Host Defense Peptide Expression in Human Cervical Cells and Regulation by 1,25-Dihydroxyvitamin D3 in the Presence of Cytokines and Bacterial Endotoxin.

Host defense peptides (HDPs) in the pregnant female reproductive tract provide protection against infection. The relationship between HDPs and infection/inflammation is poorly understood. Therefore, we investigated the regulation of HDPs by 1α, 25-dihydroxyvitamin D3 (1,25-(OH)2) in the presence/absence of infectious/inflammatory agents. Endocervical epithelial cells (END1/E6E7, n = 6) were exposed to 1,25-(OH)2, calcipotriol, interleukin 1ß (IL-1ß), granulate-macrophage colony-stimulating factor (GM-GSF), and lipopolysaccharide (LPS). Elafin, human beta defensin (hBD2), cathelicidin, secretory leucocyte protease inhibitor, interleukin 8, 1,25-(OH)2 receptor, and toll-like receptor 4 (TLR4) expression was determined using quantitative polymerase chain reaction and/or enzyme-linked immunosorbent assay. Host defense peptide gene and protein expression was assessed in cervicovaginal cells/fluid, respectively, from first trimester pregnant women (n = 8-12). Interleukin 1ß induced elafin and hBD2. The 1,25-(OH)2 induced cathelicidin expression in the presence of IL-1ß and LPS. The 1,25-(OH)2 also attenuated IL-1ß-induced IL-8 expression and LPS enhancement of TLR4. Host defense peptides and TLR4 profiles in cervicovaginal cells and fluid samples from pregnant women were similar to END1/E6E7 cells. In conclusion, HDPs are differentially regulated in END1/E6E7 cells. The 1,25-(OH)2 induction of cathelicidin and suppression of IL-8 highlights a mechanism by which 1,25-(OH)2 supplementation could enhance the pregnant innate immune defenses.

High-Fat Diet Induces Unexpected Fatal Uterine Infections in Mice with aP2-Cre-mediated Deletion of Estrogen Receptor Alpha.

Estrogen receptor alpha (ERα) is a major regulator of metabolic processes in obesity. In this study we aimed to define the relevance of adipose tissue ERα during high-fat diet (HFD)-induced obesity using female aP2-Cre-/+/ERαfl/fl mice (atERαKO). HFD did not affect body weight or glucose metabolism in atERαKO- compared to control mice. Surprisingly, HFD feeding markedly increased mortality in atERαKO mice associated with a destructive bacterial infection of the uterus driven by commensal microbes, an alteration likely explaining the absence of a metabolic phenotype in HFD-fed atERαKO mice. In order to identify a mechanism of the exaggerated uterine infection in HFD-fed atERαKO mice, a marked reduction of uterine M2-macrophages was detected, a cell type relevant for anti-microbial defence. In parallel, atERαKO mice exhibited elevated circulating estradiol (E2) acting on E2-responsive tissue/cells such as macrophages. Accompanying cell culture experiments showed that despite E2 co-administration stearic acid (C18:0), a fatty acid elevated in plasma from HFD-fed atERαKO mice, blocks M2-polarization, a process known to be enhanced by E2. In this study we demonstrate an unexpected phenotype in HFD-fed atERαKO involving severe uterine bacterial infections likely resulting from a previously unknown negative interference between dietary FAs and ERα-signaling during anti-microbial defence.

MMP-9/RECK Imbalance: A Mechanism Associated with High-Grade Cervical Lesions and Genital Infection by Human Papillomavirus and Chlamydia trachomatis.

BACKGROUND: Matrix metalloproteinases (MMP) are important enzymes in the tumor microenvironment associated with progression of cervical intraepithelial neoplasia (CIN) toward squamous cell carcinoma (SCC) of the cervix. However, the role of MMPs in the inflammatory process associated with Chlamydia trachomatis infection concomitant with the carcinogenic process driven by HPV has not yet been addressed. In the present study, we analyzed the state of the MMP-9-RECK axis in cervical carcinogenesis. METHODS: The levels of MMP-9 and RECK expression were analyzed by immunocytochemistry in liquid-based cytology samples from 136 women with high-grade cervical lesions (CIN2/CIN3) and cervical SCC diagnosed by LLETZ, and in 196 women without cervical neoplasia or CIN1. Real-time qPCR was performed to analyze expression of MMP-9 and RECK in 15 cervical samples. The presence of HPV-DNA and other genital pathogens was evaluated by PCR. RESULTS: We found a higher expression of MMP-9 [OR, 4.2; 95% confidence interval (CI), 2.2-7.8] and lower expression of RECK (OR, 0.4; 95% CI, 0.2-0.7) in women with CIN2/CIN3/SCC when compared with women from the control group (no neoplasia/CIN1). A statistically significant association was also found between MMP-9/RECK imbalance and infection by alpha-9 HPV and C. trachomatis. The prevalence of C. trachomatis infection was significantly higher in women with high-grade cervical disease (OR, 3.7; 95% CI, 1.3-11.3). CONCLUSIONS: MMP-9/RECK imbalance in cervical smears is significantly associated with high-grade cervical diseases and infection by alpha-9 HPV and C. trachomatis. IMPACT: MMP-9/RECK imbalance during cervical inflammation induced by C. trachomatis might play a role in HPV-mediated cervical carcinogenesis.

Metabolomics analysis of cervical cancer, cervical intraepithelial neoplasia and chronic cervicitis by 1H NMR spectroscopy.

Metabolomics profiles of serum samples from women with chronic cervicitis, cervical intraepithelial neoplasia (CIN), and cervical cancer were characterized by proton nuclear magnetic resonance (1H NMR). These spectral profiles were subjected to partial least-squares discriminant analysis (PLS-DA), and good discriminations between cancerand non-cancer groups (chronic cervicitis and CIN) were achieved by multivariate modeling of serum profiles. The main metabolites contributing to these discriminations, as highlighted by multivariate analysis and confirmed by spectral integration, were formate, tyrosine, ß-glucose, inositol, glycine, carnitine, glutamine, acetate, alanine, valine, isoleucine, and very-low-density lipoprotein (VLDL). Metabolomics analysis for chronic cervicitis, CIN, and cervical cancer is significant, which give a systemic metabolic response of these female diseases. The systemic metabolic response may be used to identify the potential biomarkers for the diseases.

Expressions of survivin, P16(INK4a), COX-2, and Ki-67 in cervical cancer progression reveal the potential clinical application.

PURPOSE OF INVESTIGATION: To explore the significance of survivin, P16(INK4a), COX-2, and Ki-67 expressions for prediction of cervical cancer progression. MATERIALS AND METHODS: A retrospective study was performed in 129 cases including 24 squamous carcinoma of the cervix (SCC), 70 cervical intraepithelial neoplasias (CIN), 15 cervical condyloma acuminatum (CCA), ten chronic cervicitis (CC), and ten normal cervix (NC). Protein expressions were evaluated using immunohistochemistry. RESULTS: Survivin, P16(INK4a); COX-2, and Ki-67 were highly expressed in SCC and CIN compared with others. Their expression rates were gradually increased in CIN I, CIN II, CIN III, and SCC groups, showing 72.00%, 88.00%, 90.00%, and 95.83% for P16(INK4a), 68.00%, 84.00%, 95.00% and 100.00% for COX-2, 76.00%, 96.00%, 100.00%, and 100.00 for Ki-67, respectively. There were significant correlations between survivin and P16(INK4a), COX-2, Ki-67, as well as P16(INK4a) and Ki-67. CONCLUSION: Survivin, P16(INK4a), COX-2 and Ki-67 play critical roles for development and progression of cervical cancer.

Expression of P16 in high-risk human papillomavirus related lesions of the uterine cervix in a government hospital, Malaysia.

BACKGROUND: Cervical cancer is one of the most common cancers affecting women worldwide. It is well established that human papilloma virus (HPV) infection is the prime risk factor in the development of cervical cancer. The current screening and diagnostic tests have limitations in identifying the range of lesions caused by HPV. The current study aims to evaluate the diagnostic value of p16 immunohistochemical (IHC) investigation in high-risk human papillomavirus (HR-HPV) related lesions of the uterine cervix in Hospital Tuanku Jaafar, Seremban, Malaysia. METHODS: A total of 75 cases were selected from the records of Pathology services, Hospital Tuanku Ja'afar, Seremban. The samples were collected in three separate groups (n=25 per group) as Carcinoma cervix, Carcinoma in situ and Chronic cervicitis. The demographic data of the patients and the representative paraffin blocks were retrieved from Hospital Tuanku Ja'afar, Seremban. The immunohistochemical staining with p16 and HPV 16 L1 were done on all cases. The staining intensity and density were observed and compared among the three groups of cases. RESULTS: Immunohistochemistry of p16INK4A staining shows nil (0/25) expression in the cervicitis patients, 72% (18/25) in CIN patients and 100% (25/25) in cervical carcinoma. HPV 16 L1 was positive in 100% (25/25) of cervicitis patients, 96% (24/25) of CIN patients and 40% (10/25) of cervical cancers patients. A chi square test was used to analyze the result and the obtained p value was <0.05. CONCLUSION: p16 expression was strongly observed in cervical cancer and minimally observed in cervicitis. Thus indicating p16 immunohistochemistry investigations can aid in diagnosing the different categories of cervical lesions into benign, insitu and malignant. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_202.

Progressive loss of E-cadherin immunoexpression during cervical carcinogenesis.

PURPOSE: To investigate E-cadherin immunoexpression during cervical carcinogenesis. METHODS: We assessed the immunohistochemical expression of E-cadherin in squamous intraepithelial lesions (SIL - 52 cases), squamous cell carcinoma (SCC) of the uterine cervix (23 cases) and also in eight cases of cervicitis. RESULTS: The results show very different E-cadherin membrane expression levels when cervicitis (88%), SILs (73%) and SCC (17%) were compared. In SILs, higher E-cadherin loss was seen in less differentiated cells in the basal third of the epithelium. This study suggests that the absence of E-cadherin expression in the membrane is a molecular event that is observed more often in SCC of the uterine cervix than in SILs or cervicitis. CONCLUSIONS: E-cadherin is an essential molecule during the process of cervical carcinogenesis and in this context exhibits a different expression pattern according to the epithelial thickness layer.

Progressive loss of E-cadherin immunoexpression during cervical carcinogenesis

PURPOSE: To investigate E-cadherin immunoexpression during cervical carcinogenesis. METHODS: We assessed the immunohistochemical expression of E-cadherin in squamous intraepithelial lesions (SIL - 52 cases), squamous cell carcinoma (SCC) of the uterine cervix (23 cases) and also in eight cases of cervicitis. RESULTS: The results show very different E-cadherin membrane expression levels when cervicitis (88%), SILs (73%) and SCC (17%) were compared. In SILs, higher E-cadherin loss was seen in less differentiated cells in the basal third of the epithelium. This study suggests that the absence of E-cadherin expression in the membrane is a molecular event that is observed more often in SCC of the uterine cervix than in SILs or cervicitis. CONCLUSIONS: E-cadherin is an essential molecule during the process of cervical carcinogenesis and in this context exhibits a different expression pattern according to the epithelial thickness layer. .

The prognosis significance of TGF-ß1 and ER protein in cervical adenocarcinoma patients with stage Ib~IIa.

The incidence of stage Ib~IIa of cervical adenocarcinoma accounts about 60 to 70% of all patients. This study aims to investigate the prognostic significance of protein estrogen receptor alpha (ERα) and transforming growth factor beta 1 (TGF-ß1) level in different glandular epithelia of the cervix. In this study, immunohistochemistry was used to detect ERα and TGF-ß1 in carcinomas and incisal margins of 66 cases with cervical adenocarcinoma, 20 cases with normal cervix, and 20 cases with chronic cervicitis. Uni- and multivariate analysis was applied to evaluate the prognostic significance of TGF-ß1 and ERα in carcinomas. The results indicated that the positive expression of TGF-ß1 in carcinomas was 71.21%, significantly higher compared to that in the normal cervix (35%) and chronic cervicitis (55%) (χ(2) = 8.901, P = 0.012). Similarly, the positive expression of ERα in the carcinomas was 68.18%, significantly higher compared to the normal cervix (35%) and chronic cervicitis (50%) (χ(2) = 7.693, P = 0.021). Both TGF-ß1 and ERα in the carcinomas were associated with the vaginal recurrence, infection of HPV, depth of infiltration, and lymphatic metastasis (P < 0.05). The conjugation of TGF-ß1 and ERα was an independent prognostic factor for cervical adenocarcinoma. Survival curve showed that the positive TGF-ß1 and ERα indicated a short lifetime of patient with cervical adenocarcinoma. In conclusion, the expression of TGF-ß1 and ERα protein in the carcinomas had a significant prognostic value in a patient of stage Ib~IIa in cervical adenocarcinoma.

Hypoxia promotes the proliferation of cervical carcinoma cells through stimulating the secretion of IL-8.

To explore whether hypoxia and interleukin 8 (IL-8) regulate the viability and apoptosis of cervical carcinomas cells and the possible mechanism. We evaluated the expression of hypoxia inducible factor-1α (HIF-1α), IL-8 and its receptors (CXCR1 and CXCR2) in cervical cancer and cervicitis tissues by immunohistochemistry. Then the effects of hypoxia and IL-8 on the viability and apoptosis of HeLa and SiHa cells were detected by the SRB and apoptosis assays. Here we observed that the expression of HIF-1α, IL-8 and CXCR1 in cervical cancer tissues was significantly higher than that in cervicitis tissues. Hypoxic condition stimulated the secretion of IL-8 and the expression of CXCR1 and CXCR2 on HeLa and SiHa cells. Recombinant human IL-8 enhanced the viability and reduced the apoptosis in HeLa and SiHa cells. HeLa and SiHa cells cultured in 1% oxygen showed the increased viability and apoptosis, and the former effect could be partly reversed by anti-human IL-8 neutralizing antibody. This data suggested that IL-8 secreted by cervical carcinomas cells induced by hypoxia can stimulate the viability of cervical carcinomas cells in an autocrine dependent manner, and contribute to the pathogenesis of cervical cancer.

[Cervical glandular intraepithelial neoplasia: a clinicopathologic and immunohistochemical analysis of 80 cases].

OBJECTIVE: To assess the clinicopathologic characteristics of cervical glandular intraepithelial neoplasia (CGIN) and to evaluate the usefulness of EnVision immunohistochemistry of various markers in identifying early invasive cervical adenocarcinoma (ICA) and its precursor lesions. METHODS: Clinical and pathological characteristics of 80 cases of high grade CGIN (HCGIN), 20 ICA, and 20 cervicitis were reviewed along with immunohistochemical studies of p16, Ki-67, CEA, CA125 and bcl-2. RESULTS: The clinical features of HCGIN were similar to those of high grade cervical intraepithelial neoplasia (CIN). Fourty four cases (55.0%) accompanied with CIN and 9 cases (11.3%) accompanied with early cervical squamous cell carcinoma (SCC). The positive rates of p16, CEA and Ki-67 in 80 cases of HCGIN were 100.0%, 63.8% and 73.8%, respectively. The positive rates of p16, CEA and Ki-67 in 20 ICA were 18/20, 16/20 and 20/20, respectively. The positive rates of p16, CEA and Ki-67 in 20 cervicitis were 1/20, 1/20 and 3/20, respectively. There was a significantly increased expression of p16, CEA and Ki-67 in ICA and HCGIN compared with cervicitis (P < 0.01). Ki-67 expression increased in ICA compared to HCGIN (P < 0.05). There was no statistical difference in CEA expression between ICA and HCGIN (P > 0.05). CA125 showed strong but nonspecific expression. Bcl-2 was negative or occasionally positive in each groups. CONCLUSIONS: HCGIN is frequently accompanied with CIN and SCC. The combined staining of p16, CEA and Ki-67 provides additional aid in the diagnosis of early stage cervical adenocarcinoma and its precursor lesions. The sensitivity of p16 and Ki-67 markers for HCGIN is higher than that of CEA. CA125 and bcl-2 immunostains offer no helpful in identifying HCGIN.

Plasma and mucosal HIV viral loads are associated with genital tract inflammation in HIV-infected women.

BACKGROUND: Systemic and mucosal inflammation may play a role in HIV control. A cross-sectional comparison was conducted among women in the Women's Interagency HIV Study to explore the hypothesis that compared with HIV-uninfected participants, women with HIV, and, in particular, those with high plasma viral load (PVL) have increased levels of mucosal and systemic inflammatory mediators and impaired mucosal endogenous antimicrobial activity. METHODS: Nineteen HIV-uninfected, 40 HIV-infected on antiretroviral therapy (ART) with PVL ≤ 2600 copies/mL (low viral load) (HIV-LVL), and 19 HIV-infected on or off ART with PVL >10,000 (high viral load) (HIV-HVL) were evaluated. Immune mediators and viral RNA were quantified in plasma and cervicovaginal lavage (CVL). The CVL antimicrobial activity was also determined. RESULTS: Compared to HIV-uninfected participants, HIV-HVL women had higher levels of mucosal but not systemic proinflammatory cytokines and chemokines, higher Nugent scores, and lower Escherichia coli bactericidal activity. In contrast, there were no significant differences between HIV-LVL and HIV-uninfected controls. After adjusting for PVL, HIV genital tract shedding was significantly associated with higher CVL concentrations of IL-6, IL-1ß, MIP-1α, and CCL5 (RANTES) and higher plasma concentrations of MIP-1α. High PVL was associated with higher CVL levels of IL-1ß and RANTES, as well as with higher Nugent scores, lower E. coli bactericidal activity, smoking, and lower CD4 counts; smoking and CD4 count retained statistical significance in a multivariate model. CONCLUSIONS: Further study is needed to determine if the relationship between mucosal inflammation and PVL is causal and to determine if reducing mucosal inflammation is beneficial.

Immunohistochemical expression of RAGE and its ligand (S100A9) in cervical lesions.

Altered expressions of receptor for advanced glycation end-products (RAGE) and its ligand (S100A9) are observed in many cancers and play a key role in inflammation-associated cancer. In our previous study, by two-dimensional gel electrophoresis followed by mass spectrometry, the expression of S100A9 protein was found to increase in squamous cervical cancer compared with adjacent normal cervical tissues. Therefore, in the present study we observed the expressions of S100A9 and RAGE in 30 chronic cervicitis, 50 cervical intraepithelial neoplasia (CIN), and 40 squamous cervical cancer (SCC) using immunohistochemical analysis and analyzed the differential expression and possible role of S100A9 and RAGE in cancer development. Immunohistochemical findings were as follows: the expressions of S100A9 and RAGE were demonstrated in chronic cervicitis, CIN, and SCC. Moreover, their expressions were gradually increasing as the tumor progressed. In SCC, the staining scores of S100A9 and RAGE were significantly higher in well-differentiated tumors compared to moderately and poorly differentiated tumors. The expression of S100A9 in epithelial cells exhibited a positive correlation to RAGE expression in chronic cervicitis, CIN, and SCC. There were no significant difference of S100A9 immunoreactivity in stromal cells among chronic cervicitis, CIN, and SCC. Moreover, there was no correlation between S100A9 immunoreactivity in stromal cells of SCC and clinicopathological parameters. Finally, double immunohistochemistry illustrated that RAGE and S100A9 co-express in SCC. In conclusion, RAGE binds its ligand (S100A9), which plays an important role in the development of SCC. In addition, the expressions of S100A9 and RAGE in SCC tumor cells were closely associated with histological differentiation.

Expression of P-Akt, NFkappaB and their correlation with human papillomavirus infection in cervical carcinoma.

PURPOSE: To investigate the expression of P-Akt and NFkappaB and their correlation with human papillomavirus (HPV) infection in cervical carcinoma. MATERIAL AND METHODS: Expression of P-Akt and NFkappaB was detected by an immunohistochemical SP technique with HPV DNA detetion by PCR in 26 cases of cervical carcinoma tissues, 18 cases of cervical intraepithelial neoplasia tissues (CINI / n = 5, CINII / n = 3, CINIII / n = 10) and 19 cases of chronic cervicitis tissues. The different expressions of P-Akt and NFkappaB were compared in different pathological types of cervical carcinoma (cervical squamous cell carcinoma, cervical adenocarcinoma), different pathological grading (high, medium, poorly differentiated) and different clinical stage (FIGO I to IV). The relationships between P-Akt and NFkappaB, respectively, with HPV infection in cervical carcinoma were analyzed. RESULTS: The positive expression rate of P-Akt in chronic cervicitis tissues, CIN and cervical carcinoma tissues was 21.05%, 66.67%, and 92.31%, respectively. There was no obvious difference in the expression of P-Akt in cervical carcinoma in different pathological types or in pathological grading and no obvious difference in different clinical stages. The positive expression rate of NFkappaB in chronic cervicitis tissues, CIN and cervical carcinoma tissues was 10.52%, 72.22% and 96.15%, respectively; there was no statistically significant difference among the groups for different pathological types and there was no obvious difference in different pathological grading or different clinical stage. There was an obviously positive correlation between P-Akt and NFkappaB expression rate and degree of disease (r = 0.998, p < 0.05). Cervical carcinoma and CIN cases totaled 44; the positive expression rate of P-Akt was 87.55% in 32 cases of positive HPV-DNA of the 44 cases, and the positive expression rate of P-Akt was only 16.70% in 12 cases of negative HPV-DNA of the 44 cases. The positive expression rate of NFkappaB was obviously higher in the HPV DNA positive than in the HPV-DNA negative cases. There was a statistically significant difference among the groups (p < 0.05). CONCLUSION: The positive expression rate of P-Akt and NFkappaB was closely related with cervical disease extent, and closely related with HPV infection in cervical carcinoma. This study suggests that P-Akt and NFkappaB more probably play an important role in the occurrence of cervical carcinoma.

Significance and expression of aquaporin 1, 3, 8 in cervical carcinoma in Xinjiang Uygur women of China.

Overexpression of several aquaporins (AQPs) has been reported in different types of human cancer but their role in carcinogenesis, for example in the cervix, have yet to be clearly defined. In this study, expression of AQPs in cervical carcinomawas investigated by real-time PCR, immunofluorescent and immunohistochemical assays and evaluated for correlations with clinicopathologic variables. AQP1, 3, 8 exhibited differential expression in cervical carcinoma, corresponding CIN and mild cervicitis. AQP1 was predominantly localized in the microvascular endothelial cell in the stroma of mild cervicitis, CIN and cervical carcinoma. AQP3 and AQP8 were localized in the membrane of normal squamous epithelium and carcinoma cells, local signals being more common than diffuse staining. AQP1 and AQP3 expression was remarkably stronger in cervical cancer than in mild cervicitis and CIN2-3 (P<0.05). AQP8 expression was highest in CIN2-3 (91.7%), but levels in cervical carcinoma were also higher than in mild cervicitis. AQP1, AQP3, AQP8 expression significantly increased in advanced stage, deeper infiltration, metastatic lymph nodes and larger tumor volume (P<0.05). Our findings showed that AQPs might play important roles in cervical carcinogenesis and tumour progression in Uygur women.

[Death-associated protein kinase promoter (DAPK) hypermethylation in uterine cervical cancer and intraepithelial neoplasia in Uyghur nationality women].

OBJECTIVE: To investigate the methylation levels of death-associated protein kinase (DAPK) in Uyghur female patients with different cervical lesions in Xinjiang, and to discuss the relationship of the expression and significance of DAPK in normal cervix, chronic cervicitis, cervical intraepithelial neoplasia (CINI, CIN II/III) and invasive cervical squamous cell carcinoma. METHODS: 30 cases of normal cervix and chronic cervicitis, 30 cases of CINI, 30 cases of CINII/III and 30 cases of cervical squamous cell carcinoma were tested by methylation specific PCR (MSP). Expressions of DAPK in 30 cases of normal cervix and chronic cervicitis, 30 cases of CINI, 30 cases of CINII/III and 30 cases of cervical squamous cell carcinoma were assayed using immunohistochemical SP staining. RESULTS: The methylation rate of DAPK gene in normal cervix and chronic cervicitis was 3.33%, 10% in cervical intraepithelial neoplasia CINI, 36.7% in CINII/III, and 63.3% in invasive cervical squamous cell carcinoma. The methylation rate of DAPK in the SCC group was significantly higher than that in the other groups (P < 0.05). Aberrant promoter methylation of the DAPK gene was positively correlated with the degree of cervical lesions. The positive rate of DAPK protein in normal cervix and chronic cervicitis was 93.3%, 83.3% in cervical intraepithelial neoplasia CINI, 60.0% in CINII/III, and 33.3% in invasive cervical squamous cell carcinoma. The expression of DAPK in the SCC group was significantly lower than that in the other groups (P < 0.05). The positive rate of DAPK protein was negatively correlated with the degree of cervical lesions (r(s) = -0.603, P < 0.001). CONCLUSIONS: Methylation of DAPK is involved in the cervical carcinogenesis and DAPK gene promoter methylation occurs in the early development of cervical cancer in Uyghur women in Xinjiang. Detection of DAPK gene methylation may provide a basis for use in early detection of cervical cancer. DAPK protein expression is decreasing even disappears along with the progression of cervical lesions.

Overexpression of Y-box binding protein-1 in cervical cancer and its association with the pathological response rate to chemoradiotherapy.

The aim of this study was to evaluate the expression of Y-box binding protein-1 (YB-1) in nonneoplastic cervical tissue and cervical cancer tissue and to evaluate its relationship with chemoradiosensitivity in the cases of cervical cancer. We performed immunohistochemical studies to examine YB-1 expression among 59 patients with cervical cancer, 30 with cervical intraepithelial neoplasia (CIN), and 30 with cervicitis. The mean YB-1 histological score(HSCORE)values for cervicitis, cervical CIN, and cervical cancer tissues were 22.3, 39, and 84.4, respectively. The mean YB-1 HSCORE value was 80.0 for cervical cancer patients who showed complete pathological response to chemoradiotherapy and 144.3 for cervical cancer patients who showed partial pathological response. Our data showed that the YB-1 expression was the highest in cervical cancer tissue, followed by cervical CIN tissue, and then cervicitis tissues. High YB-1 expression resulted in a lower pathological response rate in patients of cervical cancer than low YB-1 expression did. Our results implied that YB-1 may play a role in the genesis of cervical cancer and that high YB-1 expression decreases the chemoradiosensitivity of cervical cancers.

Cervicovaginal inflammatory cytokines and sphingomyelinase in women with and without bacterial vaginosis.

INTRODUCTION: The objective is to analyze proinflammatory cytokines [interleukin-1ß (IL-1ß), interleukin-6 and tumor necrosis factor-α] and sphingomyelinase in women with bacterial vaginosis (BV), cervicitis and vaginitis. METHODS: From January 2009 to June 2010, human immunodeficiency virus (HIV)-negative, nonpregnant, married women, living with husband, aged 20 to 40 years were recruited from a slum at Hyderabad, India, after taking written consent. One hundred forty-six women including 61 women with BV, 47 women with intermediate flora and 38 women with normal vaginal flora were evaluated for local proinflammatory cytokines and sphingomyelinase. Cervicitis and vaginitis were also analyzed by scoring white blood cells in the cervix and vaginal smears, respectively. RESULTS: Of the 146 women, 50.7% had cervicitis and 19.5% had vaginitis. IL-1ß, tumor necrosis factor-α and interleukin-6 levels were significantly high in women with cervicitis (P < 0.001) and vaginitis (P < 0.001) and IL-1ß in BV (P < 0.005), intermediate flora (P < 0.05) when compared with normal women. High vaginal pH was associated with IL-1ß. Neutral sphingomelinase showed an inverse association (P < 0.05) with cervicitis. Acid sphingomelinase directly correlated with IL-1ß although not significantly. CONCLUSIONS: This study shows proinflammatory response not only in BV but also in women with vaginitis and cervicitis. These conditions are likely to be important in promoting the transmission of HIV-1 and should be the focus of HIV prevention strategies.