Characteristics and survival of head and neck cancer by HPV status: a cancer registry-based study

Elucidation of the role of human papillomavirus (HPV) in the etiology and prognosis of squamous carcinomas of the head and neck (HNSCC) is essential to optimize prevention and treatment strategies for this disease. We analyzed 385 HNSCC tissue blocks identified through a population-based cancer registry in Metropolitan Detroit for HPV DNA using a broad-spectrum PCR technique (SPF10-LiPA25) to correlate with patient and tumor characteristics and overall survival. Overall, HPV DNA (any type) was detected in 29.4% of all HNSCC, but it was significantly more prevalent (50.6%) in oropharyngeal sites (N=81), where 90% of HPV were type 16, than in other sites. HPV prevalence (any type) in oropharyngeal sites was highest in patients with a negative smoking indicator, Caucasians and in regional tumor stage. Likewise, only in oropharyngeal sites did patients overall positive to HPV show significantly better survival compared with HPV-negative patients, notably among those who had been irradiated. The best and the worst survival from cancer in oropharyngeal sites were found, respectively, among HPV-positive patients with negative smoking indicator and among HPV-negative patients with positive smoking indicator. The results of this study revealed that the presence of HPV DNA was associated with patients' specific characteristics and better overall survival exclusively in oropharyngeal sites. To define the fraction of HNSCC preventable by HPV vaccination or amenable to less aggressive treatment, however, tobacco exposure and HPV markers other than DNA presence need to be taken into account.     

Nanobody-based targeting of the macrophage mannose receptor for effective in vivo imaging of tumor-associated macrophages

Tumor-associated macrophages (TAM) are an important component of the tumor stroma and exert several tumor-promoting activities. Strongly pro-angiogenic TAMs that reside in hypoxic tumor areas highly express macrophage mannose receptor (MMR, CD206). In this study, we targeted MMR(+) TAMs using nanobodies, which are single-domain antigen-binding fragments derived from Camelidae heavy-chain antibodies. MMR-specific nanobodies stained TAMs in lung and breast tumor single-cell suspensions in vitro, and intravenous injection of (99m)Tc-labeled anti-MMR nanobodies successfully targeted tumor in vivo. Retention of the nanobody was receptor-specific and absent in MMR-deficient mice. Importantly, co-injection of excess unlabeled, bivalent anti-MMR nanobodies reduced nanobody accumulation in extratumoral organs to background levels, without compromising tumor uptake. Within tumors, the (99m)Tc-labeled nanobodies specifically labeled MMR(+) TAMs, as CCR2-deficient mice that contain fewer TAMs showed significantly reduced tumor uptake. Further, anti-MMR nanobodies accumulated in hypoxic regions, thus targeting pro-angiogenic MMR(+) TAMs. Taken together, our findings provide preclinical proof of concept that anti-MMR nanobodies can be used to selectively target and image TAM subpopulations in vivo. Cancer Res; 72(16); 4165-77. ?2012 AACR.     

Temperature-induced changes in structural and physicochemical properties of vernix caseosa

The skin of the third trimester fetus and early newborn exhibits a complex, multifunctional, highly hydrated but viscous skin-surface biofilm called vernix caseosa (VC). During birth, VC undergoes a substantial change from an aqueous and warm surrounding into a gaseous and colder environment postnatally. The aim of this study was to investigate the structural and physicochemical changes in VC, which accompany physiologically relevant variations in environment parameters, such as temperature and humidity. A remarkable difference was observed in water release and uptake properties: dehydration and rehydration processes take place two to four times faster at 37 degrees C than at room temperature (RT). The dehydration was irreversible; rehydration was only possible to a final weight of 55% (37 degrees C) and 46% (RT) of the pre-desiccation weight. Differential scanning calorimetry showed two different overlapping phase transitions within physiological temperature range. Investigation of the lipid organization by Fourier transform infrared spectroscopy and small-angle X-ray diffraction revealed a more disordered state of lipids at 37 degrees C than at RT, which might explain the faster dehydration and rehydration process at 37 degrees C as well as the changes in thermotropic rheological behavior. In conclusion, we demonstrated that VC properties adjust to the fundamental change from the intrauterine to the post-natal environment.     

Hypertension and exposure to noise near airports: the HYENA study

BACKGROUND: An increasing number of people are exposed to aircraft and road traffic noise. Hypertension is an important risk factor for cardiovascular disease, and even a small contribution in risk from environmental factors may have a major impact on public health. OBJECTIVES: The HYENA (Hypertension and Exposure to Noise near Airports) study aimed to assess the relations between noise from aircraft or road traffic near airports and the risk of hypertension. METHODS: We measured blood pressure and collected data on health, socioeconomic, and lifestyle factors, including diet and physical activity, via questionnaire at home visits for 4,861 persons 45-70 years of age, who had lived at least 5 years near any of six major European airports. We assessed noise exposure using detailed models with a resolution of 1 dB (5 dB for United Kingdom road traffic noise), and a spatial resolution of 250 x 250 m for aircraft and 10 x 10 m for road traffic noise. RESULTS: We found significant exposure-response relationships between night-time aircraft as well as average daily road traffic noise exposure and risk of hypertension after adjustment for major confounders. For night-time aircraft noise, a 10-dB increase in exposure was associated with an odds ratio (OR) of 1.14 [95% confidence interval (CI), 1.01-1.29]. The exposure-response relationships were similar for road traffic noise and stronger for men with an OR of 1.54 (95% CI, 0.99-2.40) in the highest exposure category (> 65 dB; p(trend) = 0.008). CONCLUSIONS: Our results indicate excess risks of hypertension related to long-term noise exposure, primarily for night-time aircraft noise and daily average road traffic noise.