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Immunohistochemical expression of cyclooxygenase isoenzymes and downstream enzymes in human lung tumors. 总被引:14,自引:0,他引:14
PURPOSE:Prostanoids are important mediators of pulmonary vaso- and bronchotone regulation and strongly influence inflammatory reactivity. The product of cyclooxygenase (Cox), prostaglandin H(2), is further metabolized via downstream enzymes into the different effective metabolites. The specific cellular equipment with certain downstream enzymes crucially determines the cellular reactivity by generation of functionally different prostanoid metabolites. EXPERIMENTAL DESIGN: To elucidate the role of arachidonic acid metabolism via the cyclooxygenase pathway in different human lung tumors, expression of cyclooxygenase isoenzymes (Cox-1 and Cox-2) and downstream enzymes of prostanoid metabolism was investigated in human non-small cell lung cancer and normal human lung tissue by immunohistochemical techniques. RESULTS: In comparison to strong Cox-1 reactivity in airways and endothelial cells of normal lung specimens, only 4 of 15 adenocarcinomas showed infrequent Cox-1 expression. All lung cancer specimens displayed an increased Cox-2 immunostaining pattern with strong reactivity in adenocarcinomas and lower reactivity in squamous cell carcinomas. Adenocarcinomas and squamous cell carcinomas were also positive for thromboxane A(2) synthase, prostaglandin D(2) synthase, and prostaglandin E(2) synthase, but not for prostacyclin synthase. Endothelial cells of vessels found within or near the tumor show extensive immunostaining of Cox-2 and thromboxane A(2) synthase, whereas endothelial cells of normal lung specimens, in contrast, expressed Cox-1 and prostacyclin synthase. CONCLUSIONS: We conclude that non-small cell lung cancer shows a specific Cox-/downstream-enzyme expression pattern, which is specifically altered in lung tumor cells and tumor supplying vessels in contrast to normal lung tissue. This may have major impact on tumor progression and tumor-associated inflammation via an altered prostanoid metabolism with consecutive tumor-associated blood flow distribution. 相似文献
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Wolfgang Schuette Sylke Nagel Thomas Blankenburg Christine Lautenschlaeger Klaus Hans Ernst-Wilhelm Schmidt Ina Dittrich Hans Schweisfurth Ludwig Fischer von Weikersthal Aruna Raghavachar Angelika Reissig Monika Serke 《Journal of clinical oncology》2005,23(33):8389-8395
PURPOSE: A phase III study to determine whether a weekly docetaxel schedule improves the therapeutic index compared with the classic 3-weekly schedule. PATIENTS AND METHODS: Patients with stage IIIB-IV non-small-cell lung cancer (NSCLC) were randomly assigned to docetaxel 75 mg/m2 on day 1 every 3 weeks (3-weekly) and 35 mg/m2 on days 1, 8, and 15 (weekly) for < or = eight cycles. End points included survival (primary), toxicity, and response. RESULTS: Of 215 patients enrolled, 208 (103 in the 3-weekly arm and 105 in the weekly arm) were assessable for response. At baseline, 24.5% of patients (51 out of 208) had received prior paclitaxel therapy and 43.3% of patients (90 out of 208) had been progression-free for more than 3 months after first-line therapy. After 12 months' follow-up, median survival was 6.3 months (95% CI, 4.68 to 7.84 months) with 3-weekly docetaxel and 9.2 months (95% CI, 5.83 to 12.59 months) with weekly docetaxel (P = .07) after a median of four (range, one to eight) and two (range, one to eight) treatment cycles, respectively. Overall, response rates were 12.6% v 10.5% with 3-weekly versus weekly docetaxel. Significantly fewer patients reported grade 3 to 4 toxicities with weekly docetaxel versus 3-weekly docetaxel (P < or = .05). There were significantly lower rates of grade 3 to 4 anemia (P < or = .05), leucopenia (P < .0001), and neutropenia (P < or = .001) with weekly versus 3-weekly treatment. No grade 3 to 4 thrombocytopenia or mucositis was reported. CONCLUSION: Weekly docetaxel 35 mg/m2 demonstrated similar efficacy and better tolerability than standard 3-weekly docetaxel 75 mg/m2 and can be recommended as a feasible alternative second-line treatment option for patients with advanced NSCLC. 相似文献
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Coeliac trunk (CT) is a ventral branch of abdominal aorta (AA) supplying the foregut through its three main branches, left gastric (LGA), common hepatic (CHA) and splenic artery (Standring et al., 2009). Branching pattern of CT may vary from above mentioned classical three to four, five or six. Additional branches include inferior phrenic artery, dorsal pancreatic artery, middle colic or accessory middle colic artery (Hamilton and Mossman, 1972; Amonoo‐Kuofi et al., 1995). Anastmosis between CT and Superior mesenteric artery (SMA) which supplies the midgut derivatives in the form of Bühler's arcade (1‐2%) is present posterior to the body of pancreas (Douard et al., 2006; McNulty et al., 2001). Anastomoses between SMA and Inferior mesenteric artery (IMA) which supplies hindgut derivatives are also documented (Lange et al, 2007; Van Damme and Bonte, 1990). Until recently no communications between arteries of foregut and hindgut were reported (Manoharan et al., 2010; Patel et al., 2010; Stimec et al., 2011). We report the first cadaveric finding demonstrating a direct communication between the stems of CT and left colic artery (LCA) via a fourth anomalous CT branch in the absence of any co‐existing stenosis or aneurysm in the main vessels. Clin. Anat. 26:984–986, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
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In the last 10 years, we have witnessed an extensive development of instrumental techniques in analytical methods for determination of various molecules and ions at very low concentrations. Nevertheless, the presence of interfering components of complex samples hampered the applicability of new analytical strategies. Thus, additional sample pre-treatment steps were proposed to overcome the problem. Solid sorbents were used for clean-up samples but insufficient selectivity of commercial materials limited their utility. Here, the application of molecularly imprinted polymers (MIPs) or ion-imprinted polymers (IIPs) in the separation processes have recently attracted attention due to their many advantages, such as high selectivity, robustness, and low costs of the fabrication process. Bulk or monoliths, microspheres and core-shell materials, magnetically susceptible and stir-bar imprinted materials are applicable to different modes of solid-phase extraction to determine target analytes and ions in a very complex environment such as blood, urine, soil, or food. The capability to perform a specific separation of enantiomers is a substantial advantage in clinical analysis. The ion-imprinted sorbents gained interest in trace analysis of pollutants in environmental samples. In this review, the current synthetic approaches for the preparation of MIPs and IIPs are comprehensively discussed together with a detailed characterization of respective materials. Furthermore, the use of sorbents in environmental, food, and biomedical analyses will be emphasized to point out current limits and highlight the future prospects for further development in the field. 相似文献
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CA Thompson T Waldhör ES Schernhammer M Hackl C Vutuc G Haidinger 《Wiener klinische Wochenschrift》2012,124(15-16):493-499
BACKGROUND: Despite a recent decline in smoking behavior in many European countries, lung cancer rates remain high, especially in Central and Eastern Europe. This paper aims to describe trends in smoking behavior and lung cancer incidence and mortality, including histopathological classification of lung cancer, in a Central European country: Austria. METHODS: Using data from the Austrian Central Cancer Registry, we calculated age-standardized incidence, histopathology-specific incidence, and age-standardized and birth cohort-specific mortality rates for all lung cancer cases in Austria. Using national survey data, we estimated prevalence of smoking in the Austrian population. Our analysis covers the time period from 1970 to 2009. RESULTS: In 2009, lung cancer incidence rates were 41.3/100,000 and 18.5/100,000 and mortality rates were 36.3/100,000 and14.5/100,000, for males and females, respectively. Male lung cancer rates declined but increased steadily in females over the past three decades. In 2009, the most common histological type is adenocarcinoma, which reflects a shift from predominantly squamous cell carcinoma and large cell carcinoma in the mid 1980s. In 2009, 27?% of men and 19?% of women were smokers, which represent a rise of smoking rates in women, especially in younger women, and a decline in the men. CONCLUSIONS: While in Austrian men the lung cancer rates, in accordance with their decreasing prevalence of smoking, declined over the past 30 years, the increasing smoking prevalence and lung cancer rates in women remain a public health concern. Antismoking laws and public health initiatives to curtail smoking habits are needed in Austria, especially targeting younger women. 相似文献