ABSTRACT
INTRODUCTION: Protein p16 has been extensively studied as a potential biomarker for precursor lesions to distinguish cervical Intraepithelial neoplasia (CIN) from their mimics. However, the use of p16 as prognostic biomarker for diagnosis of cervical cancer and precancer is controversial. This study focuses on the assessment of peer-reviewed scientific data related to the use of p16 to predict disease severity and its controversies. METHODS: We reviewed publications in MEDLINE/PubMed assessing the clinical, diagnostic and prognostic significance of p16 in CIN and cervical cancer; we included publications from 2009 to June 2017. RESULTS: The use of p16 as a prognostic marker is still unreliable, although it could be a useful tool for diagnosis of Cervical Intraepithelial Neoplasia lesions with undetermined morphology. Moreover, p16 appears to be a specific marker of high-risk oncogenic HPV infection. CONCLUSION: This review shows the potential utility and drawbacks of p16 for clinical practice and the diagnosis of cervical cancer. Further studies are required to substantiate the role of p16 in conjunction with other more sensitive and specific biomarkers for diagnosing CIN and predicting its progression.
INTRODUÇÃO: A proteína p16 tem sido estudada como um biomarcador potencialmente específico de lesões cervicais precursoras e como uma forma de diferenciar as lesões parecidas com Neoplasia intra-epitelial cervical (NIC). Contudo existem várias controvérsias sobre a utilização de p16 como um biomarcador prognóstico e como uma ferramenta para o diagnóstico de câncer cervical e de lesões pré-câncer. O objetivo deste estudo foi a revisão de dados científicos por pares de bases, relacionados com a utilização da p16 e suas controvérsias. MÉTODOS: O estudo foi projetado como uma revisão da literatura das publicações do Medline/PubMed que avaliam o significado clínico, diagnóstico ou prognóstico do p16 em lesões de NIC e no câncer cervical no período de janeiro de 2009 a junho de 2017. RESULTADOS: o uso do p16 como um marcador prognóstico ainda não é confiável, apesar de que a p16 poderia ser uma ferramenta útil para o diagnóstico em lesões de NIC com morfologia indeterminada. Além disso, a p16 parece ser um marcador específico de infecção por HPV de alto risco oncogênico. CONCLUSÃO: A presente revisão mostra a potencial utilidade da proteína p16, bem como os inconvenientes para uso clínico-patológico e diagnóstico no câncer cervical. Contudo são necessários mais estudos para fundamentar o papel da p16 em conjunto com os outros biomarcadores mais sensíveis e específicos para diagnosticar NIC e prever a sua progressão.
Subject(s)
Humans , Biomarkers, Tumor , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Dysplasia , Papillomavirus InfectionsABSTRACT
Objective To observe the effects of Bushen Huoxue Formula on free radical metabolism and p16 protein expression in heart of aged rats; To discuss its protective mechanism to the heart of aged rats.Methods One hundred were divided into young control group, the natural aging group,Bushen HuoxueFormula high-, medium- and low-dose groups, with 20 rats in each group. Each medication group was given relevant medicine for gavage, once a day for 16 weeks. 1 hour after the last administration, after the rats were sacrificed, serum and heart were taken. The contents of NO and MDA and activities of CAT and SOD in serum and myocardial,β-galactosidase enzyme and p16 protein expression in myocardial tissue were detected.ResultsCompared with the natural aging group, NO content and SOD activity in the serum of rats inBushen Huoxue Formula high-dose group increased significantly (P<0.05) and MDA content in allBushen Huoxue Formula groups decreased (P<0.01); NO content, CAT and SOD activity in the myocardial tissue of rats inBushen HuoxueFormula high-dose group increased significantly, and MDA content decreased significantly (P<0.05). CAT activity in allBushen HuoxueFormula groups increased (P<0.05,P<0.01).β-galactosidase enzyme and p16 protein expression in myocardial tissue in allBushen Huoxue Formula groups decreased.Conclusion Bushen Huoxue Formula can in hibit the aging of myocardial-aged rats, and the mechanism might be related to its anti-oxidative damage and inhibition of tumor suppressor gene p16 expression.
ABSTRACT
Objective To investigate the correlation between human papilloma virus(HPV) 16/18 infection and the expression of Rb and p16 protein in bladder cancer tissue,and to analyze the relationship between HPV infection and the incidence of bladder cancer.Methods The expression of HPV16/18 E6 and E7 gene encoded protein,RB and p16 were detected by immunohistochemical method in 40 cases of bladder cancer and 40 cases of normal bladder tissues,and the correlation between them and pathological grading,stage of international union of cancer(UICC),whether recurrence or not after receiving surgery was analyzed.Results In bladder cancer tissues,HPV16/18 E6 and E7 gene encoded protein,RB and p16 positive rates were 65%,47.5%,42.5%,compared with the positive rate of normal bladder tissue samples(22.5%,92.5%,87.5%),the differences were statistically significant(P0.05).The expression of HPV16/18 E6 and E7 gene encoded protein and Rb,p16 protein were not significantly correlated(P>0.05),The expression of Rb and p16 protein were negatively correlated(P<0.05).Conclusion HPV 16/18 infection is related to the occurrence and development of bladder cancer,but its mechanism might not be related to the abnormal expression of Rb and p16 protein.
ABSTRACT
Objective To explore the effects of both folic acid,p16 protein expression and their interaction on progression of cervical cancerization.Methods Participants were pathologically diagnosed new cases,including 80 women with normal cervical (NC),55 patients with low-grade cervical intraepithelial neoplasia (CIN Ⅰ),55 patients with high-grade cervical intraepithelial neoplasia (CIN Ⅱ/Ⅲ) and 64 patients with cervical squamous cell carcinoma (SCC).Serum folate levels were detected by microbiological assay method while p16 protein expression levels were measured by Western-blot.In vitro,cervical cancer cell lines C33A (HPV negative) and Caski (HPV16 positive) were treated with different concentrations of folate.Proliferation and apoptosis of cells and the levels of p16 protein expression were measured in groups with different folic acid concentrations.Results Results showed that the levels of serum folate were (5.96± 3.93) ng/ml,(5.08±3.43) ng/ml,(3.92 ± 2.59) ng/ml and (3.18 ± 2.71) ng/ml,and the levels ofpl6 protein were 0.80 ± 0.32,1.33 ± 0.52,1.91 ± 0.77,and 2.09 ± 0.72 in the group of NC,CIN Ⅰ,CIN Ⅱ/Ⅲ and SCC,respectively.However,the levels of serum folate decreased (trend X2 =32.71,P＜ 0.001) and p 16 protein expression increased (trend x2=56.06,P＜0.001) gradually along with the severity of cervix lesions.An additive interaction was seen between serum folate deficiency and high expression of p l 6 protein in the CIN Ⅰ,CIN n/Ⅲ and SCC group.Results in vitro showed that,with the increase of folate concentration,the inhibition rate of cell proliferation (C33A:r=0.928,P=0.003;Caski:r=0.962,P=0.001) and the rate on cell apoptosis (C33A:r=0.984,P＜0.001;Caski:r=0.986,P＜0.001) all increased but the levels of p16 protein expression (C33A:r=-0.817,P=0.025;Caski:r=-0.871,P=0.011) reduced.The proliferation inhibition rate (C33A:r=-0.935,P=0.002;Caski:r=-0.963,P=0.001) and apoptosis rate of cells (C33A:r=-0.844,P=0.017;Caski:r=-0.898,P=0.006) were negatively correlated with the levels of p16 protein expression.Conclusions Our findings indicated that both serum folate deficiency and high expression of p16 protein could increase the risk of cervical cancer and cervix precancerous lesion,and there was an additive interaction between them.Our findings suggested that folic acid supplementation could reverse the abnormal expression of p16 protein,and effectively promote apoptosis and inhibit proliferation in cervical carcinoma cells.
ABSTRACT
Objective To explore the effects of both folic acid,p16 protein expression and their interaction on progression of cervical cancerization.Methods Participants were pathologically diagnosed new cases,including 80 women with normal cervical (NC),55 patients with low-grade cervical intraepithelial neoplasia (CIN Ⅰ),55 patients with high-grade cervical intraepithelial neoplasia (CIN Ⅱ/Ⅲ) and 64 patients with cervical squamous cell carcinoma (SCC).Serum folate levels were detected by microbiological assay method while p16 protein expression levels were measured by Western-blot.In vitro,cervical cancer cell lines C33A (HPV negative) and Caski (HPV16 positive) were treated with different concentrations of folate.Proliferation and apoptosis of cells and the levels of p16 protein expression were measured in groups with different folic acid concentrations.Results Results showed that the levels of serum folate were (5.96± 3.93) ng/ml,(5.08±3.43) ng/ml,(3.92 ± 2.59) ng/ml and (3.18 ± 2.71) ng/ml,and the levels ofpl6 protein were 0.80 ± 0.32,1.33 ± 0.52,1.91 ± 0.77,and 2.09 ± 0.72 in the group of NC,CIN Ⅰ,CIN Ⅱ/Ⅲ and SCC,respectively.However,the levels of serum folate decreased (trend X2 =32.71,P＜ 0.001) and p 16 protein expression increased (trend x2=56.06,P＜0.001) gradually along with the severity of cervix lesions.An additive interaction was seen between serum folate deficiency and high expression of p l 6 protein in the CIN Ⅰ,CIN n/Ⅲ and SCC group.Results in vitro showed that,with the increase of folate concentration,the inhibition rate of cell proliferation (C33A:r=0.928,P=0.003;Caski:r=0.962,P=0.001) and the rate on cell apoptosis (C33A:r=0.984,P＜0.001;Caski:r=0.986,P＜0.001) all increased but the levels of p16 protein expression (C33A:r=-0.817,P=0.025;Caski:r=-0.871,P=0.011) reduced.The proliferation inhibition rate (C33A:r=-0.935,P=0.002;Caski:r=-0.963,P=0.001) and apoptosis rate of cells (C33A:r=-0.844,P=0.017;Caski:r=-0.898,P=0.006) were negatively correlated with the levels of p16 protein expression.Conclusions Our findings indicated that both serum folate deficiency and high expression of p16 protein could increase the risk of cervical cancer and cervix precancerous lesion,and there was an additive interaction between them.Our findings suggested that folic acid supplementation could reverse the abnormal expression of p16 protein,and effectively promote apoptosis and inhibit proliferation in cervical carcinoma cells.
ABSTRACT
PURPOSE: The aim of this study was to determine the expressions of Rb, p16, and cyclin D1 in soft tissue sarcomas, and we also wanted to identify the prognostic factors according to the clinicalpathologic features. MATERIALS AND METHODS: We reviewed the charts and radiographic films of 66 sarcoma patients. Tissue samples were collected from these patients. Immunochemistry was performed using formalin-fixed, paraffin-embedded tissue samples to examine the expressions of p16, Rb, and cyclin D1 proteins. RESULTS: The median duration of overall survival was 47.8 months (range, 20.0 to 70.7 months) and the 5 years survival rate was 39%. As for the correlation between the degree of immunohistochemical staining for Rb protein and the histological tumor grades, there was a significant difference with a p-value of 0.019. However, no significant correlation was shown for p16 and cyclin D1. The overall survival duration of the Rb negative group (staining cell <20%) and the heterogeneous group (cell staining 20 to 80%) was 53.5+/-6.6 months and the overall survival duration of the Rb homogeneous group was 18.3+/-6.4 months, and there was a significant difference with a p-value of 0.016. However, no significant difference was shown between the survival rate according to the p16 and cyclin D1 expressions. On the multivariate analysis that was done with Rb, p16, the tumor size, grade and site, and patient age, the Rb gene expression was the most significant independent prognostic factor with a risk ratio of 3.01 (p=0.04). CONCLUSION: The expression of Rb protein was correlated with the histologic grade and overall survival of patients with soft tissue sarcomas.
Subject(s)
Humans , Cyclin D1 , Cyclins , Genes, Retinoblastoma , Immunochemistry , Multivariate Analysis , Odds Ratio , Proteins , Retinoblastoma Protein , Sarcoma , Survival Rate , X-Ray FilmABSTRACT
Objective To explore the silence of B-cell specific Moloney murine leukaemia virus insertion site 1(Bmi-1)by RNA interference on the proliferation of human leukemia cell line K562 and its mechanisms.Methods Small interfering RNA(siRNA)targeting Bmi-1 gene was designed and double-stranded siRNA was chemically synthesized.After double-stranded siRNA was transfected into K562 cells with Lipofectamine 2000,the proliferation of K562 cells was detected by MTT colorimetry,cell cycle was determined by flow cytometry,and the expression of Bmi-1 and P16 were analyzed by Western blotting.Results The siRNA targeting human Bmi-1 gene effectively prolonged the double time of K562 cells,increased the percentage of cells at G1 phase,and the expression of Bmi-1 was significantly down-regulated but the expression of P16 was up-regulated.Conclusion The siRNA targeting human Bmi-1 gene inhibits the proliferation of K562 cells,and up-regulates the expression of P16 in the cells.
ABSTRACT
OBJECTIVE: Recently p16 gene has been found as a new factor for cervical carcinogenesis. The purpose of this study is to investigate the p16 protein alteration in invasive cervical cancers, and to find the correlation with the p53 protein overexpression, HPV infection and the clinicopathologic prognostic parameters, as well as to predict the prognosis by examining the influences of the p16 gene, p53 gene, HPV to the survival rate. MATERIAL & METHODS: We examined 29 invasive cervical cancer patients who visited and operated in Obstetrics & Gynecology department of Kosin University Gospel Hospital from Jan. 1994 to Dec. 1995. We investigated clinicopathologic parameters and p16 protein alteration, p53 protein overexpression, HPV 16, 18 infection in these patients. p16 protein and p53 protein were examined by immunohistochemistry method and HPV was done by PCR method. The survival rate was examined by Kaplan-Meier method. RESULTS: The rate of p16 protein alteration, p53 protein overexpression, HPV infection were respectively 31% (9/29), 72.4% (21/29), 80.6% (26/29), and all of these factors had no statistical correlations with the clinicopathologic parameters (p>0.05).Among the 21 positive cases for p53 protein overexpression, p16 protein alteration was positive in 6 (28.6%), negative in 15 (71.4%) cases and among the 8 negative cases for p53 overexpression, p16 showed positive in 3 (37.5%), negative in 5 (62.5%). Finally among the 26 positive cases of HPV infection, p16 alteration was positive in 9 (34.6%) and negative in 17 (65.4%) and all of the 3 HPV infection negative cases showed no p16 alteration. The p16 alteration had no significant correlation with the p53 overexpression and HPV infection.The total 5 years survival rate in 29 cases of invasive cervical cancer patients was 86.2%. In the negative group of p16 protein alteration the survival rate was 80% and the positive group was all alive. In the positive groups of p53 protein overexpression and HPV infection the survival rate were 80.9% and 84.6% respectively and the negative groups were all alive. And these factors had no significant correlation with the survival rates. CONCLUSION: This results indicate that p16 protein alteration had no correlation with clinicopathologic prognostic parameters and survival rates in invasive cervical cancer. In addition p16 protein alteration had no correlation with p53 protein overexpression and HPV infection respectively.
Subject(s)
Humans , Carcinogenesis , Genes, p16 , Genes, p53 , Gynecology , Human papillomavirus 16 , Immunohistochemistry , Obstetrics , Polymerase Chain Reaction , Prognosis , Survival Rate , Uterine Cervical NeoplasmsABSTRACT
Purpose:To study the clinical value of preoperative examination of P16 protein , immunohistochemical method was used to examinate the expression of the protein in tissues obtained through the fibrobronchoscopic brushing and biopsy.Methods:All of the patients who found lesions of lung by radiology were gotten the fibrobronchoscopy to get the spicements. All of the specimens were examinted for expression of P16 protein. The expressions of P16 protein in lung carcinoma group , benign lung disease group and blind biopsy group were compared.Results:The positive expression rates of p16 protein of lung carcinoma group , lung benign disease group and blind biopsy groups are : 55.0%, 95.0% and 62.5%. Conclusions:Difference was found between malignant and benign lung diseases.Examination of p16 protein expression for blind biopsy groups has some values in diagnosis of lung carcinoma.
ABSTRACT
Objective The main purpose of the present study was to reveal the correlation among the CT and p53?p16 protein of non-small cell lung carcinoma(NSCLC).Methods The expression of p53?p16 protein in 52 cases by SABC immunohistochemical technique and the relationship to CT appearance were analysed.Results (1)The experssion of p53 protein of NSCLC was significantly higher than that of their adjacent tissues and their normal lung tissues(?
ABSTRACT
0 05). A negative correlation was found between p16 expressions and the histological grade, clinical TNM stage, lymph-node metastasis and 5-years survival rate(P0 05), but associated with histological grade and lymph-node metastasis(P
ABSTRACT
Objective:To study the anti proliferation and inducing apoptosis effects of cytokine induced killer cells CIK cells on MGC 803 gastric cancer cell lines and to probe its underlying mechanism.Methods:To detect the anti proliferation and the cytotoxicity of CIK cells on MGC 803 gastric cancer line by MTT assay.The morphological changes of the apoptosis cell were observed by HE stain, scanning and transmission electron microscope. The positive expression of p53, p16,C myc were determined by immunocytochemistry (ICC).Results:MTT assay showed that the inhibitive rate inhanced obviously with the addition of Effect/Target rate and extension of time ( P
ABSTRACT
Objective To investigate aberrant methylation in the promoter area of p16 gene and p16 protein expression in human pancreatic carcinoma and in the corresponding tumor-adjacent tissues,and evaluate their role in the carcinogenesis and progression of tumor and its clinical significance.Methods Immunohistochemistry and MSP(methylation-specific PCR)were performed on 46 samples of pancreatic carcinoma and their corresponding tumor-adjacent tissue specimens for p16 and its methylation.Results Expression rate of p16 protein was 41.3%(19/46)in pancreatic carcinomas,95.7%(44/46)in corresponding tumor-adiucent tissues.Through MSP,the methylation rate in pancreatic carcinomas was 39.1%.No gene methylation was found in 19 cases expressing p16 protein.p16 gene methylation was closely related to p16 protein expression in pancreatic carcinoma(P0.05);but were significantly related to the PTNM staging,histological differentiation,distant metastasis and lymph node metastasis(P
ABSTRACT
Objective To study the expression of human telomerase reverse transcriptase (hTERT) and P16 protein and their relation with telomerase activity in the carcinogenesis of acute leukemia. Methods Telomerase activity and hTERTmRNA were detected in 40 patients with acute leukemia and 20 normal controls by TRAP and RT-PCR, respectively; P16 protein was examined by immunocytochemical method. Results The positive rates of telomerase activity and hTERTmRNA were 75% and 80% in 40 cases of acute leukemia, respectively, whereas neither hTERTmRNA nor telomerase activity was detected in normal controls. There was a significant correlation between the expression of hTERTmRNA and telomerase activity (r= 0.65, P