Decreasing of p27(Kip1)and cyclin E protein levels is associated with progression from superficial into invasive bladder cancer

The p27(Kip1)(p27) protein is a cyclin-dependent kinase inhibitor of the transition from G1 to S phase. It has been reported that decreased p27 protein level is a negative prognostic indicator in human tumours including bladder cancer. We studied the relationship between protein levels of p27, cyclin E and Ki-67 and clinicopathological features of 145 consecutive Japanese patients with transitional cell carcinoma of the bladder using immunohistochemical staining. Low protein levels of p27 were associated with low staining of cyclin E (P = 0.0302), high Ki-67 index (P = 0.0306), poorly differentiated grade (P = 0.0006), muscle invasion (P = 0.0019) and lymph node metastsis (P = 0.0002). Low staining of cyclin E and high Ki-67 index correlated with poorly differentiated grade, muscle invasion and lymph node metastsis. Cyclin E protein levels was inversely related with Ki-67 index (P = 0.0002). Kaplan-Meier plots of survival rate in patients with low versus high p27 staining showed that low protein levels of p27 were associated with a shortened disease-free and overall survival (P< 0.0001 and P< 0.0001, respectively). Similarly, low staining of cyclin E and high Ki-67 index correlated with a shortened disease-free and overall survival. On multivariate analysis using Cox proportional hazards model, low protein levels of p27 and high Ki-67 index were independent predictors of shortened disease-free (P< 0.0001, P = 0.0031, respectively), and low protein levels of p27, low staining of cyclin E and high Ki-67 index of overall survival (P = 0.0017, P = 0.0009, P = 0.0003, respectively). In superficial bladder tumours (Ta, T1; 86 patients), significant correlations were observed between low p27 staining and high Ki-67 index and early recurrence (P = 0.0048, P = 0.0178, respectively). Among the recurrenced superficial tumours (35 patients), the tumours which remained at a low stage showed high protein levels of p27 and cyclin E, and the tumours which progressed to invasive disease showed a gradual decrease in p27 and cyclin E protein levels over time. Our findings suggest that decreased protein levels of p27 and cyclin E play a role in the progression of bladder cancer and to evaluate these protein levels may be useful in management of the diseases.     

Unique induction of p21(WAF1/CIP1)expression by vinorelbine in androgen-independent prostate cancer cells

To study the mechanisms of the development of hormone refractory prostate cancer, we established an androgen-independent (AI) prostate cancer cell line derived from hormone-dependent (AD) LNCaP cells. Our previous studies have demonstrated that AI cells are deficient in expression of p21(WAFl/CIP1) (p21) due to overexpressed AR and are resistant to apoptosis. In this study, the induction of p53 and p21 expression by vinorelbine (Navelbine) was compared between AD and AI cells in an attempt to understand the difference(s) in apoptotic signalling pathways in these cells. Using a series of deletion of p21 reporter constructs, we found that vinorelbine mediated p21 induction in a p53-dependent manner in AD cells. In contrast, p21 expression restored by vinorelbine in AI cells was found to be through both p53-dependent and-independent pathways. In the absence of two p53 binding sites, Spl-3 and Spl-4 sites, in the promoter of human p21 gene, were found to be required for vinorelbine-mediated p21 activation. No p21 induction was observed by paclitaxel in AI cells. Exposure of AI cells to paciltaxel followed by vinorelbine produced synergism. Our data, thus, provide a basis for the synergistic combination of vinorelbine and paclitaxel for the treatment of advanced prostate cancer.     

Androgen receptor expression in relation to apoptosis and the expression of cell cycle related proteins in prostate cancer

The expression of several genes involved in the regulation of cell cycle and apoptosis may be regulated via the androgen receptor (AR) in the prostate. AR may have a role in the prognosis of prostatic carcinoma. The aim was to examine AR expression status and its relationship with markers of proliferation, apoptosis and cell cycle control in prostate cancer. Expression of AR, bcl-2, bax, Ki-67 and p53 was examined in paraffin-embedded tissues from 50 cases of prostate carcinoma by immunohistochemistry and evaluated using an index of staining. Detection of apoptotic cells was performed by TUNEL method. Correlation between AR expression and apoptosis, proliferation index, bcl-2, bax and p53 and also clinicopathological parameters including stage, pathological grade and Gleason score were determined. AR expression was observed in all cases with mean expression of 81%±15 and mean staining index of 141±65. No correlation was found between AR expression and apoptosis detected in patients. The mean AR staining index was 170±72 in bcl-2 positive tumors versus 120±53 in bcl-2 negative tumors showing a significant association between AR and bcl-2 expression (p=0.015). AR expression also showed a significant association with bcl-2/bax ratio (r=0.321, p=0.023) and Ki-67 proliferation staining index (r=0.396, p=0.004). Although a significant correlation between Ki-67 and p53 with differentiation status of the tumors was observed (p<0.004) no correlation was found with AR. AR expression showed no prognostic value regarding its correlation with stage and differentiation status of the prostate carcinoma. However, its significant correlation with Ki-67 and bcl-2 that are markers of cell survival suggest its contribution to tumor cell progression.     

Chemically induced rat mammary tumor treated with tamoxifen showed decreased expression of cyclin D1, cyclin E, and p21

We studied the effects of tamoxifen (TAM) on the growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumor and the expression of cyclin D1, cyclin E, p21^Cip1, and estrogen receptors (ER) by performing immunohistochemistry and Western blot analysis. When tumor size reached between 10 and 15 mm in the largest dimension, the rats were divided into a DMBA-control group and a DMBA-TAM group. The administration of TAM markedly decreased the tumor development and showed decreased expression of bromodeoxyuridine, cyclin D1, cyclin E, and p21^Cip1 when compared with those of the DMBA-control group; however, a few tumors showed progressive growth in spite of TAM treatment. These tumors had decreased expression of ER. This study suggests that TAM suppresses tumor development through the down-expression of cyclin D1 and cyclin E.     

Expression of cyclins A and D and p21(waf1/cip1) proteins in renal cell cancer and their relation to clinicopathological variables and patient survival.

We have studied 118 renal cell carcinomas to analyse the expressions of cyclins A and D1 and p21(waf1/cip1), and their relationship to clinical and histopathological parameters as well as to clinical outcome. Cyclins A and D1 and cyclin-dependent kinase inhibitor p21 (waf1/cip1) were not expressed in normal renal tissue. Staining signals of cyclin D1 and p21(waf1/cip1) were always nuclear but cyclin A was also expressed in the cytoplasm of the tumour cells. The mean (range) fractions of cyclin A, cyclin D1 and p21(waf1/cip1)-positive tumour cells were 2.2% (range 0-20%), 23.3% (range 0-90%) and 6.8% (range 0-70%) respectively. The expression of cyclin A was related to venous invasion, high nuclear grade, high mitotic rate, high Ki-67 and high PCNA expressions (P < or = 0.006 for all). The expression of cyclin D1 was linked with age over 65 years, low nuclear grade and high p53 expression (P < or = 0.05 for all). An inverse correlation was present between p21(waf1/cip1) and cyclin D1 (P = 0.011). Cyclin A predicted survival in the entire study group (P = 0.0014), in T1-4/N0-2/M0 (P = 0.0007) and in T1-2/N0/M0 tumours (P = 0.0007). Cyclin A was also a powerful predictor of disease-free survival in T1-4/N0/M0 (P = 0.0027) tumours (P = 0.0007). Cyclin D1 and p21(waf1/cip1) were not significantly related to survival or disease-free survival in any of the groups. In the entire material the independent prognostic factors were the presence of distant metastases (relative risk (RR) 5.16, P < 0.001), T category (RR 2.68, P < 0.001), Ki-67 expression (RR 1.02, P = 0.026) and cyclin A expression (RR 1.12, P = 0.001). The independent predictors in T1-4/N0/M0 tumours were T-category (RR 2.67, P = 0.001) and cyclin A (RR 1.21, P < 0.001), and in T1-2/N0/M0 tumours the only significant predictor was cyclin A (RR 1.19, P = 0.0002). In renal cell carcinoma, cyclin A is a powerful and independent prognostic factor in all clinical stages of the disease, whereas cyclin D1 and p21(waf1/cip1) have no prognostic value.     

c-Myc overexpression sensitises colon cancer cells to camptothecin-induced apoptosis

The proto-oncogene c-Myc is overexpressed in 70% of colorectal tumours and can modulate proliferation and apoptosis after cytotoxic insult. Using an isogenic cell system, we demonstrate that c-Myc overexpression in colon carcinoma LoVo cells resulted in sensitisation to camptothecin-induced apoptosis, thus identifying c-Myc as a potential marker predicting response of colorectal tumour cells to camptothecin. Both camptothecin exposure and c-Myc overexpression in LoVo cells resulted in elevation of p53 protein levels, suggesting a role of p53 in the c-Myc-imposed sensitisation to the apoptotic effects of camptothecin. This was confirmed by the ability of PFT-alpha, a specific inhibitor of p53, to attenuate camptothecin-induced apoptosis. p53 can induce the expression of p21(Waf1/Cip1), an antiproliferative protein that can facilitate DNA repair and drug resistance. Importantly, although camptothecin treatment markedly increased p21(Waf1/Cip1) levels in parental LoVo cells, this effect was abrogated in c-Myc-overexpressing derivatives. Targeted inactivation of p21(Waf1/Cip1) in HCT116 colon cancer cells resulted in significantly increased levels of apoptosis following treatment with camptothecin, demonstrating the importance of p21(Waf1/Cip1) in the response to this agent. Finally, cDNA microarray analysis was used to identify genes that are modulated in expression by c-Myc upregulation that could serve as additional markers predicting response to camptothecin. Thirty-four sequences were altered in expression over four-fold in two isogenic c-Myc-overexpressing clones compared to parental LoVo cells. Moreover, the expression of 10 of these genes was confirmed to be significantly correlated with response to camptothecin in a panel of 30 colorectal cancer cell lines.     

Leptin-induced growth of human ZR-75-1 breast cancer cells is associated with up-regulation of cyclin D1 and c-Myc and down-regulation of tumor suppressor p53 and p21WAF1/CIP1

Summary Obesity has been recognized as a risk factor for breast cancer. Adipocyte-derived leptin may play as a paracrine regulator on the growth of breast cancer cells. Expression of both leptin and its OB-Rb receptor was detected in human breast cancer ZR-75-1 cells and further induced by leptin, suggesting that both expression and message mediation of leptin were autoregulated by itself. With cell counting and MTT assay, we had observed leptin stimulated ZR-75-1 growth in dose- and time-dependent manners. To study what steps of cell cycle progression leptin may involve in, we analyzed cell-cycle profile with flow cytometric analysis, mRNA and protein expressions of four cell-cycle regulators with RT-PCR and Western blotting analysis. Under the treatment of leptin, the G1 arrest of cells was reduced accompanied with up-regulation of G1 phase-specific cyclin D1 and proto-oncogene c-Myc, but down-regulation of cyclin-dependent kinase inhibitor p21^WAF1/CIP1 and tumor suppressor p53. Furthermore, JAK2 inhibitor AG490, PI3K/Akt inhibitor Wortmannin, and MEK/ERK1/2 inhibitor PD98059 were efficiently prevented leptin-promoted cell growth. Effect of cooperation between leptin and estrogen on ZR-75-1 growth had been observed. Collectively, the results showed that the proliferative effect of leptin on ZR-75-1 was associated with the up-regulation of cyclin D1 and c-Myc and down-regulation of tumor suppressor p53 and p21^WAF1/CIP1 plausibly through a hypothesized JAK2-PI3K/Akt-MEK/ERK pathway. The leptin- and OB-Rb-expressing capability of ZR-75-1 created a possible autocrine control of leptin, in which signal could be effectively amplified by itself, on cell growth.     

Reduced p21(WAF1/CIP1) protein expression is predominantly related to altered p53 in hepatocellular carcinomas

To investigate the relationship between the expression of p21(WAF1/CIP1) protein and p53 status and the possible role of the two proteins in hepatocellular carcinomas (HCCs), we examined the expression of p21(WAF1/CIP1) and p53 immunohistochemically in 81 tumours from 65 patients with hepatocellular carcinoma. p21(WAF1/CIP1) protein was absent from 59 of 81 tumours (72.8%), and altered p53 expression was found in 43 (53.1%). p21(WAF1/CIP1) expression was significantly associated with p53 status (P = 0.0008); 38 of 59 tumours lacking p21(WAF1/CIP1) protein were accompanied by altered p53 expression. Further analyses showed that p21(WAF1/CIP1) expression was inversely correlated with p53 expression in hepatitis C virus (HCV)-related HCCs, but not in HBV-related hepatocellular carcinomas and hepatocellular carcinomas without viral infection. All 11 tumours with intrahepatic metastasis showed altered p21(WAF1/CIP1) or p53 expression. In contrast, no intrahepatic metastasis was found in any of the 17 tumours without abnormal expression of either of the two proteins. These results suggest that: (1) different modes of p21(WAF1/CIP1) regulation are involved in HCCs differing in their hepatitis viral infection status, and p21(WAF1/CIP1) expression appears to be predominantly related to altered p53 in HCV-related HCCs; (2) disruption of the p53-p21(WAF1/CIP1) cell-cycle-regulating pathway may contribute to malignant progression of HCC.     

Lycorine hydrochloride inhibits melanoma cell proliferation,migration and invasion via down-regulating p21Cip1/WAF1

Lycorine hydrochloride (LH) is an active ingredient sourced from the medicinal herb Lycoris radiata. Previous studies have suggested that LH exerts tumor suppression activity in several human cancers. However, the anti-cancer effect of LH in melanoma and the potential molecular mechanisms still need to be further studied. p21^Cip1/WAF1, unlike its traditional cyclin-dependent kinase (CDK) inhibitor role, is believed to act as an oncogene under certain cellular conditions. In this research, an increased expression of p21^Cip1/WAF1 was found in human melanoma tissues and positively related to the tumor invasion depth. High level of p21^Cip1/WAF1 was found to correlate with bad outcomes of melanoma patients by Kaplan-Meier survival analysis. Functional experiments demonstrated that the proliferation, migration and invasion ability of A375 and MV3 melanoma cells was powerfully inhibited by LH through inducing S phase cell cycle arrest and regulating epithelial-mesenchymal transition (EMT). In NOD/SCID mice model, LH effectively inhibited the xenograft tumor growth and lung metastasis of A375 cells. Further research revealed that LH reduced p21^Cip1/WAF1 protein by accelerating its ubiquitination. Importantly, the LH-induced suppression of cell proliferation and metastasis was rescued by p21^Cip1/WAF1 overexpression, both in vitro an in vivo. Taken together, LH, which suppresses the proliferation and metastasis of melanoma cells via down-regulating p21^Cip1/WAF1, is expected to be developed as an effective medicine for melanoma therapy.     

Bowen病皮损中p21WAF1蛋白、Ki-67蛋白的表达及其意义

  目的 探讨Bowen病中细胞周期调节蛋白p21WAF1及Ki-67蛋白的表达和意义。方法 用免疫组织化学SP法检测35例Bowen病和12名正常人皮肤黏膜组织中p21WAF1蛋白、Ki-67蛋白的表达和分布。结果 正常人皮肤黏膜组织中p21WAF1蛋白阴性表达、Ki-67蛋白表达仅见于基底层；Bowen病皮损中，p21WAF1蛋白、Ki-67蛋白的表达均增高，与正常人皮肤黏膜相比较差异均有统计学意义（P值均＜0.01）。结论 Bowen病中p21WAF1的高表达可能与肿瘤细胞的分化有关。     

三阴性乳腺癌患者中FOXA1与雌激素受体β的表达及其相关性研究

背景与目的：研究显示雌激素受体β(estrogen receptor beta,ERβ)在三阴性乳腺癌(triple negative breast cancer,TNBC)中的表达与TNBC患者的预后可能存在正相关,而ERβ和雌激素受体α(estrogen receptor alpha,ERα)存在高度同源性,ERα的表达和活性与叉头框蛋白A1(fork head box protein A1,FOXA1)密切相关。该研究旨在分析FOXA1和ERβ在TNBC中的表达情况及其与临床病理指标及预后的相关性。方法：收集2011年11月—2013年12月北京协和医院乳腺癌标本,根据ERα、孕激素受体(progesterone receptor,PR)和人表皮生长因子受体2(human epidermal growth factor receptor 2,HER-2)的表达情况,筛选出TNBC。根据ERβ表达,随机选取ERβ阳性和阴性的乳腺癌标本各30例,应用免疫组化检测样本中FOXA1表达情况。由于染色不佳及飞片等原因,最终获得染色情况佳的标本共48例(ERβ阴性20例,ERβ阳性28例)。比较TNBC中FOXA1及ERβ表达的相关性及其与各临床病理指标及预后之间的关系。结果：FOXA1总体阳性率为35.4%(17/48),其中ERβ阳性组FOXA1阳性率为35.7%(10/28),ERβ阴性组FOXA1阳性率为35%(7/20),两组差异无统计学意义(P=0.83),即FOXA1的表达与ERβ的表达无相关性。FOXA1阳性组与FOXA1阴性组的患者年龄、肿瘤大小、腋窝淋巴结转移数目、肿瘤分级、肿瘤分期、诺丁汉预后指数(Nottingham prognostic index,NPI)和无病生存率(disease free survival,DFS)差异均无统计学意义;两组Ki-67指数差异具有统计学意义(P<0.01),即在FOXA1阳性组中Ki-67指数显著低于FOXA1阴性组,两者呈负相关。结论：在TNBC中,FOXA1的表达与ERβ的表达差异无统计学意义,FOXA1的表达与Ki-67指数呈负相关,提示FOXA1阳性表达的三阴性乳腺癌细胞增殖性较低。     

Predictive value of decreased p27Kip1 protein expression for the recurrence-free and long-term survival of prostate cancer patients

The p27Kip1 gene has been identified as inductor of cell cycle arrest at the G1 checkpoint to prevent entry of somatic cells into the S phase of the cell cycle when substantial DNA damage has occurred. It has been suggested that decreased expression of the p27Kip1 protein may contribute to the development of human malignancies due to loss of critical antiproliferative mechanisms. In the present study, 95 specimens (T1-T4) from 95 randomly selected patients undergoing radical prostatectomy at the Urological Department of Hannover University (82 patients) as well as in the Josef Hospital Regensburg (13 patients) between 1981 and 1992 for whom tissue blocks for immunohistochemical investigation were available, were investigated for different biological and clinical characteristics as possible predictors for recurrence-free and long-term survival: age, depth of tumour infiltration, histological grade, lymph node status, as well as decreased expression of the p27Kip1 protein. After a median follow-up up of 56 months (24-151 months), seven of 21 (33%) patients (Group 1) with loss of p27Kip1 protein expression or a relative amount of <10% of positively stained tumour cells developed recurrent disease in contrast to 17 of 74 (23%) patients (Group 2) with retained p27Kip1 protein expression (> or =10% of positively stained tumour cells). The median recurrence-free survival was 14 months (5-40 months) for patients from Group 1 and 31 months (7-133 months) for Group 2 patients (P = 0.02). In multivariate analysis, loss of p27Kip1 protein expression was identified as the only independent prognostic parameter for recurrence-free survival. In contrast, neither the univariate nor the multivariate analysis showed a correlation between loss of p27Kip1 protein expression and the long-term survival of the patients. Prospective studies are urgently needed to confirm the independent prognostic value of decreased p27Kip1 protein expression together with overexpression of the p53 tumour suppressor protein in patients with localized prostate cancer. The availability of more refined prognostically important biological variables in addition to established prognostic factors like tumour stage or Gleason score might help decision making in patients at high risk for the development of local recurrence or systemic tumour progression.     

极光激酶A p53及p21 WAF1协同表达在非小细胞肺癌预后中的价值

目的：探讨极光激酶（ Aurora A）、Ki?67、p53和p21 WAF1在行根治术非小细胞肺癌（ NSCLC）患者预后中的价值。方法采用免疫组化检测Aurora A、Ki?67、p53和p21 WAF1在58例NSCLC根治术后患者中的表达情况,分析各指标的表达与患者临床病理特征及预后的关系。结果Aurora A、Ki?67、p53和p21 WAF1在NSCLC中的阳性率分别为89．7％（52／58）、53．4％（31／58）、46．6％（27／58）和34．5％（20／58）。 Aurora A高表达患者的淋巴结转移率为69．2％,高于低表达者（37．8％, P＝0．045）。 Aurora A低表达组和高表达组患者的3年生存率分别为75．0％和46．0％,差异有统计学意义（ P＝0．039）。 Aurora A高表达和p53阳性组、Aurora A高表达或p53阳性组、Aurora A低表达和p53阴性组患者的3年生存率分别为40．0％、65．0％和82．1％,差异有统计学意义（ P＝0．039）。 Cox多因素分析结果显示,Aurora A和p53联合检测为影响NSCLC患者预后的独立因素（ P＝0．015）。结论Aurora A和p53为影响 NSCLC 患者预后的不良因素,与 p53突变相关的 Aurora A 高表达为影响NSCLC患者预后的独立不良因素。     

Amplified centrosomes in breast cancer: a potential indicator of tumor aggressiveness

Molecular mechanisms leading to genomic instability and phenotypic variation during tumor development and progression are poorly understood. Such instability represents a major problem in the management of breast cancer because of its contribution to more aggressive phenotypes as well as chemoresistance. In this study we analyzed breast carcinomas and tumor-derived cell lines to determine the relationship between centrosome amplification and established prognostic factors. Our results show that centrosome amplification can arise independent of ER or p53 status and is a common feature of aneuploid breast tumors. Centrosome amplification is associated with mitotic spindle abnormalities in breast carcinomas and thus may contribute to genomic instability and the development of more aggressive phenotypes during tumor progression.     

ICRAC controls the rapid androgen response in human primary prostate epithelial cells and is altered in prostate cancer

Labelled 5α-dihydrotestosterone (DHT) binding experiments have shown that expression levels of (yet unidentified) membrane androgen receptors (mAR) are elevated in prostate cancer and correlate with a negative prognosis. However, activation of these receptors which mediate a rapid androgen response can counteract several cancer hallmark functions such as unlimited proliferation, enhanced migration, adhesion and invasion and the inability to induce apoptosis. Here, we investigate the downstream signaling pathways of mAR and identify rapid DHT induced activation of store-operated Ca²⁺ entry (SOCE) in primary cultures of human prostate epithelial cells (hPEC) from non-tumorous tissue. Consequently, down-regulation of Orai1, the main molecular component of Ca²⁺ release-activated Ca²⁺ (CRAC) channels results in an almost complete loss of DHT induced SOCE. We demonstrate that this DHT induced Ca²⁺ influx via Orai1 is important for rapid androgen triggered prostate specific antigen (PSA) release. We furthermore identified alterations of the molecular components of CRAC channels in prostate cancer. Three lines of evidence indicate that prostate cancer cells down-regulate expression of the Orai1 homolog Orai3: First, Orai3 mRNA expression levels are significantly reduced in tumorous tissue when compared to non-tumorous tissue from prostate cancer patients. Second, mRNA expression levels of Orai3 are decreased in prostate cancer cell lines LNCaP and DU145 when compared to hPEC from healthy tissue. Third, the pharmacological profile of CRAC channels in prostate cancer cell lines and hPEC differ and siRNA based knock-down experiments indicate changed Orai3 levels are underlying the altered pharmacological profile. The cancer-specific composition and pharmacology of CRAC channels identifies CRAC channels as putative targets in prostate cancer therapy.     

MicroRNA-196a promotes cervical cancer proliferation through the regulation of FOXO1 and p27Kip1

Background:

The phosphoinositide 3-kinase (PI3K)/Akt signalling pathway appears to be a key regulator in cervical carcinogenesis. However, the downstream regulatory mechanism of PI3K/Akt signalling remains largely unknown.

Methods:

The expression of miR-196a in cervical cancer cell lines and cervical cancer tissues was examined using real-time PCR. The effects of miR-196a on PI3K/Akt signalling and cellular proliferation were evaluated by bromodeoxyuridine labelling, 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazoliumbromide, colony formation assays and luciferase assays.

Results:

The expression level of miR-196a was markedly increased in cervical cancer tissues and cell lines compared with normal cervical tissue and normal cervical squamous cells. Upregulation of miR-196a was correlated with advanced tumour stage and poor overall and recurrence-free survival in cervical cancer patients. Upregulation of miR-196a enhanced G1/S-phase transition and the proliferative ability of cervical cancer cells, whereas suppression of miR-196a had the opposite effect. Using bioinformatics and biological approaches, we showed that FOXO1 and p27^Kip1, two key effectors of PI3K/Akt signalling, were direct targets of miR-196a.

Conclusions:

Our findings suggest that miR-196a has an important role in promoting human cervical cancer cell proliferation and may represent a novel therapeutic target of microRNA-mediated suppression of cell proliferation in cervical cancer.     

Expressions of cyclin D1 and p27kip1 in carcinogenesis of stomach mucosa

Objective  To evaluate the relationship between the expressions of cyclin D1 and p27^kip1 in the canceration course of the stomach. Methods  The immunohistochemical staining technique (SP method) was used to detect the expressions of cyclin D1, p27^kip1 in chronic superficial gastritis (CSG), chronic atrophic gastritis (CAG), intestinal metaplasia (IM), dysplasia (DYS), gastric carcinoma (GCA) biopsy specimens. Results  The positive cyclin D1 expression rates increased with the progressing from CAG→IM→DYS→GCA respectively, and those in IM, DYS and GCA were different from those in CSG, P < 0.05, while DYS group was indifferent from GCA group, P > 0. 05. The positive p27^kip1 expression rates decreased with the mucosa progressing from CAG→IM→DYS→GCA. There was a negative correlation between the expression cyclin D1 and p27^kip1 (Y = −0.53, P = 0.000). Conclusion  Expression rates of cyclin D1 in the canceration course of the stomach mucosa trend were increased and those of p27^kip1 were decreased; the abnormal expressions of them were found in the early term of the canceration course of the stomach mucosa, and the inverse expression suggests there may be a negative feedback regulatory loop between cyclin D1 and p27^kip1.     

Ki-67和CK34βE12在前列腺癌鉴别诊断中的应用

目的探讨Ki-67及CK34βE12在前列腺癌鉴别诊断中的应用。方法应用免疫组化S-P法检测24例前列腺癌和30例前列腺增生病变组织中Ki-67及CK34βE12的表达情况。结果平均Ki-67增生指数在24例前列腺癌为0.45±0.21,在30例前列腺增生为0.12±0.09,前列腺癌中Ki-67表达高于前列腺增生,差异有显著性(P<0.01)。CK34βE12表达在前列腺癌中均为阴性,前列腺增生30例均为阳性表达(P<0.001)。结论Ki-67和CK34βE12在前列腺良恶性疾病中的表达水平不同,Ki-67高表达和CK34βE12阴性表达有助于诊断前列腺癌。     

前列腺癌组织Ki-67表达及其临床意义的研究

目的:探讨核增殖抗原Ki-67在前列腺癌组织中的表达及其对临床的意义。方法:应用免疫组化SP法检测64例前列腺癌和81例前列腺增生手术或活检标本中Ki-67的表达情况。结果:64例前列腺癌组织中Ki-67表达有40例,81例前列腺增生中Ki-67表达有8例,其灵敏度63%,特异性90%,两组比较差异有统计学意义,χ2=40.05,P<0.005;前列腺癌各临床分期的Ki-67表达也不同,A、B期与C、D期比较差异也有统计学意义,χ2=21.12,P<0.005。结论:Ki-67可作为前列腺增生与前列腺癌的鉴别、前列腺癌的临床分期以及预后判断的一种新的重要参考指标。     

前列腺癌组织Ki-67表达及其临床意义的研究

目的：探讨核增殖抗原Ki-67在前列腺癌组织中的表达及其对临床的意义。方法：应用免疫组化SP法检测64例前列腺癌和81例前列腺增生手术或活检标本中Ki-67的表达情况。结果：64例前列腺癌组织中Ki-67表达有40例，81例前列腺增生中Ki-67表达有8例，其灵敏度63％，特异性90％，两组比较差异有统计学意义，χ^2=40．05，P〈o．005；前列腺癌各临床分期的Ki-67表达也不同，A、B期与C、D期比较差异也有统计学意义，χ^2=21．12，P〈0．005。结论：Ki-67可作为前列腺增生与前列腺癌的鉴别、前列腺癌的临床分期以及预后判断的一种新的重要参考指标。