• Title/Summary/Keyword: critical cancer

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CT Simulation Technique for Craniospinal Irradiation in Supine Position (전산화단층촬영모의치료장치를 이용한 배와위 두개척수 방사선치료 계획)

  • Lee, Suk;Kim, Yong-Bae;Kwon, Soo-Il;Chu, Sung-Sil;Suh, Chang-Ok
    • Radiation Oncology Journal
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    • v.20 no.2
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    • pp.165-171
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    • 2002
  • Purpose : In order to perform craniospinal irradiation (CSI) in the supine position on patients who are unable to lie in the prone position, a new simulation technique using a CT simulator was developed and its availability was evaluated. Materials and Method : A CT simulator and a 3-D conformal treatment planning system were used to develop CSI in the supine position. The head and neck were immobilized with a thermoplastic mask in the supine position and the entire body was immobilized with a Vac-Loc. A volumetrie image was then obtained using the CT simulator. In order to improve the reproducibility of the patients' setup, datum lines and points were marked on the head and the body. Virtual fluoroscopy was peformed with the removal of visual obstacles such as the treatment table or the immobilization devices. After the virtual simulation, the treatment isocenters of each field were marked on the body and the immobilization devices at the conventional simulation room. Each treatment field was confirmed by comparing the fluoroscopy images with the digitally reconstructed radiography (DRR)/digitally composite radiography (DCR) images from the virtual simulation. The port verification films from the first treatment were also compared with the DRR/DCR images for a geometrical verification. Results : CSI in the supine position was successfully peformed in 9 patients. It required less than 20 minutes to construct the immobilization device and to obtain the whole body volumetric images. This made it possible to not only reduce the patients' inconvenience, but also to eliminate the position change variables during the long conventional simulation process. In addition, by obtaining the CT volumetric image, critical organs, such as the eyeballs and spinal cord, were better defined, and the accuracy of the port designs and shielding was improved. The differences between the DRRs and the portal films were less than 3 mm in the vertebral contour. Conclusion : CSI in the supine position is feasible in patients who cannot lie on prone position, such as pediatric patienta under the age of 4 years, patients with a poor general condition, or patients with a tracheostomy.

DNA Damage-inducible Phosphorylation of p53 at Ser20 is Required for p53 Stabilization

  • Yang, Dong-Hwa;Rhee, Byung-Kirl;Yim, Tae-Hee;Lee, Hye-Jin;Kim, Jungho
    • Animal cells and systems
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    • v.6 no.3
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    • pp.263-269
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    • 2002
  • The p53 tumor suppressor gene is among the most frequently mutated and studied genes in human cancer, but the mechanisms by which it sur presses tumor formation remain unclear. DNA damage regulates both the protein levels of p53 and its affinity for specific DNA sequences. Stabilization of p53 in response to DNA damage is caused by its dissociation from Mdm2, a downstream target gene of p53 and a protein that targets p53 for degradation in the proteosome. Recent studies have suggested that phosphorylation of human p53 at Ser20 is important for stabilizing p53 in response to DNA damage through disruption of the interaction between Mdm2 and p53. We generated mice with an allele encoding changes at Ser20, known to be essential for p53 accumulation following DNA damage, to enable analyses of p53 stabilization in vivo. Our data showed that the mutant p53 was clearly defective for full stabilization of p53 in response to DNA damage. We concluded that Ser20 phosphorylation is critical for modulating the negative regulation of p53 by Mdm2, probably through phosphorylation-dependent inhibition of p53-Mdm2 interaction in the physiological context.

Thiazinogeldanamycin, a New Geldanamycin Derivative Produced by Streptomyces hygroscopicus 17997

  • Ni, Siyang;Wu, Linzhuan;Wang, Hongyuan;Gan, Maoluo;Wang, Yucheng;He, Weiqing;Wang, Yiguang
    • Journal of Microbiology and Biotechnology
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    • v.21 no.6
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    • pp.599-603
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    • 2011
  • A new geldanamycin (GDM) derivative was discovered and isolated from the fermentation broth of Streptomyces hygroscopicus 17997. Its chemical structure was elucidated as thiazinogeldanamycin by LC-MS, sulfur analysis, and NMR. The addition of cysteine to the fermentation medium significantly stimulated the production level of thiazinogeldanamycin, suggesting cysteine as a precursor of thiazinogeldanamycin production. Although showing a decreased cytotoxicity against HepG2 cancer cells, thiazinogeldanamycin exhibited an improved water solubility and photostability. Thiazinogeldanamycin may represent the first natural GDM derivative characterized so far that uses GDM as its precursor. Its appearance also clearly indicates that an appropriate end-point of fermentation is of critical importance for the maximal production of GDM by Streptomyces hygroscopicus 17997.

Dietary Transformation of Lipid in the Rumen Microbial Ecosystem

  • Kim, Eun Joong;Huws, Sharon A.;Lee, Michael R.F.;Scollan, Nigel D.
    • Asian-Australasian Journal of Animal Sciences
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    • v.22 no.9
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    • pp.1341-1350
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    • 2009
  • Dietary lipids are rapidly hydrolysed and biohydrogenated in the rumen resulting in meat and milk characterised by a high content of saturated fatty acids and low polyunsaturated fatty acids (PUFA), which contributes to increases in the risk of diseases including cardiovascular disease and cancer. There has been considerable interest in altering the fatty acid composition of ruminant products with the overall aim of improving the long-term health of consumers. Metabolism of dietary lipids in the rumen (lipolysis and biohydrogenation) is a major critical control point in determining the fatty acid composition of ruminant lipids. Our understanding of the pathways involved and metabolically important intermediates has advanced considerably in recent years. Advances in molecular microbial technology based on 16S rRNA genes have helped to further advance our knowledge of the key organisms responsible for ruminal lipid transformation. Attention has focused on ruminal biohydrogenation of lipids in forages, plant oils and oilseeds, fish oil, marine algae and fat supplements as important dietary strategies which impact on fatty acid composition of ruminant lipids. Forages, such as grass and legumes, are rich in omega-3 PUFA and are a useful natural strategy in improving nutritional value of ruminant products. Specifically this review targets two key areas in relation to forages: i) what is the fate of the lipid-rich plant chloroplast in the rumen and ii) the role of the enzyme polyphenol oxidase in red clover as a natural plant-based protection mechanism of dietary lipids in the rumen. The review also addresses major pathways and micro-organisms involved in lipolysis and biohydrogenation.

Antinociceptive role of neurotensin receptor 1 in rats with chemotherapy-induced peripheral neuropathy

  • Yin, Mei;Kim, Yeo-Ok;Choi, Jeong-Il;Jeong, Seongtae;Yang, Si-Ho;Bae, Hong-Beom;Yoon, Myung-Ha
    • The Korean Journal of Pain
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    • v.33 no.4
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    • pp.318-325
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    • 2020
  • Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect of anti-cancer drugs. Neurotensin receptors (NTSRs) are widely distributed within the pain circuits in the central nervous system. The purpose of this study was to determine the role of NTSR1 by examining the effects of an NTSR1 agonist in rats with CIPN and investigate the contribution of spinal serotonin receptors to the antinociceptive effect. Methods: Sprague-Dawley rats (weight 150-180 g) were used in this study. CIPN was induced by injecting cisplatin (2 mg/kg) once a day for 4 days. Intrathecal catheters were placed into the subarachnoid space of the CIPN rats. The antiallodynic effects of intrathecally or intraperitoneally administered PD 149163, an NTSR1 agonist, were evaluated. Furthermore, the levels of serotonin in the spinal cord were measured by high-performance liquid chromatography. Results: Intrathecal or intraperitoneal PD 149163 increased the paw withdrawal threshold in CIPN rats. Intrathecal administration of the NTSR1 antagonist SR 48692 suppressed the antinociceptive effect of PD 149163 given via the intrathecal route, but not the antinociceptive effect of intraperitoneally administered PD 149163. Intrathecal administration of dihydroergocristine, a serotonin receptor antagonist, suppressed the antinociceptive effect of intrathecally administered, but not intraperitoneally administered, PD 149163. Injecting cisplatin diminished the serotonin level in the spinal cord, but intrathecal or intraperitoneal administration of PD 149163 did not affect this reduction. Conclusions: NTSR1 played a critical role in modulating CIPN-related pain. Therefore, NTSR1 agonists may be useful therapeutic agents to treat CIPN. In addition, spinal serotonin receptors may be indirectly involved in the effect of NTSR1 agonist.

Interferon consensus sequence binding protein : Not essential for interferon α-mediated antiviral response to vesicular stomatitis virus infection in HL-60 cells

  • Park, Byung-Kiu
    • IMMUNE NETWORK
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    • v.1 no.2
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    • pp.109-115
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    • 2001
  • Background: The role of the interferon consensus sequence binding protein (ICSBP), a member of interferon regulatory factor family, in protecting against a vesicular stomatitis virus (VSV) infection has not been firmly elucidated. Thus, it was investigated utilizing the human promyelocytic leukemia HL-60 cells which do not express ICSBP. Methods: HL-60 cells were stably transfected with plasmid containing cDNA for either ICSBP or DNA binding domain (DBD) and tested for their VSV-susceptibilities. The susceptibility of each transfectant group to a VSV infection was determined by a plaque assay at 1 h, 24 h, and 48 h post-infection in the presence (500 IU/ml) or absence of interferon ${\alpha}$ ($IFN{\alpha}$). Results: In the absence of $IFN{\alpha}$, the three groups showed similar sensitivities to a VSV infection. However, when pre-treated with IFN, the viral titers in both the ICSBP and control clones steadily decreased over 48 h of incubation, indicating the existence of $IFN{\alpha}$-mediated protection against VSV infection. The $IFN{\alpha}$-treated ICSBP clones appeared to be more resistant to infection compared with the control clones, although the difference was not great. On the contrary, the viral titers in the $IFN{\alpha}$-treated DBD clones increased at 24 h then decreased by 48 h. Conclusion: The expression of truncated ICSBP (DBD) does not appear to underlie the impaired protection against a VSV infection in the DBD clones, since even the control clones lacking ICSBP were protected from a VSV infection. This suggests that ICSBP does not play a critical role in the $IFN{\alpha}$- mediated anti-VSV response of HL-60 cells, although it appears to confer some resistance to a VSV infection.

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Pharmacophore Modeling and Molecular Dynamics Simulation to Find the Potent Leads for Aurora Kinase B

  • Sakkiah, Sugunadevi;Thangapandian, Sundarapandian;Kim, Yong-Seong;Lee, Keun-Woo
    • Bulletin of the Korean Chemical Society
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    • v.33 no.3
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    • pp.869-880
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    • 2012
  • Identification of the selective chemical features for Aurora-B inhibitors gained much attraction in drug discovery for the treatment of cancer. Hence to identify the Aurora-B critical features various techniques were utilized such as pharmacophore generation, virtual screening, homology modeling, molecular dynamics, and docking. Top ten hypotheses were generated for Aurora-B and Aurora-A. Among ten hypotheses, HypoB1 and HypoA1 were selected as a best hypothesis for Aurora-B and Aurora-A based on cluster analysis and ranking score, respectively. Test set result revealed that ring aromatic (RA) group in HypoB1 plays an essential role in differentiates Aurora-B from Aurora-A inhibitors. Hence, HypoB1 used as 3D query in virtual screening of databases and the hits were sorted out by applying drug-like properties and molecular docking. The molecular docking result revealed that 15 hits have shown strong hydrogen bond interactions with Ala157, Glu155, and Lys106. Hence, we proposed that HypoB1 might be a reasonable hypothesis to retrieve the structurally diverse and selective leads from various databases to inhibit Aurora-B.

Level of radiation dose in university hospital non-insured private health screening programs in Korea

  • Lee, Yun-Keun
    • Environmental Analysis Health and Toxicology
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    • v.31
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    • pp.7.1-7.6
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    • 2016
  • Objectives The aim of this study is to evaluate radiation exposure resulting from the comprehensive health examinations of selected university hospital programs and to present basic data for research and management strategies on the health effects of medical radiation exposure. Methods Radiation-based diagnostic studies of the comprehensive health examination programs of ten university hospitals in Seoul, Korea, as introduced in their websites, were analyzed. The medical radiation studies of the programs were reviewed by radiologists. Only the effective doses of the basic studies were included in the analysis. The optional studies of the programs were excluded. Results Among the 190 comprehensive health examination programs, 132 programs (69.5%) included computed tomography studies, with an average of 1.4 scans. The average effective dose of radiation by program was 3.62 mSv for an intensive program for specific diseases; 11.12 mSv for an intensive program for cancer; 18.14 mSv for a premium program; and 24.08 mSv for an overnight program. A higher cost of a programs was linked to a higher effective dose (r=0.812). The effective doses of the examination programs for the same purposes differed by as much as 2.1 times by hospital. Inclusion of positron emission tomography-computed tomography was the most critical factor in determining the level of effective dose. Conclusions It was found that radiation exposure dose from comprehensive health exam programs targeted for an asymptomatic, healthy public reached between 3.6 and 24 times the annual dose limit for the general public. Relevant management policies at the national level should be provided to minimize medical radiation exposure.

Application of Apoptogenic Pretreatment to Enhance Anti-tumor Immunity of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)-secreting CT26 Tumor Cells

  • Jun, Do-Youn;Jaffee, Elizabeth M;Kim, Young-Ho
    • IMMUNE NETWORK
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    • v.5 no.2
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    • pp.110-116
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    • 2005
  • Background: As an attempt to develop a strategy to improve the protective immune response to GM-CSF-secreting CT26 (GM-CSF/CT26) tumor vaccine, we have investigated whether the apoptogenic treatment of GM-CSF/CT26 prior to vaccination enhances the induction of anti-tumor immune response in mouse model. Methods: A carcinogeninduced mouse colorectal tumor, CT26 was transfected with GM-CSF gene using a retroviral vector to generate GM-CSF-secreting CT26 (CT26/GM-CSF). The CT26/GM-CSF was treated with ${\gamma}$-irradiation or mitomycin C to induce apoptosis and vaccinated into BALB/c mice. After 7 days, the mice were injected with a lethal dose of challenge live CT26 cells to examine the protective effect of tumor vaccination in vivo. Results: Although both apoptotic and necrotic CT26/GM-CSF vaccines were able to enhance anti-tumor immune response, apoptotic CT26/GM-CSF induced by pretreatment with ${\gamma}$-irradiation (50,000 rads) was the most potent in generating the anti-tumor immunity, and thus 100% of mice vaccinated with the apoptotic cells remained tumor free for more than 60 days after tumor challenge. Conclusion: Apoptogenic pretreatment of GM-CSF-secreting CT26 tumor vaccine by ${\gamma}$-irradiation (50,000 rads) resulted in a significant enhancement in inducing the protective anti-tumor immunity. A rapid induction of apoptosis of CT26/GM-CSF tumor vaccine at the vaccine site might be critical for the enhancement in anti-tumor immune response to tumor vaccine.

Identification and Validation of Symptom Clusters in Patients with Hepatocellular Carcinoma (간세포암 환자의 증상군 분류와 타당도 검증)

  • Cho, Myung-Sook;Kwon, In-Gak;Kim, Hee-Sun;Kim, Kyung-Hee;Ryu, Eun-Jung
    • Journal of Korean Academy of Nursing
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    • v.39 no.5
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    • pp.683-692
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    • 2009
  • Purpose: The purpose of this study was to identify cancer-related symptom clusters and to validate the conceptual meanings of the revealed symptom clusters in patients with hepatocellular carcinoma. Methods: This study was a cross-sectional survey and methodological study. Patients with hepatocellular carcinoma (N=194) were recruited from a medical center in Seoul. The 20-item Symptom Checklist was used to assess patients' symptom severity. Selected symptoms were factored using principal-axis factoring with varimax rotation. To validate the revealed symptom clusters, the statistical differences were analyzed by status of patients' performance status, Child-Pugh classification, and mood state among symptom clusters. Results: Fatigue was the most prevalent symptom (97.4%), followed by lack of energy and stomach discomfort. Patients' symptom severity ratings fit a four-factor solution that explained 61.04% of the variance. These four factors were named pain-appetite cluster, fatigue cluster, itching-constipation cluster, and gastrointestinal cluster. The revealed symptom clusters were significantly different for patient performance status (ECOG-PSR), Child-Pugh class, anxiety, and depression. Conclusion: Knowing these symptom clusters may help nurses to understand reasonable mechanisms for the aggregation of symptoms. Efficient symptom management of disease-related and treatment-related symptoms is critical in promoting physical and emotional status in patients with hepatocellular carcinoma.