adults, and the X-ray repair complementing group 1 gene (XRCC1) is an important candidate gene influencing its risk. The objective of this study was to detect the influence of XRCC1 genetic polymorphisms on glioma risk. Materials and Methods: A total of 629 glioma patients and 641 cancer-free subjects were enrolled in this case-control study. The genotypes of the c.1471G>A genetic polymorphism were determined by created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods. The influence of the XRCC1 genetic polymorphism on glioma risk was evaluated by association analysis. Results: Our data indicated that the alleles/genotype of this genetic variant was statistically associated with glioma risk. The AA genotype was statistically associated with the increased risk of glioma compared to the GG wild genotype (odds ratios (OR) = 1.89, 95% CI 1.25-2.87, P = 0.003). The allele-A may contribute to increased the susceptibility to glioma (OR = 1.23, 95% CI 1.04-1.46, P = 0.017). Conclusions: These preliminary findings indicate that the c.1471G>A genetic polymorphism of XRCC1 has the potential to influence glioma susceptibility, and might be used as molecular marker for assessing glioma risk.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.4905-4908
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• 2012

Aim: Glioma cancer is the most common type of adult brain tumor. Recent genome-wide association studies (GWAS) have identified various new susceptibility regions and here we conducted an extensive analysis of associations between 12 single nucleotide polymorphisms (SNPs) and glioma risk. Methods: A total of 197 glioma cases and 197 health controls were selected, and 9 SNPs in 8 genes were analyzed using the Sequenom MassARRAY platform and Sequenom Assay Design 3.1 software. Results: We found the MAF among selected controls were consistent with the MAF from the NCBI SNP database. Among 9 SNPs in 8 genes, we identified four significant SNP genotypes associated with the risk of glioma, C/C genotype at rs730437 and T/T genotype at rs1468727 in ERGF were protective against glioma, whereas the T/T genotype at rs1799782 in XRCC1 and C/C genotype at rs861539 in XRCC3 conferred elevated risk. Conclusion: Our comprehensive analysis of nine SNPs in eight genes suggests that the rs730437 and rs1468727 in ERGF, rs1799782 in XRCC1 gene, and rs861539 in XRCC3 gene are associated with glioma risk. These findings indicate that genetic variants of various genes play a complex role in the development of glioma.

• Polymer(Korea)
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• v.32 no.1
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• pp.90-93
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• 2008

We developed a variety of polymeric jelly phantoms that can be used in hyperthermia using an electromagnetic wave as an auxiliary cancer therapy. Particularly, using an appropriate material composed of polyethylene, deionized water, and sodium chloride, jelly phantoms for brain was prepared. Also, their electrical properties were characterized by measuring the dielectric constant and conductivity. As the results, overall electrical values of the phantoms decreased with increasing the amount of the components of the materials, excepted for sodium chloride. Additionally, storage characteristics of the phantoms showed a sustainable stability up to 6 months. Based on the experimental results, it can be proposed that jelly phantoms containing a ferro-magnetic particle could be a potential material for cancer therapy following the further study on the temperature elevation effect and the evaluation of electromagnetic properties of the materials.

• Proceedings of the Ginseng society Conference
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• 1998.06a
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• pp.270-280
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• 1998

Ginseng is one of the most widely used medicinal plants, particularly in East Asian countries. Certain fractions or purified ingredients of ginseng have been shown to exert inhibitory effects on growth of cancer cells in culture or on tumorigenesis in experimental animals. Moreover, a recent epidemiologic study reveals that ginseng intake is associated with a reduced risk for environmentally related cancers such as esophageal, gastric, colorectal, and pulmonary tumors. Heat treatment of Panax ginseng C. A. Meyer at the temperature higher than that applied to the conventional preparation of red ginseng yielded a mixture of saponins with potent antioxidative properties. Thus, the methanol extract of heat-processed ginseng (designated as'NGMe') attenuated lipid peroxidation in rat brain homogenates induced by ferric ion or ferric ion plus ascorbic acid. Furthermore, the extract protected against strand scission in f Xl 74 supercoiled DNA Induced by UV photolysis of H2O2 and was also capable of scavenging superoxide generated in vitro by xanthine/xanthine oxidate or in differentiated human promyelocytic leukemia (HL-60) cells by the tumor promoter,12-0-tetvade- canoylphorbol-13-acetate (TPA). Since tumor promotion is closely linked to oxidative stress, we have determined possible anti-tumor promotional effects of NGMe on two-stage mouse skin tumorigenesis. Topical application of NGMe onto shaven backs of female ICR mice 10 min prior to TPA significantly ameliorated skin papillomagenesi s initiated by 7,12-dimethylbenz (a) anthracene (DMBA).'Likewise, TPA-induced epidermal ornithine decarboxylase activity and elevation of tumor necrosis factor-a were suppressed signifies%fly by NGMe pretreatment. NGMe topically applied onto surface of hamster buccal pouch 10 min before each topical application of DMBA inhibited oral carcinogenesis by 76olo in terms of multiplicity. Taken together, these results suggest that processed Panax ginseng C. A. Meyer has potential cancer chemopreventive activities.

• BMB Reports
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• v.52 no.7
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• pp.445-450
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• 2019

TTYH2 is a calcium-activated, inwardly rectifying anion channel that has been shown to be related to renal cancer and colon cancer. Based on the topological prediction, TTYH2 protein has five transmembrane domains with the extracellular N-terminus and the cytoplasmic C-terminus. In the present study, we identified a vesicle transport protein, ${\beta}$-COP, as a novel specific binding partner of TTYH2 by yeast two-hybrid screening using a human brain cDNA library with the C-terminal region of TTYH2 (TTYH2-C) as a bait. Using in vitro and in vivo binding assays, we confirmed the protein-protein interactions between TTYH2 and ${\beta}$-COP. We also found that the surface expression and activity of TTYH2 were decreased by co-expression with ${\beta}$-COP in the heterologous expression system. In addition, ${\beta}$-COP associated with TTYH2 in a native condition at a human colon cancer cell line, LoVo cells. The over-expression of ${\beta}$-COP in the LoVo cells led to a dramatic decrease in the surface expression and activity of endogenous TTYH2. Collectively, these data suggested that ${\beta}$-COP plays a critical role in the trafficking of the TTYH2 channel to the plasma membrane.