• Title/Summary/Keyword: Tumor localization

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Parametric Images of Standardized Uptake Values using P-18-FDG Attenuation Corrected Whole Body PET (F-18-FDG감쇠보정 전신 PET을 이용한 표준섭취계수 추정과 매개변수 영상의 구성)

  • Kim, Kyeong-Min;Kwark, Cheol-Eun;Lee, Dong-Soo;Jeong, Jae-Min;Chung, June-Key;Lee, Myung-Chul;Koh, Chang-Soon;Kim, Yong-Jin
    • The Korean Journal of Nuclear Medicine
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    • v.30 no.4
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    • pp.560-569
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    • 1996
  • Background and Purpose : Standardized uptake value(SUV) has been used as a quantitative index for differentiating benign and malignant tumors with F-18-FDG PET In this study, we produced whole body parametric images of SUV(WBPIS) by body weight normalization, and validated the values by comparison with SUV's calculated with regional scans. Subjects and Methods : Whole body scans were followed by regional scans sequentially on 23 patients. In whole body study, transmission and emission scans were acquired for 2 minutes and 6 minutes for each bed position, respectively. In regional study, transmission and emission scans were acquired for 20 minutes. Measured and segmented/ smoothed attenuation correction were applied using these 2 min transmission scans in whole body studies. The effects of attenuation correction on SUVs were evaluated quantitatively using F-18 filled cylindrical phantom. The mean and peak SUVs obtained from WBPIS were compared with SUVs of the regional scans. Results : In phantom studies, with any method of attenuation correction using regional or whole body studies of phantom, SUVs were nearly consistent. In whole body scan, SUV obtained using measured attenuation correction method was a little higher than SUV of regional scan. SUV obtained using segmented/smoothed attenuation correction method was a little lower. In patient studies, WBPIS using segmented/smoothed attenuation correction method was much smoother and more readable. SUVs of WBPIS obtained with both methods of attenuation correction were well correlated with SUVs of regional scans(r=0.9). SUVs of WBPIS with measured attenuation correction method were 5% lower than SUVs of regional scans. SUVs of WBPIS with segmented/smoothed attenuation correction method were 10% lower than SUVs of regional scans. The differences of SUVs of WBPIS by the two attenuation correction methods were relatively small compared with the possible differences derived from biological characteristics of tumors. Conclusion : We concluded that WBPIS could be useful in the quantification of tumor as well as in localization of whole body lesions, which were often outside the field of view in regional scan. WBPIS made using segmented/smoothed attenuation correction method could be used in clinical routines and SUVs from attenuation corrected F-18-FDG PET could be used interchangeably with SUVs of regional studies.

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Potential Reproductive Toxicity Study of p53 Expressing Adenoviral Vector in Mice (아데노바이러스 유전자치료벡터의 생식독성 연구)

  • Rhee, Gyu-Seek;Kwack, Seung-Jun;Kim, Soon-Sun;Lee, Rhee-Da;Seok, Ji-Hyun;Chae, Soo-Young;Chung, Soo-Youn;Kim, Seung-Hee;Lee, Seung-Hoon;Park, Kui-Lea
    • Korean Journal of Microbiology
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    • v.43 no.3
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    • pp.151-158
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    • 2007
  • The possibility of inadvertent introduction of therapeutic gene expressing viral vectors has raised safety concerns about germ-line infection. Particularly, for indications such as prostate cancer and ovarian cancer, the proximity of the point of viral administration to organs of the reproductive system raises concerns regarding inadvertent germ-line transmission of genes carried by the virus vector. To evaluate the safety of in vivo adenovirus mediated gene transfer, we explored the biodistribution, persistance and potential germ-line transmission of p53-expressing adenovirus (Ad-CMV-p53). Both male and female Balb/c mice were injected with $1{\times}10^9$ PFU of Ad-CMV-p53. The PCR analysis showed that there were detectable vector sequences in liver, kidney, spleen, seminal vesicle, epididymis, prostate, ovary, and uterus. The RT-PCR analysis for detecting inserted gene, p53 showed that Ad-CMV-p53 viral RNA were present in spleen, prostate and ovary. Direct injected male and female mice of adenovirus vector into testis and ovary were mated and their of offspring were evaluated for germ-line transmission of the adenoviral vector. The PCR and RT-PCR analysis showed no evidence of germline transmission, although vector sequences were detected in DNA extracted from gonadal tissues. Real-time PCR result confirmed a significant decrease of adenovirus in gonad tissues 1 week after injection. We have also analysed the cell specific localization of viral DNA in gonad tissues by using in-situ PCR. Positive signals were detected in interstitial tissue but not in seminiferous tubule in sperm. In the case of ovary, adenovirus signal were localized to the stromal tissue, but no follicular signals were observed. Together, these data provide strong evidence that the risk of the Inadvertent germ-line transmission of vector sequences following intraperitoneal or direct injection into genito-urinary system of adenovirus is extremely low.

Lymphotoxin β Receptor Stimulation Is Linked to MLCK Activity and Suppresses Stress Fiber Formation in Agonistic Anti-LTβR Antibody-stimulated Fibroblastic Reticular Cells (FRC에서 agonistic anti-LTβR antibody의 LTβR 자극은 MLCK 연관성 및 stress fiber 형성에 대한 강력한 억제 작용)

  • Kim, Min Hwan;Lee, Jong-Hwan
    • Journal of Life Science
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    • v.27 no.10
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    • pp.1199-1206
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    • 2017
  • The lymphotoxin ${\beta}$ receptor ($LT{\beta}R$), a member of the tumor necrosis factor receptor family, plays an important role in lymphoid tissue's architecture and organogenesis. We found that $LT{\beta}R$ stimulation induced changes in stress fibers (SFs) in fibroblastic reticular cells (FRCs). MLCK and ROCK play critical roles in the regulation of SF formation in cells. The present study was performed to investigate the antifibrotic effects on SF regulation of $LT{\beta}R$ signaling, with a focus on MLCK inhibition. The effect of $LT{\beta}R$ on the SF change was analyzed using immunoblot and fluorescence assays and agonistic $anti-LT{\beta}R$ antibody-treated FRCs. In addition, we checked the level of Rho-guanosine diphosphate (GDP)/guanosine triphosphate (GTP) exchange activity with FRC lysate. Phospho-ezrin proteins acting as membrane-cytoskeleton linkers completely de-phosphorylated in agonistic $anti-LT{\beta}R$ antibody-treated FRCs. The actin bundles rearranged into SFs, where phospho-myosin light chain (p-MLC) co-localized in FRCs. ML7-treated FRCs completely blocked SFs and showed retraction and shrinkage processes comparable to those observed in agonistic $anti-LT{\beta}R$ antibody-treated cells. Inhibition of ROCK activity induced changes in the actin cytoskeleton organization; however, some SFs remained in the cells, while they were completely disrupted by MLCK inhibition with ML7. We showed that the phosphorylation of MLC was completely abolished with $LT{\beta}R$ stimulation in FRCs. When $LT{\beta}R$ was stimulated with the agonistic $anti-LT{\beta}R$ antibody, the Rho-GDP/GTP exchange activity was reduced, however, the activity was not completely abolished. Collectively, the results illustrated that MLCK was potently responsible for the SF regulation triggered via $LT{\beta}R$ signaling in FRCs.

H2AX Directly Interacts with BRCA1 and BARD1 via its NLS and BRCT Domain Respectively in vitro (H2AX의 BRCA1 NLS domain과 BARD1 BRCT domain 각각과의 in vitro 상호 결합)

  • Bae, Seung-Hee;Lee, Sun-Mi;Kim, Su-Mi;Choe, Tae-Boo;Kim, Cha-Soon;Seong, Ki-Moon;Jin, Young-Woo;An, Sung-Kwan
    • KSBB Journal
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    • v.24 no.4
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    • pp.403-409
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    • 2009
  • H2AX, a crucial component of chromatin, is implicated in DNA repair, cell cycle check point and tumor suppression. The aim of this study was to identify direct binding partners of H2AX to regulate cellular responses to above mechanisms. Literature reviews and bioinformatical tools were attempted intensively to find binding partners of H2AX, which resulted in identifying two potential proteins, breast cancer-1 (BRCA1) and BRCA1-associated RING domain 1 (BARD1). Although it has been reported in vivo that BRCA1 co-localizes with H2AX at the site of DNA damage, their biochemical mechanism for H2AX were however only known that the complex monoubiquitinates histone monomers, including unphosphorylated H2AX in vitro. Therefore, it is important to know whether the complex directly interacts with H2AX, and also which regions of these are specifically mediated for the interaction. Using in vitro GST pull-down assay, we present here that BRCA1 and BARD1 directly bind to H2AX. Moreover, through combinational approaches of domain analysis, fragment clonings and in vitro binding assay, we revealed molecular details of the BRCA1-H2AX and BARD1-H2AX complex. These data provide the potential evidence that each of the BRCA1 nuclear localization signal (NLS) and BARD1 BRCA1 C-terminal (BRCT) repeat domain is the novel mediator of H2AX recognition.