Purpose: The pathologic interactions between tumor and host immune cells within the tumor microenvironment create an immunosuppressive network that promotes tumor growth and protects the tumor from immune attack. In this study, we examined the contribution of the immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) on this phenomenon. Experimental Design: Expression of IDO was analyzed in colorectal cancer cell lines by reverse transcription-PCR and functional enzyme activity was assessed by high-pressure liquid chromatography. Semiquantitative immunohistochemistry was used to evaluate IDO expression in the tissue samples of 143 patients with colorectal carcinoma, and was then correlated with the number of tumor-infiltrating T cells and clinical variables. Results: In vitro IDO expression and functional enzyme activity in colorectal cancer cells was found to be strictly dependent on IFN-g stimulation. Immunohistochemical scores revealed IDOhigh expression in 56 of143 (39.2%) tumor specimens, whereas 87 of143 (60.8%) cases showed low IDO expression levels. IDO-high expression was associated with a significant reduction of CD3+ infiltratingT cells (46.02 F 7.25) as compared with tissue samples expressing low IDO (19.42 F 2.50; P = 0.0003). Furthermore, IDO-high immunoreactivity significantly correlated with the frequency of liver metastases (P = 0.003). Kaplan-Meier analysis showed the crossing of survival curves at 45 months. By multivariate Cox's analysis, IDO-high expression emerged as an independent prognostic variable (<45 months, P = 0.006; >45 months, P = 0.04).Conclusion: IDO-high expression by colorectal tumor cells enables certain cancer subsets to initially avoid immune attack and defeat the invasion of Tcells via local tryptophan depletion and the production of proapoptotic tryptophan catabolites. Thus, IDO significantly contributes to disease progression and overall survival in patients with colorectal cancer.Colorectal cancer is the most common gastrointestinal malignancy and one of the leading causes of cancer-related deaths worldwide (1). Five-year overall survival rates range from 90% for stage I to 75% and 50% for stage II and III
Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0-2 weeks, 3-4 weeks and 5-6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3-4.8), 3.9 (2.6-5.1) and 3.6 (2.0-5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9-2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2-8.7) vs. 2.4% (95%CI 1.4-3.4) vs. 1.3% (95%CI 0.6-2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay.
Evidence for temperature-dependent electron band dispersion in a pentacene thin film polymorph on graphite is provided by angle- and energy-dependent ultraviolet photoelectron spectroscopy. The bands derived from the highest occupied molecular orbital exhibit dispersion of approximately 190 meV at room temperature, and approximately 240 meV at 120 K. Intermolecular electronic coupling in pentacene thin films is thus confirmed to be dependent on temperature and possibly crystal structure, as suggested by additional infrared absorption measurements.
Expression of IL-6 and TNFalpha mRNA is more pronounced in adipose compared to liver tissue in patients with severe obesity. Our results highlight excessive weight loss as a successful anti-inflammatory strategy.
Nanosized 2D ceria islands randomly distributed over the Pt(111) surface have been prepared by oxidation of the nucleating Ce submonolayer and characterized using XPS and STM for coverages of 0.3 and 0.7 ML. Catalytic CO oxidation over the resulting, well-defined CeO x /Pt(111) model catalytic system of the "inverse supported catalyst" type has been studied using the UHV chamber as a flow reactor. The CO 2 production rate was monitored mass spectrometrically in the temperature range of 413 to 553 K at variable CO/O 2 compositions in the 10 -5 mbar pressure range. The behavior of the present CeO x /Pt(111) system in the CO oxidation reaction is summarized in kinetic phase diagrams separating regions of high and low reactivity (both monostable) and that of bistability. A significantly enhanced reactivity and a remarkable shift of the bistable region of the reaction toward higher CO pressures were observed when compared to a clean Pt(111) surface. An "active border" concept is proposed to explain the strong local enhancement of catalytic activity.
BACKGROUND: Human adipose tissue expresses and releases proinflammatory cytokines and these measures of chronic inflammation have recently been associated with obesity. HYPOTHESIS: To test whether the proinflammatory state is reversible in subjects undergoing weight loss by surgical measures. SUBJECTS AND METHODS: Twenty morbidly obese women participated in this prospective study. Subjects were examined for fat mass, high-sensitive C-reactive protein (hs-CRP), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-a) before and 1 y after Swedish adjustable gastric banding. RESULTS: Anthropometric measures displayed a significant reduction of the body mass index (BMI) from 41.6 AE 5.4 to 30.8 AE 6.1 kg=m 2 and the fat mass from 53.9 AE 10.3 to 29.8 AE 12.1 kg (mean AE s.d.). Hs-CRP levels decreased significantly from 1.33 AE 1.21 mg=dl in pre-gastric banding subjects to 0.40 AE 0.61 mg=dl in post-gastric banding subjects, respectively. IL-6 and TNF-a levels did not differ significantly between pre-and post-gastric banding subjects. CONCLUSIONS: We speculate that in these patients the marked reduction in C-reactive protein might be beneficial in reducing their cardiovascular risk and is not solely mediated by IL-6 and TNF-a.
One-stage procedure prevents from cholangitis, cholecystitis and recurrent ileus caused by further gallstones but bears the risk of enteric or biliary leakage after fistula closure. It should therefore be reserved for patients presenting in good general condition with a low degree of cholecystitis.
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