Tumor-specific lytic path “hyperploid progression mediated death”: Resolving side effects through targeting retinoblastoma or p53 mutant

A major advance was made to reduce the side effects of cancer therapy via the elucidation of the tumor-specific lytic path “hyperploid progression-mediated death” targeting retinoblastoma (Rb) or p53-mutants defective in G1 DNA damage checkpoint. The genetic basis of human cancers was uncovered through the cloning of the tumor suppressor Rb gene. It encodes a nuclear DNA-binding protein whose self-interaction is regulated by cyclin-dependent kinases. A 3D-structure of Rb dimer is shown, confirming its multimeric status. Rb assumes a central role in cell cycle regulation and the “Rb pathway” is universally inactivated in human cancers. Hyperploidy refers to a state in which cells contain one or more extra chromosomes. Hyperploid progression occurs due to continued cell-cycling without cytokinesis in G1 checkpoint-defective cancer cells. The evidence for the triggering of hyperploid progression-mediated death in RB-mutant human retinoblastoma cells is shown. Hence, the very genetic mutation that predisposes to cancer can be exploited to induce lethality. The discovery helped to establish the principle of targeted cytotoxic cancer therapy at the mechanistic level. By triggering the lytic path, targeted therapy with tumor specificity at the genetic level can be developed. It sets the stage for systematically eliminating side effects for cytotoxic cancer therapy.     

38例视网膜母细胞瘤的临床和误诊分析

目的 探讨视网膜母细胞瘤（retinoblastoma，RB）的临床特征、病理分类和误诊原因，尽可能减少错误的临床诊治。方法 对我科于1999-2004年间收集的38例临床诊断为视网膜母细胞瘤（retinoblastoma，RB）的病例资料进行回顾性分析。结果在38例疑似病例中，34例病理诊断为视网膜母细胞瘤，4例为Coats病。结论掌握相关的影像学知识和综合分析疑难病例的临床资料将有助于视网膜母细胞瘤的正确诊断和处理。     

肝细胞癌SCT表现特征与Rb,PCNA的关系

目的　探讨肝细胞癌 (HCC)SCT (spiralCT)表现特征与癌细胞中视网膜母细胞瘤基因(Rb)、增殖细胞核抗原 (PCNA)表达的关系。方法　对 39例 (41个病灶 )经手术病理证实且行SCT动、静脉双期增强扫描的肝细胞癌病例 ,观察每个病灶的SCT表现特征 :肿瘤的大小、包膜、侵袭危险性、强化类型和肝硬化情况。用免疫组化法检测癌组织中Rb ,PCNA表达 ,分析评价SCT表现特征与蛋白之间的关系。结果　HCCSCT图像中肿瘤大小、包膜形成、侵袭危险性、强化类型和周围肝组织有无硬化与Rb蛋白之间无统计学意义 (P >0 .0 5 )。肿瘤大小、侵袭危险性、强化类型与PCNA之间有统计学意义 (P <0 .0 5 )。结论　肝细胞癌的SCT表现特征与PCNA的表达相关 ,根据其表现特征 ,可在一定程度上推测肿瘤组织PCNA表达情况 ,这有助于HCC的早期诊断及治疗方案的选择     

Rb基因对人视网膜母细胞瘤株SO-Rb50的影响

目的：探讨视网膜母细胞瘤（Rb）的发生与Rb基因（Rb1）缺失、失活等异常的关系。方法：用逆转录病毒载体pDOR与全长4．7kb野生型Rb1cDNA构建逆转录病毒表达载体pDOR－Rb1+。用脂质体介导法将pDOR－Rb1+转入CRIP包装细胞系。结果：实验产生了0．5X105Cfu具有一次感染能力的重组逆转病毒。利用该病毒感染SO-Rb50，经G418筛选，获得了抗G418细胞群体。运用PCR及Southern杂交技术对转染细胞进行检测，结果表明该抗G418细胞中有完整的外源Rb1存在。Northern杂交发现其Rb1mRNA表达水平有所提高。对细胞群体生长速率、软琼脂集落形成能力的测定表明，外源Rb1的表达使SO-Rb50在软琼脂中集落形成能力降低，而群体生长速率无明显影响。结论：外源Rb1对SO-Rb50恶性表型有一定影响。     

Cerebral primitive neuro-ectodermal tumour following treatment of a unilateral retinoblastoma

Summary Cerebral primitive neuro-ectodermal tumour (PNET) occurring as a second primary malignancy in childhood is exceedingly rare. We present a 7-year-old boy who developed a proven supratentorial PNET five years after enucleation and radio-/chemotherapy for a sporadic, unilateral retinoblastoma with optic nerve invasion. The association with this malignant eye disease as well as the effect of irradiation and multi-agent chemotherapy on second tumour induction are evaluated.     

视网膜母细胞瘤的CT表现及临床价值

目的 探讨视网膜母细胞瘤的CT表现在其诊断、鉴别诊断中的价值。方法 回顾分析27例经病理或临床证实的视网膜母细胞瘤的CT表现。结果 视网膜母细胞瘤CT表现：27例均以眼球后部软组织肿块为特征，其中24例(25只眼)肿块内伴钙化；3例肿块无钙化，可见斑点状、斑片状低密度坏死及囊变。结论 CT可以显示肿瘤的形态、大小、内部特征及累及范围，有助于诊断和鉴别诊断。     

Tissue-specific tumor suppressor activity of retinoblastoma gene homologs p107 and p130

The retinoblastoma gene family consists of three genes: RB, p107, and p130. While loss of pRB causes retinoblastoma in humans and pituitary gland tumors in mice, tumorigenesis in other tissues may be suppressed by p107 and p130. To test this hypothesis, we have generated chimeric mice from embryonic stem cells carrying compound loss-of-function mutations in the Rb gene family. We found that Rb/p107- and Rb/p130-deficient mice were highly cancer prone. We conclude that in a variety of tissues tumor development by loss of pRB is suppressed by its homologs p107 and p130. The redundancy of the retinoblastoma proteins in vivo is reflected by the behavior of Rb-family-defective mouse embryonic fibroblasts in vitro.     

Molecular mechanisms of virus-induced carcinogenesis: the interaction of viral factors with cellular tumor suppressor proteins

Accumulating evidence indicates that tumor viruses represent a major etiological factor in a significant portion of human cancers. These cancers include human papillomavirus induced anogenital cancers, hepatitis B and C virus associated hepatocellular carcinomas, nasopharyngeal carcinomas and lymphomas linked to Epstein-Barr virus infection, and human T cell leukemia virus associated adult T cell leukemias. This review summarizes the recent progress made in understanding the molecular mechanisms of viral carcinogenesis, with a particular focus on the interaction of viral factors with cellular tumor suppressor proteins. The functional inactivation of tumor suppressor proteins may represent a common strategy by which several tumor viruses contribute to malignant cell transformation.Abbreviations EBV Epstein-Barr virus - E6AP E6-associated protein - HBV Hepatitis B virus - HCC Hepatocellular carcinoma - HPV Human papillomavirus - HTLV Human T cell leukemia virus - pRb Retinoblastoma protein - RB Retinoblastoma - SV40 Simian virus 40     

Expression of cyclin D1, retinoblastoma gene protein, and p16 MTS1 protein in atypical adenomatous hyperplasia and adenocarcinoma of the lung

 To clarify the events leading to the disruption of cell growth control that occurs during the development of pulmonary adenocarcinoma (AC), we used immunohistochemistry to evaluate the expression of G1 cycle regulators, cyclin D1, Rb protein (pRb), and p16 MTS1 protein and the tumour proliferation marker, Ki 67, both in AC of the lung and in its precursor lesion, atypical adenomatous hyperplasia (AAH). The frequency of lesions with cyclin D1 overexpression was relatively high in AAH (47–89%), but was decreased in early AC (28%) and overt AC (35%). The loss of pRb expression was rare in both AAH (0–18%) and early AC (0%), and was infrequent even in overt AC (13%). The loss of p16 expression was also relatively infrequent in both the premalignant and the malignant lesions (11–25%). Our results suggest that overexpression of cyclin D1 is an early event and plays an important part in tumorigenesis in the case of lung AC. However, cyclin D1 overexpression is not required for the development and maintenance of a malignant phenotype. It is likely that some cyclin D1-independent pathways other than Rb and p16 abnormalities have an important role in the malignant transformation from AAH to early AC. Received: 8 July 1997 / 26 September 1997     

Diagnosis of retinoblastoma by fine-needle aspiration and aqueous cytology

This article reports the cytodiagnosis of three cases of retinoblastoma in children aged 1.5, 2.5, and 5 yr. Two of them were diagnosed by fine-needle aspiration cytology of the primary tumor and one by aqueous cytology. The tumor cells were usually round to oval, small and uniform, with scanty cytoplasm; they generally occurred in closely packed clusters of variable sizes. We discuss the differential diagnosis of retinoblastoma with other round-cell tumors of childhood involving the orbit.