This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ http://www.infectagentscancer.com The latest articles from Infectious Agents and Cancer (ISSN 1750-9378) published by BioMed Central Background: The binding of Abs to the CD4-binding site (CD4bs) of HIV-1 envelope gp120 has been shown to obstruct the processing and generation of helper epitopes from this antigen, resulting in poor presentation of various gp120 epitopes by MHC class II to CD4 T cells. However, the physiologic significance of these inhibitory anti-CD4bs Abs in vivo has remained unclear. In this study, we evaluated the immunologic effects of anti-CD4bs Abs in vivo using a murine model. Results: Animals were immunized with recombinant envelope proteins with or without CD4-binding activity (designated CD4bs+ Env and CD4bs– Env, respectively). As expected, anti-CD4bs Abs were generated only after immunization with CD4bs+ Env and not with CD4bs– Env. The presence of anti-CD4bs Abs was associated with lower levels of envelope-specific lymphoproliferation in animals immunized with CD4bs+ Env. To further determine the specific role of the anti-CD4bs Abs, we immunized mice with gp120 in the presence of an inhibitory anti-CD4bs mAb or a non-inhibitory anti-gp120 mAb. The data show that the presence of anti-CD4bs mAb reduced CD4 T cell responses to gp120. However, we also detected significantly higher titers of anti-gp120 Abs following immunization with gp120 and the anti-CD4bs mAb. Conclusion: Anti-CD4bs Abs can exert discordant effects on the gp120-specific CD4 T cell and Ab responses in vivo, indicating the importance of these particular Abs in influencing both the cellular and the humoral immune responses against HIV-1. http://www.infectagentscancer.com/content/3/1/11 Maria Luisa Visciano, Michael Tuen, Pei-de Chen and Catarina E Hioe Infectious Agents and Cancer 2008, 3:11 2008-07-18 doi:10.1186/1750-9378-3-11 Infectious Agents and Cancer 1750-9378 3 11 2008-07-18 Background: The association of the human herpesvirus-8/Kaposi's sarcoma (KS)-associated herpesvirus (HHV-8/KSHV) serology with various malignancies in Tanzania is not currently well established while previous studies were based on either PCR or immunofluorescence assays [IFA] but not with a sensitive enzyme-linked immunosorbent assay (ELISA). Selected archival diagnostic biopsies (n = 184) and sera from indigenous patients with KS (n = 120), non-KS tumors (n = 24) and non-neoplastic lesions (n = 40) at Muhimbili National Hospital (MNH), Tanzania, were evaluated by diagnostic histopathology, immunohistology [anti-HHV-8 latency-associated nuclear antigen (LANA)] and serology for HIV (ELISA) and HHV-8 (IFA and ELISA). Results: About 66.3% (n = 122) cases including AIDS-associated Kaposi's sarcoma (AKS) (n = 93), reactive conditions (n = 28) and only one non-KS tumour were HIV positive. Endemic KS (EKS) patients were mostly males (96.3%, 26/27) who were less (69.9%, 65/93) predominant in AIDS-associated (AKS). A high (89%) percentage of patients with anti-HHV-8 antibodies was found in the cohort including the HIV positive (92%) cases, males (81.2%), KS patients (93%), non-KS tumors (92%), and reactive conditions (75%). All HHV-8 seronegative KS cases were nodular stage whereas both sera and corresponding biopsies from early stage KS were HHV-8+. Assay sensitivity, positive predictive value (PPV) and specificity were 98.6%, 93.5% and 16.7% for IFA and 93.5%, 98.6% and 50.0% for ELISA respectively. Conclusion: HHV-8 seroprevalence at MNH appears high as expected among AKS cases and males but also in non-KS patients. ELISA showed a combination of high HHV-8 sensitivity as well as higher PPV and specificity than IFA which however, showed higher sensitivity. The apparent stage-dependent, inverted serum HHV-8 immunoreactivity supports a notion of viral immune-segregation during KS development. Routine HHV-8 screening should be considered particularly in patients at risk of KS and for selection of blood/organ donations. http://www.infectagentscancer.com/content/3/1/10 Amos R Mwakigonja, Pawan Pyakurel, Parviz Kokhaei, Fatemeh Pak, Leonard K Lema, Ephata E Kaaya and Peter Biberfeld Infectious Agents and Cancer 2008, 3:10 2008-06-30 doi:10.1186/1750-9378-3-10 Infectious Agents and Cancer 1750-9378 3 10 2008-06-30 Background: At present, seroreactivity is not a valuable parameter for diagnosis of Human Papillomavirus (HPV) infection but, it is potentially valuable as marker of viral exposure in elucidating the natural history of this infection. More data are needed to asses the clinical relevance of serological response to HPV.ObjectivesThe objective was to assess the clinical and epidemiological correlates of HPV-seroreactivity in a cohort of HIV-negative and HIV-positive women. Methods: Seroreactivity of 96 women, evaluated in an ELISA test based on denatured HPV16 late (L) and early (E) antigens, was correlated with their clinical and epidemiological data previously collected for a multi-centre Italian study, HPV-PathogenISS study. Results: No significant correlation was found between HPV DNA detection and seroreactivity. Women, current smokers showed significantly less seroreactivity to L antigens as compared with the non-smokers. HIV-positive women showed significantly less (66.7%) antibody response as compared with HIV-negative women (89.3%), with particularly impaired response to L antigens. Women, HIV-positive and current smokers, showed by far the lowest seroprevalence (33.3%) as compared to 75.9% among all other women (OR = 0.158; 95%CI 0.036–0.695, p = 0.014; Fisher's exact test). Importantly, this association did not loose its significance when controlled for confounding from age (continuous variable) in multivariate analysis or using Mantel-Haenszel test for age-groups. Conclusion: It is tempting to speculate that HIV-positive current smokers comprise a special high-risk group, with highly impaired immunological response that could prevent eradication of persistent HPV infections and thus contribute to development of CIN3/CC. http://www.infectagentscancer.com/content/3/1/9 Colomba Giorgi, Paola Di Bonito, Felicia Grasso, Stefania Mochi, Luisa Accardi, Maria Gabriella Donà, Margherita Branca, Silvano Costa, Luciano Mariani, Alberto Agarossi, Marco Ciotti, Kari Syrjänen and the HPV-PathogenISS group. Infectious Agents and Cancer 2008, 3:9 2008-06-26 doi:10.1186/1750-9378-3-9 Infectious Agents and Cancer 1750-9378 3 9 2008-06-26 IntroductionThe raw incidence of cancer of the uterine cervix is Spain is 7,8 per 100.000 inhabitants (adjusted incidence is 5.6). The incidence of this tumor is still low, but a steady increase has been seen, probably related to increasing risk factors.AimTo determine the frequency of infection by different types of human papillomavirus (HPV) in Papanicolau smears from women with and without cancer of the uterine cervix in Spain.Patients and methodsA case-control study was performed in women with and without cervical cancer from Zaragoza, Spain. Pap smears from 600 cases (540 women with cervical intraepithelial neoplasms (CIN) and 60 with invasive cancer) and 1200 controls (women without those lesions) were tested by polymerase chain reaction (PCR) and typed by oligonucleotide microarray-based detection. Results: HPV was detected in 93.3% of all samples with invasive cancer versus 17.5% of controls. OR for invasive cancer was 55 (95% CI 21.5–140,5). Statistically significant associations were also found for different grades of cervical dysplasia. Conclusion: The strong association found between HPV infection, specifically types 16 and 18 and cancer of the uterine cervix in Zaragoza, Spain, stresses the importance of ongoing efforts to institute a vaccine program with recently approved HPV vaccines in order to prevent cervical cancer in this population. http://www.infectagentscancer.com/content/3/1/8 Milagros Bernal, Isabel Burillo, Jose I Mayordomo, Manuel Moros, Rafael Benito and Joaquina Gil Infectious Agents and Cancer 2008, 3:8 2008-05-29 doi:10.1186/1750-9378-3-8 Infectious Agents and Cancer 1750-9378 3 8 2008-05-29 Background: Cervical cancer is the most frequently diagnosed malignancy among women in southern Vietnam where its incidence is one of the highest observed worldwide. Results: Cervical HPV DNA infection was measured in a cross-sectional sample of 282 female sex workers (FSW) in Soc Trang province in southern Vietnam. HPV DNA was detected in 85% of FSW and prevalence did not vary by age. Thirty-five HPV genotypes were detected; HPV 52 was the most common type. Half of HPV-positive women were infected with oncogenic types and 37% were infected with multiple genotypes. The prevalence of oncogenic HPV infection was lower among FSW with more formal education (adj. prevalence ratio = 0.63, 95% CI 0.42–0.93), those servicing 25 or more clients per month (adj. PR = 0.66 95% CI 0.48–0.92), and those engaging in withdrawal prior to ejaculation (adj. PR = 0.68, 95% CI 0.53–0.87). Oncogenic HPV prevalence was higher among FSW with regular male partners who had other female partners (adj. PR = 1.75, 95% CI 1.34–2.28) and FSW who were HIV+ (adj. PR = 1.42, 95% CI 1.08–1.88). Conclusion: Our results demonstrate that although cervical HPV infection is extremely common among FSW in southern Vietnam, prevalence varies by education level, sexual activity, habits of regular partners, and HIV status. http://www.infectagentscancer.com/content/3/1/7 Brenda Y Hernandez and Thuong Vu Nguyen Infectious Agents and Cancer 2008, 3:7 2008-04-23 doi:10.1186/1750-9378-3-7 Infectious Agents and Cancer 1750-9378 3 7 2008-04-23 Background: Human papillomavirus detection is very important for the evaluation of prevention strategies in cervical cancer. In the Azorean population, the virus prevalence has never been studied, and there is no data available to preview a successful outcome with HPV vaccination. In this article, our objective is to characterise the HPV genotypes in Terceira Island, contributing for the epidemiological knowledge on the virus infection. Results: Cervical samples were collected from 289 women aged 16–81 in the Gynaecological Outpatient Clinic of the Hospital de Santo Espírito de Angra do Heroísmo (HSEAH). HPV DNA was amplified by Polymerase Chain Reaction using the general consensus primers PGMYO9/PGMY11. Commercially available Papillomavirus Clinical Arrays® kits (Genomica) were used to perform HPV genotyping. 30 women were HPV positive, with a median age of 41 years old. Our results show that the overall HPV prevalence was 10.49%. Seventeen genotypes were identified, including 58.82% high risk, 17.65% low risk and 23.53% undetermined risk. Conclusion: Unlike other epidemiological studies, HPV31 was the most frequent type (26.67%) in Terceira Island, followed by HPV16 (10.00%), HPV51, HPV53, HPV70 and HPV82 (6.67%). Further studies are needed to investigate if the HPV types found in our population are associated with the risk of progression to high-grade squamous intraepithelial lesions or cervical cancer. http://www.infectagentscancer.com/content/3/1/6 Isa Dutra, Margarida R Santos, Marta Soares, Ana R Couto, Maria Bruges-Armas, Fernando Teixeira, Luísa Monjardino, Shirley Hodgson and Jácome Bruges-Armas Infectious Agents and Cancer 2008, 3:6 2008-04-21 doi:10.1186/1750-9378-3-6 Infectious Agents and Cancer 1750-9378 3 6 2008-04-21 ObjectivesTo evaluate the prevalence of human papillomavirus (HPV) types, and risk factors for HPV positivity across cervix, vagina and anus, we conducted a study among 138 women with human immunodeficiency virus (HIV).GoalCompare the prevalence of different HPV types and the risk factors for HPV positivity in three sites. Results: The most frequently detected HPV types in all sites were, in decreasing order, HPV16, 53, 18, 61 and 81. Agreement between the cervix and vagina was good (kappa 0.60 – 0.80) for HPV16 and 53 and excellent (Kappa > 0.80) for HPV18 and 61. HPV positivity was inversely associated with age for all combinations including the anal site. Conclusion: In HIV positive women, HPV18 is the most spread HPV type found in combinations of anal and genital sites. The relationship of anal to genital infection has implications for the development of anal malignancies. Thus, the efficacy of the current HPV vaccine may be considered not only for the cervix, but also for prevention of HPV18 anal infection among immunossuppressed individuals. http://www.infectagentscancer.com/content/3/1/5 Maria Alice G Gonçalves, Giorgia Randi, Annie Arslan, Luisa L Villa, Marcelo N Burattini, Silvia Franceschi, Eduardo Antonio Donadi and Eduardo Massad Infectious Agents and Cancer 2008, 3:5 2008-03-14 doi:10.1186/1750-9378-3-5 Infectious Agents and Cancer 1750-9378 3 5 2008-03-14 Nowadays, there is increasing evidence that some pathogenic bacteria can contribute to specific stages of cancer development. The concept that bacterial infection could be involved in carcinogenesis acquired a widespread interest with the discovery that H. pylori is able to establish chronic infections in the stomach and that this infection is associated with an increased risk of gastric adenocarcinoma and mucosa associated lymphoid tissue lymphoma. Chronic infections triggered by bacteria can facilitate tumor initiation or progression since, during the course of infection, normal cell functions can come under the control of pathogen factors that directly manipulate the host regulatory pathways and the inflammatory reactions.Renowned publications have recently corroborated the molecular mechanisms that link bacterial infections, inflammation and cancer, indicating certain strains of Escherichia coli as a risk factor for patients with colon cancer. E. coli is a normal inhabitant of the human intestine that becomes highly pathogenic following the acquisition of virulence factors, including a protein toxin named cytotoxic necrotizing factor 1 (CNF1). This toxin permanently activates the small GTP-binding proteins belonging to the Rho family, thus promoting a prominent polymerization of the actin cytoskeleton as well as a number of cellular responses, including changes in protein expression and functional modification of the cell physiology. CNF1 is receiving an increasing attention as a putative factor involved in transformation because of its ability to: (i) induce COX2 expression, an immediate-early gene over-expressed in some type of cancers; (ii) induce a long-lasting activation of the transcription factor NF-kB, a largely accepted marker of tumor cells; (iii) protect epithelial cells from apoptosis; (iv) ensue the release of pro-inflammatory cytokines in epithelial and endothelial cells; and (v) promote cellular motility. As cancer may arise through dysfunction of the same regulatory systems, it seems likely that CNF1-producing E. coli infections can contribute to tumor development.This review focuses on the aspects of CNF1 activity linked to cell transformation with the aim of contributing to the identification of a possible carcinogenic agent from the microbial world. http://www.infectagentscancer.com/content/3/1/4 Sara Travaglione, Alessia Fabbri and Carla Fiorentini Infectious Agents and Cancer 2008, 3:4 2008-03-12 doi:10.1186/1750-9378-3-4 Infectious Agents and Cancer 1750-9378 3 4 2008-03-12 Background: Prevalence of high risk (HR) human papillomavirus (HPV) types in the states of San Luis Potosí (SLP) and Guanajuato (Gto), Mexico, was determined by restriction fragment length-polymorphism (RFLP) analysis on the E6 ~250 bp (E6-250) HR-HPV products amplified from cervical scrapings of 442 women with cervical intraepithelial neoplasia and invasive carcinoma (280 from SLP and 192 from Gto). Fresh cervical scrapings for HPV detection and typing were obtained from all of them and cytological and/or histological diagnoses were performed on 383. Results: Low grade intraepithelial squamous lesions (LSIL) were diagnosed in 280 cases (73.1%), high grade intraepithelial squamous lesions (HSIL) in 64 cases (16.7%) and invasive carcinoma in 39 cases (10.2%). In the 437 cervical scrapings containing amplifiable DNA, only four (0.9%) were not infected by HPV, whereas 402 (92.0%) were infected HR-HPV and 31 (7.1%) by low-risk HPV. RFLP analysis of the amplifiable samples identified infections by one HR-HPV type in 71.4%, by two types in 25.9% and by three types in 2.7%. The overall prevalence of HR-HPV types was, in descending order: 16 (53.4%) > 31 (15.6%) > 18 (8.9%) > 35 (5.6) > 52 (5.4%) > 33 (1.2%) > 58 (0.7%) = unidentified types (0.7%); in double infections (type 58 absent in Gto) it was 16 (88.5%) > 31 (57.7%) > 35 (19.2%) > 18 (16.3%) = 52 (16.3%) > 33 (2.8%) = 58 (2.8%) > unidentified types (1.0%); in triple infections (types 33 and 58 absent in both states) it was 16 (100.0%) > 35 (54.5%) > 31 (45.5%) = 52 (45.5%) > 18 (27.3%). Overall frequency of cervical lesions was LSIL (73.1%) > HSIL (16.7%) > invasive cancer (10.2%). The ratio of single to multiple infections was inversely proportional to the severity of the lesions: 2.46 for LSIL, 2.37 for HSIL and 2.15 for invasive cancer. The frequency of HR-HPV types in HSIL and invasive cancer lesions was 16 (55.0%) > 31 (18.6%) > 35 (7.9%) > 52 (7.1%) > 18 (4.3%) > unidentified types (3.6%) > 33 (2.9%) > 58 (0.7%). Conclusion: Ninety percent of the women included in this study were infected by HR-HPV, with a prevalence 1.14 higher in Gto. All seven HR-HPV types identifiable with the PCR-RFLP method used circulate in SLP and Gto, and were diagnosed in 99.3% of the cases. Seventy-one percent of HR-HPV infections were due to a single type, 25.9% were double and 2.7% were triple. Overall frequency of lesions was LSIL (73.1%) > HSIL (16.7%) > invasive cancer (10.2%), and the ratio of single to multiple infections was inversely proportional to severity of the lesions: 2.46 for LSIL, 2.37 for HSIL and 2.15 for invasive cancer. The frequency of HR-HPV types found in HSIL and invasive cancer was 16 (55.0%) > 31 (18.6%) > 35 (7.9%) > 52 (7.1%) > 18 (4.3%) > unidentified types (3.6%) > 33 (2.9%) > 58 (0.7%). Since the three predominant types (16, 31 and 18) cause 77.9% of the HR-HPV infections and immunization against type 16 prevents type 31 infections, in this region the efficacy of the prophylactic vaccine against types 16 and 18 would be close to 80%. http://www.infectagentscancer.com/content/3/1/3 Rubén López-Revilla, Luz A Martínez-Contreras and Mireya Sánchez-Garza Infectious Agents and Cancer 2008, 3:3 2008-02-28 doi:10.1186/1750-9378-3-3 Infectious Agents and Cancer 1750-9378 3 3 2008-02-28 Background: The diagnosis of late onset breast cancer in a father, mother, and daughter living in the same house for decades suggested the possibility of an environmental agent as a common etiological factor. Both molecular and epidemiological data have indicated a possible role for the mouse mammary tumor virus (MMTV), the etiological agent of breast cancer in mice, in a certain percentage of human breast tumors. The aim of this study was to determine if MMTV might be involved in the breast cancer of this cluster of three family members. Results: MMTV-like envelope (env) and long terminal repeat (LTR) sequences containing the MMTV superantigen gene (sag) were detected in the malignant tissues of all three family members. The amplified env gene sequences were 98.0%–99.6% homologous to the MMTV env sequences found in the GR, C3H, and BR6 mouse strains. The amplified LTR sequences containing sag sequences segregated to specific branches of the MMTV phylogenetic tree and did not form a distinct branch of their own. Conclusion: The presence of MMTV-like DNA sequences in the malignant tissues of all three family members suggests the possibility of MMTV as an etiological agent. Phylogenetic data suggest that the MMTV-like DNA sequences are mouse and not human derived and that the ultimate reservoir of MMTV is most likely the mouse. Although the route by which these family members came to be infected with MMTV is unknown, the possibility exists that such infection may have resulted from a shared exposure to mice. http://www.infectagentscancer.com/content/3/1/2 Polly R Etkind, Alexandre FR Stewart and Peter H Wiernik Infectious Agents and Cancer 2008, 3:2 2008-02-28 doi:10.1186/1750-9378-3-2 Infectious Agents and Cancer 1750-9378 3 2 2008-02-28 A decrease in the incidence of human immune deficiency virus-associated Kaposi sarcoma (HIV-KS) and regression of some established HIV-KS lesions is evident after the introduction of highly active anti-retroviral treatment (HAART), and is attributed to generalized immune restoration, to the reconstitution of human herpesvirus (HHV)-8 specific cellular immune responses, and to the decrease in HIV Tat protein and HHV-8 loads following HAART. However, a small subset of HIV-seropositive subjects with a low CD4+ T cell count at the time of introduction of HAART, may develop HIV-KS as immune reconstitution inflammatory syndrome (IRIS) within 8 weeks thereafter. http://www.infectagentscancer.com/content/3/1/1 Liviu Feller and Johan Lemmer Infectious Agents and Cancer 2008, 3:1 2008-01-21 doi:10.1186/1750-9378-3-1 Infectious Agents and Cancer 1750-9378 3 1 2008-01-21