Cell kinetic markers in cutaneous squamous and basal cell carcinoma of the head and neck

IntroductionProliferation markers play a significant role in the biologic behavior of tumors. Geminin is a known inhibitor of the cell cycle and DNA replication and has not been previously reported in cutaneous basal and squamous cell carcinomas of the head and neck.ObjectivesWe aimed to investigate proliferation markers ki67, MCM2, and geminin in head and neck cutaneous basal and squamous cell carcinomas.MethodsForty cases of each tumor were immuostained with ki67, MCM2, and geminin followed by assessment of labeling indices (LIs). MCM2/ki67- and geminin/ki67-ratios were also determined; t-test was used for statistical analysis (p < 0.05).ResultsThere was no significant difference in ki67 (p = 0.06) and MCM2 (p = 0.46) between cutaneous basal and squamous cell carcinomas; however, geminin LI was significantly higher in squamous cell carcinomas compared to cutaneous basal cell carcinomas (p < 0.001). Only geminin/ki67 showed a significant difference between the two tumors with the ratio showing significantly higher numbers in squamous cell carcinomas (p = 0.015).ConclusionsGeminin could be regarded as an effective factor in the pathogenesis of head and neck cutaneous cutaneous basal cell carcinomas and squamous cell carcinomas and may be one of the responsible elements in the difference between the biologic behavior of these tumors.     

人T淋巴细胞白血病系Jurkat细胞中Cdtl和Geminin的表达

目的探讨细胞复制允许因子Cdtl和复制抑制因子Geminin在白血病细胞中的表达,为阐明白血病的发病机制提供理伦依据。方法培养白血病细胞系Jurkat细胞,以处于对数生长期的Jurkat细胞作实验组,以正常人外周血淋巴细胞作对照组。利用RT—PCR方法检测细胞中Cdtl和GemininmRNA的表达,进行半定量分析;利用流式细胞仪对细胞荧光强度进行定量分析,以检测细胞中的Cdtl和Geminin蛋白的表达。结果（1）处于对数生长期的Jurkat细胞CdtlmRNA及蛋白表达显著高于对照组（P〈0．05）。（2）处于对数生长期的Jurkat细胞GemininmRNA及蛋白的表达显著高于对照组（P〈0．05）。结论人T淋巴细胞性白血病细胞系Jurkat细胞,Cdtl、Geminin的表达水平较正常人外周血淋巴细胞显著增高,Cdtl、Geminin可能与白血病细胞恶性增殖有关。     

人T淋巴细胞白血病系Jurkat细胞中Cdt1和Geminin的表达

目的探讨细胞复制允许因子Cdt1和复制抑制因子Geminin在白血病细胞中的表达,为阐明白血病的发病机制提供理伦依据。方法培养白血病细胞系Jurkat细胞,以处于对数生长期的Jurkat细胞作实验组,以正常人外周血淋巴细胞作对照组。利用RT-PCR方法检测细胞中Cdt1和Geminin mRNA的表达,进行半定量分析;利用流式细胞仪对细胞荧光强度进行定量分析,以检测细胞中的Cdt1和Geminin蛋白的表达。结果 (1)处于对数生长期的Jurkat细胞Cdt1 mRNA及蛋白表达显著高于对照组(P0.05)。(2)处于对数生长期的Jurkat细胞Geminin mRNA及蛋白的表达显著高于对照组(P0.05)。结论人T淋巴细胞性白血病细胞系Jurkat细胞,Cdt1、Geminin的表达水平较正常人外周血淋巴细胞显著增高,Cdt1、Geminin可能与白血病细胞恶性增殖有关。     

CDK4和Geminin在胶质瘤中的表达及其与预后的关系

目的：探讨细胞周期依赖性激酶4（cyclin-dependent kinase 4,CDK4）和Geminin在胶质瘤中的表达及其临床病理意义。方法：采用免疫组织化学方法,检测70例胶质瘤中CDK4和Geminin的表达,分析CDK4和Geminin的表达和其相关性,以及二者与胶质瘤临床病理因素及生存时间的关系。 结果：CDK4、Geminin在胶质瘤中的总阳性率分别为70.0%（49/70）、75.7%（53/70）;Ⅱ、Ⅲ、Ⅳ级胶质瘤中CDK4阳性率分别为52.8%（19/36）、84.6%（22/26）、100.0%（8/8）,Geminin阳性率分别为58.3%（21/36）、92.3%（24/26）、100.0%（8/8）,CDK4和Geminin在不同级别胶质瘤中的表达有显著差异（P＜0.05）。且二者表达呈正相关;CDK4、Geminin阳性表达与肿瘤大小及细胞核分裂像多少有关（P＜0.05）,与患者年龄、性别以及肿瘤组织有无坏死无关（P＞0.05）;Kaplan-Meier单因素统计分析结果显示 CDK4、Geminin阳性表达组的患者术后生存时间明显短于CDK4、Geminin阴性表达组（P＜0.001）。结论：CDK4和Geminin表达与胶质瘤的分级、预后有关,联合检测CDK4和Geminin有助于判断胶质瘤恶性程度及评估预后。     

Cdt1 overexpression drives colorectal carcinogenesis through origin overlicensing and DNA damage

Chromatin licensing and DNA replication factor 1 (CDT1), a protein of the pre-replicative complex, is essential for loading the minichromosome maintenance complex (MCM) helicases onto the origins of DNA replication. While several studies have shown that dysregulation of CDT1 expression causes re-replication and DNA damage in cell lines, and CDT1 is highly expressed in several human cancers, whether CDT1 deregulation is sufficient to enhance tumorigenesis in vivo is currently unclear. To delineate its role in vivo, we overexpressed Cdt1 in the mouse colon and induced carcinogenesis using azoxymethane/dextran sodium sulfate (AOM/DSS). Here, we show that mice overexpressing Cdt1 develop a significantly higher number of tumors with increased tumor size, and more severe dysplastic changes (high-grade dysplasia), compared with control mice under the same treatment. These tumors exhibited an increased growth rate, while cells overexpressing Cdt1 loaded greater amounts of Mcm2 onto chromatin, demonstrating origin overlicensing. Adenomas overexpressing Cdt1 showed activation of the DNA damage response (DDR), apoptosis, formation of micronuclei, and chromosome segregation errors, indicating that aberrant expression of Cdt1 results in increased genomic and chromosomal instability in vivo, favoring cancer development. In line with these results, high-level expression of CDT1 in human colorectal cancer tissue specimens and colorectal cancer cell lines correlated significantly with increased origin licensing, activation of the DDR, and microsatellite instability (MSI). © 2022 The Pathological Society of Great Britain and Ireland.     

Minichromosome maintenance 2 and 5 expressions are increased in the epithelium of hereditary gingival fibromatosis associated with dental abnormalities

INTRODUCTION:

Gingiva fibromatosis is a relatively rare condition characterized by diffuse enlargement of the gingiva, which is caused by expansion and accumulation of the connective tissue.

OBJECTIVE:

The aim of the present study was to investigate proliferative and apoptotic biomarker expression in normal gingiva and two forms of gingival fibromatosis.

METHODS:

Archived tissue specimens of hereditary gingival fibromatosis, gingival fibromatosis and dental abnormality syndrome and normal gingiva were subject to morphological analysis and immunohistochemical staining. The results were analyzed statistically.

RESULTS:

Proteins associated with proliferation were found in the nuclei of epithelial cells from the basal and suprabasal layers, whereas apoptotic proteins were detected in the cytoplasm of the upper layers of the epithelium. Increased expressions of minichromosome maintenance proteins 2 and 5 were observed in the gingival fibromatosis and dental abnormality syndrome samples. In contrast, geminin expression was higher in normal gingiva samples. No difference in the expression of apoptotic proteins was observed among the groups.

CONCLUSION:

Our findings support a role for augmented proliferation of epithelial cells within the overgrown tissues associated with gingival fibromatosis or dental abnormality syndrome. However, our data suggest that different biological mechanisms may account for the pathogenesis of different types of gingival fibromatosis.     

Geminin expression in small lung adenocarcinomas: Implication of prognostic significance

Geminin is an important molecule which plays a role in cell cycle regulation, and this has been considered to be a useful biomarker of cell proliferation. The purpose of this study was to evaluate the pathological and prognostic significance of geminin expression in small lung adenocarcinoma (AC). We performed Western blot analysis of five human lung AC cell lines and immunohistochemistry on 100 surgically resected specimens of lung AC with a diameter less than 3 cm. We counted the number of positively stained tumor cells, and calculated the labeling indices (LIs). Geminin proteins were variably detected in all five cell lines examined on Western blotting. The mean LIs for geminin, Ki-67, and MCM7 were 7.5%, 12.3%, and 18.5%, respectively. The geminin LIs were associated with some clinicopathological profiles including gender, histological grade, subtypes, N-status, p-factor, and tumor stage. A significantly worse prognosis was noted in the higher geminin LIs group than in the lower group (p < 0.01). Multivariate Cox regression analysis also confirmed that geminin LIs was an independent prognostic marker in stage IA lung AC patients. These results suggest that geminin is overexpressed in small lung ACs, and geminin LIs might be a useful prognostic indicator in patients with lung AC.     

Geminin基因过表达对VSMCs表型转化的影响

目的探讨Geminin基因过表达对血管平滑肌细胞(vascular smooth muscle cells,VSMCs)表型转化的影响。方法构建真核表达载体pEGFP-N1-Geminin,脂质体2000介导转染不同表型(去分化型和分化型)的大鼠VSMCs株,设置阳性组、阴性组和空白组(n=3),检测转染效果、VSMCs主要表型标志物(α-actin、OPN)和肌动蛋白相关蛋白1(actinrelated protein,ARP1)的变化情况。结果 Geminin基因成功过表达VSMCs株。与2个对照组(阴性组和空白组)比较,分化型VSMCs中表型标志物(α-actin和OPN)及ARP1含量变化不大;去分化型VSMCs中,OPN在阳性组中表达下调,与2个对照组(阴性组和空白组)比较差异具有统计学意义(P<0.05),α-actin和ARP1在阳性组中表达上调,与2个对照组(阴性组和空白组)比较差异具有统计学意义(P<0.05),免疫共沉淀实验结果提示经protein G plus-Agarose沉淀ARP1相互作用蛋白复合物后,用Geminin抗体进行Western blot检测,可以检测到Geminin的表达。结论 Geminin基因过表达有助于VSMCs由去分化型向分化型转化;免疫共沉淀结果提示Geminin和ARP1之间存在相互作用,ARP1可能参与了上述VSMCs表型转化过程。     

Geminin、Ki-67和HPV检测对早期宫颈上皮内瘤变的诊断价值

目的:探讨Geminin、Ki-67和HPV检测对早期宫颈上皮内瘤变的诊断价值。方法:采用免疫组化SP法检测Geminin、Ki-67在126例宫颈上皮内瘤变(CIN)组织、50例慢性宫颈炎宫颈组织及30例正常宫颈组织中的表达；采用HC2的方法检测HPV的载量。用Spearman秩相关分析Geminin、Ki-67分别与HPV感染的相关性。结果:Geminin、Ki-67在CIN组织中阳性表达率高于宫颈炎组和对照组(P＜0.05)；Geminin、Ki-67在宫颈炎组和对照组中阳性表达率差异无统计学意义(P＞0.05)；Geminin、Ki-67在CIN组织中阳性表达率CINIII组＞CINII组＞CINI组，组间比较差异有统计学意义(P＜0.05)；HPV在宫颈病变组织中阳性表达率CINIII组＞CINII组＞CINI组＞宫颈炎组＞对照组，组间比较差异有统计学意义(P＜0.05)；Geminin、Ki-67表达分别与HPV感染呈正相关(P＜0.05)；Geminin、Ki-67和HPV联合检测的特异度和精确度最高。 结论:不同CIN分期病变组织Geminin、Ki-67表达水平和HPV感染率差异较大，可通过HPV、Geminin、Ki-67联合检测对早期CIN进行辅助诊断。