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진행성 비호지킨 림프종 환자에서 ICE 구제 요법에 의한 조혈모세포 가동화 후 자가 말초혈액 조혈모세포이식
이제중,이병환,김여경,변정래,이일권,박무림,정익주,김형준 대한조혈모세포이식학회 2003 대한조혈모세포이식학회지 Vol.8 No.1
연구배경: 비호지킨 림프종에서 자가 말초혈액 조혈모세포이식술이 폭넓게 이용됨으로 인해서, 높은 치료효과뿐만 아니라 조혈모세포의 가동화 효율이 높은 구제 요법이 요구되었다. 방법: 본 연구에서는 진행성 비호지킨 림프종에서 ICE 요법을 이용하여 조혈모세포를 가동화시킨 후 자가 말초혈액 조혈모세포이식이 시행하였던 환자를 후향적으로 분석하였다. 결과: 대상 환자의 중앙 연령은 38세(범위, 16~61)였으며, ICE 요법은 환자당 4주기(범위, 1~6주기)가 투여되었고, 투여 간격은 중앙값이 24일(범위, 16~36일)이었다. 고위험도 관해군을 제외한 13예의 환자 중 완전반응은 7예(53.8%), 부분반응은 4예(30.8%), 진행성질환은 2예(15.4%)를 보였다. 치료에 따른 3~4등급의 혈액학적 독성은 중성구감소증이 13예(81.3%), 혈소판감소증이 7예(42.8%)에서 관찰되었다. 조혈모세포 채집은 ICE 요법 후 중앙값이 12일(범위, 6~20일)에 시행되었고, 각 ICE 요법당 채집한 단핵구치는 중앙값이 5.75× 10^(8)/체중, CD34^(+) 세포는 중앙값이 1.25× 10^(6)/체중, CFU-GM치는 중앙값이 1.19× 10^(5)/체중이었다. 조혈모세포이식은 11예에서 시행되었고, 중앙 추적기간 401일에 평가한 2년 전체생존율은 70.1±14.7%, 1년 및 2년 무사건생존율은 각각 60.7±15.4%와 32.3±17.1%를 보였다. 결론: ICE 요법은 재발성/불응성 비호지킨 림프종 환자에서 높은 치료 반응률과 만족할 만한 조혈모세포 가동화를 보여 주었지만, 치료에 대한 순응도가 낮아서 투여 간격이 연장되는 문제점을 안고 있어서, 우리나라 환자의 실정에 적합한 구제요법에 대한 연구가 필요할 것으로 생각된다. Background: Due to the extensive application of high-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT), a salvage chemotherapeutic regimen with high response rate as well as effective capacity of PBSC mobilization is needed in non-Hodgkin's lymphoma (NHL). Methods: We analyzed the applicability of ICE (ifosphamide, carboplatin, and etoposide) regimen in NHL patients who underewent autologous PBSCT. Results: The median age was 38 years (range, 16~61 years), the patients received median 4 cycles (range, 1~6 cycles) of ICE regimen, and the median interval between each chemotherapeutic cycle was 24 days (range, 16~36 days). There were 7 (53.8%) complete responses, 4 (30.8%) partial responses, and 2 (15.4%) progressive diseases after ICE regimen. Toxicity included grade 3/4 neutropenia and throm bocytopenia in 13 (81.3%) and 7 (42.8%) patients, respectively. PBSC collection began on median day 12 (range, 6~20 days) after ICE therapy. The median number of mononuclear cells, CD34+ cells, and CFU-GM was 5.75× 10^(8)/kg, 1.25× 10^(6)/kg, and 1.19× 10^(5)/kg, respectively. With a median follow- up of 401 days, the patients who underwent autologous PBSCT had overall survival with 70.1±14.7% at 2 year and event free survival with 60.7±15.4% and 32.3±17.1% at 1 year and 2 years, respectively. Conclusion: ICE chemotherapy is an effective cytoreduction and mobilization regimen in patients with NHL, but profound myelosuppression with delayed recovery might pose difficulties in applying for Korean patients. Further evaluation for appropriate salvage regimens in Korean patients should be needed.
KIM, Il Yong,HWANG, In Koo,CHOI, Ji Won,YOO, Ki-Yeon,KIM, Yo Na,YI, Sun Shin,WON, Moo-Ho,LEE, In Se,YOON, Yeo Sung,SEONG, Je Kyung Japanese Society of Veterinary Science 2009 The Journal of veterinary medical science Vol.71 No.6
<P>In this study, we observed and compared the effects of a high cholesterol diet (HCD) on cell proliferation and differentiation in the subgranular zone of the dentate gyrus of C57BL/6N (B6, susceptible strain) and C3H/HeN (C3H, resistant strain) mice. Ki67 (a marker for cell proliferation) positive cells) were significantly decreased in HCD-fed B6 mice compared to those in B6 (49.7%) and C3H mice fed a low cholesterol diet (LCD). In addition, doublecortin (DCX, a marker for cell differentiation or neuroblasts)-immunoreactive cells in HCD-fed B6 mice were significantly decreased compared to those in LCD-fed B6 and C3H mice. These results suggest that B6 strains are sensitive to HCD, which impairs cell proliferation and differentiation.</P>
Effects of Methimazole on the Onset of Type 2 Diabetes in Leptin Receptor-Deficient Rats
HWANG, In Koo,KIM, Il Yong,KIM, Yo Na,YI, Sun Shin,LEE, Yu Hee,JU, Eun Jeong,LEE, In Se,PARK, In-Sun,WON, Moo-Ho,YOON, Yeo Sung,SEONG, Je Kyung Japanese Society of Veterinary Science 2009 The Journal of veterinary medical science Vol.71 No.3
<P>We investigated the effects of methimazole, an anti-thyroid drug, on the onset of type 2 diabetes in Zucker diabetic fatty (ZDF) rats. For this, 0.03% methimazole was administered to 7-week-old, pre-diabetic ZDF rats in drinking water for 5 weeks and the animals were sacrificed at 12 weeks of age. Methimazole treatment to ZDF rats significantly reduced blood glucose levels, food intake, body weight, and serum T3 levels. Hepatocytes in ZDF-methi rats were more densely stained with eosin than those in ZDF rats because of low fat accumulation in ZDF-methi hepatocytes. The pancreatic islet in ZDF-methi rats was normal compared to that in ZDF rats. Glucagon, not insulin, immunoreactivity in ZDF-methi rats was significantly higher than that in ZDF-methi rats. These suggest that methimazole treatment may delay the onset of type 2 diabetes in leptin receptor-deficient rats and also suggests that thyroid hormones may be necessary for the onset of diabetes.</P>
FGF-2 inhibits TNF-α mediated apoptosis through up-regulation of Bcl2-A1 and Bcl-xL in ATDC5 cells
( Hey Ryun Kim ),( Youn Moo Heo ),( Kyoung Il Jeong ),( Yong Min Kim ),( Hae Lan Jang ),( Kwang Yeol Lee ),( Chang Yeol Yeo ),( Sung Hoon Kim ),( Hak Kyo Lee ),( Seung Ryul Kim ),( Eung Gook Kim ),( J 생화학분자생물학회 (구 한국생화학분자생물학회) 2012 BMB Reports Vol.45 No.5
FGF-2 is involved in cell survival, proliferation, apoptosis, and angiogenesis in a wide variety of cells. FRGRs, PI3K and MAP kinases are well known mediators of FGF signaling. Despite its known roles during many developmental processes, including osteogenesis, there are few known targets of FGF-2. In the present study, we identified Bcl2-A1 and Bcl-xL as two prominent targets involved in promoting cell survival. Pretreatment of ATDC5 cells with FGF-2 increased cell survival, while siRNAs specific for Bcl2-A1 and Bcl-xL compromised the anti- apoptotic effect of FGF-2, sensitized the cells to apoptosis triggered by TNF-α. Chemical inhibition of FGFR, NFkB, and PI3K activity by PD173074, pyrrolidine dithiocarbamate, and LY294002 respectively abrogated the FGF-2-mediated induction of Bcl2-A1 and Bcl-xL expression. Taken together, our data demonstrate that a subset of Bcl2 family proteins are the targets of FGF-2 signaling that promotes the survival of ATDC5 cells. [BMB reports 2012; 45(5): 287-292]
Polymorphisms involved in the folate metabolizing pathway and risk of multiple myeloma
Kim, Hee Nam,Kim, Yeo-Kyeoung,Lee, Il-Kwon,Lee, Je-Jung,Yang, Deok-Hwan,Park, Kyeong-Soo,Choi, Jin-Su,Park, Moo Rim,Jo, Deog Yeon,Kim, Hyeoung-Joon Wiley Subscription Services, Inc., A Wiley Company 2007 American journal of hematology Vol.82 No.9
<P>Folate and methionine metabolism plays an essential role in both DNA synthesis and methylation. Polymorphisms in the genes of the folate-dependent enzymes have been shown to affect disease susceptibility. We conducted a Korean population-based case-control study to evaluate whether genetic variation in folate metabolism may have a role in the risk of multiple myeloma (MM). The study subjects were 173 patients with MM and 1,700 population-based controls. The polymorphisms studied include methylenetetrahydrofolate reductase (MTHFR) 677 C > T and 1298 A > C, methionine synthase (MS) 2756 A > G, methionine synthase reductase (MTRR) 66A > G, thymidylate synthase (TS) 28-bp repeat (2R→3R) and 6-bp deletion/insertion. MS 2756 AG genotypes were associated with a 1.5-fold lower risk of MM (OR = 0.66, 95%CI; 0.43–0.99, P = 0.047). There was no association between MTHFR C677T, A1298C, MTRR A66G, TS 2R→3R and 6-bp deletion/insertion polymorphisms and MM. These results suggest that MTHFR C677T, A1298C, MTRR A66G, TS 2R→3R, and 6-bp deletion/insertion do not significantly factor into the pathogenesis of MM in the Korean population, but that MS A2756G polymorphism may play an important role. Am. J. Hematol., 2007. © 2007 Wiley-Liss, Inc.</P>