硼替佐米治疗套细胞淋巴瘤的分子学机制

套细胞淋巴瘤(MCL)是生存期最短的非霍奇金淋巴瘤(NHL),目前尚不能根治.硼替佐米是第一个用于治疗血液系统恶性肿瘤的蛋白酶体抑制剂,主要用于多发性骨髓瘤(MM)及复发难治性MCL的治疗.探讨硼替佐米治疗MCL的相关机制,其中包括调节细胞周期、影响细胞凋亡、干扰MCL的微环境以及与其他抗肿瘤药物的协同作用等,有助于未来合理应用硼替佐米治疗MCL.     

特异性下调GRP78基因表达对卵巢癌细胞耐药性的影响

目的:探讨RNA干扰技术沉默葡萄糖调节蛋白78(GRP78)基因对人卵巢癌细胞耐药性的影响,阐明GRP78基因沉默逆转肿瘤细胞耐药性的生物学机制.方法:构建pSilencerTM3.0-H1-GRP78 siRNA重组质粒,脂质体介导转染至SKOV3/DDP细胞;RT-PCR和Western blotting法检测GRP78基因的蛋白的表达;Western blotting法检测caspase-4和caspase-3蛋白表达;流式细胞术检测细胞凋亡率.结果:转染GRP78 siRNA重组质粒的SKOV3/DDP细胞GRP78基因和蛋白表达较转染空质粒组明显降低(P<0.05);加用顺铂后,转染GRP78 siRNA重组质粒细胞组较未转染GRP78 siRNA重组质粒细胞组caspase-4和caspase-3表达明显增加(P<0.05),细胞凋亡率也明显增加(P<0.05).结论:抑制GRP78基因表达能通过上调caspase-4和caspase-3表达及增加顺铂诱导的SKOV3/DDP细胞凋亡率,降低SKOV3/DDP细胞对顺铂的耐药性.     

Cyclin D1和bcl-2在B细胞淋巴瘤中的表达及其在鉴别诊断中的意义

B细胞淋巴瘤根据免疫表型可分为不同亚型,且不同亚型侵袭度不同,预后也有很大差异.Cyclin D1是已被证实与肿瘤有最直接关系的细胞周期蛋白,在大多B细胞淋巴瘤[套细胞淋巴瘤(MCL)、慢性淋巴细胞白血病(CLL)、边缘区淋巴瘤(MZL)、弥漫大B细胞淋巴瘤(DLBCL)等」中均有表达.多数B细胞淋巴瘤[滤泡性淋巴瘤(FL)、DLBCL等]都能可见易位活化的bcl-2表达增强.Cyclin D1及bcl-2作为B细胞淋巴瘤重要的细胞周期蛋白及抗凋亡基因,在淋巴瘤的鉴别诊断中起重要作用,其检测及检测手段的灵敏度和特异度具有重要的临床价值.     

长春应用化学研究所设计合成新型稀土基磁性亲和材料

蛋白质的可逆磷酸化修饰是生物体内普遍存在的信息转导调节方式,几乎参与生命活动的所有过程,在细胞的增殖、发育和分化,细胞信号转导、转录和翻译,细胞的周期调控、蛋白降解和新陈代谢,细胞生存、细胞凋亡和肿瘤发生等方面发挥着重要的作用。目前已知许多人类疾病的发生都与异常的蛋白质磷酸化修饰有关,而且一些疾病     

环巴胺诱导大肠癌Caco-2细胞凋亡效应和线粒体蛋白质组学研究

目的:探讨环巴胺对大肠癌Caco-2细胞的促凋亡效应,在线粒体蛋白水平阐明其作用机制.方法:取对数生长期大肠癌Caco-2细胞分为环巴胺处理组及阴性对照组,以5、10、20和40 μmol·L-1环巴胺处理Caco-2细胞,分别应用MTS法及流式细胞术测定Caco-2细胞生长抑制率及凋亡率,采用nano LC-ESI-MS方法检测环巴胺处理组与阴性对照组细胞线粒体蛋白质组学差异.结果:环巴胺处理组Caco-2细胞分别经10、20和40 μmol·L-1环巴胺作用24、48和72 h后,生长抑制率(分别为23.1%±1.8%,46.2±0.9%,53.4±2.3%;45.1%±2.8%,73.0%±2.5%,81.2%±1.6%;59.7±2.3%,87.5±1.4%,91±1.06%)明显高于阴性对照组(1.8%±0.2%,2.5%±0.1%,3.7%±0.3%)(P<0.01);经5、10、20和40 μmol·L-1环巴胺作用于Caco-2细胞48 h后,细胞凋亡率分别为24.1%±1.3%、31.7%±1.6%、50.5%±2.3%和64.0%±1.9%,明显高于阴性对照组(14.4%±0.7%)(P<0.01).蛋白质组学差异分析,环巴胺作用后,Caco-2细胞线粒体共有32种蛋白表达下调,25种蛋白表达上升,这些蛋白功能主要涉及细胞凋亡、细胞骨架、核酸、核糖体及蛋白质代谢等,其中与凋亡关系密切的蛋白包括ATF6、Clusterin、OPA1、RGD1565411和Cofilin.结论:环巴胺通过阻断Hedgehog(HH)通路,抑制大肠癌Caco-2细胞增殖,其机制与促进细胞凋亡有关;环巴胺可明显改变Caco-2细胞线粒体蛋白表达,其差异与凋亡关系密切.     

多发性骨髓瘤骨髓单个核细胞缺氧诱导因子1α mRNA的表达及其临床意义

目的 探讨多发性骨髓瘤(MM)患者缺氧诱导因子1 α(HIF-1 α)基因mRNA表达和临床各指标的相关性,了解HIF-1 α基因在MM患者中的表达和意义.方法 应用实时荧光定量聚合酶链反应(RQ-PCR)28例检测MM患者和22例骨科外伤患者或非血液系统恶性肿瘤患者(对照组)骨髓单个核细胞中的HIF-1 α mRNA,以β-actin作为内参照,用SDS分析软件测定Ct值,用2-△△Ct表示目的 基因的量.结果 HIF-1 α mRNA在MM骨髓单个核细胞中表达为对照组的12.68倍,HIF-1 α mRNA水平(以-△Ct表示)与患者血清β2-微球蛋白(r=0.575,P=0.000)、红细胞沉降率(r=0.522,P=0.000)、乳酸脱氢酶(r=0.286,P=0.044)、C反应蛋白(r=0.356,P=0.011)水平呈正相关,与患者血红蛋白(Hb)水平呈负相关(r=-0.556,P=0.000).结论 HIF-1 α mRNA在MM组织中高表达,与临床多项指标有关,可作为临床监测指标之一,有可能成为肿瘤分子靶向治疗中新的靶点.     

黏蛋白1基因磁转染树突状细胞诱导细胞毒性T细胞抗膀胱肿瘤免疫效应的研究

目的:探讨黏蛋白1(mucins 1,MUC1)基因磁转染体外人树突状细胞(dendritic cell,DC)的可行性,观察其诱导的特异性抗MUC1膀胱癌CTL的免疫效应.方法:以葡聚糖磁性纳米颗粒(DMN)作为载体,在多聚赖氨酸(PLL)的辅助下,通过静电作用结合MUC1基因的真核表达载体pEGFP-C1-MUC1,在钕-铁-硼稀土强磁块的磁场作用下转染DC,荧光显微镜下观察及流式细胞术检测转染效率,并用RT-PCR法检测转基因DC中MUC1基因的表达;再将转染MUC1基因的DC与自体T细胞共培养,并分别用乳酸脱氢酶释放法检测所致敏的细胞毒性T淋巴细胞(cytotoxic lymphocyte,CTL)对MUCI特异性抗膀胱癌(膀胱肿瘤BIU87细胞系)的杀伤活性,用透射电镜观察CTL诱导靶细胞凋亡情况;ELISA法测定MUC1基因修饰后的DC刺激自体T细胞分泌IFN-γ的能力.结果:pEGFP-C1-MUC1转染效率为10%左右,荧光显微镜下可观察到明显绿色荧光蛋白的表达,RT-PCR法可检测到MUC1条带,转染MUC1基因的DC与自体T细胞混合培养后能诱导出MUC1特异性的CTL,对BIU87细胞的杀伤实验表明T-DC-MUC1的杀伤活性显著高于对照组T-DC-pEGFP-C1和T-DC诱导的CTL(P均<0.05);在透射电镜下也可观察到部分BIU87膀胱肿瘤细胞出现了细胞核核仁消失,染色质浓集于核膜周围等早期凋亡表现;基因修饰后的DC能刺激自体T细胞分泌高水平的IFN-γ,明显高于未转染的DC(P<0.05).结论:葡聚糖磁性纳米颗粒在同定磁场的作用下成功将MUC1基因转入DC,并可有效诱导出特异性抗MUC1膀胱癌的细胞毒性T细胞.     

NF-κB信号通路的阻断对皮肤鳞癌SCL-1细胞凋亡的影响

目的:利用siRNA技术抑制核因子-kappa B(nuclear factor-kappa B,NF-κB)亚单位p65基因的表达,研究其对p65表达的抑制作用,并探讨其对皮肤鳞癌SCL-1细胞凋亡的影响.方法:将终浓度为50 nmol/L的p65 siR-NA转染皮肤鳞癌SCL-1细胞,通过RT-PCR检测p65 mRNA的表达;利用Western blotting检测p65、bcl-2和bax蛋白表达,利用Caspase-Glo(R)-3/7,8和9检测试剂盒检测caspase-3/9的活性;最后通过流式细胞术检测细胞凋亡.结果:p65 siRNA转染SCL-1细胞后的48 h,p65 mRNA的表达水平最低,与0 h相比,差异有统计学意义(0.23±0.10vs.0.66±0.05,P＜0.05);转染48 h后,p65和bcl-2蛋白表达水平下调,而促凋亡蛋白bax的表达上升,进一步caspase-3/9的活性也显著升高.流式细胞术结果表明,p65 siRNA能明显诱导SCL-1细胞发生凋亡,其早期凋亡的比率为20.28%±1.87%,显著高于未处理组和对照siRNA组(凋亡率分别为9.13%±1.51%和9.37%±1.38%,F=47.532,P＜0.01).结论:p65 siRNA能够阻断皮肤鳞癌细胞中NF-κB信号通路,并下调抑凋亡蛋白bcl-2的表达,上调促凋亡蛋白bax的表达以及提高caspase的活性,提示NF-κB信号通路有望成为皮肤鳞癌基因治疗的分子靶点.     

Bid基因的研究进展

近年来,对Bid蛋白的功能、Bid对细胞凋亡的调控及多种因素对Bid的调控等方面的研究推动了临床治疗的发展.Bid受凋亡信号刺激后形成截短型Bid片段(tBid),促进细胞色素C释放导致细胞凋亡,Bid介导受损组织发生凋亡,在许多疾病的发生及进展中起重要作用.在一部分疾病中Bid还显示出促凋亡和促增殖的双重作用.对影响Bid诱导凋亡过程的多因素研究也为实体瘤和恶性血液病的治疗提供了新的思路.     

Bcl-2参与SCID小鼠体内齐墩果酸诱导HL-60细胞凋亡的调控作用

目的:观察齐墩果酸(OA)对白细胞移植模型小鼠脾脏浸润白血病细胞凋亡数量和Bcl-2蛋白表达的影响,探讨OA对白血病模型鼠的治疗作用机制.方法:取浓度为2×107mL-1体外培养的人早幼粒系白血病HL-60细胞0.5 mL,腹腔注射重症联合免疫缺陷(SCID)小鼠,构建SCID小鼠的HL-60细胞移植瘤模型;模型成功后小鼠分为用药组、白血病模型对照组,并设正常对照组.用药组以200 mg·kg-1OA皮下注射,用药2周后观察各组小鼠的一般状态、外周血象及骨髓象白细胞分类情况,病理学检查脾白血病细胞浸润程度,TUNEL方法测定脾浸润白血病细胞凋亡率,免疫组织化学检测HL-60细胞凋亡相关基因Bcl-2蛋白表达率.结果:成功建立SCID小鼠的HL-60细胞移植瘤模型;用药组小鼠体质量[(15.0±0.8) g]明显高于模型组小鼠[(13.9±0.9) g](P<0.01),小鼠生存期[(50.3±5.5) d]明显高于模型组小鼠[(37.1±4.4) d](P<0.01);与模型组比较,用药组外周血白血病细胞有向正常白细胞分化趋势,可见分叶的白血病细胞,骨髓象中幼稚细胞减少,脾浸润情况改善;用药组小鼠脾浸润白血病细胞凋亡率高于模型组(P<0.01),Bcl-2蛋白表达阳性细胞百分率低于模型组(P<0.01).结论:成功建立白血病移植瘤鼠模型;OA可改变白血病移植瘤模型鼠的一般状态,延长生存期;OA通过降低Bcl-2表达可诱导白血病细胞凋亡.     

Inactivation of the p15INK4B and p16INK4 genes in hematologic malignancies

The recently discovered p15INK4B and p16INK4 genes encoding cell cycle regulating proteins, map to a region on chromosome 9p21 that is commonly deleted in a variety of malignant diseases. The p16INK4 gene has now been shown to be a tumor suppressor gene. It is frequently inactivated in cancer and is possibly the second most often mutated gene in human malignant disease after p53. The role of the p15INK4B and p16INK4 genes in hematologic malignancies has been the subject of intense investigation since their discovery. In this review we address the function and possible role in tumorigenesis of the p15INK4B and p16INK4 genes and discuss their significance as prognostic markers in hematologic malignancies.     

Tumor suppressor genes and their role in abnormal production of leukocytes (leukemogenesis)

The retinoblastoma susceptibility gene (RB) and p53 gene are now known to be the prototypes for a class of tumor suppressor genes. Both genes act as a regulator of cell cycle transition at G1/S in many types of cell lineages. Underphosphorylated form of RB protein (Rd) acts as a growth suppressor by blocking exit from G1 through a specific binding to E2F or promoter region of certain growth-associated genes. Phosphorylation of Rb can be viewed as inactivating Rb and allowing cell cycle progression to occur. Differentiation of hematopoietic cell is accompanied with the loss of ability to phosphorylate Rb, indicating that Rb plays an important role in hematopoietic cell growth and differentiation. Abnormalities of RB gene may, therefore, predispose to the development of hematologic malignancies. DNA rearrangement was reported to be present in 1.5-12.1% of cases with primary leukemias, and the absence of RB protein was also observed in 6.3-23.2%. The abnormalities of p53 gene were also frequently observed in hematologic malignancies. DNA rearrangement of p53 was observed in 20-30% of the cases with blastic crisis of CML. Point mutation at the "hot spot" was reported in many types of leukemias, especially in cell lines established from these cases.     

Adoptive immunotherapy for leukemia: donor lymphocytes transduced with the herpes simplex thymidine kinase gene for remission induction. HGTRI 0103

This study will evaluate the safety and efficacy of allogenic donor lymphocyte infusions in patients who have relapsed hematologic malignancies after allogeneic bone marrow transplantation (BMT). Donor lymphocyte transfusions have resulted in the cure of some patients with relapsed leukemia or lymphoproliferative disorder after allogeneic BMT, but has been complicated by the development of graft versus host disease (GvHD). We hypothesize that a retroviral vector containing the Herpes simplex thymidine kinase (HStk) gene will allow for retention of the anti-leukemia response of transfused donor lymphocytes while allowing for the adverse effects of GVHD to be mitigated. Patients with relapsed hematologic malignancies after allogeneic BMT will be infused with ex vivo gene modified donor lymphocytes. The Herpes Simplex thymidine kinase (HStk) gene will be transduced into the cells ex vivo using LTKOSN. 1 vector supernate. Insertion of the HStk gene into lymphocytes confers a sensitivity to the anti-herpes drug ganciclovir (GCV). This selective destruction of donor lymphocytes in situ will be used to abrogate the effect of graft versus host disease, if it develops.     

Single-chain immunotoxins targeted to CD40 for the treatment of human B-lineage hematologic malignancies

Immunotoxins, in chemical conjugate form, have shown limited efficacy in clinical trials in patients with hematologic malignancies. Single-chain immunotoxins (SCIT) provide for enhanced therapeutic efficacy over chemical conjugate forms without additional toxicity and thus may result in improved antitumor activity. We have evaluated two SCITs targeted to CD40, a receptor expressed on most B-lineage hematologic malignancies, for the treatment of non-Hodgkin's lymphoma and multiple myeloma. Both SCITs, G28-5 sFv-PE40 and BD1-G28-5 sFv, were highly potent and specifically cytotoxic against non-Hodgkin's lymphoma and multiple myeloma cell lines. G28-5 sFv-PE40 has proven to be efficacious in SCID mice bearing human non-Hodgkin's lymphoma and multiple myeloma xenografts. Antitumor activity has also been noted in preliminary studies using BD1-G28-5 sFv in non-Hodgkin's lymphoma models. The data presented here indicate that these agents should be considered for use in clinical trials in patients with refractive non-Hodgkin's lymphoma, multiple myeloma and other CD40-expressing hematologic malignancies.     

Treatment of anemia in myelodysplastic syndromes with granulocyte colony-stimulating factor plus erythropoietin: results from a randomized phase II study and long-term follow-up of 71 patients

Malignant gliomas are rather refractory to current therapeutic approaches including surgery, radiotherapy, chemotherapy and immunotherapy. Acquired alterations in the pathways required for apoptotic cell death are thought to be responsible to the failure of glioma to respond to therapy. Here we have examined the expression of several proteins involved in the susceptibility to apoptosis in 20 human gliomas, including the BCL-2 family proteins BCL-2, BCL-X, BAX and MCL-1, as well as p53 and RB. Most gliomas expressed several BCL-2 family proteins. There was good correlation between expression of the functional antagonists, BCL-2/BCL-X and BAX, suggesting that changes in the BCL-2+BCL-X/BAX ratio are not responsible for the differential response of glioma patients to chemotherapy. The immunochemistry data were also analysed in regard to response to therapy and clinical outcome. All patients had cytoreductive surgery and received radiotherapy and nitrosourea-based adjuvant chemotherapy. There was no prominent association of outcome with the expression patterns of p53, RB, BCL-2, BCL-X or BAX. We find, however, that expression of the MCL-1 protein is associated with early tumour recurrence and shorter survival in this group of glioma patients. This preliminary observation will have to be confirmed in a larger independent sample of glioma patients.     

Hematopoietic malignancies demonstrate loss-of-function mutations of BAX

The BCL-2 gene family regulates the susceptibility to apoptotic cell death in many cell types during embryonic development and normal tissue homeostasis. Deregulated expression of anti-apoptotic BCL-2 can be a primary aberration that promotes malignancy and also confers resistance to chemotherapeutic agents. Recently, studies of Bax-deficient mice have indicated that the pro-apoptotic BAX molecule can function as a tumor suppressor. Consequently, we examined human hematopoietic malignancies and found that approximately 21% of lines possessed mutations in BAX, perhaps most commonly in the acute lymphoblastic leukemia subset. Approximately half were nucleotide insertions or deletions within a deoxyguanosine (G8) tract, resulting in a proximal frame shift and loss of immunodetectable BAX protein. Other BAX mutants bore single amino acid substitutions within BH1 or BH3 domains, demonstrated altered patterns of protein dimerization, and had lost death-promoting activity. Thus, mutations in the pro-apoptotic molecule BAX that confer resistance to apoptosis are also found in malignancies.     

Chimeric homeobox gene E2A-PBX1 induces proliferation, apoptosis, and malignant lymphomas in transgenic mice

Expression of the homeobox fusion gene E2A-PBX1 under control of the immunoglobulin heavy chain enhancer efficiently induced malignancies in transgenic mice. All animals died before 5 months of age with lymphomas that demonstrated phenotypes consistent with transitional intermediate thymocytes (CD4+/CD8+/CD3med). E2A-PBX1 also markedly altered lymphoid development in pretumorous animals, reducing the number of thymocytes and bone marrow B lineage progenitors to 20% of normal levels. In spite of the observed reductions in lymphoid cells, premalignant animals contained significantly increased numbers of cycling thymocytes, but a higher proportion was also undergoing apoptosis, suggesting that increased cell death resulted in the marked lymphopenias. These data indicate that the chimeric homeodomain protein E2A-PBX1 paradoxically induces both proliferation and apoptosis in lymphoid cells, suggesting an in vivo association between nuclear oncogene-induced cell cycle progression and programed cell death.     

Women''s anger: relationship of suppression to blood pressure

Myeloablative therapy followed by allogeneic bone marrow transplantation (BMT) has proven to be curative therapy in patients with hematologic malignancies. Relapse, however, remains a major cause of treatment failure for patients with advanced disease. During the past 15 years, we have gained considerable experience with the combination of fractionated total-body irradiation (FTBI) and etoposide followed by allogeneic BMT for hematologic malignancies. In an attempt to decrease post-transplant relapse rates, 67 patients under the age of 50 years with high-risk or advanced-stage hematological malignancies received an intensified regimen of FTBI and etoposide plus cyclophosphamide followed by BMT from a genotypically-matched related donor. The regimen consisted of 1320 cGy of FTBI in 11 fractions, 60 mg/kg of etoposide (VP-16), and 60 mg/kg of cyclophosphamide (CY). Fifty-three patients received cyclosporine and prednisone for graft-vs.-host disease (GVHD) prophylaxis and 14 patients received cyclosporine, methotrexate, and prednisone. Diagnosis at BMT included 45 patients with acute leukemia, 7 patients with chronic leukemia, and 15 patients with high-grade non-Hodgkin's lymphoma (NHL). Actuarial disease-free survival (DFS) at 3 years was 42% +/- 12% for the entire group with a median follow-up of 50 months (range 20-74) for 28 patients who remain alive in continued complete remission (CR). Actuarial 3-year-DFS was 38% +/- 14% in 52 patients with acute or chronic leukemia and 60% +/- 25% in 15 patients with NHL with relapse rates of 45% +/- 16% and 21% +/- 11%, respectively. DFS at 3 years was 40% +/- 18% in 32 patients with acute leukemia in 1st relapse or 2nd CR or chronic myelogenous leukemia in accelerated phase, and was 32% +/- 22% in 20 patients with more advanced disease. Regimen related mortality occurred in 9 patients (4, veno-occlusive disease of the liver; 2, multi-organ failure; 1, diffuse alveolar hemorrhage; 1, central nervous system (CNS) hemorrhage; 1, adult respiratory distress syndrome (ARDS). The combination of FTBI, etoposide, and cyclophosphamide followed by allogeneic BMT is an effective and relatively well-tolerated regimen for patients with advanced hematologic malignancies. The role for this regimen should be further defined by prospective clinical trials.     

Fluorescence in situ hybridization analyses of hematologic malignancies reveal frequent cytogenetically unrecognized 12p rearrangements

Thirty-two hematologic malignancies--nine with cytogenetically identified 12p abnormalities and 23 with whole or partial losses of chromosome 12--were selected for fluorescence in situ hybridization (FISH) investigations of 12p. These analyses revealed structural 12p changes, such as translocations, deletions, insertions, inversions and amplification, in 20 cases. ETV6 rearrangements were detected in three acute leukemias. One acute undifferentiated leukemia had t(4;12)(q12;p13) as the sole anomaly. The second case, an acute myeloid leukemia (AML), displayed complex abnormalities involving, among others, chromosomes 9 and 12. The third case, also an AML, had an insertion of the distal part of ETV6 into chromosome arm 11q and into multiple ring chromosomes, which also contained chromosome 11 material, resulting in an amplification of a possible fusion gene. The fusion partners in these cases remain to be identified. Thirty-one additional breakpoints on 12p could be characterized in detail. The majority of these breaks were shown to result in interchromosomal rearrangements, possibly indicating the location of hitherto unrecognized genes of importance in the pathogenesis of hematologic malignancies. The FISH analyses disclosed terminal or interstitial 12p deletions in 18 cases. Seven myeloid malignancies showed deletions restricted to a region, including ETV6 and CDKN1B, which has been reported to be frequently lost in leukemias. In four cases, the deletions involved both these genes, whereas two AML displayed loss of CDKN1B but not ETV6, supporting previously reported findings indicating a region of deletion not including this gene. However, one myelodysplastic syndrome lacked one copy of ETV6 but not CDKN1B. Hence, we suggest a minimal region of deletion on 12p located between the ETV6 and CDKN1B genes.     

Impaired response to hepatitis B vaccine in children receiving anticancer chemotherapy

Serologic responses to hepatitis B vaccine were investigated in 197 pediatric cancer patients. The patients, ages 1 to 21 years, comprised 66 with solid tumors, 101 with hematologic malignancies and 30 with various benign conditions. Of them 51 were receiving cytotoxic chemotherapy and 114 had not received chemotherapy for 0.2 to 11 years. Three doses of plasma-derived hepatitis B vaccine (20 micrograms) were given at 0, 1 and 6 months; and antibody concentrations to hepatitis B surface antigen were determined at 3, 6 and 8 months. The geometric mean antibody concentration after 3 vaccine doses was 1076 mIU/ml in cancer patients receiving chemotherapy and 18,833 mIU/ml in cancer patients not receiving chemotherapy. The protective titer of antibody (> or = 10 mIU/ml) was reached after 3 doses of vaccine by 67% of patients receiving chemotherapy and by 97% of those not receiving chemotherapy. The patients being treated for solid tumors had weaker responses than those being treated for hematologic malignancies: after 3 vaccine doses no response was observed in 6 of 11 patients with solid tumors compared with 3 of 25 of patients with hematologic malignancies. Children receiving anticancer chemotherapy have essentially weaker responses to hepatitis B vaccine than children not receiving chemotherapy or those with benign conditions. This reflects the profound immunosuppression during chemotherapy. The effect of more intensive immunization schedules should be investigated.