Tumor-associated stroma is typified by a persistent, non-resolving inflammatory response that enhances tumor angiogenesis, growth and metastasis. Inflammation in tumors is instigated by heterotypic interactions between malignant tumor cells, vascular endothelium, fibroblasts, immune and inflammatory cells. We found that tumor-associated adipocytes also contribute to inflammation. We have analyzed peritumoral adipose tissue in a syngeneic mouse melanoma model. Compared to control adipose tissue, adipose tissue juxtaposed to implanted tumors exhibited reduced adipocyte size, extensive fibrosis, increased angiogenesis and a dense macrophage infiltrate. A mouse cytokine protein array revealed up-regulation of inflammatory mediators including IL-6, CXCL1, MCP-1, MIP-2 and TIMP-1 in peritumoral versus counterpart adipose tissues. CD11b(+) macrophages contributed strongly to the inflammatory activity. These macrophages were isolated from peritumoral adipose tissue and found to over-express ARG1, NOS2, CD301, CD163, MCP-1 and VEGF, which are indicative of both M1 and M2 polarization. Tumors implanted at a site distant from subcutaneous, anterior adipose tissue were strongly growth-delayed, had fewer blood vessels and were less populated by CD11b(+) macrophages. In contrast to normal adipose tissue, micro-dissected peritumoral adipose tissue explants launched numerous vascular sprouts when cultured in an ex vivo model. Thus, inflamed tumor-associated adipose tissue fuels the growth of malignant cells by acting as a proximate source for vascular endothelium and activated pro-inflammatory cells, in particular macrophages.

One-way endobronchial valves (EBV) have been shown to relieve symptoms of emphysema, particularly in patients without collateral ventilation (CV) between the target and adjacent lobes. In this study, we investigated the ability of the bronchoscopic Chartis Pulmonary Assessment System(TM) to predict treatment response by determining the presence of CV.EBV patients (n=80) underwent a pre-treatment Chartis assessment. Before and 30 days after implantation, high-resolution CT scans were taken to determine target lobe volume reduction (TLVR). A pre- to post-treatment reduction of ≥350 mL was defined as significant. In addition, clinical outcomes (FEV1, 6-minute walk test and SGRQ) were compared over the same time period.Of the 51 patients classified as having an absence of CV according to their Chartis reading, 36 showed a TLVR ≥350 mL. Twenty-nine patients were classified as having CV, and of these 24 did not meet this TLVR cut-off. Chartis showed an accuracy level of 75% in predicting whether or not the TLVR cut-off would be reached. Those predicted to respond showed significantly greater TLVR (p < 0.0001) and FEV1 improvement (p=0.0013) than those predicted not to respond.Chartis is a safe and effective method of predicting response to EBV treatment.

Background: Bronchoscopic thermal vapor ablation (BTVA) ablates emphysematous tissue through a localized inflammatory response followed by contractive fibrosis and tissue shrinkage leading to lung volume reduction that should not be influenced by collateral ventilation. Objectives: To determine the correlation of clinical data from a trial of BTVA with fissure integrity visually assessed by computed tomography (CT). Methods: We conducted a single-arm study of patients with upper lobe-predominant emphysema (n = 44). Patients received BTVA either to the right upper lobe or left upper lobe, excluding the lingula. Primary efficacy outcomes were forced expiratory volume in 1 s (FEV(1)) and St. George's Respiratory Questionnaire (SGRQ) at 6 months. Lobar volume reduction from CT was another efficacy outcome measurement. The fissure of the treated lobe was analyzed visually on preinterventional CT. Incompleteness of the small fissure, the upper half of the right large fissure and the whole left large fissure were estimated visually in 5% increments, and the relative amount of fissure incompleteness was calculated. Pearson correlation coefficients were calculated for the association between fissure incompleteness and change in efficacy outcomes (baseline to 6 months) of BTVA. Results: A total of 38 out of 44 patients (86%) had incompleteness in the relevant fissure. Calculated relevant fissure incompleteness was a mean of 13% of fissure integrity (range 0-63). Correlation coefficients for the association of incompleteness with outcomes were as follows: FEV(1)= 0.17; lung volume reduction =-0.27; SGRQ score =-0.10; 6-min walk distance = 0.0; residual volume (RV)=-0.18, and RV/total lung capacity =-0.14. Conclusions: Lobar fissure integrity has no or minimal influence on BTVA-induced lung volume reduction and improvements in clinical outcomes.

Pyrene-fused tetraazaporphyrins were synthesized from pyrene-4,5-dicarbonitrile precursors using a recently reported procedure as the key step for the asymmetric substitution of pyrene. Metal-free, zinc- and lead-centered pyrenocyanines were obtained and their optical properties as well as their molecular assembly in the solution and bulk phases and at the liquid/solid interface were studied. The characteristic Q-band appears broadened, most likely owing to distortion of the molecule introduced by the steric demand of the angularly extended aromatic residue. The angular annulation does not bathochromically shift the Q-band as far as would have been expected for the linear case. Peripheral substitution with linear and branched alkoxy chains affords solubility of the compounds in organic solvents. The influence of the distinct steric demand of the substituents on aggregation was investigated for metal-centered pyrenocyanines by using temperature-dependent (1)H NMR and UV/Vis spectroscopy. The self-assembly at the liquid/solid interface was studied using scanning tunneling microscopy. The alkoxy substituents facilitate the anchoring of these slightly non-planar molecules on the surface of graphite. Pyrenocyanine molecules form well-ordered 2D arrays in which the molecules are arranged in rows. The angular annulation of the pyrenocyanine residue leads to characteristic adsorption behavior at the liquid/solid interface, in which the molecules adsorb in two different adsorption geometries. The alkoxy side-chains give rise to a discotic columnar superstructure and induce distinct thermotropic behavior. Dependent on the steric demand of the branched chains and the central metal atom, the molecules are rotated with respect to each other to form helical organization.

The oxidation of the antiviral drug acyclovir (ACV) and its main biotransformation product carboxy-acyclovir (carboxy-ACV) by ozone was investigated. Both compounds have recently been detected in surface water, and carboxy-ACV has also been detected in drinking water. The experiments revealed a strong pH dependence of the oxidation of ACV and carboxy-ACV with reaction rate constants increasing by 4 orders of magnitude between the protonated, positively charged form (k(ox,PH(+)), ∼2.5 × 10(2) M(-1) s(-1)) and the deprotonated, negatively charged form (k(ox,P(-)), 3.4 × 10(6) M(-1) s(-1)). At pH 8 a single oxidation product was formed which was identified via LC-LTQ-Orbitrap MS and NMR as N-(4-carbamoyl-2-imino-5-oxoimidazolidin)formamido-N-methoxyacetic acid (COFA). Using Vibrio fischeri , an acute bacterial toxicity was found for COFA while carboxy-ACV revealed no toxic effects. Ozonation experiments with guanine and guanosine at pH 8 led to the formation of the respective 2-imino-5-oxoimidazolidines, confirming that guanine derivatives such as carboxy-ACV are undergoing the same reactions during ozonation. Furthermore, COFA was detected in finished drinking water of a German waterworks after ozonation and subsequent activated carbon treatment.

Background.  Malignant melanoma (MM) is a very aggressive tumour. Although surgical excision of MM in the early stages has a very good prognosis, it often fails to completely inhibit tumour progression. Methylene blue photodynamic therapy (MB-PDT) is a technique that induces tissue damage by reactive oxygen species (ROS). Aim.  To investigate the efficacy of and potential use of MB-PDT in restraining the aggressiveness of MM by analysing levels of proliferating cell nuclear antigen (PCNA) and heparanase (HPSE, a molecular marker of cell invasion) in a mouse model. Methods.  Expression of PCNA and two HPSE isoforms were analysed using immunohistochemistry (IHC) after MB-PDT in mice. Tumour volume and weight were also measured. Results.  Two treatments with MB-PDT promoted a decrease of 99% decrease in tumour volume and 75% in tumour weight compared with untreated mice (P < 0.05). Using IHC, a decrease in expression of 75% for PCNA and 95% for both HPSE isoforms (P < 0.05) was found. Conclusion.  MB-PDT is a cheap and efficient method of decreasing MM volume and thus disease progression. This reduction is mediated by downregulation of PCNA and heparanases.

OBJECTIVE:To compare cued recall measures with other memory and nonmemory tests regarding their association with a biomarker profile indicative of Alzheimer disease (AD) in CSF among patients with mild cognitive impairment (MCI). METHODS:Data were obtained by the German Dementia Competence Network. A total of 185 memory clinic patients fulfilling broad criteria for MCI (1 SD deficit in memory tests or in nonmemory tests) were assessed with an extended neuropsychological battery, which included the Free and Cued Selective Reminding Test (FCSRT), the word list learning task from the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery (CERAD-NP), and the Logical Memory (LM) paragraph recall test from the Wechsler Memory Scale-Revised. CSF was obtained from all patients. RESULTS:A total of 74 out of 185 subjects with MCI (40%) had a CSF profile consistent with AD (Aβ(1-42)/tau ratio; CSF AD+ group). FCSRT measures reflecting both free and cued recall discriminated best between CSF AD+ and CSF AD- patients, and significantly improved CSF AD classification accuracy, as compared with CERAD delayed recall and LM delayed recall. CONCLUSIONS:Cued recall deficits are most closely associated with CSF biomarkers indicative of AD in subjects with MCI. This novel finding complements results from prospective clinical studies and provides further empirical support for cued recall as a specific indicator of prodromal AD, in line with recently proposed research criteria.

BACKGROUND Older smokers are often not encouraged to quit smoking due to the erroneous idea that it is too late for such interventions. OBJECTIVE To compare smoking cessation rates among older and younger treatment seekers, and to evaluate whether age is an obstacle to smoking cessation. DESIGN AND METHODS Smokers (n = 987) were submitted to the same behavioural programme plus pharmacotherapy at the Smoking Cessation Clinic of Hospital Sao Lucas, in Porto Alegre, Brazil, from July 2004 to June 2009. Quit rates were evaluated at 2, 6 and 12 months. Abstinence was confirmed by exhaled carbon monoxide < 10 ppm. Volunteers were grouped by age <60 and ≥60 years. RESULTS Abstinence rates (±SD) in the younger group were respectively 57.1%(±1.9), 46.8%(±2.1) and 43.5%(±2.7) at 2, 6 and 12 months of follow-up. Rates for the ≥60 year group were respectively 67.4%(±4.3), 52.3%(±5.4) and 53.3%(±5.4; log rank test, P = 0.073). The difference was also not statistically significant using Cox regression (adjusted HR 0.90, 95%CI 0.66-1.22, P = 0.48). CONCLUSIONS In this real-world setting, treatment for smoking cessation led to similar abstinence rates in older and younger smokers. These results may have implications for clinical practice and smoking cessation policies for low- and middle-income countries such as Brazil.

Purpose: To compare citrate-coated very small superparamagnetic iron oxide particles (VSOP) with gadofosveset trisodium as blood pool contrast agents for cardiac magnetic resonance angiography (CMRA) in pigs. Materials and Methods: Animal experiments were approved by the responsible authority. 10 CMRA-like examinations were performed at 1.5 T after administration of VSOP (0.06 mmol Fe/kg; 5 examinations) and gadofosveset trisodium (0.03 mmol Gd/kg; 5 examinations). The CMRA protocol included ECG-gated inversion-recovery-prepared T1-weighted gradient echo imaging (IR-GRE; one slice) and ECG-gated inversion recovery prepared steady state free precession imaging (IR SSFP; one slice) before and 1, 3, 5, 10, 15, 20, 25, 30, 40, 50, and 60 min after injection. At each time point, three different inversion times (TI; 200 msec, 300 msec, and 400 msec) were applied. Contrast-to-noise ratios (CNR) between blood and myocardium were calculated and compared using mixed linear models. Results: No significant differences of CNR were found between IR-GRE and IR SSFP. At 3 and 5 min after contrast agent administration, VSOP showed a significantly higher CNR than gadofosveset trisodium when TI of 200 msec and 300 msec were applied (TI of 200 msec at 3 min: 8.2 ± 0.7 vs. 5.4 ± 0.7; TI of 200 msec at 5 min: 7.9 ± 0.7 vs. 3.5 ± 0.8; TI of 300 msec at 3 min: 11.7 ± 0.7 vs. 8.8 ± 0.8; TI of 300 msec at 5 min: 11.4 ± 0.7 vs. 8.0 ± 0.8; p < 0.05). Moreover, significant differences in favor of VSOP were found for all time points from 10 to 40 min irrespective of TI (p < 0.05). Conclusion: VSOP has superior blood-pool properties compared to gadofosveset trisodium resulting in prolonged improvement of CNR on CMRA.