Hepatocellular carcinoma (HCC) frequently results from synergism between chemical and infectious liver carcinogens. Worldwide, the highest incidence of HCC is in regions endemic for the foodborne ...contaminant aflatoxin B1 (AFB1) and hepatitis B virus (HBV) infection. Recently, gut microbes have been implicated in multisystemic diseases including obesity and diabetes. Here, the hypothesis that specific intestinal bacteria promote liver cancer was tested in chemical and viral transgenic mouse models.
Helicobacter-free C3H/HeN mice were inoculated with AFB1 and/or Helicobacter hepaticus. The incidence, multiplicity and surface area of liver tumours were quantitated at 40 weeks. Molecular pathways involved in tumourigenesis were analysed by microarray, quantitative real-time PCR, liquid chromatography/mass spectrometry, ELISA, western blot and immunohistochemistry. In a separate experiment, C57BL/6 FL-N/35 mice harbouring a full-length hepatitis C virus (HCV) transgene were crossed with C3H/HeN mice and cancer rates compared between offspring with and without H hepaticus.
Intestinal colonisation by H hepaticus was sufficient to promote aflatoxin- and HCV transgene-induced HCC. Neither bacterial translocation to the liver nor induction of hepatitis was necessary. From its preferred niche in the intestinal mucus layer, H hepaticus activated nuclear factor-kappaB (NF-kappaB)-regulated networks associated with innate and T helper 1 (Th1)-type adaptive immunity both in the lower bowel and liver. Biomarkers indicative of tumour progression included hepatocyte turnover, Wnt/beta-catenin activation and oxidative injury with decreased phagocytic clearance of damaged cells.
Enteric microbiota define HCC risk in mice exposed to carcinogenic chemicals or hepatitis virus transgenes. These results have implications for human liver cancer risk assessment and prevention.
The propagation of partons from hard scattering through the Quark Gluon Plasma produced in A+A collisions at RHIC and the LHC is represented in theoretical analyses by the transport coefficient qˆ ...and predicted to cause both energy loss of the outgoing partons, observed as suppression of particles or jets with large transverse momentum pT, and broadening of the azimuthal correlations of the outgoing di-jets or di-hadrons from the outgoing parton-pair, which has not been observed. The widths of azimuthal correlations of di-hadrons with the same trigger particle pTt and associated pTa transverse momenta in p+p and Au+Au are so-far statistically indistinguishable as shown in recent as well as older di-hadron measurements and also with jet-hadron and hadron-jet measurements. The azimuthal width of the di-hadron correlations in p+p collisions, beyond the fragmentation transverse momentum, jT, is dominated by kT, the so-called intrinsic transverse momentum of a parton in a nucleon, which can be measured. The broadening should produce a larger kT in A+A than in p+p collisions. The present work introduces the observation that the kT measured in p+p collisions for di-hadrons with pTt and pTa must be reduced to compensate for the energy loss of both the trigger and away parent partons when comparing to the kT measured with the same di-hadron pTt and pTa in Au+Au collisions. This idea is applied to a recent STAR di-hadron measurement, with result 〈qˆL〉=2.1±0.6 GeV2. This is more precise but in agreement with a theoretical calculation of 〈qˆL〉=14−14+42 GeV2 using the same data. Assuming a length 〈L〉≈7 fm for central Au+Au collisions the present result gives qˆ≈0.30±0.09 GeV2/fm, in fair agreement with the JET collaboration result from single hadron suppression of qˆ≈1.2±0.3 GeV2/fm at an initial time τ0=0.6 fm/c in Au+Au collisions at sNN=200 GeV.
Here, several methods of generating three constituent quarks in a nucleon are evaluated which explicitly maintain the nucleon's center of mass and desired radial distribution and can be used within ...Monte Carlo Glauber frameworks. The geometric models provided by each method are used to generate distributions over the number of constituent quark participants (Nqp) in p+p,d+Au, and Au+Au collisions. The results are compared with each other and to a previous result of Nqp calculations, without this explicit constraint, used in measurements of √SNN = 200 GeV p+p,d+Au, and Au+Au collisions at the BNL Relativistic Heavy Ion Collider.
1 Developmental
Neuroendocrinology Laboratory, Douglas Hospital Research Center,
and 2 Department of Neurology and
Neurosurgery, McGill University, Montreal H4H-1R3;
3 Neuropeptide Physiology
...Laboratory, Montreal Children's Hospital Research Institute and
Department of Pediatrics, McGill University, Montreal H3H-1P3;
4 Signal Transduction
Laboratories, Department of Biochemistry, University of Alberta,
Edmonton, Canada T6G-2S2; and
5 Department of Physiology,
University of California, San Francisco, California 94143
High-fat feeding induces insulin resistance
and increases the risk for the development of diabetes and coronary
artery disease. Glucocorticoids exacerbate this hyperinsulinemic state,
rendering an individual at further risk for chronic disease. The
present studies were undertaken to determine whether dietary
fat-induced increases in corticosterone (B) reflect alterations in the
regulatory components of the hypothalamic-pituitary-adrenal (HPA) axis.
Adult male rats were maintained on a high-fat (20%) or control (4%) diet for varying periods of time. Marked elevations in light-phase spontaneous basal B levels were evident as early as 7 days after fat
diet onset, and B concentrations remained significantly elevated up to
21 days after fat diet onset compared with controls. In contrast, there
were no significant effects on any parameters of spontaneous growth
hormone secretory profiles, thus providing support for the specificity
of the effects on the HPA axis. In a second study, all groups of rats
fed the high-fat diet for 1, 9, or 12 wk exhibited significantly
elevated levels of plasma adrenocorticotropic hormone, B, fatty acid,
and glucose before, during, and/or at 20, 60, and/or
120 min after the termination of a restraint stress. Furthermore, 12-wk
fat-fed animals showed a significant resistance to insulin compared
with normally fed controls. There were no differences in negative
feedback efficacy in high-fat-fed rats vs. controls. Taken together,
these results suggest that dietary fat intake acts as a background form
of chronic stress, elevating basal B levels and enhancing HPA responses
to stress.
glucocorticoids; adrenocorticotropic hormone; corticosterone; fatty
acid; glucose
Development of a novel synthesis method to create a complex collagen-based biopolymer that promises to possess the necessary material properties for a bone graft substitute.
In this study, we ...developed a novel synthesis method to create a complex collagen-based biopolymer that promises to possess the necessary material properties for a bone graft substitute. The synthesis was carried out in several steps. In the first step, a ring-opening polymerization reaction initiated by hydroxyapatite nanoparticles was used to polymerize d,l-lactide and glycolide monomers to form poly(lactide-co-glycolide) co-polymer. In the second step, the polymerization product was coupled with succinic anhydride, and subsequently was reacted with N-hydroxysuccinimide in the presence of dicyclohexylcarbodiimide as the cross-linking agent, in order to activate the co-polymer for collagen attachment. In the third and final step, the activated co-polymer was attached to calf skin collagen type I, in hydrochloric acid/phosphate buffer solution and the precipitated co-polymer with attached collagen was isolated. The synthesis was monitored by proton nuclear magnetic resonance, infrared and Raman spectroscopies, and the products after each step were characterized by thermal and mechanical analysis. Calculations of the relative amounts of the various components, coupled with initial dynamic mechanical analysis testing of the resulting biopolymer, afforded a preliminary assessment of the structure of the complex biomaterial formed by this novel polymerization process.
The many different theoretical studies of energy loss of a quark or gluon traversing a medium have one thing in common: the transport coefficient of a gluon in the medium, denoted q̂, which is ...defined as the mean 4-momentum transfer-square, q2, by a gluon to the medium per gluon mean free path, λmfp. In the original BDMPSZ formalism, the energy loss of an outgoing parton, −dE/dx, per unit length (x) of a medium with total length L, due to coherent gluon bremsstrahlung is proportional to the q2 and takes the form: −dEdx≃αS〈q2(L)〉=αsμ2L/λmtp=αsq^L, where µ, is the mean momentum transfer per collision. Thus, the total energy loss in the medium goes like L2. Additionally, the accumulated momentum-square, 〈 kT2 〉, transverse to a gluon traversing a length L in the medium is well approximated by 〈kT2〉≈〈q2(L)〉=q^L. A simple estimate shows that the 〈kT2〉≈q^L should be observable at RHIC at sNN=200 GeV via the broadening of di-hadron azimuthal correlations resulting in an azimuthal width ∼2 larger in Au+Au than in p + p collisions. Measurements relevant to this issue will be discussed as well as recent STAR jet results presented at QM2014 1. Other topics to be discussed include the danger of using forward energy to define centrality in p(d)+A collisions for high pT measurements, the danger of not using comparison p + p data at the same s in the same detector for RAA or lately for RpA measurements. Also, based on a comment at last year's 9th workshop that the parton energy loss is proportional to dNch/dη 2, new results on the dependence of the shift in the pT spectra in A+A collisions from the TAA-scaled p + p spectrum (to be discussed in detail in another presentation 3) will be shown.
Gender- and Smoking-Related Bladder Cancer Risk Castelao, J. Esteban; Yuan, Jian-Min; Skipper, Paul L. ...
JNCI : Journal of the National Cancer Institute,
04/2001, Letnik:
93, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Background: There is growing evidence that, when smoking habits are comparable, women incur a higher risk of lung cancer than men. Because smokers are also at risk for bladder cancer, we investigated ...possible sex differences in the susceptibility to bladder cancer among smokers. Methods: A population-based, case–control study was conducted in Los Angeles, CA, involving 1514 case patients with bladder cancer and 1514 individually matched population control subjects. Information on tobacco use was collected through in-person interviews. Peripheral blood was collected from study participants to measure 3- and 4-aminobiphenyl (ABP)–hemoglobin adducts, a marker of arylamine exposure. Data were analyzed to determine whether the risk of bladder cancer differs between male and female smokers and whether female smokers exhibit higher levels of ABP–hemoglobin adducts than male smokers with comparable smoking habits. All statistical tests were two-sided. Results: Cigarette smokers had a statistically significant 2.5-fold higher risk (95% confidence interval = 2.1 to 3.0) of bladder cancer than never smokers. Use of filtered versus nonfiltered cigarettes, low-tar versus higher tar cigarettes, or the pattern of inhalation did not modify the risk. The risk of bladder cancer in women who smoked was statistically significantly higher than that in men who smoked comparable numbers of cigarettes (P = .016 for sex–lifetime smoking interaction). Consistent with the sex difference in smoking-related bladder cancer risk, the slopes of the linear regression lines of the 3- and 4-ABP–hemoglobin adducts by cigarettes per day were statistically significantly steeper in women than in men (P values for sex differences <.001 and .006, respectively). Conclusion: The risk of bladder cancer may be higher in women than in men who smoked comparable amounts of cigarettes.
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