• Title/Summary/Keyword: 방사선유전자

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Synergistic Effects of 5-Fluorouracil (FU) and Curcumin on Human Cervical Cancer Cells (5-fluorouracil과 curcumin의 복합투여에 의한 자궁암세포의 성장억제와 p53유전자 발현의 상승 효과)

  • Ahn, Seong-Ho;Kim, Dong-Heui;Kang, Jung-Hoon;Lee, Myeong-Seon
    • Applied Microscopy
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    • v.40 no.4
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    • pp.229-235
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    • 2010
  • Cervical cancer is associated with low antioxidant status. It has a high prevalence especially amongst woman in Asia and is a leading cause of cancer death. Cancer chemotherapy in vivo improved in cases with high p53 expression in the tumor tissue. The restoration of p53 levels could be a potential strategy to increase chemoresponsiveness. Under circumstances where damage is extensive, p53 plays a direct role in trigering apoptosis. To investigate the effect of curcumin (CMN) as an antioxidant agent on anticancer agent 5-fluorouracil (5FU) induced apoptosis and p53 expression, HPV-18 positive HeLa cells were treated with noncytotoxic amounts of antioxidant. Curcumin induced apoptosis in cervical cancer cells. Morphological hallmarks of apoptosis such as nuclear fragmentation and internucleosomal fragmentation of DNA were observed. CMN caused upregulation of p53 expression, evident from Western blotting data and also increased the susceptibility/apoptosis induced by 5FU. These results show that increasing drug sensitivity of cervical cancer cells by upregulation of p53 using CMN is novel approach and could have a possible therapeutic potential in cervical cancer.

Oncolytic Viruses - A New Era for Cancer Therapy (종양 용해성 바이러스-암 치료에서의 새 시대)

  • Ngabire, Daniel;Niyonizigiye, Irvine;Kang, Min-jae;Kim, Gun-Do
    • Journal of Life Science
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    • v.29 no.7
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    • pp.824-835
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    • 2019
  • In recent decades, oncolytic viruses (OVs) have extensively been investigated as a potential cancer drug. Oncolytic viruses have primarily the unique advantage in the fact that they can only infect and destroy cancer cells. Secondary, oncolytic viruses induce the activation of specific adaptive immunity which targets tumor-associated antigens that were hidden during the initial cancer progression. In 2015, one genetically modified oncolytic virus, talimogene laherparepvec (T-VEC), was approved by the American Food and Drug Administration (FDA) for the treatment of melanoma. Currently, various oncolytic viruses are being investigated in clinical trials as monotherapy or in combination with preexistent cancer therapies like immunotherapy, radiotherapy or chemotherapy. The efficacy of oncolytic virotherapy relies on the balance between the induced anti-tumor immunity and the anti-viral response. Despite the revolutionary outcome, the development of oncolytic viruses for the treatment of cancer faces a number of obstacles such as delivery method, neutralizing antibodies and induction of antiviral immunity due to the complexity, variability and reactivity of tumors. Intratumoral administration has been successful reducing considerably solid tumors with no notable side effects unfortunately some tumors are not accessible (brain) and require a systemic administration of the oncolytic viruses. In order to overcome these hurdles, various strategies to enhance the efficacy of oncolytic viruses have been developed which include the insertion of transgenes or combination with immune-modulatory substances.

Cell-type-specific Gene Expression Patterns in Human Carcinoma Cells followed by Irradiation (방사선에 의한 암세포주 특이적 유전자 발현 양상)

  • Park Ji-Yoon;Kim Jin-Kyu;Chai Young Gyu
    • Korean Journal of Environmental Biology
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    • v.23 no.2 s.58
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    • pp.152-156
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    • 2005
  • Ionizing radiation is a well- known therapy factor for human carcinoma cells. Genotoxic stress mediates cell cycle control, transcription and cellular signaling. In this work, we have used a microarray hybridization approach to characterize the cell type-specific transcriptional response of human carcinoma MCF-7 and HeLa cell line to $\gamma-radiation$, such as 4Gy 4hr. We found that exposure to $\gamma-ray$ alters by at least a $log_2$ factor of 1.0 the expression of known genes. Of the 27 genes affected by irradiation, 11 are down- regulated in MCF-7 cells and 2 genes induced by radiation,15 are repressed in HeLa cells. Many genes were involved in known damage- response pathways for cell cycling, transcription factor and cellular signaling response. However, in MCF-7 cells, we observed gene expression pattern in chromatin, apoptosis, stress, differentiation, cytokine, metabolism, ribosome and calcium. In HeLa cells, it showed clearly the expression changes in adhesion and migration, lysosome, brain, genome instability and translation. These insights reveal new therapy directions for studying the human carcinoma cell response to radiation.

Ceruloplasmin Gene Expression in U-937 Cells exposed to ${\gamma}$-Irradiation and $H_2$O_2 (U-937 세포에서 방사선 및 $H_2$O_2$에 의한 ceruloplasmin의 mRNA 유전자 발현)

  • 오연경;박선영;김인규;윤병수
    • Environmental Mutagens and Carcinogens
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    • v.22 no.2
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    • pp.76-82
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    • 2002
  • In human U-937 cell exposed to ${\gamma}$-irradiation and $H_2O$$_2$, the level of mRNA efrpression in ceruloplasmin gene was measured by using comparative RT.PCR (reverse transcriptase-polymerase chain reaction). At the normal growth condition, the level of ceruloplasmin transcript was estimated as 8.2% and 0.0068% of hprt (hypoxantine phosphoribosyl transferase) transcript and of $\beta$-actin transcript, respectively. In U-937 cells exposed to a dose of 100 rad ${\gamma}$-irradiation, the level of ceruloplasmin transcript was increased about 2.7 and 1.6 fold compared to un-treated cell by using compensation with the levels of hprt and $\beta$-actin transcript. By contrast, the expression of ceruloplasmin gene in U-937 cells exposed to $H_2O$$_2$(50 $\mu$M, 24 h), was shown no significant difference compared to un-treated cell. These results indicated that the expression system of ceruloplasmin gene may react only some specific oxygen species, such as reactive oxygen species induced by ${\gamma}$-irradiation.

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The mRNA Expression of Radio-Sensitive Genes Exposed to Various Dosage of Ionizing Radiation in U-937 Cell (U-937 세포에서 이온화 방사선의 조사선량에 따른 감수성 유전자들의 발현 변화)

  • 김종수;임희영;오연경;김인규;강경선;윤병수
    • Toxicological Research
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    • v.20 no.1
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    • pp.21-29
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    • 2004
  • We used cDNA microarray to assess gene expression profiles in hematopoetic cell line, U-937, exposed to low doses of ionizing irradiation. The 1,000 DNA elements on this array were PCR-amplified cDNAs selected from named human cancer related genes. According to the strength of irradiation, the levels of some gene expression were increased or decreased as dose-dependent manner. The gene expressions of Tubulin alpha, protein kinase, interferon-alpha, -beta, -omega receptor and ras homolog gene family H were significantly increased. Especially, Tubulin gene was shown 2.5 fold up-regulated manner under stress of 500 rad irradiation than 200 rad. On the other hand, fibroblast growth factor 12 and four and a half LIM domains, etc. were significantly down-regu-lated. Also, tumor protein 53(TP53) related genes that p53 inducible protein, tumor protein 53-binding protein looks of little significance as radiation sensitive manner. The radio-sensitivity of tubulin gene etc. that we proposed could be useful to rapid and correct survey for the bio-damage by exposure to low dose irradiation.

Enhancement Alogorithm of Portal Image using Neuo-Fuzzy (뉴로 퍼지를 이용한 포탈 영상의 개선 알고리듬의 연구)

  • 허수진;신동익
    • Journal of Biomedical Engineering Research
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    • v.21 no.5
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    • pp.527-535
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    • 2000
  • For a reliable patient set-up verification, better portal films are needed to track relevant features. Simulator films are compared with portal films as a reference image in radiotherapy planning. This shows some possibilities of the use of image information of simulator images for enhancement and restorations of portal images which are very poor in quality compared with the simulator images. This paper present an approach that combine an associative memory, a kind of artificial neural networks with fuzzy image enhancement technique using genetic algorithm which determines the fuzzy region of membership function by the use of maximum entropy principles. A higher portal image quality than conventional technique is achieved.

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Characteristics of Xylan Degradation and HPLC Analysis of Hydrolyzed Xylans by Deinococcus geothermalis (Deinococcus geothermalis의 Xylan 최적 분해조건 및 분해산물 분석)

  • Im, Seong-Hun;Joe, Min-Ho;Jung, Sun-Wook;Lim, Sang-Yong;Song, Hyun-Pa;Kim, Dong-Ho
    • Korean Journal of Microbiology
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    • v.46 no.3
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    • pp.308-312
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    • 2010
  • Deinococcus geothermalis is a moderate thermophillic radiation resistant bacterium producing greater abundance of sugar metabolism enzymes than other Deinococcus species. In this study, optimal condition for xylanolytic activity of D. geothermalis was determined and xylooligosaccharides from oat spelt, beechwood, and birchwood xylan hydrolysates by this organism were analyzed through HPLC. Reducing sugar yield was increased in the order of beechwood, birchwood, and oat spelt xylan. D. geothermalis displayed maximal xylanolytic activity at $40^{\circ}C$ and pH 8.0. Magnesium ion increased xylanolytic activity upto 7.5 fold. Six kinds of xylooligosaccharides (xylose, xylobios, xylotriose, xylotetraose, xylopentaose, and xylohexalose) were detected from beechwood and birchwood xylan reaction products. Among them, xylose was the major product. However, only three kinds of xylooligosaccharides (xylose, xylopentaose, and xylohexalose) were clearly detected from oat spelt xylan. Gamma-ray (50 kGy) treatment of beechwood xylan, birchwood xylan and oat spelt xylan increased xylanolytic activity of D. geothermalis. The results indicate that D. geothermalis and pretreatment of radiation is useful for xylooligosaccharides production.

The Clinicopathological Factors That Determine a Local Recurrence of Rectal Cancers That Have Been Treated with Surgery and Chemoradiotherapy (직장암의 수술 후 방사선 치료 시 국소 재발의 임상 병리적 예후 인자)

  • Choi, Chul-Won;Kim, Min-Suk;Lee, Seung-Sook;Yoo, Seong-Yul;Cho, Chul-Koo;Yang, Kwang-Mo;Yoo, Hyung-Jun;Seo, Young-Seok;Hwang, Dae-Yong;Moon, Sun-Mi;Kim, Mi-Sook
    • Radiation Oncology Journal
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    • v.24 no.4
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    • pp.255-262
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    • 2006
  • $\underline{Purpose}$: To evaluate the pathological prognostic factors related to local recurrence after radical surgery and adjuvant radiation therapy in advanced rectal cancer. $\underline{Materials\;and\;Methods}$: Fifty-four patients with advanced rectal cancer who were treated with radical surgery followed by adjuvant radiotherapy and chemotherapy between February 1993 and December 2001 were enrolled in this study. Among these patients, 14 patients experienced local recurrence. Tissue specimens of the patients were obtained to determine pathologic parameters such as histological grade, depth of invasion, venous invasion, lymphatic invasion, neural invasion and immunohistopathological analysis for expression of p53, Ki-67, c-erb, ezrin, c-met, phosphorylated S6 kinase, S100A4, and HIF-1 alpha. The correlation of these parameters with the tumor response to radiotherapy was statistically analyzed using the chi-square test, multivariate analysis, and the hierarchical clustering method. $\underline{Results}$: In univariate analysis, the histological tumor grade, venous invasion, invasion depth of the tumor and the over expression of c-met and HIF-1 alpha were accompanied with radioresistance that was found to be statistically significant. In multivariate analysis, venous invasion, invasion depth of tumor and over expression of c-met were also accompanied with radioresistance that was found to be statistically significant. By analysis with hierarchical clustering, the invasion depth of the tumor, and the over expression of c-met and HIF-1 alpha were factors found to be related to local recurrence. Whereas 71.4% of patients with local recurrence had 2 or more these factors, only 27.5% of patients without local recurrence had 2 or more of these factors. $\underline{Conclusion}$: In advanced rectal cancer patients treated by radical surgery and adjuvant chemo-radiation therapy, the poor prognostic factors found to be related to local recurrence were HIF-1 alpha positive, c-met positive, and an invasion depth more than 5.5 mm. A prospective study is necessary to confirm whether these factors would be useful clinical parameters to measure and predict a radio-resistance group of patients.

Human Surfactant Protein-A(SP-A) Gene Locus Associated with Mycoplasma pneumoniae Pneumonia in Korean Children (Mycoplasma pneumoniae 폐렴과 관련된 폐 표면 활성제 단백-A(Human Surfactant Protein-A) 유전자 대립 형질)

  • Kim, Seung Soo;Lee, In Kyu;Ko, Jung Ho;Oh, Myung Ho;Bae, Chong Woo
    • Clinical and Experimental Pediatrics
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    • v.48 no.4
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    • pp.376-379
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    • 2005
  • Purpose : Mycoplasama pneumoniae is a leading cause of pneumonia and exacerbates other respiratory conditions such as asthma. Surfactant protein A(SP-A) is involved in surfactant physiology and surfactant structure, and plays a major role in innate host defense and inflammatory processes in the lung. In this study, SP-A mediated mycoplasma cidal activity. The candidate-gene approach was used to study the association between the SP-A gene locus and Mycoplasama pneumoniae pneumonia in the genetically homogeneous Korean population. Methods : PCR-cRFLP-based methodology was used to detect SP-A genotype. The forty nine children with Mycoplasama pneumoniae pneumonia were matched to 50 nomal neonates. Results : The specific frequencies for the alleles of the SP-A1 and SP-A2 gene in the study population were : $6A^2=21$ percent, $6A^3=45$ percent, $6A^4=11$ percent, $6A^8=9$ percent, $6A^{14}=8$ percent, 1A=11.3 percent, $1A^0=38$ percent, $1A^1=12.7$ percent, $1A^2=9.2$ percent, $1A^5=15.5$ percent, $1A^7=2.9$ percent, $1A^8=4.9$ percent, $1A^9=2.2$ percent, others=3.3 percent. The frequencies of specific genotypes such as $1A^2$ was higher than control group, significantly. Conclusion : $1A^2$ are susceptible factors for Mycoplasama pneumoniae pneumonia. We conclude that the SP-A gene locus($1A^2$) is an important determinant for predisposition to Mycoplasama pneumoniae pneumonia in children.

A case of Hyper-IgE syndrome with a mutation of the STAT3 gene (STAT3유전자 돌연변이 검사로 확진된 고면역글로불린E 증후군 1례)

  • Kang, Ji-Man;Suh, Jung-Min;Kim, Ji-Hyun;Kim, Hee-Jin;Kim, Yae-Jean;Lee, Hun-Seok;Shin, Young-Kee;Ahn, Kang-Mo;Lee, Sang-Il
    • Clinical and Experimental Pediatrics
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    • v.53 no.4
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    • pp.592-597
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    • 2010
  • Hyperimmunoglobulin E syndrome (HIES) is a rare immunodeficiency disease which is characterized by high serum IgE levels, eczema, and recurrent infections. Herein we present the case of a patient with HIES associated with STAT3 gene ($stat3$) mutation. A 16 year-old girl was admitted to our hospital due to hemoptysis caused by pneumonia with bronchiectasis. She had a history of recurrent skin and respiratory tract infections, such as pneumonia caused by MRSA (methicillin-resistant $Staphylococcus$ $aureus$) and $Pseudomonas$ $aeruginosa$. On physical examination, a broad round shaped nose, oral thrush, and chronic eczematous skin rash over her whole body were found. Laboratory data showed an elevated eosinophil count ($750/{\mu}L$) and total IgE level (5,001 U/mL). The patient's National Institutes of Health (NIH) score for HIES was 44. Direct sequencing of the STAT3 gene revealed that the patient was heterozygous for a missense mutation in the DNA binding domain of the STAT3 protein (c.1144C>T, p. Arg382Trp). HIES should be suspected in patients with recurrent infections and can be confirmed by clinical scoring and genetic analysis.