• Title/Summary/Keyword: Radiation biology

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The novel gene LRP15 is regulated by DNA methylation and confers increased efficiency of DNA repair of ultraviolet-induced DNA damage

  • Xu, Zhou-Min;Gao, Wei-Ran;Mei, Qi;Chen, Jian;Lu, Jing
    • BMB Reports
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    • v.41 no.3
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    • pp.230-235
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    • 2008
  • LRP15 is a novel gene cloned from lymphocytic cells, and its function is still unknown. Bioinformatic data showed that LRP15 might be regulated by DNA methylation and had an important role in DNA repair. In this study, we investigate whether the expression of LRP15 is regulated by DNA methylation, and whether overexpression of LRP15 increases efficiency of DNA repair of UV-induced DNA damage in HeLa cells. The results showed (1) the promoter of LRP15 was hypermethylated in HeLa cells, resulting a silence of its expression. Gene expression was restored by a demethylating agent, 5-aza-2'-deoxycytidine, but not by a histone deacetylase inhibitor, trichostatin A; (2) overexpression of LRP15 inhibited HeLa cell proliferation, and the numbers of cells in the G2/M phase of the cell cycle in cells transfected with LRP15 increased about 10% compared with controls; (3) cyclin B1 level was much lower in cells overexpressing LRP15 than in control cells; and (4) after exposure to UV radiation, the LRP15-positive cells showed shorter comet tails compared with the LRP15-negative cells. From these results we conclude that the expression of LRP15 is controlled by methylation in its promoter in HeLa cells, and LRP15 confers resistance to UV damage and accelerates the DNA repair rate.

Influence of Ethnicity on Survival of Breast Cancer Patients in Turkey

  • Kuzhan, Abdurahman;Adli, Mustafa;Buyukhatipoglu, Hakan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9199-9202
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    • 2014
  • Background: Kurdish women with breast cancer have more unfavorable prognostic factors than their Turkish and Arab counterparts. However, the effects of these factors on breast cancer survival among these ethnic groups remain unclear. We therefore investigated the impact of ethnicity on survival in breast cancer patients in Turkey. Materials and Methods: Ethnicity, age, stage at diagnosis, tumor characteristics, treatments given (surgery, chemotherapy, radiotherapy and hormone therapy), and survival times were recorded. Kaplan-Meier analysis was used to estimate the overall survival times and survival plots. Log-rank test was used to compare the survival curves.Results: Of the 723 breast cancer patients included in the study, 496 (68.7%) were Turkish, 189 (26.2%) were Kurdish, 37 (5.1%) were Arabic and 1 was Armenian. Kurdish women with breast cancer had larger tumor sizes and higher rates of hormone receptor negative tumors than Turkish and Arab patients. Mean follow-up time was 118.4 [95% Confidence Interval (CI): 95.4-141.3] months, and it was 129.9 (95% CI: 93.7-166.2), 124.2 (95% CI: 108.4-140.1) and 103.1 (95% CI: 85.9-120.4) months for Turkish, Arabic and Kurdish patients, respectively. Conclusions: Kurdish ethnicity is associated with higher rates of hormone receptor negative and triple-negative tumors and with worse survival. Clinical and epidemiological research is warranted to elucidate reasons underlying overall survival, variations in tumor biology, differences in treatment responsiveness, and effects of social factors among ethnic groups in Turkey.

The origin-of-cell harboring cancer-driving mutations in human glioblastoma

  • Lee, Joo Ho;Lee, Jeong Ho
    • BMB Reports
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    • v.51 no.10
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    • pp.481-483
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    • 2018
  • Glioblastoma (GBM) is the most common and aggressive form of human adult brain malignancy. The identification of the cell of origin harboring cancer-driver mutations is the fundamental issue for understanding the nature of GBM and developing the effective therapeutic target. It has been a long-term hypothesis that neural stem cells in the subventricular zone (SVZ) might be the origin-of-cells in human glioblastoma since they are known to have life-long proliferative activity and acquire somatic mutations. However, the cell of origin for GBM remains controversial due to lack of direct evidence thereof in human GBM. Our recent study using various sequencing techniques in triple matched samples such as tumor-free SVZ, tumor, and normal tissues from human patients identified the clonal relationship of driver mutations between GBM and tumor-free SVZ harboring neural stem cells (NSCs). Tumor-free SVZ tissue away from the tumor contained low-level GBM driver mutations (as low as 1% allelic frequency) that were found in the dominant clones in its matching tumors. Moreover, via single-cell sequencing and microdissection, it was discovered that astrocyte-like NSCs accumulating driver mutations evolved into GBM with clonal expansion. Furthermore, mutagenesis of cancer-driving genes of NSCs in mice leads to migration of mutant cells from SVZ to distant brain and development of high-grade glioma through the aberrant growth of oligodendrocyte precursor lineage. Altogether, the present study provides the first direct evidence that NSCs in human SVZ is the cell of origin that develops the driver mutations of GBM.

Arginine Deiminase Enhances MCF-7 Cell Radiosensitivity by Inducing Changes in the Expression of Cell Cycle-related Proteins

  • Park, Hwan;Lee, Jun-Beom;Shim, Young-Jun;Shin, Yong-Jae;Jeong, Seong-Yun;Oh, Junseo;Park, Gil-Hong;Lee, Kee-Ho;Min, Bon-Hong
    • Molecules and Cells
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    • v.25 no.2
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    • pp.305-311
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    • 2008
  • After successful clinical application, arginine deiminase (ADI) has been proposed to be a new cancer therapeutic. In the present study, we examined the effect of ADI in combination with ionizing radiation (IR) on MCF-7 cell growth and clonogenic cell death. Cell growth was inhibited by IR in a dose-dependent manner and ADI enhanced the radiosensitivity. ADI itself did not suppress the growth of MCF-7 cells due to the high level of expression of argininosuccinate synthetase (ASS), which convert citrulline, a product of arginine degradation by ADI, to arginine. Previously, it was suggested that ammonia, another product of arginine degradation by ADI, is the main cause of the growth inhibition of irradiated hepatoma cells contaminated with ADI-expressing mycoplasma [van Rijn et al. (2003)]. However, we found that ammonia is not the only factor that enhances radiosensitivity, as enhancement was also observed in the absence of ammonia. In order to identify the enhancing effect, levels of ASS and proteins related to the cell cycle were examined. ASS was unchanged by ADI plus IR, but p21 (a CDK inhibitor) was upregulated and c-Myc downregulated. These findings indicate that changes in the expressions of cell cycle proteins are involved in the enhancement of radiosensitivity by ADI. We suggest that ADI is a potential adjunct to cancer therapy.

Radiolysis of Oxygenated and Deoxygenated Glycylglycylglycine in Aqueous Solution and in the Solid State (酸素의 存在下와 無酸素下에서의 水溶液 및 固體 Glycylglycylglycine의 放射線分解)

  • Kang, Man-Sik
    • The Korean Journal of Zoology
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    • v.13 no.3
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    • pp.75-84
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    • 1970
  • Gamma-radiolyses of oxygenated and deoxygenated glycylglycylclycine in aqueous solution and in the solid state are observed, with special regards to peptied bond rupture for elucidation of radiolytic mechanism of proteins, by means of chromatorgraphic separation of degradation products, spectrophotometric quantitation of carbonyl compounds, micro-titration of amide formation, infrared spectrophptometry, and ultraviolet spectrophotometry for evaluation of radiation damage. Essential difference of peptide bond rupture is observed in solution and in the solid state, being high in the former and negligible in the latter. On the other hand, the presence of and obsence of oxygen in solution during irradiation are not so significant with respect to peptide bond rupture, except the recombination of free-radicals produced in deoxygenated solution. Peptide bond rupture in solution is attributable to the mechanisms proposed by Garrison et al.; dehydrogenation followed by hydrolysis to yield acid amide and carbonyl function as found on the basis of radiolytic products. Peptide bond attack at $\\alpha$-carbon locus might be suggestive for irradiated solid but not significant in view of low degree of peptide bond rupture.

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AUA as a Translation Initiation Site In Vitro for the Human Transcription Factor Sp3

  • Hernandez, Eric Moore;Johnson, Anna;Notario, Vicente;Chen, Andrew;Richert, John R.
    • BMB Reports
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    • v.35 no.3
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    • pp.273-282
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    • 2002
  • Sp3 is a bifunctional transcription factor that has been reported to stimulate or repress the transcription of numerous genes. Although the size of Sp3 mRNA is 4.0kb, the size of the known Sp3 cDNA sequence is 3.6kb. Thus, Sp3 functional studies have been performed with an artificially introduced start codon, and thus an amino-terminus that differs from the wild-type. Ideally, full-length cDNA expression vectors with the appropriate start codon should be utilized for these studies. Using 5'rapid amplification of cDNA ends, a full-length Sp3 cDNA clone was generated and the sequence verified in nine cell lines. No AUG initiation codon was present. However, stop codons were present in all three frames 5' to the known coding sequence. In vitro translation of this full-length cDNA clone produced the expected three isoforms-one at 100 kDa and two in the mid 60 kDa range. Electrophoretic mobility shift assays showed that the protein products had the ability to bind to the Sp1/3 consensus sequence. In vitro studies, using our Sp3 clone and site directed mutagenesis, identified the translation initiation site for the larger isoform as AUA. AUA has not been previously described as an endogenous initiation codon in eukaryotes.

Minimizing a QTL region for intramuscular fat content by characterizing the porcine Phosphodiesterase 4B (PDE4B) gene

  • Kim, Jae-Hwan;Ovilo, Cristina;Park, Eung-Woo;Fernndez, Almudena;Lee, Jun-Heon;Jeon, Jin-Tae;Lee, Jung-Gyu
    • BMB Reports
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    • v.41 no.6
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    • pp.466-471
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    • 2008
  • Three isoforms of pig PDE4B were cloned and classified as two forms: PDE4B1 and PDE4B3, which contain UCR1 and UCR2; and PDE4B2, which contains only UCR2. The amino acid sequences of each isoform showed good conservation in human and rat. PDE4B2 is expressed in a wide range of tissues, but PDE4B1 and PDE4B3 are not. Using an informative SNP for the Iberian x Landrace intercross detected from intron 12, a linkage map was constructed. The location of PDE4B was estimated at 123.6 cM outside of the QTL-CI (124-128 cM) for IMF. However, the QTL-CI for IMF was reconfirmed with high significance, and its position was narrowed down to an interval of 4 cM (the region defined by markers PDE4B and SW1881). Using radiation hybrid mapping, LEPR, LEPROT, DNAJC6, AK3L1 and AK3L2 were selected as positional and/or functional candidates related to the QTL.

Topical or oral treatment of peach flower extract attenuates UV-induced epidermal thickening, matrix metalloproteinase-13 expression and pro-inflammatory cytokine production in hairless mice skin

  • Kwak, Chung Shil;Yang, Jiwon;Shin, Chang-Yup;Chung, Jin Ho
    • Nutrition Research and Practice
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    • v.12 no.1
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    • pp.29-40
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    • 2018
  • BACKGROUND/OBJECTIVES: Ultraviolet radiation (UV) is a major cause of skin photoaging. Previous studies reported that ethanol extract (PET) of Prunus persica (L.) Batsch flowers (PPF, peach flowers) and its subfractions, particularly the ethylacetate (PEA) and n-butanol extracts (PBT), have potent antioxidant activity and attenuate the UV-induced matrix metalloproteinase (MMP) expression in human skin cells. In this study, we investigated the protective activity of PPF extract against UV-induced photoaging in a mouse model. MATERIALS/METHODS: Hairless mice were treated with PET or a mixture of PEA and PBT either topically or orally along with UV irradiation. Histological changes and biochemical alterations of mouse skin were examined. Major phenolic compounds in PPF extract were analyzed using an ACQUITY UPLC system. RESULTS: The overall effects of topical and oral treatments with PPF extract on the UV-induced skin responses exhibited similar patterns. In both experiments, the mixture of PEA and PBT significantly inhibited the UV-induced skin and epidermal thickening, while PET inhibited only the UV-induced epidermal thickening. Treatment of PET or the mixture of PEA and PBT significantly inhibited the UV-induced MMP-13 expression, but not type I collagen expression. Topical treatment of the mixture of PEA and PBT with UV irradiation significantly elevated catalase, superoxide dismutase (SOD) and glutathione-peroxidase (GPx) activities in the skin compared to those in the UV irradiated control group, while oral treatment of the mixture of PEA and PBT or PET elevated only catalase and SOD activities, but not GPx. Thirteen phytochemical compounds including 4-O-caffeoylquinic acid, cimicifugic acid E and B, quercetin-3-O-rhamnoside and kaempferol glycoside derivatives were identified in the PPF extract. CONCLUSIONS: These results demonstrate that treatment with PET or the mixture of PEA and PBT, both topically or orally, attenuates UV-induced photoaging via the cooperative interactions of phenolic components having anti-oxidative and collagen-protective activities.

Increased Expression of FosB through Reactive Oxygen Species Accumulation Functions as Pro-Apoptotic Protein in Piperlongumine Treated MCF7 Breast Cancer Cells

  • Park, Jin-Ah;Na, Han-Heom;Jin, Hyeon-Ok;Kim, Keun-Cheol
    • Molecules and Cells
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    • v.42 no.12
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    • pp.884-892
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    • 2019
  • Piperlongumine (PL), a natural alkaloid compound isolated from long pepper (Piper longum), can selectively kill cancer cells, but not normal cells, by accumulation of reactive oxygen species (ROS). The objective of this study was to investigate functional roles of expression of SETDB1 and FosB during PL treatment in MCF7 breast cancer cells. PL downregulates SETDB1 expression, and decreased SETDB1 expression enhanced caspase 9 dependent-PARP cleavage during PL-induced cell death. PL treatment generated ROS. ROS inhibitor NAC (N-acetyl cysteine) recovered SETDB1 expression decreased by PL. Decreased SETDB1 expression induced transcriptional activity of FosB during PL treatment. PARP cleavage and positive annexin V level were increased during PL treatment with FosB overexpression whereas PARP cleavage and positive annexin V level were decreased during PL treatment with siFosB transfection, implying that FosB might be a pro-apoptotic protein for induction of cell death in PL-treated MCF7 breast cancer cells. PL induced cell death in A549 lung cancer cells, but molecular changes involved in the induction of these cell deaths might be different. These results suggest that SETDB1 mediated FosB expression may induce cell death in PL-treated MCF7 breast cancer cells.

Effect of Conidial Number and Nutrition on the Germination of Conidia in Septoria glycines (분생포자수 및 영양상태가 대두갈색무늬병균의 분생포자 발아에 미치는 영향)

  • Oh Jeung Haing;Chung Hoo Sup
    • Korean journal of applied entomology
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    • v.23 no.1 s.58
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    • pp.61-67
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    • 1984
  • Conidial germination of Septoria glycines Hemmi, brown spot fungus of soybean, was studied by slide germination test. Poor conidial germination of S. glycines was observed on sterile distilled water, but potato dextrose agar(PDA) and distilled water floated with soybean leaf disc furnished a satisfactory medium for conidial germination. Exogenous supply of carbon source was essential for conidial germination, while phosphorous and potassium were not evident as that for carbon. Soluble starch was the most suitable as a carbon source for conidial germination and followed by D-glucose, D-galactose and lactose in that order. Maximum germination was attained in the $5\times10^{-2}mol$. concentration of glucose. Germination was decreased with increment of conidial concentration and was almost completely suppressed in the density of 10,000 conidia per $mm^2$. It suggested existing a self-inhibitor(s). Non-washed conidia germinated more than washed conidia and this was obvious when the conidia density was over $2\times10^3$ conidia per $mm^2$ on the dry agar block.

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