Prognostic implications of immunohistochemically detected YKL-40 expression in breast cancer

BACKGROUND: YKL-40 has been implicated as a mediator of collagen synthesis and extracellular matrix re-modeling as well as mitogenesis. Elevated serum levels of YKL-40 have been associated with worse survival in a variety of malignancies including breast cancer. We wished to determine if immunohistochemically detected expression had prognostic implications in breast cancer. METHODS: A prospectively collected database of breast cancer patients treated at the University Hospital of Newark was used for analysis. Immunohistochemistry was performed on archived tumor tissue from 109 patients for whom full clinical information and follow up was available. RESULTS: YKL-40 expression was noted in 37 patients (34%). YKL-40 immunoreactivity significantly correlated with larger tumor size, poorer tumor differentiation, and a greater likelihood of being estrogen and/or progesterone receptor negative. No significant correlation was demonstrated between YKL-40 status and nodal stage. At a mean follow up of 3.2 years, disease-free survival was significantly worse in the subset of patients whose tumors demonstrated YKL-40 expression compared to the non-expressors. In multivariate analysis, YKL-40 status was independent of T-stage and N-stage in predicting disease recurrence. CONCLUSION: Immunoreactivity for YKL-40 was a significant predictor of breast cancer relapse in this subset of patients. This was independent of T or N-stage and suggests that tumor immunohistochemistry for this protein may be a valuable prognostic marker in breast cancer

YKL-40 tissue expression and plasma levels in patients with ovarian cancer

<p>Abstract</p> <p>Background</p> <p>YKL-40 (chitinase-3-like-1) is a member of "mammalian chitinase-like proteins". The protein is expressed in many types of cancer cells and the highest plasma YKL-40 levels have been found in patients with metastatic disease, short recurrence/progression-free intervals, and short overall survival. The aim of the study was to determine the expression of YKL-40 in tumor tissue and plasma in patients with borderline ovarian tumor or epithelial ovarian cancer (OC), and investigate prognostic value of this marker.</p> <p>Methods</p> <p>YKL-40 protein expression was determined by immunohistochemistry in tissue arrays from 181 borderline tumors and 473 OC. Plasma YKL-40 was determined by ELISA in preoperative samples from 19 patients with borderline tumor and 76 OC patients.</p> <p>Results</p> <p>YKL-40 protein expression was found in cancer cells, tumor associated macrophages, neutrophils and mast cells. The tumor cell expression was higher in OC than in borderline tumors (p = 0.001), and associated with FIGO stage (p < 0.0001) and histological subtype (p = 0.0009). Positive YKL-40 expression (≥ 5% staining) was not associated with reduced survival. Plasma YKL-40 was also higher in patients with OC than in patients with borderline tumors (p < 0.0001), and it was positively correlated to serum CA-125 (p < 0.0001) and FIGO stage (p = 0.0001). Univariate Cox analysis of plasma YKL-40 showed association with overall survival (p < 0.0001). Multivariate Cox analysis, including plasma YKL-40, serum CA125, FIGO stage, age and radicality after primary surgery as variables, showed that elevated plasma YKL-40 was associated with a shorter survival (HR = 2.13, 95% CI: 1.40–3.25, p = 0.0004).</p> <p>Conclusion</p> <p>YKL-40 in OC tissue and plasma are related to stage and histology, but only plasma YKL-40 is a prognostic biomarker in patients with OC.</p

Planet formation in Binaries

Spurred by the discovery of numerous exoplanets in multiple systems, binaries have become in recent years one of the main topics in planet formation research. Numerous studies have investigated to what extent the presence of a stellar companion can affect the planet formation process. Such studies have implications that can reach beyond the sole context of binaries, as they allow to test certain aspects of the planet formation scenario by submitting them to extreme environments. We review here the current understanding on this complex problem. We show in particular how each of the different stages of the planet-formation process is affected differently by binary perturbations. We focus especially on the intermediate stage of kilometre-sized planetesimal accretion, which has proven to be the most sensitive to binarity and for which the presence of some exoplanets observed in tight binaries is difficult to explain by in-situ formation following the "standard" planet-formation scenario. Some tentative solutions to this apparent paradox are presented. The last part of our review presents a thorough description of the problem of planet habitability, for which the binary environment creates a complex situation because of the presence of two irradation sources of varying distance.Comment: Review chapter to appear in "Planetary Exploration and Science: Recent Advances and Applications", eds. S. Jin, N. Haghighipour, W.-H. Ip, Springer (v2, numerous typos corrected

Distance to high-voltage power lines and risk of childhood leukemia:An analysis of confounding by and interaction with other potential risk factors

We investigated whether there is an interaction between distance from residence at birth to nearest power line and domestic radon and traffic-related air pollution, respectively, in relation to childhood leukemia risk. Further, we investigated whether adjusting for potential confounders alters the association between distance to nearest power line and childhood leukemia. We included 1024 cases aged <15, diagnosed with leukemia during 1968-1991, from the Danish Cancer Registry and 2048 controls randomly selected from the Danish childhood population and individually matched by gender and year of birth. We used geographical information systems to determine the distance between residence at birth and the nearest 132-400 kV overhead power line. Concentrations of domestic radon and traffic-related air pollution (NOx at the front door) were estimated using validated models. We found a statistically significant interaction between distance to nearest power line and domestic radon regarding risk of childhood leukemia (p = 0.01) when using the median radon level as cut-off point but not when using the 75th percentile (p = 0.90). We found no evidence of an interaction between distance to nearest power line and traffic-related air pollution (p = 0.73). We found almost no change in the estimated association between distance to power line and risk of childhood leukemia when adjusting for socioeconomic status of the municipality, urbanization, maternal age, birth order, domestic radon and traffic-related air pollution. The statistically significant interaction between distance to nearest power line and domestic radon was based on few exposed cases and controls and sensitive to the choice of exposure categorization and might, therefore, be due to chance

Impact and relationship of anterior commissure and time-dose factor on the local control of T1N0 glottic cancer treated by 6 MV photons

<p>Abstract</p> <p>Background</p> <p>To evaluate prognostic factors that may influence local control (LC) of T1N0 glottic cancer treated by primary radiotherapy (RT) with 6 MV photons.</p> <p>Methods</p> <p>We retrospectively reviewed the medical records of 433 consecutive patients with T1N0 glottic cancer treated between 1983 and 2005 by RT in our institution. All patients were treated with 6 MV photons. One hundred and seventy seven (41%) patients received 52.5 Gy in 23 fractions with 2.5 Gy/fraction, and 256 (59%) patients received 66 Gy in 33 fractions with 2 Gy/fraction.</p> <p>Results</p> <p>The median follow-up time was 10.5 years. The 10-year LC rates were 91% and 87% for T1a and T1b respectively. Multivariate analysis showed LC rate was adversely affected by poorly differentiated histology (Hazard Ratio [HR]: 7.5, <it>p </it>= 0.035); involvement of anterior commissure (HR: 2.34, <it>p </it>= 0.011); fraction size of 2.0 Gy (HR: 2.17, <it>p </it>= 0.035) and tumor biologically effective dose (BED) < 65 Gy₁₅(HR: 3.38, <it>p </it>= 0.017).</p> <p>Conclusions</p> <p>The negative impact of anterior commissure involvement could be overcome by delivering a higher tumor BED through using fraction size of > 2.0 Gy. We recommend that fraction size > 2.0 Gy should be utilized, for radiation schedules with five daily fractions each week.</p

Prevalence and Risk Factors of Porcine Cysticercosis in Angónia District, Mozambique

Taenia solium is an important zoonosis in many developing countries. Cysticercosis poses a serious public health risk and incurs sizeable economic losses to pig production. Because data on the epidemiology of porcine cysticercosis in Mozambique are scarce, the present study was conducted to determine the prevalence and risk factors for porcine cysticercosis. A cross-sectional survey was carried out in 11 villages in Angónia district, Tete province in northwestern Mozambique. Between September and November, 2007, a total of 661 pigs were tested serologically and examined by tongue inspection. Serum samples were tested for the presence of circulating parasite antigen using a monoclonal antibody-based sandwich enzyme-linked immunosorbent assay (Ag-ELISA). In addition, a questionnaire survey to collect information on pig production, occurrence and transmission of porcine cysticercosis, risk factors and awareness of porcine cysticercosis was conducted in the selected households from which pigs were sampled. Two hundred thirty-one samples (34.9%) were found positive by the Ag-ELISA, while by tongue inspection on the same animals cysticerci were detected in 84 pigs (12.7%). Increasing age (OR = 1.63; 95% CI = 1.13–2.37) and free-range pig husbandry system (OR = 3.81; 95% CI = 2.08–7.06) were important risk factors for porcine cysticercosis in the district. The present findings indicate that porcine cysticercosis is endemic in the region, and that increasing pig age and pig husbandry practices contribute significantly to porcine cysticercosis transmission. Further epidemiological studies on the prevalence and transmission of porcine cysticercosis in rural communities in Mozambique are needed to enable collection of more baseline data and implementation of effective control strategies within the country

Prevention of Diabetes in NOD Mice by Repeated Exposures to a Contact Allergen Inducing a Sub-Clinical Dermatitis

BACKGROUND: Type 1 diabetes is an autoimmune disease, while allergic contact dermatitis although immune mediated, is considered an exposure driven disease that develops due to epicutaneous contact with reactive low-molecular chemicals. The objective of the present study was to experimentally study the effect of contact allergens on the development of diabetes in NOD mice. As the link between contact allergy and diabetes is yet unexplained we also examined the effect of provocation with allergens on Natural Killer T (NKT) cells, since involvement of NKT cells could suggest an innate connection between the two diseases. METHOD: NOD mice 4 weeks of age were exposed, on the ears, to two allergens, p-phenylenediamine and 2,4-dinitrochlorobenzene respectively, to investigate the diabetes development. The mice were followed for a maximum of 32 weeks, and they were either repeatedly exposed to the allergens or only sensitized a week after arrival. The stimulation of NKT cells by the two allergens were additionally studied in C57BL/6 mice. The mice were sensitized and two weeks later provocated with the allergens. The mice were subsequently euthanized at different time points after the provocation. RESULTS: It was found that repeated application of p-phenylenediamine reduced the incidence of diabetes compared to application with water (47% vs. 93%, P = 0.004). Moreover it was shown that in C57BL/6 mice both allergens resulted in a slight increment in the quantity of NKT cells in the liver. Application of the allergens at the same time resulted in an increased number of NKT cells in the draining auricular lymph node, and the increase appeared to be somewhat allergen specific as the accumulation was stronger for p-phenylenediamine. CONCLUSION: The study showed that repeated topical application on the ears with a contact allergen could prevent the development of diabetes in NOD mice. The contact allergens gave a non-visible, sub-clinical dermatitis on the application site. The preventive effect on diabetes may be due to stimulation of peripheral NKT cells, as shown for provocation with p-phenylenediamine in the C57BL/6 mouse. This epicutaneous procedure may lead to new strategies in prevention of type 1 diabetes in humans

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration