Disrupted G1 to S phase clearance via cyclin signaling impairs liver tissue repair in thioacetamide-treated type 1 diabetic rats

Previously we reported that a nonlethal dose of thioacetamide (TA, 300 mg/kg) causes 90% mortality in type 1 diabetic (DB) rats because of irreversible acute liver injury owing to inhibited hepatic tissue repair, primarily due to blockage of G(0) to S phase progression of cell division cycle. On the other hand, DB rats receiving 30 mg TA/kg exhibited equal initial liver injury and delayed tissue repair compared to nondiabetic (NDB) rats receiving 300 mg TA/kg, resulting in a delay in recovery from liver injury and survival. The objective of the present study was to test the hypothesis that impaired cyclin-regulated progression of G(1) to S phase of the cell cycle may explain inhibited liver tissue repair, hepatic failure, and death, contrasted with delayed liver tissue repair but survival observed in the DB rats receiving 300 in contrast to 30 mg TA/kg. In the TA-treated NDB rats sustained MAPKs and cyclin expression resulted in higher phosphorylation of retinoblastoma (pRb), explaining prompt tissue repair and survival. In contrast, DB rats receiving the same dose of TA (300 mg/kg) exhibited suppressed MAPKs and cyclin expression that led to inhibition of pRb, inhibited tissue repair, and death. On the other hand, DB rats receiving 30 mg TA/kg exhibited delayed up regulation of MAPK signaling that delayed the expression of CD1 and pRb, explaining delayed stimulation of tissue repair observed in this group. In conclusion, the hepatotoxicant TA has a dose-dependent adverse effect on cyclin-regulated pRb signaling: the lower dose causes a recoverable delay, whereas the higher dose inhibits it with corresponding effect on the ultimate outcomes on hepatic tissue repair; this dose-dependent adverse effect is substantially shifted to the left of the dose response curve in diabetes.     

视网膜母细胞瘤抗原致敏的树突状细胞疫苗抗SO-RB50细胞系的实验研究

目的　研究视网膜母细胞瘤 (RB)抗原致敏的树突状细胞 (DC)疫苗体外特异性对RB细胞系SO RB50 杀伤作用 ,为进一步研究RB的治疗提供新的思路。方法　以RB细胞的蛋白抗原体外冲击致敏健康人 (正常对照组 )及RB患者 (患者组 )来源的成熟DC ,并将其与自体T细胞混合培养 ,诱导出抗SO RB50 的特异性细胞毒性T淋巴细胞 (CTL) ,以Burkitt淋巴瘤Raji细胞作为对照靶细胞 ,采用噻唑蓝 (MTT)分别比较CTL对SO RB50 和Raji细胞的杀伤率及正常对照组与RB患者组来源特异性杀伤率的组间差异性。结果　对SO RB50 与Raji 2种靶细胞 ,正常对照组和RB患者组的CTL细胞毒作用均随着效靶比的增加而增加 ,对SO RB50 细胞的杀伤作用各效靶比均强于相应效靶比的Raji细胞(P <0 .0 1) ;各效靶比正常对照组CTL对SO RB50 细胞的特异性杀伤作用均显著强于RB患者组CTL(P <0 .0 1) ;而各效靶比正常对照组与RB患者组CTL对Raji细胞的非特异性杀伤作用则相近 ,两者比较 ,差异无显著意义 (P >0 .0 5 )。结论　应用RB抗原负载DC可诱导出针对SO RB50 细胞抗原特异性的CTL ,这种方法对RB的治疗可能具有潜在的临床应用价值。     

The technique of ophthalmic arterial infusion therapy for patients with intraocular retinoblastoma

Recently, there has been increasing interest in treating intraocular retinoblastoma with systemic chemotherapy combined with focal laser therapy and cryotherapy instead of radiotherapy. We developed a system of selective ophthalmic arterial infusion (SOAI) therapy, administering melphalan, the agent which had the greatest effect on retinoblastoma in a clonogenic assay. The SOAI system consists of a combination of a micro-balloon, a guiding catheter, and a flushing hub. After selective catheterization to the cervical segment of the internal carotid artery by the guiding catheter, the micro-balloon was propelled to the portion just distal to the orifice of the ophthalmic artery. During temporary occlusion of the internal carotid artery, melphalan was infused from the introduced catheter tip. We treated 187 patients with intraocular retinoblastoma with SOAI; 563 SOAIs were performed for 610 eyes. The technical success rate was 97.51%. Fourteen examinations failed. No significant complication due to catheterization (including brain infarction) was detected. SOAI, using the balloon occlusion technique, is safe, and its use will prevent the side effects that occur with systemic chemotherapy, and eliminate the need for irradiation and enucleation.     

p16、Rb蛋白在胸腺癌中表达及与预后的关系

[目的］检测p16、Rb蛋白在胸腺癌中表达及预后的意义。[方法]应用免疫组织化学方法（SP）法,对54例胸腺癌标本进行检测。[结果]p16、Rb蛋白在良、恶性胸腺癌及胸腺癌中阳性表达率分别为66.67％（12/18）、70．00％（14／20）、31．25％（5／16,p＜0.05）;61．11%（11周/18)、75．00%（15/20）、43.70%（7/16,P＜0．05）。p16、比蛋白阳性表达与胸腺癌的类型、临床分期、预后有关。〔结论〕p16、Rb蛋白参与胸腺癌细胞增殖并影响其分化,可作为监测预后有效的指标。     

Oncogenic activities of human papillomaviruses

Infectious etiologies for certain human cancers have long been suggested by epidemiological studies and studies with experimental animals. Important support for this concept came from the discovery by Harald zur Hausen's group that human cervical carcinoma almost universally contains certain “high-risk” human papillomavirus (HPV) types. Over the years, much has been learned about the carcinogenic activities of high-risk HPVs. These studies have revealed that two viral proteins, E6 and E7, that are consistently expressed in HPV-associated carcinomas, are necessary for induction and maintenance of the transformed phenotype. Hence, HPV-associated tumors are unique amongst human solid tumors in that they are universally caused by exposure to the same, molecularly defined oncogenic agents, and the molecular signal transduction pathways subverted by these viral transforming agents are frequently disrupted in other, non-virus-associated human cancers.     

Rb基因产物与胆囊癌生物学特性的关系

目的 探讨Ｒｂ蛋白与胆囊癌的肿瘤生物学行为的关系。方法 采用免疫组化ＳＰ染色方法检测４１例胆囊癌、７例胆囊腺癌及１４例胆囊炎石蜡标本Ｒｂ蛋白表达水平。结果 Ｒｂ蛋白表达阳性率在胆囊癌组为５８．７％，明显低于胆囊炎（１００％）及胆囊腺瘤组（１００％）；且低分化癌组与高、中分化癌组，Ｓ４、Ｓ５期与Ｓ１、Ｓ２、及Ｓ３期比较均有显著性差异（Ｐ〈０．０５）。结论 Ｒｂ蛋白表达与胆囊癌的分化程度、浸润深度及预     

化学减容治疗眼内期视网膜母细胞瘤

目的观察眼内期视网膜母细胞瘤患儿接受化学减容治疗的疗效。方法对2000年1月至2004年12月间于中山眼科中心行化学减容治疗眼内期视网膜母细胞瘤的9例患儿10只眼进行观察分析。其中男性5例，女性4例；单侧1例，双侧8例。首次就诊时平均年龄为31个月（11-95个月），首次化疗时平均年龄为36．1个月（11-97个月）。结果5只眼（5例患者）化疗效果较好，化疗结束后基底直径平均减少了31．1％（-0．2％-59．3％），厚度平均减少了50．6％（28．6％-83．2％），其中1例在化疗结束18个月后肿瘤复发行眼球摘除，其余4例随访至今（平均20个月）无复发及转移。4只眼在治疗中肿瘤持续长大或出现新的病灶而行摘除眼球；1例因出现脑转移在化疗2个疗程后死亡。眼球保留率为40％。所有9例患者可耐受化疗引起的副作用，无严重并发症发生。结论化学减容对眼内期视网膜母细胞瘤有一定的疗效，是一种有潜力的保守治疗方法。     

Genomic DNA Analysis of Rat Retinal Tumor Induced by Adenovirus Type 12

To elucidate the pathogenesis of human retinoblastoma, we investigated the genomic expression in retinal tumors induced by human adenovirus type 12 in rats, using various DNA probes. Seven rats received a single intraocular inoculation of concentrated virus fluid within 24 hours after birth. Intravitreous tumors were induced in two out of seven animals (28.5%) within 30 to 64 days after the inoculation. A remarkably uniform histologic feature, i.e., neuroblastic cells in association with Homer-Wright pseudorosettes, was present in all cases. The adenovirusrelated oncoprotein gene E1A and human retinoblastoma susceptibility gene were detected in the tumors by Southern blot hybridization. In situ hybridization analysis demonstrated expression of adenovirus type 12 E1A gene in the inner granular layer of the retina. It was suggested that integration of adenovirus type 12 E1A fragment with the host genome and expression of the gene were required for induction of this tumor.     

羟基磷灰石义眼台对视网膜母细胞瘤患儿眼眶发育的影响

目的:探讨对视网膜母细胞瘤(RB)患儿实施羟基磷灰石(HA)义眼台植入术后对其眼眶发育的影响及植入的最佳时机。方法:对8例一期植入患儿和11例二期植入患者进行长期随诊,并对其健、患侧眼眶发育情况进行观察比较。结果:羟基磷灰石义眼台一期植入者其健、患侧眼眶发育无显著差异(P>0.05),二期植入者其差异有显著性(P<0.01)。结论:视网膜母细胞瘤患儿行眼球摘除术后应及时放置合适的义眼台以促进其眼眶发育。