Joshua E Stern

University of Washington Seattle, Seattle, Washington, United States

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Publications (29)119.36 Total impact

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    ABSTRACT: Background: The epidemiology of high-risk human papillomavirus (hrHPV) infections in mid-adult women is not well understood. Methods: We conducted a cross-sectional analysis of 379 women 30 to 50 years of age. Vaginal samples were tested for type-specific HPV DNA by polymerase chain reaction. Sera were tested for type-specific HPV antibodies by Luminex-based assay. Assays included 13 hrHPV types (16/18/31/33/35/39/45/51/52/56/58/59/68). Self-reported health and sexual history were ascertained. Risk factors for seropositivity and DNA positivity to hrHPV were assessed in separate Poisson regression models. Results: The mean (SD) age of participants was 38.7 (6.1) years, and the median lifetime number of male sex partners was 7. Approximately two-thirds (68.1%) were seropositive for any hrHPV, 15.0% were DNA positive, and 70.7% were seropositive or DNA positive. In multivariate analyses, women who were married/living with a partner were less likely to be seropositive than single/separated women (adjusted prevalence ratio [aPR], 0.86; 95% confidence interval [CI], 0.75-0.98). Compared with never hormonal contraceptive users, current (aPR, 1.53; 95% CI, 1.01-2.29) or former (aPR, 1.64; 95% CI, 1.10-2.45) users were more likely to be seropositive. Women with a lifetime number of sex partners of 12 or more were more likely to be seropositive compared with those with 0 to 4 partners (aPR, 1.29; 95% CI, 1.06-1.56). Similar associations were seen with DNA positivity. In addition, there was a positive association between current smoking and hrHPV DNA (aPR vs. never smokers, 2.51; 95% CI, 1.40-4.49). Conclusions: Seventy-one percent of mid-adult women had evidence of current or prior hrHPV infection. Measures of probable increased exposure to HPV infection were associated with both seropositivity and DNA positivity to hrHPV, whereas current smoking was positively associated with hrHPV DNA only.
    No preview · Article · Mar 2016 · Sex Transm Dis
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    ABSTRACT: Background: Oral and fingernail human papillomavirus (HPV) detection may be associated with HPV-related carcinoma risk at these nongenital sites and foster transmission to the genitals. We describe the epidemiology of oral and fingernail HPV among mid-adult women. Methods: Between 2011 and 2012, 409 women aged 30 to 50 years were followed up for 6 months. Women completed health and behavior surveys and provided self-collected oral, fingernail, and vaginal specimens at enrollment and exit for type-specific HPV DNA testing. Concordance of type-specific HPV detection across anatomical sites was described with κ statistics. Using generalized estimating equations or exact logistic regression, we measured the univariate associations of various risk factors with type-specific oral and fingernail HPV detection. Results: Prevalence of detecting HPV in the oral cavity (2.4%) and fingernails (3.8%) was low compared with the vagina (33.1%). Concordance across anatomical sites was poor (κ < 0.20 for all comparisons). However, concurrent vaginal infection with the same HPV type (odds ratio [OR], 101.0; 95% confidence interval [CI], 31.4-748.6) and vaginal HPV viral load (OR per 1 log10 viral load increase, 2.2; 95% CI, 1.5-5.5) were each associated with fingernail HPV detection. Abnormal Papanicolaou history (OR, 11.1; 95% CI, 2.8-infinity), lifetime number of male vaginal sex partners at least 10 (OR vs. 0-3 partners, 5.0; 95% CI, 1.2-infinity), and lifetime number of open-mouth kissing partners at least 16 (OR vs. 0-15 partners, infinity; 95% CI, 2.6-infinity, by exact logistic regression) were each associated with oral HPV detection. Conclusions: Although our findings support HPV DNA deposition or autoinoculation between anatomical sites in mid-adult women, the rarity of HPV in the oral cavity and fingernails suggests that oral/fingernail HPV does not account for a significant fraction of HPV in genital sites.
    No preview · Article · Nov 2015 · Sexually transmitted diseases
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    ABSTRACT: Although risk factors for HPV infections in young women are well defined, the risk associated with meeting male sex partners via the Internet is unclear. We analyzed cross-sectional data from 282 women aged 18 to 24 years who reported using Internet dating Web sites in the past year. Women were mailed vaginal self-sampling kits for polymerase chain reaction-based HPV genotyping (including 19 oncogenic types) and sexual behavior and health history questionnaires. Generalized linear models were used to evaluate risk factors for prevalent oncogenic HPV infections. Thirty-five percent of women reported having met a male sex partner via the Internet in the past 6 months, and 42% reported a history of HPV vaccination. The prevalence of oncogenic HPV infection was 37%, and 9% of women tested positive for HPV-16 or HPV-18. Having met a male sex partner via the Internet in the past 6 months was not significantly associated with oncogenic HPV infection. In multivariate analyses, variables associated with an increased likelihood of oncogenic HPV infection included male partners in the past 6 months who were reported to have at least 1 concurrent partnership (adjusted prevalence ratio [aPR], 1.51; 95% confidence interval [CI], 1.11-2.06) and not always using condoms with male partners in the past 6 months (aPR, 1.86; 95% CI, 1.05-3.30). Self-reporting a history of receiving at least 1 dose of HPV vaccine was inversely associated with testing positive for HPV-16 or HPV-18 (aPR, 0.39; 95% CI, 0.16-0.97). Although measures of recent sexual behavior were associated with prevalent oncogenic HPV infection, male partners met online were not associated with an increased likelihood of infection in this cohort of young women.
    No preview · Article · Sep 2015 · Sexually transmitted diseases
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    ABSTRACT: Persons with Fanconi Anemia (FA) are at risk for HPV-associated cancers; however, their natural HPV exposure and infection rates are unknown as are the adequacy with which they mount antibodies to HPV vaccination. This study aimed to determine, in 62 persons with FA, seroprevalence of skin and mucosal HPV types, seroprevalence in individuals self-reporting a history of HPV vaccination, and factors associated with HPV seropositivity. Bead Luminex assay was used to determine seropositivity for HPV types 1, 2, 4 (low-risk skin); 6, 11 (low-risk mucosal, included in one HPV vaccine); 16, 18, (high-risk mucosal, included in both HPV vaccines); and 52, 58 (high-risk mucosal). Health- and behavior-related questionnaires were completed. Type-specific seroprevalence estimates and participant characteristics associated with seroprevalence were calculated. 48% reported HPV vaccination. Type-specific seropositivity in unvaccinated persons ranged from 7-21% for skin HPV types and 7-38% for mucosal HPV types. Among unvaccinated participants, adults versus children demonstrated increased HPV 1, 6, 16, and 58 seroprevalence: 45% vs. 6%, 64% vs. 22%, 64% vs. 17%, and 36% vs. 0% respectively (p-values all <0.05). Vaccinated participants versus non-vaccinated participants demonstrated increased seroprevalence for HPV 6, 11, 16, and 18: 92% vs. 38%, 92% vs. 24%, 96% vs. 34%, and 75% vs. 7% respectively (p-values all <0.0001). Our data demonstrate that unvaccinated participants had serologic evidence of prior skin and mucosal HPV infections, and that seroprevalence increased among adults; in self-reported vaccinees, seroprevalence for HPV vaccine-types was 75-96%. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Preview · Article · Feb 2015 · Clinical and vaccine Immunology: CVI
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    ABSTRACT: In order to elucidate the role of epigenetic alterations in the development of cutaneous squamous cell carcinoma (SCC), we analyzed both gene-specific promoter hypermethylation and repetitive sequence hypomethylation in cutaneous SCC as well as normal skin tissue samples. We showed that methylation of DAPK1 and CDH13 was associated with cutaneous SCC. While methylation frequency of DAPK1 was increased from sun-protected normal skin, sun-exposed normal skin, perilesional to lesional tissues, methylation of CDH13 was almost exclusively detected in cutaneous SCC tissues. Further, methylation of DAPK1 and CDH13 was neither correlated with the presence of HPV nor with the presence of p53 mutations in lesional skin tissues. Finally, we detected trend of reduced methylation level of repetitive sequences from sun-protected, sun-exposed normal skin samples to perilesional, and lesional tissues from SCC patients. We conclude that both gene-specific hypermethylation and repetitive sequence hypomethylation are present in cutaneous SCC tissue samples; these epigenetic changes might represent an independent pathway in the development of cutaneous SCC.
    No preview · Article · Jan 2015 · Cell Biochemistry and Biophysics
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    Preview · Article · Jan 2015 · Journal of Cancer Therapy
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    ABSTRACT: Objective We conducted a cross-sectional study to describe the prevalence and correlates of type-specific human papillomavirus DNA in the oral cavities of persons with Fanconi Anemia.Materials and Methods Oral swabs were collected from 67 participants with Fanconi Anemia and tested for 27 human papillomavirus genotypes using polymerase chain reaction-based methods.ResultsParticipants were a mean of 18.6 (standard deviation, 10.0) years of age (range 4 to 47 years). The prevalence of oral human papillomavirus infection was 7.5%, and the prevalence of high-risk human papillomavirus infection was 6.0%. Human papillomavirus type 16 was not detected in any samples. Prevalence was higher in adults than in children (13% versus 3% in those ≥18 versus <18 years of age). Among adults, prevalence was higher in males than in females (25.0% versus 9.1% respectively).Conclusions Prevalence of oral human papillomavirus infection in persons with Fanconi Anemia was comparable to estimates from other studies in the general population. However, in contrast to previous studies, we did not identify human papillomavirus type 16 (the type found in most human papillomavirus-related head and neck cancers) in any participants.This article is protected by copyright. All rights reserved.
    No preview · Article · Aug 2014 · Oral Diseases
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    ABSTRACT: Oncogenic human papillomavirus (HPV) viral load may inform the origin of newly detected infections and characterize oncogenic HPV natural history in midadult women. From 2007 to 2011, we enrolled 521 25-65-year-old-female online daters and followed them triannually with mailed health and sexual behavior questionnaires and kits for self-sampling for PCR-based HPV DNA testing. Samples from oncogenic HPV positive women were selected for type-specific DNA load testing by real-time PCR with adjustment for cellularity. Linear or logistic regression models were used to evaluate relationships between viral levels, health and sexual behavior, and longitudinal oncogenic HPV detection. Type-specific viral levels were borderline significantly higher in oncogenic HPV infections that were prevalent versus newly detected (p = 0.092), but levels in newly detected infections were higher than in infections redetected after intercurrent negativity (p < 0.001). Recent sex partners were not significantly associated with viral levels. Compared with prevalent infections detected intermittently, the likelihood of persistent (OR = 4.31, 95% CI: 2.20-8.45) or single-time (OR = 1.32, 95% CI: 1.03-1.71) detection increased per 1-unit increase in baseline log10 viral load. Viral load differences between redetected and newly detected infections suggest a portion of new detections were due to new acquisition, although report of recent new sex partners (a potential marker of new infection) was not predictive of viral load; oncogenic HPV infections in midadult women with new partners likely represent a mix of new acquisition and reactivation or intermittent detection of previous infection. Intermittent detection was characterized by low viral levels, suggesting that intermittent detection of persisting oncogenic HPV infection may be of limited clinical significance.
    No preview · Article · Apr 2014 · International Journal of Cancer
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    ABSTRACT: Despite the strong evidence of HPV infection as the etiological agent in a subset of oral cancer, oral α-HPV detection is rare in healthy individuals, and little is known of the existing of novel HPV types in oral cavity. We determined whether novel HPV types can be isolated from oral rinse samples collected from healthy individuals. We performed rolling circle amplification (RCA) coupled with degenerated PCR assay on 48 oral rinse samples to amplify novel HPV types. Full length HPV DNA was cloned using long range PCR. Quantitative type specific Taqman assays were used to determine the prevalence of novel HPV types in 158 archived oral tissue samples. We were able to isolate four novel human papillomavirus types. Full length HPV DNA was cloned for three of the four novel HPV types. All four HPV types belong to the genus Gammapapillomavirus (γ-PV), where HPV 171 is most closely related to HPV 169, showing 88% similarity; HPV 172 is most closely related to HPV 156, showing 70% similarity; HPV 173 is most closely related to HPV 4, showing 73% similarity; oral sample lavage (OSL) 37 is most closely related to HPV 144, showing 69% similarity. Finally, we showed that HPV 173 was rarely present in oral tissues (2/158), HPV 172 was only detected in normal oral tissues (25/76), and HPV 171 was more prevalent in malignant oral tissues (17/82 vs. 10/76, p=0.21). Novel γ-HPV types are present in oral cavity of healthy individuals.
    No preview · Article · Nov 2013 · Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology
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    ABSTRACT: miRNA expression in HOSE cell lines, normal ovaries, and benign ovarian tumors. Expression of miR-181d, miR-368, and miR-370 was significantly different between cell lines and normal ovaries as well as between cell lines and benign tumors. In addition, expression of miR-30c and miR-30e-3p was significantly different between cell lines and normal ovaries, and expression of miR-30c was significantly different between normal ovaries and benign tumors. (PDF 49 kb)
    Preview · Dataset · Aug 2012
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    ABSTRACT: 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. 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. 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. 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.
    Full-text · Article · Aug 2012 · World Journal of Surgical Oncology
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    ABSTRACT: 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. 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. 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. hr-HPV initiates a local Th2 inflammation at an early stage, involving antibody forming cells, and fosters an immunosuppressive microenvironment that aids tumor progression.
    No preview · Article · Jul 2012 · Gynecologic Oncology
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    ABSTRACT: 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.
    Full-text · Article · Apr 2012 · PLoS ONE
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    ABSTRACT: MicroRNA expression is severely disrupted in carcinogenesis, however limited evidence is available validating results from cell-line models in human clinical cancer specimens. MicroRNA-21 (mir-21) and microRNA-143 (mir-143) have previously been identified as significantly deregulated in a range of cancers including cervical cancer. Our goal was to investigate the expression patterns of several well-studied microRNA species in cervical samples and compare the results to cell line samples. We measured the expression of mir-21 and mir-143 in 142 formalin-fixed, paraffin embedded (FFPE) cervical biopsy tissue blocks, collected from Dantec Oncology Clinic, Dakar, Senegal. MicroRNA expression analysis was performed using Taqman-based real-time PCR assays. Protein immunohistochemical staining was also performed to investigate target protein expression on 72 samples. We found that mir-21 expression increased with worsening clinical diagnosis but that mir-143 was not correlated with histology. These observations were in stark contrast to previous reports involving cervical cancer cell lines in which mir-143 was consistently down-regulated but mir-21 largely unaffected. We also identified, for the first time, that cytoplasmic expression of Programmed Cell Death Protein 4 PDCD4; a known target of mir-21) was significantly lower in women with invasive cervical carcinoma (ICC) in comparison to those with cervical intraepithelial neoplasia (2-3) or carcinoma in situ (CIN2-3/CIS), although there was no significant correlation between mir-21 and PDCD4 expression, despite previous studies identifying PDCD4 transcript as a known mir-21 target. Whilst microRNA biomarkers have a number of promising features, more studies on expression levels in histologically defined clinical specimens are required to investigate clinical relevance of discovery-based studies. Mir-21 may be of some utility in predictive screening, given that we observed a significant correlation between mir-21 expression level and worsening histological diagnosis of cervical cancer.
    Full-text · Article · Dec 2011 · PLoS ONE
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    ABSTRACT: We report the first, to our knowledge, findings describing the relationships between both static and dynamic analysis parameters of 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) PET and the expression of the proliferation marker Ki-67, and the protein expression and enzymatic activity of thymidine kinase-1 (TK1) in surgically resected lung lesions. Static and dynamic analyses (4 rate constants and 2 compartments) of (18)F-FLT PET images were performed in a cohort of 25 prospectively accrued, clinically suspected lung cancer patients before surgical resection (1 lesion was found to be benign after surgery). The maximal and overall averaged expression of Ki-67 and TK1 were determined by semiquantitative analysis of immunohistochemical staining. TK1 enzymatic activity was determined by in vitro assay of extracts prepared from flash-frozen samples of the same tumors. Static (18)F-FLT uptake (partial-volume-corrected maximum-pixel standardized uptake value from 60- to 90-min summed dynamic data) was significantly correlated with the overall (ρ = 0.57, P = 0.006) and maximal (ρ = 0.69, P < 0.001) immunohistochemical expressions of Ki-67 and TK1 (overall expression: ρ = 0.65, P = 0.001; maximal expression: ρ = 0.68, P < 0.001) but not with TK1 enzymatic activity (ρ = 0.34, P = 0.146). TK1 activity was significantly correlated with TK1 protein expression only when immunohistochemistry was scored for maximal expression (ρ = 0.52, P = 0.029). Dynamic analysis of (18)F-FLT PET revealed correlations between the flux constant (K(FLT)) and both overall (ρ = 0.53, P = 0.014) and maximal (ρ = 0.50, P = 0.020) TK1 protein expression. K(FLT) was also associated with both overall (ρ = 0.59, P = 0.005) and maximal (ρ = 0.63, P = 0.002) Ki-67 expression. We observed no significant correlations between TK1 enzyme activity and K(FLT). In addition, no significant relationships were found between TK1 expression, TK1 activity, or Ki-67 expression and any of the compartmental rate constants. The absence of observable correlations of the imaging parameters with TK1 activity suggests that (18)F-FLT uptake and retention within cells may be complicated by a variety of still undetermined factors in addition to TK1 enzymatic activity.
    No preview · Article · Aug 2011 · Journal of Nuclear Medicine
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    ABSTRACT: Antiretroviral therapy for HIV-2 infection is hampered by intrinsic resistance to many of the drugs used to treat HIV-1. Limited studies suggest that the integrase inhibitors (INIs) raltegravir and elvitegravir have potent activity against HIV-2 in culture and in infected patients. There is a paucity of data on genotypic variation in HIV-2 integrase that might confer intrinsic or transmitted INI resistance. We PCR amplified and analyzed 122 HIV-2 integrase consensus sequences from 39 HIV-2-infected, INI-naive adults in Senegal, West Africa. We assessed genetic variation and canonical mutations known to confer INI-resistance in HIV-1. No amino acid-altering mutations were detected at sites known to be pivotal for INI resistance in HIV-1 (integrase positions 143, 148 and 155). Polymorphisms at several other HIV-1 INI resistance-associated sites were detected at positions 72, 95, 125, 154, 165, 201, 203, and 263 of the HIV-2 integrase protein. Emerging genotypic and phenotypic data suggest that HIV-2 is susceptible to the new class of HIV integrase inhibitors. We hypothesize that intrinsic HIV-2 integrase variation at "secondary" HIV-1 INI-resistance sites may affect the genetic barrier to HIV-2 INI resistance. Further studies will be needed to assess INI efficacy as part of combination antiretroviral therapy in HIV-2-infected patients.
    Full-text · Article · Jul 2011 · PLoS ONE
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    ABSTRACT: It remains unknown whether tobacco smoke induces DNA hypermethylation as an early event in carcinogenesis or as a late event, specific to overt cancer tissue. Using MethyLight assays, we analyzed 316 lung tissue samples from 151 cancer-free subjects (121 ever-smokers and 30 never-smokers) for hypermethylation of 19 genes previously observed to be hypermethylated in nonsmall cell lung cancers. Only APC (39%), CCND2 (21%), CDH1 (7%), and RARB (4%) were hypermethylated in >2% of these cancer-free subjects. CCND2 was hypermethylated more frequently in ever-smokers (26%) than in never-smokers (3%). CCND2 hypermethylation was also associated with increased age and upper lobe sample location. APC was frequently hypermethylated in both ever-smokers (41%) and never-smokers (30%). BVES, CDH13, CDKN2A (p16), CDKN2B, DAPK1, IGFBP3, IGSF4, KCNH5, KCNH8, MGMT, OPCML, PCSK6, RASSF1, RUNX, and TMS1 were rarely hypermethylated (<2%) in all subjects. Hypermethylation of CCND2 may reflect a smoking-induced precancerous change in the lung.
    Full-text · Article · Mar 2011 · Journal of Oncology
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    ABSTRACT: Human gammadelta (γδ) T cells play an important role in protective immunity in HIV-1 and simian immunodeficiency virus infection; their role in HIV-2 infection is unknown. To determine the role of γδ T cells in control of plasma viral load and CD4 T-cell count in HIV-1 and HIV-2 infections in West Africa. Thirty HIV-1 and 25 HIV-2 treatment-naive chronically infected individuals, and 20 HIV-seronegative individuals from Senegal were studied using multiparametric flow cytometry to investigate the frequencies and phenotypes of peripheral γδ T cells. γδ T-cell parameters and correlates of HIV disease progression were assessed. : We observed an expansion of Vδ1 T-cell populations in both HIV-1 and HIV-2 infection. However, unlike HIV-1 infection, no significant contraction of the frequency of total Vδ2 T cells was observed in HIV-2 infection. Significantly lower frequencies of CD4Vδ2 T cells were observed in HIV-2-infected individuals. Furthermore, frequencies of CD28CD45RO and CD27CD28CD45RO Vδ2 T cell were low in HIV-1-infected individuals. Vδ2 T-cell activation levels were elevated in both HIV-1-infected and HIV-2-infected individuals. The frequency of HLA-DRCD38-activated Vδ1 and Vδ2 T cells was associated with a decline in CD4 T-cell counts and increased viral load in both HIV-1 and HIV-2 infection. Although maintaining the normal frequency of total Vδ2 T cells, HIV-2 infection reduces the frequency of CD4Vδ2 T cells and alters the frequencies of subsets of Vδ1 T cells. Both HIV-1 and HIV-2 infection induce γδ T-cell activation, and this activation is associated with the disease progression.
    No preview · Article · Mar 2011 · JAIDS Journal of Acquired Immune Deficiency Syndromes
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    ABSTRACT: Hepatocellular carcinoma (HCC) is known to be associated with both HBV and HCV. While epigenetic changes have been previously reported to be associated with hepatocellular carcinoma (HCC), whether the epigenetic profile of HBC associated HCC differs from that of HCV-associated HCC is unclear. We analyzed DNA methylation of ten genes (APC, CCND2, CDKN2A, GSTP1, HOXA9, RARB, RASSF1, RUNX, SFRP1, and TWIST1) using MethyLight assays on 65 archived liver tissue blocks. Three genes (APC, CCND2, and GSTP1) were frequently methylated in normal liver tissues. Five genes (APC, CDKN2A, HOXA9, RASSF1, and RUNX) were significantly more frequently methylated in malignant liver tissues than normal liver tissues. Among HCC cases, HOXA9, RASSF1 and SFRP1 were methylated more frequently in HBV-positive HCC cases, while CDKN2A were significantly more frequently methylated in HCV-positive HCC cases. Our data support the hypothesis that HCC resulting from different viral etiologies is associated with different epigenetic changes.
    Full-text · Article · Apr 2010 · Experimental and Molecular Pathology
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    ABSTRACT: We previously identified a number of genes which were methylated significantly more frequently in the tumor compared to the non-cancerous lung tissues from non-small cell lung cancer (NSCLC) patients. Detection of methylation profiles of genes in NSCLC could provide insight into differential pathways to malignancy and lead to strategies for better treatment of individuals with NSCLC. We determined the DNA methylation status of 27 genes using quantitative MethyLight assays in lung tumor samples from 117 clinically well-characterized NSCLC patients. Hypermethylation was detected in one of more of the genes in 106 (91%) of 117 cases and was detected at high levels (percentage methylation reference (PMR)> or =4%) in 79% of NSCLC cases. Methylation of APC, CCND2, KCNH5 and, RUNX was significantly more frequent in adenocarcinomas compared to squamous cell carcinomas (SCC), while methylation of CDKN2A was more common in SCC. Hypermethylation of KCNH5, KCNH8, and RARB was more frequent in females compared to males. Hypermethylation of APC and CCND2 was inversely associated with proliferation score assessed by Ki-67 level. Our findings of differential gene hypermethylation frequencies in tumor tissues from patients with adenocarcinoma or squamous cell cancers and in females compared to males suggests that further investigation is warranted in order to more fully understand the potential disparate pathways and/or risk factors for NSCLC associated with histologic type and gender.
    Full-text · Article · Nov 2009 · Lung cancer (Amsterdam, Netherlands)