Ki-67、增殖细胞核抗原、P53在脑膜瘤中的表达及意义

目的 :通过对 Ki- 6 7、增殖细胞核抗原、P5 3在脑膜瘤中的表达 ,进一步研究其与肿瘤的良、恶性及肿瘤复发的关系 ,从而更好判断其生物学行为。方法 :行脑膜瘤全切除手术治疗 ( Simpson's Grade or Grade )并经 9～12 4个月 ( 4 8± 9)随访的 6 0例 ,采用 SP免疫组化法 ,检测手术切除石蜡包埋的肿瘤标本的 Ki- 6 7、增殖细胞核抗原、P5 3抗原 ,以显微镜下的细胞核内出现棕色颗粒为阳性 ,计算 3者的标记指数 ( L abeling Index) .对患者的临床资料与肿瘤细胞的标记指数的差异性进行统计学分析。结果 :Ki- 6 7、增殖细胞核抗原、P5 3在不同病理形态脑膜瘤中的表达具有显著性差异 ( P<0 .0 5 ) ,恶性脑膜瘤、非典型性脑膜瘤中的表达明显高于良性脑膜瘤 ;同样在复发性脑膜瘤中其表达也明显高于非复发性脑膜瘤 ( P<0 .0 5 ) ;良性脑膜瘤中 Ki- 6 7、增殖细胞核抗原的表达在复发组明显高于非复发组 ( P<0 .0 5 ) ,而 P5 3的表达在复发组与非复发组无统计学意义 ( P>0 .0 5 )。结论 :( 1) Ki- 6 7、增殖细胞核抗原、P5 3的表达与病理分型和脑膜瘤术后复发有关。 ( 2 )良性脑膜瘤结合 Ki- 6 7、增殖细胞核抗原的表达情况可用来判断预后即有无复发的可能 ,从而进一步来指导临床治疗     

肾盂输尿管癌细胞增殖与凋亡的相关性

目的探讨Ki-67和凋亡（Apoptosis）在肾盂输尿管癌中的表达及其与肿瘤细胞分级、病理分期及预后的关系。方法采用SABC法和TUNEL法对34例肾盂输尿管癌行Ki-67和凋亡检测。结果Ki-67和凋亡在肿瘤细胞分级间存在显著差异,Ki-67index：G2与G1比较P〈0.05,G3与G2比较P〈0.05,G3与G1比较P〈0.01;Apoptosis index：G2与G1比较P〈0.05,G3与G2比较P〈0.05,G3与G1比较P〈0.01。Ki-67和凋亡在肿瘤病理分期的T3与T1及T2与T1之间有显著差异,T2与T1比较P〈0.05,T3与T1比较P〈0.01,但T3与T2比较P〉0.05;Ki-67index以20%为界分为二组,Apoptosis index以3%为界分为二组,组间生存率有显著差异（P〈0.05）。Ki-67在肾盂输尿管癌中的表达与凋亡一致。结论肾盂输尿管癌细胞增殖与凋亡密切相关;凋亡可作为临床判断肾盂输尿管癌恶性程度、病理分期、细胞分级以及预后的一种客观量化指标。     

尖锐湿疣中乳头瘤病毒感染与P53和ki-67表达的关系

目的　探讨尖锐湿疣中乳头瘤病毒 (HPV)感染与 P5 3和 ki- 6 7的关系。　方法　采用免疫组织化学方法对 82例尖锐湿疣的 HPV感染、P5 3和 ki- 6 7的表达进行观察。　结果　 HPV阳性者 2 4例 (2 9.3% ) ,P5 3阳性表达 2 0例 (2 4 .4 % ) ,ki- 6 7阳性表达 2 1例 (2 5 .6 % )。2 4例 HPV阳性者中 ,P5 3阳性表达 10例 (41.7% ) ,ki- 6 7阳性表达 11例 (45 .8% ) ,经关联分析 ,皮损中 HPV感染与 P5 3(χ2 =4 .2 4 7,P<0 .0 5 )和 ki- 6 7(χ2 =5 .6 8,P<0 .0 5 )阳性表达均有显著关联 ;而 P5 3与 ki- 6 7两者均阳性者仅有 6例 (χ2 =0 .98,P>0 .0 5 ) ,无明显关联。　结论　在尖锐湿疣中 HPV感染伴随 P5 3和 ki- 6 7表达的增加     

67Ga心肌炎症显像对小儿病毒性心肌炎的诊断价值

目的 :探讨6 7Ga心肌显像对小儿病毒性心肌炎 (VMC)诊断的临床价值。方法 :静脉注射6 7Ga 枸橼酸盐 ,48h、72h后开始显像 ,观察心脏部位放射性浓聚情况 ,并计算心 /肺 (H/L)指数 ,根据H/L指数判断心肌炎性病变的严重程度 (H/L指数 >1.2为阳性 )。结果 :78例病毒性心肌炎患儿中 ,50例阳性 (占 64% ) ,其中急性期阳性率为 84% ,恢复期阳性率为 50 % ,慢性期为 2 9% ,急性期阳性率明显高于恢复期和慢性期 (P<0 .0 5)。结论 :心肌6 7Ga放射性浓聚与心肌炎病变程度呈正相关 ,直接反映了病变心肌的炎症反应情况 ,对诊断VMC有较高的临床价值 ,并对VMC治疗、预后有指导作用     

Relationship between apoptosis and proliferation in secondary tumors of the brain

A correlation between apoptosis and proliferation in astrocytomas and oligodendrogliomas, but not in glioblastomas, has been previously reported. An index for apoptosis and proliferation was established for each tumor in a series of 20 brain metastases, and its correlation was studied using the Spearman rank correlation test. Apoptosis index (AI) ranged between 1 and 78% (mean ± SD: 11.48 ± 16.4). Proliferation index (PI) ranged between 2.4 and 21% (mean ± SD: 8.23 ± 4.8). When the relationship between AI and PI was studied, a clear correlation was found (r: 0.8965, 95% CI: 0.74–0.95; P < 0.0001). Therefore, it is concluded that a clear correlation exists between proliferation and apoptosis in secondary tumors of the brain.     

Potential doubling time and tumour doubling time in meningiomas and neurinomas

Summary Cell kinetic study plays an important role in treatment planning of brain tumour patients. MIB-1 antibody has recently become available, which detects Ki-67 antigen even in the formalin-fixed paraffin-embedded specimens. We performed MIB-1 immunostaining in 50 meningiomas and 50 neurinomas, and estimated the cell cycle time (tc) and potential doubling time (Tpot) from MIB-1 staining index (MIB-1 SI) and mitotic index (MI). MIB-1 SI logarithmically correlated with MI in both meningiomas and neurinomas. The tc and the Tpot were expressed as a function of the mitosis time (tm), while the tm is known to be around one hour and not exceeding two hours. When the tm was assumed to be one hour, the average tcs of meningiomas and neurinomas were 6.53±3.56 days and 7.67±3.27 days, respectively. The Tpots were447 × (MIB-1 SI)^–1.29 × tm in meningiomas, and490 × (MIB-1 SI) ^–0.98 × tm in neurinomas.The tumour doubling times (Tds) were calculated from serial imaging studies in 22 neurinomas and 15 meningiomas. The Tds were formulated as794 × (MIB-1 SI) ^–0.83 in meningiomas and1380 × (MIB-1 SI) ^–0.97 in neurinomas. Most of the Tds correlated well with the Tpots in meningiomas and neurinomas, and exceeded values of the Tpot when the tm is assumed to be one hour, although a few tumours showed unexpectedly longer Tds. The Tpot and the tc estimated from MIB-1 SI and MI are clinically useful parameters for predicting the growth potential of meningiomas and neurinomas where no other simple methods are available.     

Histochemical study of pituitary adenomas with Ki-67 and anti-DNA polymerase α monoclonal antibodies,bromodeoxyuridine labeling,and nucleolar organizer region counts

Summary The growth potential of 65 pituitary adenomas was determined by histochemical analysis with Ki-67 and anti-DNA polymerase monoclonal antibodies, bromodeoxyuridine (BrdUdR) labeling, and counts of argyrophilic nucleolar organizer regions (Ag-NORs). The mean proliferating cell indices (PCIs) determined by Ki-67 and anti-DNA polymerase and the BrdUdR labeling index (LI) were generally very low [1.0±0.2%, 1.1±0.2%, and 0.5±0.1% (±SE), respectively]. Apart from adrenocorticotropic hormone-positive adenomas, which had significantly higher indices, there were no statistically significant differences in the indices among the other subtypes of pituitary adenomas. Recurrent tumors had higher Ki-67 and DNA polymerase PCIs and BrdUdR LIs (3.6%, 4.2%, 1.4%) than primary tumors (0.8%, 0.8%, 0.3%; P<0.005). The number of Ag-NORs did not correlated significantly with any of the three indices. The mean number of Ag-NORs was higher in nonfunctioning adenomas than in functioning adenomas (2.04 vs 1.66, P<0.005); among prolactin-positive adenomas, those treated preoperatively with bromocriptine had more Ag-NORs than untreated tumors (1.75 vs 1.57, P<0.005). These results suggest that the Ki-67 and DNA polymerase PCIs and the BrdUdR LI predict the growth potential of individual pituitary adenomas, whereas the number of Ag-NORs appears to correlate with hormone production rather than with the proliferative potential.Supported by grants CA-13525 and CA-50210 from the National Cancer Institute, by a grant from the Phi Beta Psi Sorority, and by Grant-in-Aid A 63771083 from the Ministry of Education, Science, and Culture of Japan     

Prodrugs of 5-Iodo-2′-Deoxyuridine for Enhanced Ocular Transport

Problems associated with the use of 5-iodo-2-deoxyundine (IDU) in the treatment of herpes simplex keratitis can be attributed largely to the polar nature of IDU resulting in its poor permeability across the lipoidal epithelial layer of the corneal membrane. Five aliphatic 5-esters of IDU were synthesized and evaluated as prodrugs for potential use in the treatment of deep ocular infections such as stromal keratitis, iritis, and even retinitis. A parabolic relationship between in vitro corneal membrane permeability and carbon chain length of prodrugs is evident. For a given prodrug, enzymatic hydrolysis proceeded most readily in iris–ciliary body, followed by cornea and aqueous humor. An increase in carbon chain length made the prodrugs more enzymatically labile but more resistant to chemical hydrolysis at pH 7.4 and 34°C. The 5-butyryl ester of IDU exhibited an approximately fourfold increase in aqueous humor IDU concentration relative to IDU at 25 min following instillation of 25-µl 5 mM solutions.     

Correlation between the Ki-67 antigen in the brainstem and physiological data on sleep apnea in SIDS victims

Background: The Ki-67 antigen appears in all human proliferating cells during late G1, S, M and G2 phases of the cell cycle, but is consistently absent in the G_o phase (noncycling) cells. The correlation between Ki-67 in the brainstem and sleep apnea in victims of the sudden infant death syndrome (SIDS) was investigated to elucidate cell kinetics in the brainstem of this condition, which is still the main cause of postneonatal infant death. Materials and methods: Twenty-six cases of SIDS occurred among 38 infants dying under 6 months of age in a cohort of 27,000 infants studied prospectively to characterize their sleep–wake behavior. All the infants had been recorded during one night in a pediatric sleep laboratory some 3–12 weeks before death. The frequency and duration of sleep apnea were analyzed. At autopsy, brainstem material was collected and immunohistochemistry for Ki-67 was carried out. The density of Ki-67-positive neurons was measured semiquantitatively. Correlation analyses were carried out between the density of Ki-67-positive neurons and the data on sleep apnea. Results: Except in two cases in SIDS victims and in one control, the detection of Ki-67 was negative. No correlation analysis between the Ki-67 and of sleep apnea was found. Conclusions: There were no abnormal cell kinetics detected by the demonstration of Ki-67 antigen in the brainstems of SIDS victims.