The epidemiology of conjunctival squamous cell carcinoma in Uganda

As part of a larger investigation of cancer in Uganda, we conducted a case–control study of conjunctival squamous cell carcinoma in adults presenting at hospitals in Kampala. Participants were interviewed about social and lifestyle factors and had blood tested for antibodies to HIV, KSHV and HPV-16, -18 and -45. The odds of each factor among 60 people with conjunctival cancer was compared to that among 1214 controls with other cancer sites or types, using odds ratios, estimated with unconditional logistic regression. Conjunctival cancer was associated with HIV infection (OR 10.1, 95% confidence intervals [CI] 5.2–19.4; P<0.001), and was less common in those with a higher personal income (OR 0.4, 95% CI 0.3–1.2; P<0.001). The risk of conjunctival cancer increased with increasing time spent in cultivation and therefore in direct sunlight (χ2 trend=3.9, P=0.05), but decreased with decreasing age at leaving home (χ2 trend=3.9, P=0.05), perhaps reflecting less exposure to sunlight consequent to working in towns, although both results were of borderline statistical significance. To reduce confounding, sexual and reproductive variables were examined among HIV seropositive individuals only. Cases were more likely than controls to report that they had given or received gifts for sex (OR 3.5, 95% CI 1.2–10.4; P=0.03), but this may have been a chance finding as no other sexual or reproductive variable was associated with conjunctival cancer, including the number of self-reported lifetime sexual partners (P=0.4). The seroprevalence of antibodies against HPV-18 and -45 was too low to make reliable conclusions. The presence of anti-HPV-16 antibodies was not significantly associated with squamous cell carcinoma of the conjunctiva (OR 1.5, 95% CI 0.5–4.3; P=0.5) and nor were anti-KSHV antibodies (OR 0.9, 95% CI 0.4–2.1; P=0.8). The 10-fold increased risk of conjunctival cancer in HIV infected individuals is similar to results from other studies. The role of other oncogenic viral infections is unclear

Entry of Human Papillomavirus Type 16 by Actin-Dependent, Clathrin- and Lipid Raft-Independent Endocytosis

Infectious endocytosis of incoming human papillomavirus type 16 (HPV-16), the main etiological agent of cervical cancer, is poorly characterized in terms of cellular requirements and pathways. Conflicting reports attribute HPV-16 entry to clathrin-dependent and -independent mechanisms. To comprehensively describe the cell biological features of HPV-16 entry into human epithelial cells, we compared HPV-16 pseudovirion (PsV) infection in the context of cell perturbations (drug inhibition, siRNA silencing, overexpression of dominant mutants) to five other viruses (influenza A virus, Semliki Forest virus, simian virus 40, vesicular stomatitis virus, and vaccinia virus) with defined endocytic requirements. Our analysis included infection data, i.e. GFP expression after plasmid delivery by HPV-16 PsV, and endocytosis assays in combination with electron, immunofluorescence, and video microscopy. The results indicated that HPV-16 entry into HeLa and HaCaT cells was clathrin-, caveolin-, cholesterol- and dynamin-independent. The virus made use of a potentially novel ligand-induced endocytic pathway related to macropinocytosis. This pathway was distinct from classical macropinocytosis in regards to vesicle size, cholesterol-sensitivity, and GTPase requirements, but similar in respect to the need for tyrosine kinase signaling, actin dynamics, Na+/H+ exchangers, PAK-1 and PKC. After internalization the virus was transported to late endosomes and/or endolysosomes, and activated through exposure to low pH

Distribution of mutation frequencies among Salmonella enterica isolates from animal and human sources and genetic characterization of a Salmonella Heidelberg hypermutator

International audienc

Human papillomaviruses and cancer in Uganda.

In a case-control study in Uganda, we examined associations between different cancer sites or types in relation to antibodies against human papillomaviruses (HPV)-16, -18 and -45. For each cancer site or type, the control group comprised all other cancers excluding those known, or thought to be associated with HPV infection (cancers of the uterine cervix, penis and eye). Among controls the seroprevalence of antibodies was 11% (68/616) against HPV-16, 5% (29/605) against HPV-18 and 6% (35/605) against HPV-45. Antibodies against HPV-16 were significantly associated with only two cancers: uterine cervix [prevalence of antibodies 27% (51/191); odds ratio (OR) 2.0, 95% confidence interval (CI) 1.2-3.1, P=0.01] and penis [prevalence of antibodies 27% (4/15); OR 6.4, 95% CI 1.7-24.3, P=0.01]. For both cancers, the risk increased with increasing anti-HPV-16 antibody titre (Ptrend=0.01 for each). No cancer site or type was significantly associated with antibodies against HPV-18 and -45

An insight into an intriguing oxidative biotransformation pathway of 5-O-caffeoylquinic acid by a gut bacterium

International audienceMicrobiota is known to play a pivotal role in generating bioavailable and bioactive low-molecular-weight metabolites from dietary polyphenols. 5-O-caffeoylquinic acid (5-CQA), one of the main polyphenols found in human diet, was submitted to a resting cell biotransformation study using three gut bacteria species Lactobacillus reuteri, Bacteroides fragilis and Bifidobacterium longum. These bacteria were selected according to their belonging to the main phyla found in human gut microbiota. Our study highlighted the ability of only one of the strains studied, L. reuteri, to bioconverse 5-CQA into various metabolites due to the expression of the cinnamoyl esterase enzyme as the first step. Interestingly, one known natural compound, esculetin, was described for the first time as a 5-CQA-derived metabolite after conversion by a gut bacterium, the other metabolites had already been reported. This evidence highlighted an interesting oxidative pathway occurring in vivo by intestinal microbiota leading to esculetin. This molecule was also identified after electrochemical and enzymatic oxidations of caffeic acid. The oxidation capacity of L. reuteri led to less diverse metabolites in comparison to those obtained either electrochemically and enzymatically where dimers and trimers were reported. Thus, esculetin may have interesting and benefical biological effects on gut microbiota, which should be further evaluated. Novel synbiotics could be formulated from the association of L. reuteri with 5-CQA