• 제목/요약/키워드: Hydroxyurea (HU)

검색결과 14건 처리시간 0.028초

만성 골수성 백혈병에 대한 유전자 재조합 인터페론 α-2a와 hydroxyurea의 항암효과 (Antitumor effects of recombinant human interferon α-2a and hydroxyurea against chronic myelogenous leukemia)

  • 김창환;이범준;박종환;박재학
    • 대한수의학회지
    • /
    • 제40권1호
    • /
    • pp.166-172
    • /
    • 2000
  • Prior to a clinical trial, the in vitro and in vivo antitumor effects of a new recombinant human interferon ${\alpha}-2a$ (rHu/IFN ${\alpha}-2a$) with/without hydroxyurea (HU) were investigated using chronic myelogenous leukemia (CML)-derived cell lines (K562 and KU812F) and BALB/c nude. mice transplanted with KU812F cells. The rHu/IFN ${\alpha}-2a$ ($10^4-10^6IU/ml$) strongly inhibited proliferation of both cell lines and the combined treatments with HU ($10{\mu}g/ml$) were more effective. In nude mice transplanted with KU812F cells. rHu/IFN ${\alpha}-2a(1{\times}10^6IU$) inhibited tumor growth by 42-65% at 15-21 days post-transplantation (DPT). The combined treatment of rHu/IFN ${\alpha}-2a (5{\times}10^5IU$) with HU (0.25mg/g b.w.) inhibited the tumor growth by 48-67% at 12-21 DPT. In addition, the treatment of rHu/IFN ${\alpha}-2a$ ($5{\times}10^6IU\;or\;1{\times}10^7IU$) rejected tumor transplantation by 40%. These results suggest that the new rHU/IFN ${\alpha}-2a$ alone or with HU is effective on CML cell lines.

  • PDF

Clinical management of suspected intracranial meningioma in three dogs with pulsed high-dose hydroxyurea

  • Cho, Jae-Geum;Song, Kun-Ho;Seo, Kyoung-Won
    • 대한수의학회지
    • /
    • 제58권2호
    • /
    • pp.103-106
    • /
    • 2018
  • Three aged dogs, all over 15 years old, with multiple seizure events and various neurologic signs such as head turn and ataxia were brought to the referring hospital. Two cases were tentatively diagnosed with intracranial meningioma based on magnetic resonance imaging, and one case was histopathologically confirmed as meningioma at necropsy. All dogs improved after initiation of pulsed high-dose hydroxyurea (HU) treatment. Clinical sign relapses were managed by repeating high-dose HU without obvious side effects. Pulsed high-dose HU can be applied when clinical signs are refractory to the traditionally recommended dosage for intracranial meningioma in dogs.

DNA 회복 저해제 Cytosine Arabinoside, 3-Aminobenzamide 및 Hydroxyurea가 방사선에 의해 유도된 소핵과 이수성에 미치는 영향 (Effect of Cytosine Arabinoside, 3-Aminobenzamide and Hydroxyurea on the frequencies of radiation-induced micronuclei and aneuploidy in human lymphocytes)

  • 조윤희;김양지;강창모;하성환;정해원
    • Journal of Radiation Protection and Research
    • /
    • 제30권4호
    • /
    • pp.209-219
    • /
    • 2005
  • 소핵분석은 방사선의 생물학적 선량계로서 활용되고 있으나 이의 생성 기전은 아직까지 확실치 않다. 본 연구에서는 사람 림프구에 방사선을 조사한 후 DNA 손상회복 저해물질, Cytosine Arabinoside(Ara C)와 3-Aminobenzamide(3-AB) 그리고 Hydroxyurea(HU)를 특정 세포주기에 처리하고 소핵분석과 FISH기법을 이용하여 방사선에 의한 소핵 및 이수성의 정도를 구명하고자 하였다. 방사선 선량에 따라 소핵과 이수성의 빈도는 양반응 관계를 보이며 증가하였고 DNA 손상회복 저해물질 처리 후 소핵의 빈도는 모든 DNA 손상 회복 저해물질에 의해 증가하였으며 Ara C, 3AB, HU 순으로 나타났다. 이수성의 빈도는 HU와 Ara C에 의해서 크게 증가하였으나, 3AB는 아무런 영향을 주지 않았다. 또한 1번 염색체가 4번 염색체보다 방사선에 의한 소핵형성 및 이수성에 더 많이 관여되었다. 본 연구 결과, 방사선에 의한 소핵 및 이수성의 형성 과정은 여러 다른 기전이 관여하고 있음을 알 수 있었다.

Knock-down of human MutY homolog (hMYH) decreases phosphorylation of checkpoint kinase 1 (Chk1) induced by hydroxyurea and UV treatment

  • Hahm, Soo-Hyun;Park, Jong-Hwa;Ko, Sung-Il;Lee, You-Ri;Chung, In-Sik;Chung, Ji-Hyung;Kang, Lin-Woo;Han, Ye-Sun
    • BMB Reports
    • /
    • 제44권5호
    • /
    • pp.352-357
    • /
    • 2011
  • The effect of human MutY homolog (hMYH) on the activation of checkpoint proteins in response to hydroxyurea (HU) and ultraviolet (UV) treatment was investigated in hMYH-disrupted HEK293 cells. hMYH-disrupted cells decreased the phosphorylation of Chk1 upon HU or UV treatment and increased the phosphorylation of Cdk2 and the amount of Cdc25A, but not Cdc25C. In siMYH-transfected cells, the increased rate of phosphorylated Chk1 upon HU or UV treatment was lower than that in siGFP-transfected cells, meaning that hMYH was involved in the activation mechanism of Chk1 upon DNA damage. The phosphorylation of ataxia telangiectasia and Rad3-related protein (ATR) upon HU or UV treatment was decreased in hMYH-disrupted HEK293 and HaCaT cells. Co-immunoprecipitation experiments showed that hMYH was immunoprecipitated by anti-ATR. These results suggest that hMYH may interact with ATR and function as a mediator of Chk1 phosphorylation in response to DNA damage.

Radiation stability and radiolysis mechanism of hydroxyurea in HNO3 solution: Alpha, beta, and gamma irradiations

  • Yilin Qin;Wei Liao;Tu Lan;Fengzhen Li;Feize Li;Jijun Yang;Jiali Liao;Yuanyou Yang;Ning Liu
    • Nuclear Engineering and Technology
    • /
    • 제54권12호
    • /
    • pp.4660-4670
    • /
    • 2022
  • Hydroxyurea (HU) is a novel salt-free reductant used potentially for the separation of U/Pu in the advanced PUREX process. In this work, the radiation stability of HU were systematically investigated in solution by examining the effects of the type of rays (α, β, and γ irradiations), the absorbed dose (10-50 kGy), and the HNO3 concentration (0-3 mol L-1). The influence degree on HU radiolysis rates followed the order of the absorbed dose > the ray type > the HNO3 concentration, but the latter two had moderate effects on HU radiolysis products where NH4+ and NO2- were found to be the most abundant ones, suggesting that the differences of α, β, and γ rays should be considered in the study of irradiation effects. The radiolysis mechanism was explored using density functional theory (DFT) calculations, and it proposed the dominant radiolysis paths of HU, indicating that the radiolysis of HU was mainly a free radical reaction among ·H, eaq-, H2O, intermediates, and the radiolytic free radical fragments of HU. The results reported here provide valuable insights into the mechanistic understanding of HU radiolysis under α, β, and γ irradiations and reliable data support for the application of HU in the reprocessing of spent fuel.

Partial Mitotic Synchronization and Giemsa G-banding in Allium wakegi

  • Bong Bo Seo
    • Journal of Plant Biology
    • /
    • 제38권1호
    • /
    • pp.33-38
    • /
    • 1995
  • Hydroxyurea (HU), a DNA synthesis inhibitor, was tested as synchronizing agent in root-tip meristem of Allium wakegi. Roots were treated with 2.5mM HU for 14 h to accumulate meristem root-tip cells at the G1/S interface. After release from HU block, the cells re-entered the cell cycle with a high degree of synchrony. Synchronized mitotic frequency of A. wakegi was 22.7%, which was about 3.9 times as high as that of the control. The highest metaphase index(23.0%) was obtained when, 6 h after release from the HU block, the roots were treated with 0.05% colchicine for 2 h. Modifying various Giemsa staining protocols defined for animals and a few plant species, G-bands were visualized at prometaphase and metaphase chromosomes of A. wakegi. The higher degree of chromosome condensation, the less differential bands could be resolved. This is the first demonstration introduced partial mitotic synchronization into G-banding in plant.

  • PDF

Schizosaccbarornyces pombe에서 Escherichia coli RecA 항체에 의한 Ribonucleotide Reductase 효소활성 저해 (Ribonucleotide Reductase Activity of Schizosaccbarornyces pombe Is Inhibited by Escherichia coli RecA Antibody)

  • 이정섭;천민석;김옥봉;박종군;김시욱;박열;양영기;홍승환;박상대
    • 한국동물학회지
    • /
    • 제38권4호
    • /
    • pp.565-569
    • /
    • 1995
  • 분열형 호모인 Schizosaccbarornyces pombe에서 RecA 유사 단백질은 hydroxyurea (HU)나 methotrexate (MTX)와 같은 nucleotide pool 형성에 관여하는 효소의 저해제에 의해 유도발현된다. 본 연구에서는 대장균의 RecA 단백질과 S. pombe의 ribonucleotide reductase가 구조적으로 유사한지를 RecA 항체를 이용한 면역침전법과 [5-$^3$H]CDP를 기질로하는 thin layerchromatography방법을 통하여 알아보고자 하였다. S. pombe의 rinonucleotide reductase활성은 100mM HU에 의해 대조군에 비해 26.3% 저해되었으며, RecA 항체를 이용한 면역침전에 의해서도 43.3% 저해되었다. 이와 같은 결과는 S. pombe의 rinonucleotide reductase가 대장균의 RecA 단백질과 구조적으로 유사함을 시사하는 것이다.

  • PDF

Expression of Sara2 Human Gene in Erythroid Progenitors

  • Jardim, Denis Leonardo Fontes;Cunha, Anderson Ferreira Da;Duarte, Adriana Da Silva Santos;Santos, Camila Oresco Dos;Saad, Sara Terezinha Olalla;Costa, Fernando Ferreira
    • BMB Reports
    • /
    • 제38권3호
    • /
    • pp.328-333
    • /
    • 2005
  • A human homologue of Sar1, named Sara2, was shown to be preferentially expressed during erythropoiesis in a culture stimulated by EPO. Previous studies, in yeast, have shown that secretion-associated and Ras-related protein (Sar1p) plays an essential role in protein transport from the endoplasmic reticulum to the Golgi apparatus. Here, we report the molecular analysis of Sara2 in erythroid cell culture. A 1250 bp long cDNA, encoding a 198 amino-acid protein very similar to Sar1 proteins from other organisms, was obtained. Furthermore, we also report a functional study of Sara2 with Real-time quantitative PCR analysis, demonstrating that expression of Sara2 mRNA increases during the initial stages of erythroid differentiation with EPO and that a two-fold increase in expression occurs following the addition of hydroxyurea (HU). In K562 cells, Sara2 mRNA was observed to have a constant expression and the addition of HU also up-regulated the expression in these cells. Our results suggest that Sara2 is an important gene in processes involving proliferation and differentiation and could be valuable for understanding the vesicular transport system during erythropoiesis.

Treatment and Survival in Patients with Chronic Myeloid Leukemia in a Chronic Phase in West Iran

  • Payandeh, Mehrdad;Sadeghi, Masoud;Sadeghi, Edris
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제16권17호
    • /
    • pp.7555-7559
    • /
    • 2015
  • Background: CML includes 30% of all leukemias, and occurs from childhood to old age. The present study was a retrospective analysis of chronic phase CML patients registered to a Hematology Clinic in Kermanshah, Iran, with checking of treatment options. Materials and Methods: Between 2002 and 2014, 85 CML patients referred to our hematology clinic were enrolled in our study. We surveyed age, sex, B-symptoms, splenomegaly, Sokal score, Hasford score, treatment and survival in all patients. Philadelphia chromosome analysis was conducted for each patient by conventional cytogenetics. We compared treatment in the patients with three drugs, imatinib, hydroxyurea (HU) and interferon alpha (IFN-${\alpha}$). Results: The mean age of the patients at diagnosis was $47.5{\pm}14.5years$ (range, 23-82 years), with 43 (50.6%) being male. Some 13 (15.3%) were referred to our clinic for the first time with B-symptoms and 44 patients (51.8%) had splenomegaly. The Sokal score for 77 (90.6%) was low, 4 (4.7%) was intermediate and 4(4.7%) was high, but Hasford (Euro) scores for all patients were low. The 5-year survival rate for treated patients with imatinib, imatinib plus HU and imatinib plus HU plus IFN-${\alpha}$ was 90.5%, 81.1% and 55.6%, respectively Conclusions: The results show that imatinib therapy alone provides better survival in CML patients compared to HU or IFN-${\alpha}$. Combinations of IFN-${\alpha}$ and/or HU with imatinib probably reduce survival.

분열형 효모인 Schizosaccharomyces pombe 로부터 rqh1 돌연변이의 DNA damaging agent sensitivity를 보상하는 유전자의 특성 연구 (Isolation and Characterization of DNA Damaging Agent Sensitivity of rqh1 mutant from Schizosaccharomyce pombe)

  • 이인혜;최인순
    • 생명과학회지
    • /
    • 제17권1호
    • /
    • pp.39-44
    • /
    • 2007
  • 분열형 효모에서 Rqh1은 Top3과 함께 vegetative growth에 필수적이다. $rqh^-$ 돌연변이는 DNA damaging agent에 민감성을 보이는데 이때, 부적절한 유전자 발현, 세포 신장, 염색체의 불안전성, 비정상적인 다중격막, 발아의 결핍을 포함한 넓은 범위의 표현형을 보인다. rqh1-overexpression cell 역시 rqh1 deletion mutant에서 보이는 DNA damaging agent 민감성을 관찰할 수 있다. 논문은 nmtl promoter를 가지는 PREP vector에 Rqhl이 과발현 할 때 나타나는 DNA damaging agent 민감성를 보상하는 유전자를 찾아 $rqh1^+$의 기능을 알아보는 것이다. 여기서 보상능이 보이는 rqh156, rqh172 두 개의 돌연변이를 골라냈다. rqhl deletion mutant의 DNA damaging agent 민감성은 rqh156, rqh172의 발현에 의해 보상 되어지는 것을 확인하였다.