The E6E7 oncoproteins of cutaneous human papillomavirus type 38 interfere with the interferon pathway

Non-melanoma skin cancer is the most frequent malignancy in Caucasian populations. Evidence suggests the involvement of cutaneous Human Papillomavirus (HPV) of the genus beta () in this disease. The ability of E6 and E7 of mucosal HPV to promote cellular transformation and inhibit immune response-related pathways plays a key role in cervical carcinogenesis. HPV-38 E6 and E7 display transforming activities in in vitro and in vivo models, but their impact on immune surveillance is unknown. Here we show that HPV-38 E6 and E7 affect the IFN-induced up-regulation of MHC class I. Expression of the two viral proteins in HaCaT keratinocytes led to a decrease of MHC I levels. This down-regulation is associated with a reduction of expression of MHC I heavy chain, of the peptide chaperone TAP and of the STAT-1 downstream effector IRF-1. The down-regulation of these proteins is ultimately due to the inhibition of STAT-1 expression. Analysis of cells expressing either HPV-38 E6 or E7 suggests that these effects are primarily the result of E6 expression, although a contribution by E7 cannot be excluded. We conclude that HPV-38 encodes oncoproteins that potentially contribute to the evasion of host immune surveillance

High prevalence of bronchiectasis is linked to HTLV-1-associated inflammatory disease.

BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1), a retrovirus, is the causative agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukaemia/lymphoma (ATLL). The reported association with pulmonary disease such as bronchiectasis is less certain. METHODS: A retrospective case review of a HTLV-1 seropositive cohort attending a national referral centre. The cohort was categorised into HTLV-1 symptomatic patients (SPs) (ATLL, HAM/TSP, Strongyloidiasis and HTLV associated inflammatory disease (HAID)) and HTLV-1 asymptomatic carriers (ACs). The cohort was reviewed for diagnosis of bronchiectasis. RESULT: 34/246 ACs and 30/167 SPs had been investigated for respiratory symptoms by computer tomography (CT) with productive cough +/- recurrent chest infections the predominant indications. Bronchiectasis was diagnosed in one AC (1/246) and 13 SPs (2 HAID, 1 ATLL, 10 HAM/TSP) (13/167, RR 19.2 95 % CI 2.5-14.5, p = 0.004) with high resolution CT. In the multivariate analysis ethnicity (p = 0.02) and disease state (p < 0.001) were independent predictors for bronchiectasis. The relative risk of bronchiectasis in SPs was 19.2 (95 % CI 2.5-14.5, p = 0.004) and in HAM/TSP patients compared with all other categories 8.4 (95 % CI 2.7-26.1, p = 0.0002). Subjects not of African/Afro-Caribbean ethnicity had an increased prevalence of bronchiectasis (RR 3.45 95 % 1.2-9.7, p = 0.02). CONCLUSIONS: Bronchiectasis was common in the cohort (3.4 %). Risk factors were a prior diagnosis of HAM/TSP and ethnicity but not HTLV-1 viral load, age and gender. The spectrum of HTLV-associated disease should now include bronchiectasis and HTLV serology should be considered in patients with unexplained bronchiectasis

Effect of a chemical manufacturing plant on community cancer rates

BACKGROUND: We conducted a retrospective study to determine if potential past exposure to dioxin had resulted in increased incidence of cancer in people living near a former manufacturing plant in New South Wales, Australia. During operation, from 1928 to 1970, by-products of the manufacturing process, including dioxin and other chemical waste, were dumped into wetlands and mangroves, discharged into a nearby bay and used to reclaim land along the foreshore, leaving a legacy of significant dioxin contamination. METHODS: We selected 20 Census Collector Districts within 1.5 kilometres of the former manufacturing plant as the study area. We obtained data on all cases of cancer and deaths from cancer in New South Wales from 1972 to 2001. We also compared rates for some cancer types that have been associated with dioxin exposure. Based on a person's residential address at time of cancer diagnosis, or at time of death due to cancer, various geo-coding software and processes were used to determine which collector district the case or death should be attributed to. Age and sex specific population data were used to calculate standardised incidence ratios and standardised mortality ratios, to compare the study area to two comparison areas, using indirect standardisation. RESULTS: During the 30-year study period 1,106 cases of cancer and 524 deaths due to cancer were identified in the study area. This corresponds to an age-sex standardised rate of 3.2 cases per 1,000 person-years exposed and 1.6 deaths per 1,000 person-years exposed. The study area had a lower rate of cancer and deaths from cancer than the comparison areas. The case incidence and mortality due to lung and bronchus carcinomas and haematopoietic cancers did not differ significantly from the comparison areas for the study period. There was no obvious geographical trend in ratios when comparing individual collector districts to New South Wales according to distance from the potential source of dioxin exposure. CONCLUSION: This investigation found no evidence that dioxin contamination from this site resulted in increased cancer rates in the potentially exposed population living around the former manufacturing plant

Incidence of oral cancer in relation to nickel and arsenic concentrations in farm soils of patients' residential areas in Taiwan

<p>Abstract</p> <p>Background</p> <p>To explore if exposures to specific heavy metals in the environment is a new risk factor of oral cancer, one of the fastest growing malignancies in Taiwan, in addition to the two established risk factors, cigarette smoking and betel quid chewing.</p> <p>Methods</p> <p>This is an observational study utilized the age-standardized incidence rates of oral cancer in the 316 townships and precincts of Taiwan, local prevalence rates of cigarette smoking and betel quid chewing, demographic factors, socio-economic conditions, and concentrations in farm soils of the eight kinds of heavy metal. Spatial regression and GIS (Geographic Information System) were used. The registration contained 22,083 patients, who were diagnosed with oral cancer between 1982 and 2002. The concentrations of metal in the soils were retrieved from a nation-wide survey in the 1980s.</p> <p>Results</p> <p>The incidence rate of oral cancer is geographically related to the concentrations of arsenic and nickel in the patients' residential areas, with the prevalence of cigarette smoking and betel quid chewing as controlled variables.</p> <p>Conclusions</p> <p>Beside the two established risk factors, cigarette smoking and betel quid chewing, arsenic and nickel in farm soils may be new risk factors for oral cancer. These two kinds of metal may involve in the development of oral cancer. Further studies are required to understand the pathways via which metal in the farm soils exerts its effects on human health.</p

Radiation exposure from Chest CT: Issues and Strategies

Concerns have been raised over alleged overuse of CT scanning and inappropriate selection of scanning methods, all of which expose patients to unnecessary radiation. Thus, it is important to identify clinical situations in which techniques with lower radiation dose such as plain radiography or no radiation such as MRI and occasionally ultrasonography can be chosen over CT scanning. This article proposes the arguments for radiation dose reduction in CT scanning of the chest and discusses recommended practices and studies that address means of reducing radiation exposure associated with CT scanning of the chest

Active, but not passive cigarette smoking was inversely associated with mammographic density

The opposing carcinogenic and antiestrogenic properties of tobacco smoke may explain why epidemiologic studies have not consistently reported positive associations for active smoking and breast cancer risk. A negative relation between mammographic density, a strong breast cancer risk factor, and active smoking would lend support for an antiestrogenic mechanism. We used multivariable linear regression to assess the associations of active smoking and secondhand smoke (SHS) exposure with mammographic density in 799 pre- and early perimenopausal women in the Study of Women’s Health Across the Nation (SWAN). We observed that current active smoking was associated with 7.2% lower mammographic density, compared to never active smoking and no SHS exposure (p = 0.02). Starting to smoke before 18 years of age and having smoked ≥20 cigarettes/day were also associated with statistically significantly lower percent densities. Among nulliparous women having smoked ≥20 cigarettes/day was associated with 23.8% lower density, compared to having smoked ≤9 cigarettes/day (p &lt; 0.001). Our findings support the hypothesis that tobacco smoke exerts an antiestrogenic effect on breast tissue, but counters the known increased risk of breast cancer with smoking prior to first full-term birth. Thus, our data suggest that the antiestrogenic but not the carcinogenic effects of smoking may be reflected by breast density