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991.
Better outcome of adult acute lymphoblastic leukemia after early genoidentical allogeneic bone marrow transplantation (BMT) than after late high-dose therapy and autologous BMT: a GOELAMS trial 总被引:4,自引:4,他引:4 下载免费PDF全文
Hunault M Harousseau JL Delain M Truchan-Graczyk M Cahn JY Witz F Lamy T Pignon B Jouet JP Garidi R Caillot D Berthou C Guyotat D Sadoun A Sotto JJ Lioure B Casassus P Solal-Celigny P Stalnikiewicz L Audhuy B Blanchet O Baranger L Béné MC Ifrah N;GOELAMS 《Blood》2004,104(10):3028-3037
Various transplantation strategies have been designed to improve the poor prognosis of adult (ages 15 to 60 years) acute lymphoblastic leukemia (ALL). The GOELAL02 trial evaluated the impact of early allogeneic bone marrow transplantation (alloBMT) or delayed unpurged autologous stem cell transplantation (ASCT) for patients who had no human leukocyte antigen (HLA)-matched sibling donor or who were older than 50 years. Inclusion criteria included at least one of the following: age older than 35 years; non-T-ALL; leukocytosis greater than 30 x 10(9)/L; t(9;22), t(4;11), or t(1; 19); or failure to achieve complete remission (CR) after one induction course. Among 198 patients, the median age was 33 years. The CR rate was 80% with vincristine, idarubicine, L-asparaginase, and randomized intravenous injection or oral steroids (P = nonsignificant [ns]). AlloBMT was performed after 2 consolidation courses while ASCT was delayed after 1 additional reinduction. Intensified conditioning regimen before transplantation included etoposide, cyclophosphamide, and total body irradiation (TBI). Median follow-up was 5.1 years. The median overall survival (OS) was 29 months, with a 6-year OS of 41%. On an intent-to-treat analysis for patients younger than 50 years, alloBMT significantly improved the 6-year OS (75% versus 40% after ASCT; P = .0027). Randomized interferon-alpha maintenance had no effect on relapse or survival after ASCT. In conclusion, the outcome of adult ALL is better after early alloBMT than after delayed ASCT. 相似文献
992.
腺病毒介导RA538及反义c-myc在不同细胞系中作用及其机制 总被引:3,自引:4,他引:3
目的比较重组RA538,反义c-myc及LacZ腺病毒(adenovirus,AV)对不同靶细胞的转染效率、生物学特性并探讨其作用的分子机制.方法以人胃癌细胞(SGC7901)、食管癌细胞(EC109)及人胚肺二倍体细胞(2BS)系为靶细胞,采用LacZ基因转染X-gal染色、形态学观察、MTT,RT-PCR等方法,研究重组RA538,反义c-myc及LacZ AV对上述细胞的转染效率,生物学作用及其分子机制.结果 AV-LacZ进行重组腺病毒转导效率检测显示其对SGC7901,2BS细胞具有很高的转导效率,对EC109细胞转导效率较低.AV-RA538及AV-ASc-myc对SGC7901细胞能产生明显的生长抑制效应并诱导凋亡,其生长抑制率分别为76.3%和44.1%.AV-RA538及AV-ASc-myc对SGC7901细胞内源性c-myc,bcl-2基因的表达具有抑制作用.AV-RA538及AV-ASc-myc对EC109细胞及2BS细胞无明显的生长抑制及凋亡诱导作用,AV-RA538对EC109及2BS细胞中内源性c-myc,bcl-2基因的表达无调节作用.结论 AV载体转导效率很高,能实现目的基因在转导细胞中的高水平表达,但对不同靶细胞的转染效率存在差别.AV-RA538,AV-ASc-myc对SGC7901的生长抑制及凋亡诱导作用可能是通过AV的高效转导及抑制c-myc,bcl-2的表达而实现的.AV-RA538,AV-ASc-myc对食管癌、2BS细胞系无类似作用可能与其对上述细胞的转导的作用及内源性基因表达的作用有关. 相似文献
993.
目的探讨放射疗法在经典型皮肤卡勃基氏肉瘤(Kaposissarcoma,KS)这种罕见肿瘤治疗中的有效性。方法1986年6月~1996年12月,法国巴黎第十二大学亨利·孟德尔医院肿瘤科共收治经典型皮肤KS5例。所有病人均接受45~70KVX线局部放射治疗,共设48个照射野,剂量均<30Gy。放疗方式为:第1周10Gy,2.5Gy/次×4,休息10~15天后再行第2阶段放疗,追加剂量15~20Gy。结果完全缓解率100%。皮肤对放射的耐受良好,不影响美观。2例出现射野外新病灶,其中1例行放疗而另1例行长春花碱治疗,均完全缓解。结论放射疗法对KS可以提供有效的局部控制率并保持皮肤的完整美观,剂量20~30Gy足以使经典型皮肤KS完全缓解。 相似文献
994.
大蒜中两种新的甾体皂甙成分及其对血液凝聚性的影响 总被引:8,自引:0,他引:8
用大孔树脂(AB-8)柱层析、硅胶柱层析、Sephadex LH-20柱层析、及制备性HPLC等方法,从大蒜(Alium sativum L.)水溶性部分分到6个化合物,并鉴定其结构,它们分别是proto-iso-eruboside-B(I),eruboside-B(I),iso-eruboside-B(II),sativoside-C(IV),腺苷(V)和色氨酸(VI)。其中I和II为两个新的甾体皂甙类化合物。并测试了它们对血液系统的作用,发现大蒜总甙有抗血小板聚集和提高纤溶活性,iso-eruboside-B有明显的延长血液凝固时间和提高纤溶活性,proto-iso-eruboside-B有显著的提高纤溶活性,腺苷则有抗血小板聚集活性和提高纤溶活性,sativoside-C由于量少未测活性。其余化合物均无活性。 相似文献
995.
N Schoenmakers Y Sun B Bak ASP van Trotsenburg W Oostdijk P Voshol E Cambridge JK White P le Tissier SNM Gharavy JP Martinez-Barbera WH Stokvis-Brantsma T Vulsma MJ Kempers L Persani I Campi M Bonomi P Beck-Peccoz K Chatterjee 《Lancet》2013
BackgroundCongenital central hypothyroidism occurs either as isolated thyroid-stimulating hormone (TSH) deficiency or in conjunction with other pituitary hormone deficits. Undetected central hypothyroidism is associated with developmental delay in children and adverse cardiometabolic sequelae in adults. Hitherto, mutations in the thyrotropin-releasing hormone receptor gene (TRHR) or the TSHb subunit gene (TSHB) are the only known causes of isolated TSH deficiency.MethodsUsing whole exome and candidate gene sequencing, we have studied 11 unrelated families with males exhibiting isolated TSH deficiency, testicular enlargement, and variably low serum prolactin levels.FindingsWe have identified eight distinct mutations and two whole gene deletions disrupting the X-linked immunoglobulin superfamily member 1 gene (IGSF1) in affected males. IGSF1 encodes a pituitary-enriched plasma membrane glycoprotein; disease-associated mutations block trafficking of IGSF1 from the endoplasmic reticulum to the membrane, consistent with loss-of-protein function. Adult male IGSF1 null mice exhibit central hypothyroidism with decreased pituitary TSH content and circulating T3 levels; TSH secretion in response to TRH is blunted and pituitary TRHR mRNA levels are decreased, suggesting that impaired TRH signalling may provide the basis for hypothyroidism.InterpretationOur observations delineate a novel X-linked syndrome in which loss-of-function mutations in IGSF1 cause central hypothyroidism, testicular enlargement, and variable prolactin deficiency, and identify a previously unsuspected role for IGSF1 in hypothalamic-pituitary control of thyroid and testicular function. Variable biochemical penetrance in these families highlights the importance of genetic ascertainment in this syndrome, so that asymptomatic affected individuals can benefit from early initiation of thyroxine treatment.FundingWellcome Trust and National Institute for Health Research Biomedical Research Centre. 相似文献
996.
997.
998.
WE Marshman FRACO JP Lee FRCOphth B Jones FRCP C Schalit DBO CE Holder PhD 《Clinical & experimental ophthalmology》1998,26(3):251-254
Background: Although Duane's retraction syndrome (DRS) represents less than 5% of strabismus patients presenting to an ophthalmology department, it is a difficult management problem that is often poorly treated. The developmental defect has been isolated to early in the embryonic period, but to date a chromosomal location is still uncertain. Neuronal ceroid lipofuscinosis (NCL) or Batten's disease is a lysosomal storage disease with autosomal recessive inheritance, which has been categorized according to the age of onset of symptoms. Methods/Results: We report on a patient with DRS who developed juvenile Batten's disease. Conclusions: These two abnormalities can both be inherited, but their association has not been previously documented. 相似文献
999.
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