Clinicopathological aspects of therapy-related acute myeloid leukemia and myelodysplastic syndrome

Therapy-related myeloid neoplasm (t-MN) is a rare but devastating consequence of chemotherapy and/or radiotherapy used for the treatment of solid cancers and various hematologic malignancies. Our current understanding of the etiology is that hematopoietic clones that are contemporaneous with the primary cancer and resistant to the cytotoxic exposure have the potential to undergo selective expansion and transformation to t-MN. Consequently, a large proportion of cases are associated with adverse risk factors, resulting in limited effective treatment options. Despite the emergence of some therapies with promising activity in t-MN, most effects are short-lived and allogeneic stem cell transplantation remains the only curative option for eligible patients. This review summarizes the current literature on t-AML and t-MDS, with the aim of providing practical recommendations on the clinical evaluation and management of these conditions.     

用99Tcm-HL91评价鼠心肌缺血模型

目的 探讨乏氧心肌显像剂99Tcm-4,9-二氮-3,3,10,10-四甲基十二烷-2,11-二酮肟(HL91)用于诊断实验性缺血心肌的价值.方法 建立大鼠心肌在体缺血再灌注模型,采用体外放射自显影法检测正常对照组(6只)、缺血再灌注组(8只)及无再灌注组(8只)鼠心肌对99Tcm-HL91的摄取.结果 对照组和无再灌注组心肌未见局灶性放射性浓聚,再灌注组心肌非坏死区有较高放射性浓聚,与正常心肌组织的摄取比值为1.634±0.354.结论 99Tcm-HL91表现出较强的亲乏氧组织特性,能较好区分存活和梗死心肌.     

99Tcm-HL91乏氧显像在甲状腺结节良恶性鉴别诊断中的应用

目的 评价99Tcm4,9-二氮-3,3,10,10-四甲基十二烷-2,11-二酮肟(HL91)对甲状腺结节良恶性鉴别诊断的临床价值.方法 对58例经触诊或超声检查存在甲状腺结节的患者进行99Tcm-HL91甲状腺早期(10 min)及延迟(4 h)平面显像,应用感兴趣区(ROI)技术计算靶/非靶(T/N)比值并进行比较.组间比较采用成组设计两样本均数t检验,率的比较用χ2检验.结果 患者均经手术或细针穿刺病理检查,其中21例为甲状腺癌,37例为甲状腺良性结节.99Tcm-HL91显像诊断甲状腺癌的灵敏度、特异性和准确性分别为85.7%,94.6%和91.4%,不同甲状腺癌病理类型的显像灵敏度差异无统计学意义(χ2=0.778,P＞0.05),但结节越大灵敏度越高.甲状腺癌与甲状腺良性结节组早期及延迟相T/N比值分别为1.07±0.04,1.25±0.03和0.92±0.10,0.91±0.12,组间在10 min时T/N比值差异无统计学意义(t=1.900,P＞0.05),4 h时T/N比值差异有统计学意义(t=3.885,P＜0.001).结论 用99Tcm-HL91乏氧显像判断甲状腺结节的良恶性有一定的临床价值,显像时间以4 h为佳.     

用ROC曲线法分析99Tcm-HL91肺肿瘤阳性显像的诊断效能

目的探讨半定量分析及接受器工作特性(ROC)曲线法在99Tcm-4,9-二氮-3,3,10,10-四甲基十二烷-2,11-二酮肟(HL91)肿瘤阳性显像鉴别肺部良恶性肿块中的价值.方法经CT检查发现肺部肿块的患者50例,均经活组织检查或手术病理检查证实.根据病理检查结果分为恶性组37例和良性组13例.术前行99Tcm-HL91 2 h、4 h平面显像及4 h断层显像,分别使用视觉判断法、半定量分析及ROC曲线法分析显像结果.结果①视觉判断法99Tcm-HL91显像的灵敏度、特异性和准确性分别为97.3%、69.2%和90.0%.②肿瘤/正常肺组织(T/N)比值半定量分析及ROC曲线法恶性组2 h、4 h平面显像及4 h断层显像T/N比值分别为1.52±0.19、1.73±0.28及2.84±0.97;良性组分别为1.20±0.16、1.24±0.20及1.52±0.40.各个时相的曲线下面积分别为0.909±0.056、0.945±0.039、0.953±0.034.从99Tcm-HL91断层显像ROC曲线的界值点找到1个界点(T/N=1.76),以其作为判断良、恶性的诊断阈值,灵敏度、特异性和准确性分别为100%、84.6%和96.0%.③视觉判断法与半定量分析法比较T/N比值半定量分析及ROC曲线法使诊断的灵敏度、特异性和准确性都有提高,尤其特异性.但两种方法间差异无显著性(P均＞0.05).结论半定量分析及ROC曲线法的诊断阈值可进一步提高99Tcm-HL91肺部肿瘤阳性显像的诊断效能.     

Lack of prostanoid receptor involvement in ischemic acute renal failure in mice

Background. Thromboxane (TX) A₂ inhibition or prostaglardin (PGI₂) infusion prevents ischemic acute renal failure (ARF) in animal models. However, the pathophysiological roles of the prostanoid receptors in the development of ischemic ARF are not fully understood, partly because of the limited specificity of their inhibitors or antagonists. Methods. We investigated whether targeted disruption of the PGI₂ receptor (IP) or TXA₂ receptor (TP) genes conferred susceptibility to renal ischemic-reperfusion injury, using IP and TP knockout mice. Results. Serum creatinine concentration in TP knockout mice was not significantly different from that in wild-type controls. There were no significant histological differences between TP knockout and wild-type mice. Likewise, IP knockout mice showed no significant differences from the wild-type controls in regard to creatinine concentration or histological damage. Conclusions. Lack of TP or IP had no influence on postischemic ARF in mice, indicating that receptors for TXA₂ or PGI₂ may have minimal roles in the development of this mouse model of ischemic ARF. Received: July 5, 2001 / Accepted: April 8, 2002     

TP53 mutations in prostatic cancer. Analysis of pre- and post-treatment archival formalin-fixed tumour tissue

The TP53 gene mutation pattern in prostatic cancer was examined in relation to progression and survival, using archival formalin-fixed pre-and post-treatment tumour specimens from 84 prostatic cancer patients. Thirty-four had hormone-sensitive tumours and 50 were hormone-resistant. Six of the 34 (18 per cent) therapy-responding tumours and 19 of the 50 (38 per cent) hormone-resistant tumours showed p53 protein accumulation in the post-treatment specimen. Both pre- and post-treatment specimens from these 25 patients were analysed for mutation of the conserved regions of the TP53 gene (exons 5–8), using constant denaturant gel electrophoresis (CDGE) followed by DNA sequencing. In the post-treatment samples, mutations were detected in three of the six patients with hormone-responsive tumours and in 11 of the 19 patients with hormone-resistant tumours. The three (100 per cent) patients with therapy-responsive tumours with mutations and nine of the 11 (82 per cent) patients with therapy-resistant tumours with mutations died of the disease. Thirteen of the 14 mutations in the post-treatment specimens were transitions, 11 occurring at CpG dinucleotides in which codon 273 was involved in ten. A significantly higher proportion of tumours with mutations were poorly differentiated compared with tumours without mutation (P<0·04). Our findings indicate that TP53 mutation is a late event in tumour development of the prostate gland and that codon 273 might be a ‘hotspot’ for mutation in the progression of the disease.     

The common heat shock protein receptor CD91 is up-regulated on monocytes of advanced melanoma slow progressors

Despite advances in our understanding of tumour immunology there is no therapy of proven survival benefit for advanced melanoma. Nevertheless, disease progression is slow in a small proportion of patients with metastatic melanoma, suggesting a contribution to outcome from host factors. Recent data have indicated the importance of the heat shock protein receptor CD91 in immune responses to, and progression of, infectious disease. Here we investigate the relationship between CD91 expression and outcome in malignancy. Rare melanoma patients were recruited with advanced disease that was progressing unusually slowly. CD91 expression on their monocytes was compared with control patients with more typical rapidly advancing metastatic disease. Th1 and Th2 cytokines, as well as innate and adaptive immune subsets, were also measured in the two groups. A significant increase in median CD91 expression levels was observed in slow progressors (P = 0.006). There were no differences in other immune subset markers or inflammatory cytokines. The ability of CD91 to internalize and cross-present tumour antigens through the major histocompatibility complex class I pathway may maintain CD8-positive cytotoxic T cell responses and contribute to slow progression of advanced melanoma.     

TP73-AS1在肿瘤中的表达及调控作用

<正>随着高通量测序技术的发展,成千上万种长链非编码RNA(long non-coding RNA,lncRNA)进入人们的视野。lncRNA是一类长度超过200个核苷酸并缺少开放阅读框的不具备蛋白质编码功能的RNA~([1-2])。研究发现lncRNA参与诸多生物学进程的关键步骤,包括染色质重塑、基因转录、转录后调节和蛋白质翻译等~([3-5])。LncRNA机制的不断被阐明,也为肿瘤的研究提供了新的可能。LncRNA在多种肿瘤的增殖、迁移侵袭和抗凋亡     

Chromosome aberrations in B-cell chronic lymphocytic leukemia: reassessment based on molecular cytogenetic analysis

In B-cell chronic lymphocytic leukemia (B-CLL) clonal chromosome aberrations are detected in approximately 40–50% of tumors when using conventional chromosome banding analysis. Most studies find trisomy 12 to be the most frequent chromosome aberration, followed by structural aberrations of the long arm of chromosomes 13 and 14. Trisomy 12 and the ”14q+” marker are associated with shorter survival times, while the patients with 13q abnormalities have a favorable outcome, similar to those with a normal karyotype. The development of molecular cytogenetic techniques has greatly improved our ability to detect chromosome aberrations in tumor cells. Using fluorescence in situ hybridization, chromosome aberrations can be detected not only in dividing cells but also in interphase nuclei, an approach referred to as interphase cytogenetics. The prevalence of specific aberrations in B-CLL is currently being reassessed by interphase cytogenetics. By far the most frequent abnormality are deletions involving chromosome band 13q14, followed by deletions of the genomic region 11q22.3-q23.1, trisomy 12, deletions of 6q21-q23, and deletions/mutations of the TP53 tumor suppressor gene at 17p13. The evaluation of the true incidence of these aberrations now provides the basis for more accurate correlations with clinical characteristics and outcome. Deletions/mutations of the TP53 gene have been shown to be associated with resistance to treatment and to be an independent marker for poor survival. 11q deletions have been associated with extensive nodal involvement, rapid disease progression, and short survival times. Whether trisomy 12, 13q14, and 6q deletions have a prognostic impact awaits further study. The application of these molecular cytogenetic techniques will also contribute to the identification of the pathogenetically relevant genes that are affected by the chromosome aberrations in B-CLL. Received: 2 February 1998 / Accepted: 31 March 1998