The Ki-67 protein interacts with members of the heterochromatin protein 1 (HP1) family: a potential role in the regulation of higher-order chromatin structure.

The expression of the nuclear protein Ki-67 (pKi-67) is strictly correlated with cell proliferation. Because of this, anti-Ki-67 antibodies can be used as operational markers to estimate the growth fraction of human neoplasia in situ. For a variety of tumours, the assessment of pKi-67 expression has repeatedly been proven to be of prognostic value for survival and tumour recurrence, but no cellular function has yet been ascribed to the Ki-67 protein. This study shows that a C-terminal domain of pKi-67 (Kon21) is able to bind to all three members of the mammalian heterochromatin protein 1 (HP1) family in vitro and in vivo. This interaction can be manipulated in living cells, as evidenced by ectopic expression of GFP-tagged HP1 proteins in HeLa cells, which results in a dramatic relocalization of endogenous pKi-67. Taken together, the data presented in this study suggest a role for pKi-67 in the control of higher-order chromatin structure.     

TIPE2 Ki67在子宫内膜癌组织中的表达及对预后的评估价值

目的 探讨肿瘤坏死因子诱导蛋白8样蛋白2(TIPE2)、细胞增殖核抗原Ki67在子宫内膜癌组织中的表达及对患者预后的评估价值。方法 选取2018年1月至2020年1月河北工程大学附属医院妇科收治的子宫内膜癌患者120例作为观察组,另选取同期收治的非子宫内膜癌患者130例作为对照组,所有入组患者均接受手术治疗。回顾性收集患者的临床及病理资料,比较两组患者子宫内膜组织中TIPE2、Ki67的表达水平。同时定期对观察组患者进行随访,分析患者2年生存情况,通过Cox比例风险回归模型分析子宫内膜癌患者预后的影响因素。结果 观察组、对照组子宫内膜组织中TIPE2阳性率分别为28.33%、71.54%。与对照组相比,观察组子宫内膜组织TIPE2阳性率降低（P<0.05）;观察组、对照组子宫内膜组织中Ki67阳性率分别为33.33%、5.38%。观察组子宫内膜组织Ki67阳性率高于对照组（P<0.05）。对120例子宫内膜癌患者随访2年,至随访结束,93例患者存活,生存率77.50%。Cox模型分析结果显示,TIPE2阴性（HR=3.736,95%CI=1.016～13.157）为子宫内膜...     

Hydrolysis of Carbonates,Thiocarbonates, Carbamates,and Carboxylic Esters of α-Naphthol, β-Naphthol,and p-Nitrophenol by Human,Rat, and Mouse Liver Carboxylesterases

Thirty carbonates, thiocarbonates, carbamates, and carboxylic esters of -naphthol, -naphthol, and p-nitrophenol were synthesized and tested as substrates for liver carboxylesterases from the crude microsomal fractions of human and mouse, and purified isozymes, hydrolases A and B, from rat liver microsomes. The carbonates, thiocarbonates, and carboxylic esters of -naphthol were cleaved more rapidly than the corresponding -naphthol isomers by the mammalian liver esterases. -Naphthyl esters of acetic, propionic, and butyric acids were among the best substrates tested for these enzymes. The majority of the substrates was consistently hydrolyzed at higher rates by hydrolase B compared with hydrolase A, although the Michaelis–Menten constant (K _m) values of selected substrates differed widely with these two isozymes. Malathion was a 15-fold better substrate for hydrolase B than for hydrolase A. Compared with the corresponding carboxylates, the carbonate moiety of - and -naphthol and p-nitrophenol lowered the specific activities of the enzymes by about fivefold but improved stability under basic conditions. The optimum pH of mouse liver esterase with the acetate, methylcarbonate, and ethylthiocarbonate of -naphthol was between pH 7.0 and pH 7.6. Human and mouse liver microsomal esterase activities were about five orders of magnitude lower than the esterase activities of purified rat liver hydrolase B. A relationship between the catalytic activity of the enzymes and the lipophilicity of the naphthyl substrates indicated that (i) in the - and -naphthyl carbonate series, an inverse relationship between enzyme activity and lipophilicity of the substrates was observed, whereas (ii) in the -naphthyl carboxylate series, an increase in enzyme activity with increasing lipophilicity of the substrates up to a log P value of about 4.0 was observed, after which the enzyme activity decreased.     

p53基因表达，细胞增殖抗原Ki—67与下咽癌关系的探讨

目的 :探讨p53基因、细胞增殖抗原Ki 67在下咽癌临床分期、淋巴结转移及预后中的作用。方法 :应用免疫组织化学LASB法检测 84例下咽鳞癌石蜡标本 ,研究p53蛋白、细胞增殖抗原Ki 67的表达并与临床因素进行统计分析。结果 :下咽癌中p53阳性率为 52 4 % ;Ki 67标示率为 0～ 7% ,平均为 10 63% ,中位数为 7 2 5%。淋巴结转移组与非转移组Ki 67表达差异有显著性 (P <0 0 1)。结论 :p53基因表达可作为下咽癌诊断的标志物之一 ,Ki 67可作为临床预测下咽癌颈淋巴结转移及预后的重要参考指标。     

人脑胶质瘤Tenascin基因表达与侵袭相关性

目的 探讨Ｔｅｎａｓｃｉｎ和Ｋｉ－６７在不同级别人脑胶质瘤细胞表达情况,分析它与胶质瘤细胞的侵袭相关性。方法 采用原位杂交和化学方法,检测不同级别人脑胶质瘤组织５０例中,Ｔｅｎａｓｃｉｎ和Ｋｉ－６７表达,以细胞核增殖抗原Ｋｉ－６７表达,经细胞核增殖抗原Ｋｉ－６７阳性细胞数分析胶质瘤细胞的增殖情况,结果 胶质瘤与其增生血管内皮细胞均表达Ｔｅｎａｓｃｉｎ,Ｔｅｎａｓｃｉｎ基因表达与肿瘤细胞增殖指数呈显     

Clinical,cytological, and pathological characteristics of metastatic renal cell carcinoma to the thyroid: A study of 14 cases at a Japanese single institution

A preoperative diagnosis of metastatic renal cell carcinoma to the thyroid (MRCCT) is important for determining clinical management but is challenging even in cases with a clinical history of renal cell carcinoma (RCC). This study aimed to elucidate the clinical, cytological, and pathological characteristics of MRCCT. Fourteen MRCCT cases extracted from 18 320 malignant thyroid tumors were included in this study. Twelve MRCCT (85.7%) occurred as solitary lesions and the most frequently suspected lesions on ultrasonography were follicular tumors. On cytology, 46.2% of cases were reported as RCC or suspected RCC; a medical history of RCC and immunocytochemistry were helpful in interpretation. RCC metastasized to a follicular adenoma in 50.0% of the solitary lesions. MRCCTs with a long interval from the initial presentation, solitary lesion, and Ki-67 labeling index <10% showed significantly longer disease-free survival. MRCCT is characterized by a long interval from the initial presentation of RCC, appearance as a solitary nodule, ultrasonographic similarity to follicular tumors, sharing cytological findings with primary thyroid tumors, and high frequency of metastasis within follicular adenoma. A long interval from the initial presentation, occurrence as a solitary lesion, and low Ki-67 labeling index may be favorable prognostic factors.     

Selective incorporation of111In-labeled PHOTOFRIN™ by glioma tissuein vivo

The use of PHOTOFRIN for photodynamic therapy of human gliomas has been studied by i.v. administration and laser photosensitization. Defining the uptake of PHOTOFRIN in the patient's tumor in comparison with the surrounding normal brain tissue is highly desirable for patient selection and study ofin vivo kinetics. We utilized a non-invasive approach to the detection of PHOTOFRIN uptake in brain tumors with¹¹¹In-oxine radiolabeled PHOTOFRIN and external imaging and quantitation using a gamma camera. Biodistribution of¹¹¹In-labeled PHOTOFRIN in 13 organs was determined in four dogs and 15 mice with gliomas.^99mTc-DTPA was used as a control for nonspecific uptake. The greatest concentration of¹¹¹In-PHOTOFRIN in the brain tumor occurred at 24 hours post i.v. administration. The brain tumor PHOTOFRIN uptake was seven times greater than that of normal brain. The decreased blood background at 72 hours made this the optimum time for imaging. Specific tumor tissue uptake of¹¹¹In-PHOTOFRIN occurred, well beyond that resulting from blood-brain-barrier (BBB) breakdown.     

Triple approach for diagnosis and grading of meningiomas: Histology,morphometry of Ki-67/feulgen stainings,and cytogenetics

Summary With regard to meningioma grading and the recently introduced atypical meningioma, we evaluated 160 cases retrospectively by conventional histology and image analysis. For that, the cell nuclei were stained with a Ki-67 (MIB1)/Feulgen-method on paraffin sections, thus enabling the assessment of both the Ki-67 proliferation index and nuclear morphometric features, such as tumour cell arrangement, nuclear pleomorphism, and cellularity.It could be demonstrated that the Ki-67 proliferation index is the most important criterion for distinguishing anaplastic meningiomas (WHO grade III) (mean Ki-67 index: 11%) from those of common type (WHO grade I) (mean Ki-67 index: 0.7%). The parameter for the relative volume weighted mean nuclear volume is another valuable morphometric feature. The atypical meningioma (WHO grade II) which should represent an intermediate category between common type and anaplastic meningiomas is characterized by a mean Ki-67 proliferation index of 2.1%. Common type meningiomas which comprise almost 50% of the cases of this series have a relapse rate of 9%. Atypical and anaplastic meningiomas recurred in 29% and 50%, respectively. Since the term atypical meningioma is confusing in the context of tumour grading, the term intermediate type meningioma is proposed.Furthermore, the results of cytogenetic analyses of 142 cases of this series were evaluated and compared with the meningioma grades. Thereby, 25 cases disclosed, independent of the typical loss of one chromosome 22, cytogenetic features assumed to be progression-associated, e.g., the gain or loss of different chromosomes and the deletion of the short arm of one chromosome 1 (hyperdiploidy, increased hypodiploidy, Ip-), when correlated to the histological and morphometric findings or the high relapse rate.For meningioma diagnosis and grading, a practical guideline is proposed based upon histology, morphometry (Ki-67), and cytogenetics.     

Expression of BCL-2 oncoprotein on tumor cells and tumor-infiltrating lymphocytes (TIL) in meningiomas

The Expression of the antiapoptotic oncoprotein BCL-2 and its correlation to tumor grade in 62 meningiomas (48 classic, 9 atypical, and 5 anaplastic) using single and double immunohistochemistry was investigated. BCL-2 expression was found in two different cell populations identified as lymphocytes (BCL-2+CD3+) and tumor cells (BCL+/CD3–). Tumor-infiltrating lymphocytes (TIL) (CD3+) were found within classic (9.5% of cells), atypical (2.4% of cells), and anaplastic (1.8% of cells) meningiomas. In classic meningiomas, 66.5% of TIL were BCL-2-positive, in atypical meningiomas 79.2%, and in anaplastic meningiomas 37.9%. In 33 (68.8%) of the classic meningiomas, medium to high counts of BCL-2+ tumor cells were detected. Atypical meningiomas showed nearly equal percentages of high (two patients), medium (five patients), and low (two patients) BCL-2+ tumor cell counts, whereas anaplastic meningiomas showed only medium (two patients) and low (three patients) BCL-2 tumor cell counts or were BCL-2-negative (one patient). In summary, a significant inverse correlation between the number of BCL-2-positive tumor cells and tumor grade in meningiomas was found. These findings support the hypothesis of cell survival prolongation by the antiapoptotic ability of BCL-2 proto- oncogenes and demonstrate the prognostic relevance of BCL-2 immunoreactivity in meningiomas. Received: 10 June 1998 / Accepted: 23 February 1999