金纳米颗粒修饰及其对肝癌细胞生长和辐射损伤的影响

目的：用巯基-聚乙二醇（SH-PEG）对金纳米颗粒（AuNPs）进行化学修饰（PEG-AuNPs）并分析其对肝癌细胞存活率和辐射对肝癌细胞作用的影响。方法制备的AuNPs用SH-PEG进行化学修饰,用透射电子显微镜观测PEG-AuNPs的大小及肝癌细胞对其的摄取,应用Cell Titer-Glo发光法和克隆形成实验分别分析PEG-AuNPs对肝癌细胞的生长抑制作用和辐射对肝癌细胞作用的影响。结果制备的PEG-AuNPs的尺寸分别为14．4 nm和30．5 nm。30．5 nm PEG-AuNPs更容易被肝癌细胞摄取,表现出明显地抑制肝癌细胞生长的作用和提高辐射对肝癌细胞的杀伤作用。结论 AuNPs经过SH-PEG化学修饰,30．5 nm PEG-AuNPs对肝癌细胞的生长抑制作用和提高辐射杀伤肝癌细胞的作用强于14．4 nm PEG-AuNPs。     

血卟啉衍生物放射增敏治疗头颈鳞癌的临床研究

分析术前放疗并用血卟啉衍生物 (HPD)静脉注射增敏治疗 2 8例头颈鳞癌与 33例单纯术前放疗病例的术后病理、长期生存率及预后因素。手术标本病检实验组无瘤率 4 4 .4 % (13/ 2 8)。对照组无瘤率仅 9.1% (3/ 33) ,(P<0 .0 0 1)。实验组 5年生存率 71.4 % (2 0 / 2 8)。对照组 4 8.5 % (16 / 33) ,(P<0 .0 5 )。其中术后病检无瘤者 5年生存率 87.5 % (14/ 16 )。有肿瘤残存则生存率明显降低。实验组肿瘤 <4 cm、颈淋巴结阴性者 5年生存率 93.7% ,对照组 6 6 .7%。讨论了 HPD放射增敏原理及治疗副作用。     

Radiation therapy for Kaposi's sarcoma associated with acquired immunodeficiency syndrome: Tokyo Metropolitan Komagome Hospital experience

Background. Kaposi's sarcoma is frequently found in association with acquired immunodeficiency syndrome (AIDS). We report on radiotherapy for patients with AIDS-related Kaposi's sarcoma at Tokyo Metropolitan Komagome Hospital. Methods. Between April 1991 and May 1997, radiotherapy was given to 11 lesions in eight men with AIDS-related Kaposi's sarcoma to relieve their symptoms. The lesions involved the head and neck region, the legs, and the gastrointestinal tract. Radiotherapy was carried out with 4-MV photon through parallel opposed fields or high energy electrons. Total doses ranged from 20 to 38 Gy, with a median of 30 Gy, delivered in 2- to 3-Gy fractions. Four patients were given other treatments prior to the radiotherapy. Acute reaction was evaluated according to the modified acute radiation morbidity scoring criteria of the Radiation Therapy Oncology Group (RTOG). Results. Radiotherapy had relieved the symptoms in all patients at completion of this therapy. Lesions that involved the hard palate and vocal cords had completely disappeared. The lesions that received radiotherapy were controlled without symptoms until the patients died. Patients who had the head and neck region treated exhibited severe acute mucosal reaction (at a dose of 30 Gy, there was grade 2 morbidity by modified RTOG criteria, in two patients, and grade 3 in three patients) although the radiation therapy was completed for these patients. Conclusion. Radiotherapy promises a favorable outcome for symptom relief in AIDS-related Kaposi's sarcoma. Received: April 24, 2000 / Accepted: August 18, 2000     

食管癌放射抵抗相关基因的筛选

 目的 筛选与食管癌放射抵抗相关的基因，为指导临床个体化治疗打下基础。方法 采用基 因芯片技术检测放疗疗效差异最大的两组患者之间差异明显的CNV片段，筛选出这些CNV片段中的代表性基因。进一步从筛选出的高度相关的代表性基因中，利用qPCR进行验证。结果 基因芯片筛查的结果得到显著差异的CNV片段共5个，分别位于3、4、8、11、17号染色体，其中拷贝数缺失的（CN Loss）3个，增加的（CN Gain）1个，杂合性缺失的（LOH）1个。代表性基因分别为ROBO1、NSD2、CSMD3、CADM1、NF1。qPCR验证的放射抵抗相关基因为NSD2和CADM1，主要涉及DNA损伤修复通路和细胞黏附。结论 基因芯片筛选食管癌放射抵抗相关分子标记具有可行性。NSD2和CADM1可能是与食管癌放射抵抗的相关位点。     

电离辐射对不同放射敏感性细胞中高迁移率簇蛋白B1的诱导表达作用

目的 探讨电离辐射对已建立的宫颈癌放射抗拒细胞对比模型中高迁移率簇蛋白B1（HMGB1）和mRNA诱导表达的差异性,分析HMGB1对宫颈癌放射敏感性调控的可能性。方法人宫颈癌细胞系HeLa重复照射12次后,传代培养调整细胞状态至细胞增殖稳定,筛选得抗拒细胞系HeLaR。以2、5、10 Gy X射线分别照射亲代HeLa和HeLaR细胞,于照射后0、0.5、2、4、6、12、18、24、36、48 h收集细胞,提取蛋白质和RNA,采用Western blot和实时荧光定量PCR法分别检测样本中HMGB1蛋白和mRNA的表达情况。结果 在蛋白水平,2、5、10 Gy X射线照射后,HeLaR细胞在48 h内均表现为HMGB1表达量下降,在48 h达到未照射水平,后有增加趋势,与照射后0 h比较,2、5、10 Gy照射后6~36 h各时间点,差异具有统计学意义（t=3.574~9.754,P < 0.05）;相反,HeLa细胞在照射后6 h,其HMGB1表达逐渐增多,尤其在5和10 Gy表现明显,与照射后0 h比较,2 Gy照射后6、12、48 h（t=3.945~4.864,P < 0.05）、5 Gy照射后6、36、48 h（t=-2.875~3.295,P < 0.05）及10 Gy照射后36、48 h（t=-4.480、-4.517,P < 0.05）,差异具有统计学意义。在mRNA水平其趋势与蛋白水平基本一致。结论 不同剂量X射线照射后可诱导人宫颈癌细胞中HMGB1的表达变化,且其变化在人宫颈癌放射敏感细胞及放射抗拒细胞中不同。HMGB1可能参与人宫颈癌放射抗拒机制。     

Concurrent Etoposide,Steroid, High-dose Ara-C and Platinum chemotherapy with radiation therapy in localised extranodal natural killer (NK)/T-cell lymphoma,nasal type

PurposeRadiation combined with chemotherapy has recently been proposed to treat patients with localised extranodal natural killer (NK)/T lymphoma (ENKTL), nasal type. However, the modalities of the chemoradiotherapy combination and drug choices remain a matter of debate. We conducted a concurrent chemoradiotherapy (CCRT) study with the ESHAP (Etoposide, Steroid, High-dose Ara-C and Platinum) regimen.MethodsAn induction phase with two upfront courses of CCRT delivering a 40 Gy dose of radiation concurrently with two cycles of the ESHAP chemotherapy regimen, followed by a consolidation phase with 2–3 cycles of ESHAP chemotherapy alone.ResultsThirteen patients with localised ENKTL nasal type were enrolled between January 2005 and December 2014. The median age was 62 years. Ten and three patients had Ann Arbor stage IE and IIE disease, respectively. They all completed the induction CCRT phase. A median of two consolidation ESHAP cycles were delivered. During consolidation, 8/13 (62%) patients had a reduction in the number of chemotherapy cycles or reduced chemotherapy doses, due to haematologically adverse events. The other five patients (38%) received the full number of ESHAP cycles of chemotherapy scheduled without a dose reduction. All but one patient (92%) experienced grade 3–4 haematological toxicity. The main non-haematological grade 3–4 toxicity was mucositis in 6/13 (46%) patients. All but one patient (92%) achieved a complete remission. Two-year overall survival was 72%.ConclusionsWith optimal management of the specific toxicities induced by this treatment modality, CCRT with the ESHAP regimen yielded high efficacy against localised ENKTL, nasal type.     

Long term outcomes of severe combined immunodeficiency: therapy implications

Introduction: Newborn screening has led to a better understanding of the prevalence of Severe Combined Immunodeficiency (SCID) overall and in terms of specific genotypes. Survival has improved following hematopoietic stem cell transplantation (HCT) with the best outcomes seen following use of a matched sibling donor. However, questions remain regarding the optimal alternative donor source, appropriate use of conditioning and the impact of these decisions on immune reconstitution and other late morbidities.

Areas covered: The currently available literature reporting late effects after HCT for SCID and use of alternative therapies including enzyme replacement, alternative donors and gene therapy are reviewed. A literature search was performed on Pubmed and ClinicalTrials.gov using key words ‘Severe Combined Immunodeficiency’, ‘SCID’, ‘hematopoietic stem cell transplant’, ‘conditioning’, ‘gene therapy’, ‘SCID newborn screening’, ‘TREC’ and ‘late effects’.

Expert commentary: Newborn screening has dramatically changed the clinical presentation of newborn SCID. While the majority of patients with SCID survive HCT, data regarding late effects in these patients is limited and additional studies focused on genotype specific late effects are needed. Prospective studies aimed at minimizing the use of alkylating agents and reducing late effects beyond survival are needed. Gene therapy is being developed and will likely become a more commonly used treatment that will require separate consideration of survival and late effects.     

葡萄糖酸锗对小鼠Lewis肺癌放射增敏效应实验研究

采用动物肿瘤模型实验方法探讨葡萄糖酸锗对肿瘤的放射增敏效应。结果显示 :治疗后单药组与对照组肿瘤平均体积比较无显著差异 (P>0 .0 5 ) ,用药加放射 2 0 ,2 5 Gy组肿瘤平均体积分别明显小于单放 2 0 ,2 5 Gy组 (P<0 .0 1) ,当肿瘤体积达到 4 .4 cm3 时 (原照射体积的 4倍 )测得放射增敏比为 1.5 8～ 1.7。说明本药具有放射增敏作用 ,并能使肿瘤放射敏感性提高 5 8%～ 70 %。     

马蔺子素放射增敏治疗食管癌的疗效观察

目的:为了观察马蔺子素配合放射治疗食管癌的增敏疗效及其毒副反应.方法:从1996年6月至1997年6月采用马蔺子素配合放疗治疗食管癌患者36例(增敏组)与单纯放疗组36例(对照组),进行临床观察.结果:肿瘤消退率在增敏组为 72.2%(26/36),对照组为 52.8%(19/36),两组间差异显著( P<0.05);肿瘤消失时照射总剂量,在增敏组为 56.2Gy,对照组为64.2 Gy,增敏比为1.13.临床症状改善,进食梗阻改善率,增敏组为75%(27/36),对照组为54%(20/36),胸背疼痛消失两组无明显差异;外周白细胞低于4×10~9/L者,增敏组为22%(8/36),对照组为42%(15/36);患者1年和2年生存率,增敏组为75%(27/36)和58%(21/36),对照组为61%(22/36)和42%(15/36).结论:实验研究表明马蔺子素与放疗合用治疗食管癌可提高肿瘤消退率和近期生存率,有显著的放疗增敏作用,对患者无特殊毒副作用,可能是目前较为理想的放射增敏剂.     

Isolation of radiosensitive and radioresistant mutants from a medulloblastoma cell line

Two mutant clones, one radiosensitive (OS-3) and one resistant (OR-5), were isolated from ONS-76 after screening 2400 clones by the replica micro-well technique. These two clones exhibited significantly different radiosensitivity, with D₃₇ values of 4.7 Gy in OR-5 and 1.7 Gy in OS-3. After gamma irradiation (8 Gy), OR-5 exhibited greater G2 arrest than sensitive clone OS-3. Administration of 5 mM of caffeine resulted in greater cell killing in OR-5 than in OS-3, with an almost complete release of G2 block. These observations support the notion that the G2 block contributes to the repair process of DNA damage after irradiation. The present results suggest that clones with a large postirradiation G2 block may show a greater reduction in radiosensitivity if the G2 block is released artificially. The study of the mutant clones described herein may provide important clues to the mechanism by which glioma cells acquire radioresistance.