• 제목/요약/키워드: Wilms' tumor 1

검색결과 26건 처리시간 0.026초

Reactivation of Silenced WT1 Transgene by Hypomethylating Agents - Implications for in vitro Modeling of Chemoimmunotherapy

  • Kwon, Yong-Rim;Son, Min-Jung;Kim, Hye-Jung;Kim, Yoo-Jin
    • IMMUNE NETWORK
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    • 제12권2호
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    • pp.58-65
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    • 2012
  • Background: A cell line with transfected Wilms' tumor protein 1 (WT1) is has been used for the preclinical evaluation of novel treatment strategies of WT1 immunotherapy for leukemia due to the lack of appropriate murine leukemia cell line with endogenous WT1. However, silencing of the transgene occurs. Regarding the effects of hypomethylating agents (HMAs) on reactivation of silenced genes, HMAs are considered to be immune enhancers. Methods: We treated murine WT1- transfected C1498 (mWT1-C1498) with increasing doses of decitabine (DAC) and azacitidine (AZA) to analyze their effects on transgene reactivation. Results: DAC and AZA decreased the number of viable cells in a dose- or time-dependent manner. Quantification of WT1 mRNA level was analyzed by real-time polymerase chain reaction after mWT1-C1498 treated with increasing dose of HMA. DAC treatment for 48 h induced 1.4-, 14.6-, and 15.5-fold increment of WT1 mRNA level, compared to untreated sample, at 0.1, 1, and $10{\mu}M$, respectively. Further increment of WT1 expression in the presence of 1 and $10{\mu}M$ DAC was evident at 72 h. AZA treatment also induced up-regulation of mRNA, but not to the same degree as with DAC treatment. The correlation between the incremental increases in WT1 mRNA by DAC was confirmed by Western blot and concomitant down-regulation of WT1 promoter methylation was revealed. Conclusion: The in vitro data show that HMA can induce reactivation of WT1 transgene and that DAC is more effective, at least in mWT1-C1498 cells, which suggests that the combination of DAC and mWT1-C1498 can be used for the development of the experimental model of HMA-combined WT1 immunotherapy targeting leukemia.

WT1 유전자 돌연변이에 의해 선천성 가로막 탈장이 동반되고 조기 신부전이 초래된 선천성 신증후군 1례 (Early Onset Renal Failure in Congenital Nephrotic Syndrome associated with Congenital Diaphragmatic Hernia by WT1 Gene Mutation)

  • 박용준;오진원;최경민;김병길;이종인;송지선
    • Childhood Kidney Diseases
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    • 제13권1호
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    • pp.84-91
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    • 2009
  • 저자들은 선천성 가로막 탈장을 동반한 선천성 신증후군 신생아에서 WT1 유전자 돌연변이와 범발성맥관막 경화증으로 진단하였기에 문헌 고찰과 함께 보고하는 바이다. 본 여아는 출생 직후 선천성 가로막 탈장이 발견되어 응급 교정수술을 받았고 전신부종, 핍뇨, 단백뇨, 저알부민혈증, 고뇨소질소혈증, 고크레아티닌혈증이 지속되어 선천성 신증후군에 의한 조기 신부전으로 진단되었다. 생후 22일째부터 복막투석 시작하였으나 뇌출혈과 다기관부전으로 생후 34일째 사망하였다. 사후 신생검에서 범발성 맥관막 경화증으로 확인되었다. 염색체 검사에서 정상소견(46,XX) 보였고 사후 유전자 검사에서 Arg366Hisin WT1 과오 돌연변이를 보였다. 본 예는 선천성 신증후군에 선천성 가로막 탈장이 동반된 드문 예로 WT1 유전자의 Arg366His 과오 돌연변이가 DDS와 CDH의 발생에 병인으로 관여할 것이라는 가설을 지지하는 4번째 증례라는 점에서 중요한 의미가 있다.

Inhibitory Effect of Curcumin on WT1 Gene Expression in Patient Leukemic Cells

  • Anuchapreeda, Songyot;Limtrakul, Pornngarm;Thanarattanakorn, Pattra;Sittipreechacharn, Somjai;Chanarat, Prasit
    • Archives of Pharmacal Research
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    • 제29권1호
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    • pp.80-87
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    • 2006
  • Leukemias are common worldwide. Wilms'tumor1 (WT1) protein is highly expressed in leukemic blast cells of myeloid and lymphoid origin. Thus, WT1 mRNA serves as a tumor marker for leukemias detection and monitoring disease progression. Curcumin is well known for its anticancer property. The objective of this study was to investigate the effect of curcumin on WT1 gene expression in patient leukemic cells. The leukemic cells were collected from 70 childhood leukemia patients admitted at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand, in the period July 2003 to February 2005. There were 58 cases of acute lymphoblastic leukemia (ALL), 10 cases of acute myeloblastic leukemia (AML), and 2 cases of chronic myelocytic leukemia (CML). There were 41 males and 29 females ranging from 1 to 15 years old. Leukemic cells were cultured in the presence or absence of 10 mM curcumin for 48 h. WT1 mRNA levels were determined by RT-PCR. The result showed that curcumin reduced WT1 gene expression in the cells from 35 patients (50%). It affected the WT1 gene expression in 4 of 8 relapsed cases (50%), 12 of 24 cases of drug maintenance (50%), 7 of 16 cases of completed treatment (44%), and 12 of 22 cases of new patients (54%). The basal expression levels of WT1 gene in leukemic patient cells as compared to that of K562 cells were classified as low level (1-20%) in 6 of 20 cases (30%), medium level (21-60%) in 12 of 21 cases (57%), and high level (61-100%) in 17 of 23 cases (74%). In summary, curcumin decreased WT1 mRNA in patient leukemic cells. Thus, curcumin treatment may provide a lead for clinical treatment in leukemic patients in the future.

The Significance of N6-Methyladenosine RNA Methylation in Regulating the Hepatitis B Virus Life Cycle

  • Jae-Su Moon;Wooseong Lee;Yong-Hee Cho;Yonghyo Kim;Geon-Woo Kim
    • Journal of Microbiology and Biotechnology
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    • 제34권2호
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    • pp.233-239
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    • 2024
  • N6-methyladenosine (m6A) RNA methylation has recently emerged as a significant co-transcriptional modification involved in regulating various RNA functions. It plays a vital function in numerous biological processes. Enzymes referred to as m6A methyltransferases, such as the methyltransferase-like (METTL) 3-METTL14-Wilms tumor 1 (WT1)-associated protein (WTAP) complex, are responsible for adding m6A modifications, while m6A demethylases, including fat mass and obesity-associated protein (FTO) and alkB homolog 5 (ALKBH5), can remove m6A methylation. The functions of m6A-methylated RNA are regulated through the recognition and interaction of m6A reader proteins. Recent research has shown that m6A methylation takes place at multiple sites within hepatitis B virus (HBV) RNAs, and the location of these modifications can differentially impact the HBV infection. The addition of m6A modifications to HBV RNA can influence its stability and translation, thereby affecting viral replication and pathogenesis. Furthermore, HBV infection can also alter the m6A modification pattern of host RNA, indicating the virus's ability to manipulate host cellular processes, including m6A modification. This manipulation aids in establishing chronic infection, promoting liver disease, and contributing to pathogenesis. A comprehensive understanding of the functional roles of m6A modification during HBV infection is crucial for developing innovative approaches to combat HBV-mediated liver disease. In this review, we explore the functions of m6A modification in HBV replication and its impact on the development of liver disease.

소아복부 종괴의 방사선학적 고찰 (Radiologic Evaluation of Intraabdomenal Masses in Childhood)

  • 권혁포;변우목;황미수;김선용;장재천;박복환
    • Journal of Yeungnam Medical Science
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    • 제5권1호
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    • pp.33-42
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    • 1988
  • 최근 5년간의 소아의 복부종괴 23예를 발생빈도, 부위 및 방사선학적 소견을 중심으로 비교분석하여 다음과 같은 결론을 얻었다. 1. 전체 23예중 신경아세포종이 6예로 가장 많았고 그 다음이 Wilms 종양 5예, 담도낭종, 난소종양, 수신종 등의 순위였다. 2. 발생연령별로 분석해 본 결과 6세 이하가 78%(14예)를 차지했고 특히 후복강 종양은 6세 이하에 집중되어 있었다. 3. 부위별로는 후복강 종양이 60%(14예)로 가장 많았다. 4. 방사선학적 소견을 분석하여 본 결과 1) 단순 복부촬영상 신경아세포종의 50%에서 특징적인 석회와 음영을 볼 수 있었고 후복강 종양의 대부분에서 비특이적인 석회화 음영을 볼 수 있었다. 2) 초음파 소견상 저에코, 고에코 또는 혼합에코 등의 종괴 내부성상을 알 수 있었으나 종괴의 정확한 해부학적 위치를 파악할 수 없는 경우가 많았다. 3) 경정맥 신우 조영촬영상 신우신배의 비정상적인 소견과 신장의 전위 소견으로부터 신장내 종양과 신장의 다른 부위의 종양을 구분할 수 있었다. 4) 전산화 단층촬영상 종괴 내부의 성상뿐만 아니라 종괴의 해부학적인 위치, 주위 구조와의 관계, 임파절이나 다른 부위로의 전이유무를 알 수 있었다.

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