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author:("Feng, xinghua")
1.  HIV shedding in the oral cavity: an assessment of HIV type, immunovirologic, demographic and oral factors 
Objective
To quantify the prevalence and burden of HIV type 2 (HIV-2) and HIV-1 RNA in the oral cavity of antiretroviral therapy-naive HIV-infected Senegalese individuals and to identify correlates of oral HIV viral loads.
Design
A cross-sectional study of 163 HIV-1 and 27 HIV-2-infected antiretroviral therapy-naive Senegalese adults.
Methods
Participants received clinical and oral exams and provided blood and oral wash samples for viral load and plasma CD4 count ascertainment. Logistic and interval regression models were used to identify univariate and multivariable associations between presence and level of oral HIV RNA and various immunovirologic, local and demographic factors.
Results
Presence of detectable oral HIV RNA was less common in HIV-2-infected compared with HIV-1-infected study participants (33% vs 67%, OR 0.25, 95% CI 0.11 to 0.59). HIV type was no longer associated with oral shedding of HIV when plasma viral load was considered. Detection of oral HIV RNA was associated with increased plasma viral load in both HIV-1-infected and HIV-2-infected individuals (HIV-1, OR 1.89, 95% CI 1.24 to 2.61; HIV-2, OR 1.93, 95% CI 1.1 to 3.39). Oral HIV-1 detection was also associated with periodontal disease (OR 3.02, 95% CI 1.16 to 7.87).
Conclusions
Oral shedding of HIV-2 RNA is less common than HIV-1 RNA, a likely consequence of lower overall viral burden. Both systemic and local factors may contribute to shedding of HIV in the oral cavity.
doi:10.1136/sextrans-2011-050231
PMCID: PMC4028315  PMID: 22250179
2.  Human papillomavirus DNA is rarely detected in colorectal carcinomas and not associated with microsatellite instability: The Seattle Colon Cancer Family Registry 
Background
Persistent infection with oncogenic human papillomavirus (HPV) types-16 and -18 is an established cause of cervical and other cancers. Some studies report detection of oncogenic HPV DNA in colorectal carcinomas, with prevalence estimates as high as 84%. However, other studies report detecting no HPV DNA in colorectal tumors.
Methods
To evaluate the prevalence of HPV in colorectal cancer subsets, we conducted a case-case comparison study. This study included 555 cases of incident colorectal cancer from the Seattle Colon Cancer Family Registry (CCFR), ages 20-74, and diagnosed between 1998-2002. Standardized interviews were used to elicit demographics and risk factor data. Tumor DNA was assayed for HPV-16 and -18 DNA using real-time PCR. Microsatellite instability (MSI) status was assessed using a standard 10-marker panel and confirmed with immunohistochemical staining. Prevalence estimates were calculated for the overall sample, and stratified by patient and tumor characteristics. Fisher’s exact test was used to compare prevalence between strata.
Results
HPV-16 DNA was detected in 2% of colorectal tumors, but no HPV-18 DNA was detected. HPV-16 prevalence did not vary between cases according to sex, age, race, smoking-status, or MSI-status (P>0.05). HPV-16 prevalence in rectal carcinomas was 5% compared to 1% in colon carcinomas (P=0.03).
Conclusions
Among a large sample of colorectal carcinomas, prevalence of HPV-16 and -18 was very low. Prior studies detecting high HPV prevalence in colorectal carcinomas are likely the result of contamination from the anal canal or clinical processing.
Impact
HPV is unlikely to play a large role in colorectal carcinogenesis.
doi:10.1158/1055-9965.EPI-12-1170
PMCID: PMC3565050  PMID: 23250932
HPV; colorectal cancer; anatomic site; microsatellite instability
3.  Th2 type inflammation promotes the gradual progression of HPV-infected cervical cells to cervical carcinoma 
Gynecologic oncology  2012;127(2):412-419.
Objectives
To investigate the role of immunological parameters in tumorigenesis of cervical cancer in women infected with high risk human papillomavirus (hr-HPV), and determine whether key findings with human material can be recapitulated in the mouse TC1 carcinoma model which expresses hr-HPV epitopes.
Methods
Epithelial and lymphoid cells in cervical tissues were analyzed by immunohistochemistry and serum IL10 levels were determined by ELISA. Tumor draining lymph nodes were analyzed in the mouse TC1 model by flow cytometry.
Results
The mucosa was infiltrated by CD20+ and CD138+ cells already at cervical intraepithelial neoplasia 1 (CIN1) and infiltration increased in cervical intraepithelial neoplasia 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC), where it strongly correlated with infiltration by CD32B+ and FoxP3+ lymphocytes. GATA3+ and T-bet+ lymphoid cells were increased in ICC compared to normal, and expression in epithelial cells of the Th2 inflammation-promoting cytokine TSLP and of IDO1 was higher in CIN3/CIS and ICC. As a corollary, serum levels of IL10 were higher in women with CIN3/CIS or ICC than in normals. Finally we demonstrated in the mouse TC1 carcinoma, which expresses hr-HPV epitopes, an increase of cells expressing B cell or plasma cell markers or Fc receptors in tumor-draining than distal lymph nodes or spleen.
Conclusions
hr-HPV initiates a local Th2 inflammation at an early stage, involving antibody forming cells, and fosters an immunosuppressive microenvironment that aids tumor progression.
doi:10.1016/j.ygyno.2012.07.098
PMCID: PMC3472044  PMID: 22828962
4.  Prevalence and risk factors for oncogenic HPV infections in high-risk mid-adult women 
Sexually transmitted diseases  2012;39(11):848-856.
Background
The epidemiology of high-risk (hr) HPV infections in mid-adult women with new sex partners is undefined.
Methods
We analyzed baseline data from 518 25–65 year old female online daters. Women were mailed questionnaires and kits for self-collecting vaginal specimens for PCR-based hrHPV testing. Risk factors for infection were identified using Poisson regression models to obtain prevalence ratios (PRs).
Results
The prevalence of hrHPV infection was 35.9%. In multivariate analysis restricted to sexually active women, the likelihood of hrHPV infection was associated with abnormal Pap test history (PR=1.42, 95% CI:1.10–1.84), lifetime number of sex partners >14 (relative to 1–4; PR=2.13, 95% CI:1.13–4.02 for 15–24 partners and PR=1.91, 95% CI:1.00–3.64 for ≥25 partners), male partners with ≥1 concurrent partnership (PR=1.34, 95% CI:1.05–1.71) and male partners whom the subject met online (PR=1.39, 95% CI:1.08–1.79). Age was inversely associated with infection only in women who were sexually inactive (PR=0.67 per 5-year age difference, adjusted for Pap history and lifetime number of partners). Compared to sexually inactive women, the likelihood of infection increased with increasing risk level, (from low-risk to high-risk partners) (p<.0001 by trend test). In multivariate analysis, infection with multiple versus single hrHPV types was inversely associated with ever having been pregnant (PR=0.64, 95% CI:0.46–0.90) and recent consistent condom use (PR=0.56, 95% CI:0.32–0.97), and positively associated with genital wart history (PR=1.43, 95% CI:1.03–1.99).
Conclusions
Measures of both cumulative and recent sexual history were associated with prevalent hrHPV infection in this high-risk cohort of mid-adult women.
doi:10.1097/OLQ.0b013e3182641f1c
PMCID: PMC3476060  PMID: 23064533
HPV; human papilloma virus; mid-adult; prevalence; risk factors
5.  Disclosure of Genital Human Papillomavirus Infection to Female Sex Partners by Young Men 
Sexually Transmitted Diseases  2012;39(8):583-587.
A survey was administered to male university students testing positive for high-risk human papillomavirus. Disclosure was more likely in men with fewer partners, in main partnerships, and in longer partnerships. Disclosure was associated with discussing the Pap test/HPV vaccine with female partners and not associated with a worsening relationship.
doi:10.1097/OLQ.0b013e318254c982
PMCID: PMC3398400  PMID: 22797688
human papillomavirus; male; disclosure; sexually transmitted infection; sexual partnerships
6.  Co-administration of epithelial junction opener JO-1 improves the efficacy and safety of chemotherapeutic drugs 
Purpose
Epithelial junctions between tumor cells inhibit the penetration of anti-cancer drugs into tumors. We previously reported on recombinant adenovirus serotype 3 derived protein (JO-1), which triggers transient opening of intercellular junctions in epithelial tumors through binding to desmoglein 2 (DSG2), and enhances the anti-tumor effects of several therapeutic monoclonal antibodies. The goal of this study was to evaluate whether JO-1 co-therapy can also improve the efficacy of chemotherapeutic drugs.
Experimental Design
The effect of intravenous application of JO-1 in combination with several chemotherapy drugs including paclitaxel/Taxol™, nanoparticle albumin bound paclitaxel/Abraxane™, liposomal doxorubicin/Doxil™ and irinotecan/Camptosar™, was tested in xenograft models for breast, colon, ovarian, gastric and lung cancer. Because JO-1 does not bind to mouse cells, for safety studies with JO-1, we also used human DSG2 (hDSG2) transgenic mice with tumors that overexpressed human DSG2.
Results
JO-1 increased the efficacy of chemotherapeutic drugs, and in several models overcame drug resistance. JO-1 treatment also allowed for the reduction of drug doses required to achieve anti-tumor effects. Importantly, JO-1 co-admininstration protected normal tissues, including bone marrow and intestinal epithelium, against toxic effects that are normally associated with chemotherapeutic agents. Using the hDSG2 transgenic mouse model, we demonstrated that JO-1 predominantly accumulates in tumors. Except for a mild, transient diarrhea, intravenous injection of JO-1 (2mg/kg) had no critical side effects on other tissues or hematological parameters in hDSG2-transgenic mice.
Conclusions
Our preliminary data suggest that JO-1 co-therapy has the potential to improve the therapeutic outcome of cancer chemotherapy.
doi:10.1158/1078-0432.CCR-11-3213
PMCID: PMC3547677  PMID: 22535153
7.  MicroRNA expression in ovarian carcinoma and its correlation with clinicopathological features 
Background
MicroRNA (miRNA) expression is known to be deregulated in ovarian carcinomas. However, limited data is available about the miRNA expression pattern for the benign or borderline ovarian tumors as well as differential miRNA expression pattern associated with histological types, grades or clinical stages in ovarian carcinomas. We defined patterns of microRNA expression in tissues from normal, benign, borderline, and malignant ovarian tumors and explored the relationship between frequently deregulated miRNAs and clinicopathologic findings, response to therapy, survival, and association with Her-2/neu status in ovarian carcinomas.
Methods
We measured the expression of nine miRNAs (miR-181d, miR-30a-3p, miR-30c, miR-30d, miR-30e-3p, miR-368, miR-370, miR-493-5p, miR-532-5p) in 171 formalin-fixed, paraffin-embedded ovarian tissue blocks as well as six normal human ovarian surface epithelial (HOSE) cell lines using Taqman-based real-time PCR assays. Her-2/neu overexpression was assessed in ovarian carcinomas (n = 109 cases) by immunohistochemistry analysis.
Results
Expression of four miRNAs (miR-30c, miR-30d, miR-30e-3p, miR-370) was significantly different between carcinomas and benign ovarian tissues as well as between carcinoma and borderline tissues. An additional three miRNAs (miR-181d, miR-30a-3p, miR-532-5p) were significantly different between borderline and carcinoma tissues. Expression of miR-532-5p was significantly lower in borderline than in benign tissues. Among ovarian carcinomas, expression of four miRNAs (miR-30a-3p, miR-30c, miR-30d, miR-30e-3p) was lowest in mucinous and highest in clear cell samples. Expression of miR-30a-3p was higher in well-differentiated compared to poorly differentiated tumors (P = 0.02), and expression of miR-370 was higher in stage I/II compared to stage III/IV samples (P = 0.03). In multivariate analyses, higher expression of miR-181d, miR-30c, miR-30d, and miR-30e-3p was associated with significantly better disease-free or overall survival. Finally, lower expression of miR-30c, miR-30d, miR-30e-3p and miR-532-5p was significantly associated with overexpression of Her-2/neu.
Conclusions
Aberrant expression of miRNAs is common in ovarian tumor suggesting involvement of miRNA in ovarian tumorigenesis. They are associated with histology, clinical stage, survival and oncogene expression in ovarian carcinoma.
doi:10.1186/1477-7819-10-174
PMCID: PMC3449188  PMID: 22925189
miRNA; Ovarian tumor; Her2/neu; Survival
8.  Analysis of Tp53 Codon 72 Polymorphisms, Tp53 Mutations, and HPV Infection in Cutaneous Squamous Cell Carcinomas 
PLoS ONE  2012;7(4):e34422.
Background
Non-melanoma skin cancers are one of the most common human malignancies accounting for 2–3% of tumors in the US and represent a significant health burden. Epidemiology studies have implicated Tp53 mutations triggered by UV exposure, and human papilloma virus (HPV) infection to be significant causes of non-melanoma skin cancer. However, the relationship between Tp53 and cutaneous HPV infection is not well understood in skin cancers. In this study we assessed the association of HPV infection and Tp53 polymorphisms and mutations in lesional specimens with squamous cell carcinomas.
Methods
We studied 55 cases of histologically confirmed cutaneous squamous cell carcinoma and 41 controls for the presence of HPV infection and Tp53 genotype (mutations and polymorphism).
Results
We found an increased number of Tp53 mutations in the squamous cell carcinoma samples compared with perilesional or control samples. There was increased frequency of homozygous Tp53-72R polymorphism in cases with squamous cell carcinomas, while the Tp53-72P allele (Tp53-72R/P and Tp53-72P/P) was more frequent in normal control samples. Carcinoma samples positive for HPV showed a decreased frequency of Tp53 mutations compared to those without HPV infection. In addition, carcinoma samples with a Tp53-72P allele showed an increased incidence of Tp53 mutations in comparison carcinomas samples homozygous for Tp53-72R.
Conclusions
These studies suggest there are two separate pathways (HPV infection and Tp53 mutation) leading to cutaneous squamous cell carcinomas stratified by the Tp53 codon-72 polymorphism. The presence of a Tp53-72P allele is protective against cutaneous squamous cell carcinoma, and carcinoma specimens with Tp53-72P are more likely to have Tp53 mutations. In contrast Tp53-72R is a significant risk factor for cutaneous squamous cell carcinoma and is frequently associated with HPV infection instead of Tp53 mutations. Heterozygosity for Tp53-72R/P is protective against squamous cell carcinomas, possibly reflecting a requirement for both HPV infection and Tp53 mutations.
doi:10.1371/journal.pone.0034422
PMCID: PMC3335843  PMID: 22545084

Results 1-8 (8)