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991.
Mihajlo Djokic Maja Cemazar Peter Popovic Bor Kos Rok Dezman Masa Bosnjak Martina Niksic Zakelj Damijan Miklavcic Stojan Potrc Borut Stabuc Ales Tomazic Gregor Sersa Blaz Trotovsek 《European journal of surgical oncology》2018,44(5):651-657
Background and objectives
Electrochemotherapy provides non-thermal ablation of cutaneous as well as deep seated tumors. Based on positive results of the treatment of colorectal liver metastases, we conducted a prospective pilot study on hepatocellular carcinomas with the aim of testing the feasibility, safety and effectiveness of electrochemotherapy.Patients and methods
Electrochemotherapy with bleomycin was performed on 17 hepatocellular carcinomas in 10 patients using a previously established protocol. The procedure was performed during open surgery and the patients were followed for median 20.5 months.Results
Electrochemotherapy was feasible for all 17 lesions, and no treatment-related adverse events or major post-operative complications were observed. The median size of the treated lesions was 24 mm (range 8–41 mm), located either centrally, i.e., near the major hepatic vessels, or peripherally. The complete response rate at 3–6 months was 80% per patient and 88% per treated lesion.Conclusions
Electrochemotherapy of hepatocellular carcinoma proved to be a feasible and safe treatment in all 10 patients included in this study. To evaluate the effectiveness of this method, longer observation period is needed; however the results at medium observation time of 20.5 months after treatment are encouraging, in 15 out of 17 lesions complete response was obtained. Electrochemotherapy is predominantly applicable in patients with impaired liver function due to liver cirrhosis and/or with lesions where a high-risk operation is needed to achieve curative intent, given the intra/perioperative risk for high morbidity and mortality. 相似文献992.
Marcel Wiesweg Henning Reis Tobias Köster Moritz Goetz Karl Worm Thomas Herold Andreas Paul Alexander Dechêne Brigitte Schumacher Peter Markus Isabel Virchow Karina Kostbade Nathalie Wolf Gregor Zaun Martin Metzenmacher Kurt W. Schmid Martin Schuler Stefan Kasper 《Clinical colorectal cancer》2018,17(2):e331-e352
Background
Deregulation of signal transduction pathways plays a critical role in oncogenesis of colorectal cancer (CRC) and directly affects sensitivity to targeted therapies. Against this background we developed a comprehensive biomarker profiling program including markers of downstream signaling to study their association with clinical outcomes.Patients and Methods
A prospectively studied cohort of 160 patients with metastatic CRC was included. Standard diagnostic workup included mutational analyses of Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), and v-Raf murine sarcoma viral oncogene homolog B (BRAF). In addition, markers of mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and mammalian target of rapamycin pathway activation (phosphorylation of extracellular signal-regulated kinase [ERK], AKT, and p70 ribosomal protein S6 kinase β-1 [p70S6K]) were studied using standardized immunohistochemistry.Results
There was a significant correlation between markers of ERK and AKT activation in the full cohort. In addition, phosphorylation of p70S6K correlated strongly with ERK and AKT phosphorylation and primary tumor localization in the right colon. Subgroup analyses specified these correlations to patients with all-RAS wild type tumors. In contrast, tumors harboring RAS mutations predominantly exhibited ERK phosphorylation. Interestingly, patients with CRC showing high p70S6K phosphorylation (highest quartile) had a significantly inferior overall survival (hazard ratio [HR], 2.4; P = .002) irrespective of RAS mutational status. This effect remained significant in multivariate analysis (P = .002). A patient subgroup characterized by high p70S6K phosphorylation and right-sided primary tumors had a particularly poor prognosis with a dramatically inferior overall survival (HR, 5.2; P < .001). Patients with right-sided primary tumor and low p70S6K phosphorylation had responses to anti-epidermal growth factor receptor antibody-based therapies and overall survival similar to patients with left-sided primary tumors.Conclusion
High phosphorylation of p70S6K is a novel, independent biomarker for poor prognosis, in particular in patients with right-sided primary tumors. 相似文献993.
Markus Hecker Andree Blaukat Agnieszka T Bara Werner Müller-Esterl Rudi Busse 《British journal of pharmacology》1997,121(7):1475-1481
- Angiotensin-converting enzyme (ACE) inhibitors exert their cardiovascular effects not only by preventing the formation of angiotensin II (AII), but also by promoting the accumulation of bradykinin in or at the vessel wall. In addition, certain ACE inhibitors have been shown to augment the vasodilator response to bradykinin, presumably by an interaction at the level of the B2 receptor. We have investigated whether this is a specific effect of the ACE inhibitor class of compounds in isolated endothelium-denuded segments of the rabbit jugular vein where bradykinin elicits a constrictor response which is exclusively mediated by activation of the B2 receptor.
- Moexiprilat and ramiprilat (⩽ 3 nM) enhanced the constrictor response to bradykinin three to four fold. Captopril and enalaprilat were less active by approximately one and quinaprilat by two orders of magnitude. Moexiprilat and ramiprilat, on the other hand, had no effect on the constrictor response to AII or the dilator response to acetylcholine.
- The bradykinin-potentiating effect of the ACE inhibitors was not mimicked by inhibitors of amino-, carboxy-, metallo- or serine peptidases or the synthetic ACE substrate, hippuryl-L-histidyl-L-leucine, at a concentration which almost abolished the residual ACE activity in the vessel wall. In contrast, angiotensin-(1–7) (10 μM), an angiotensin I metabolite, significantly enhanced the constrictor response to bradykinin.
- Ramiprilat did not alter the binding of [3H]-bradykinin to a membrane fraction prepared from endothelium-denuded rabbit jugular veins or to cultured fibroblasts, and there was no ACE inhibitor-sensitive, bradykinin-induced cleavage of the B2 receptor in cultured endothelial cells.
- These findings demonstrate that ACE inhibitors selectively potentiate the B2 receptor-mediated vascular effects of bradykinin. Their relative efficacy appears to be independent of their ACE-inhibiting properties and might be related to differences in molecule structure. Moreover, the potentiation of the biological activity of bradykinin by this class of compounds does not seem to be mediated by a shift in affinity of the B2 receptor or a prevention of its desensitization, but may involve an increase in the intrinsic activity of unoccupied B2 receptor molecules.
994.
Alexander Wahba MD Gregor Rothe MD Heiko Lodes Stefan Barlage MD Gerd Schmitz MD Dietrich E. Birnbaum MD 《Journal of cardiothoracic and vascular anesthesia》1997,11(7):824-827
To assess the predictive value of variables possibly associated with blood loss after coronary artery bypass grafting (CABG). A prospective study. A university hospital. Eighty-nine patients scheduled for elective CABG. Blood samples were drawn before and after surgery. Chest tube drainage was measured hourly until removal of drains. Activation of coagulation and fibrinolysis, routine clotting tests, and expression of platelet surface antigens were analyzed using flow cytometry. A significant correlation was found among blood loss and activated partial thromboplastin time, fibrinogen, prothrombin fragment 1 + 2, D-dimers, platelet count, GPlb and P-selectin expression on platelets, use of internal thoracic artery, cross-clamp time, and thrombin-antithrombin III complex. In a multiple regression model, glycoprotein (GP) Ib expression on platelets, platelet count, use of internal thoracic artery, and D-dimers were significantly associated with blood loss. Logistic regression analysis showed that GPIb and D-dimers predicted an increased blood loss with a positive predictive value of 73% and a negative predictive value of 91%. Postoperative D-dimers and GPIb expression may be useful to exclude nonsurgical causes in bleeding patients after CABG. 相似文献
995.
996.
Effect of the histone deacetylase inhibitor resminostat on head and neck squamous cell carcinoma cell lines
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997.
Nicola Fossati R. Jeffrey Karnes Stephen A. Boorjian Marco Moschini Alessandro Morlacco Alberto Bossi Thomas Seisen Cesare Cozzarini Claudio Fiorino Barbara Noris Chiorda Giorgio Gandaglia Paolo Dell’Oglio Steven Joniau Lorenzo Tosco Shahrokh Shariat Gregor Goldner Wolfgang Hinkelbein Detlef Bartkowiak Alberto Briganti 《European urology》2017,71(6):886-893
Background
Three prospective randomised trials reported discordant findings regarding the impact of adjuvant radiation therapy (aRT) versus observation for metastasis-free survival (MFS) and overall survival (OS) among patients with pT3N0 prostate cancer treated with radical prostatectomy (RP). None of these trials systematically included patients who underwent early salvage radiation therapy (esRT).Objective
To test the hypothesis that aRT was associated with better cancer control and survival compared with observation followed by esRT.Design, setting, and participants
Using a multi-institutional cohort from seven tertiary referral centres, we retrospectively identified 510 pT3pN0 patients with undetectable prostate-specific antigen (PSA) after RP between 1996 and 2009. Patients were stratified into two groups: aRT (group 1) versus observation followed by esRT in case of PSA relapse (group 2). Specifically, esRT was administered at a PSA level ≤0.5 ng/ml.Intervention
We compared aRT versus observation followed by esRT.Outcome measurements and statistical analysis
The evaluated outcomes were MFS and OS. Multivariable Cox regression analyses tested the association between groups (aRT vs observation followed by esRT) and oncologic outcomes. Covariates consisted of pathologic stage (pT3a vs pT3b or higher), pathologic Gleason score (≤6, 7, or ≥8), surgical margin status (negative vs positive), and year of surgery. An interaction with groups and baseline patient risk was tested for the hypothesis that the impact of aRT versus observation followed by esRT was different by pathologic characteristics. The nonparametric curve fitting method was used to explore graphically the relationship between MFS and OS at 8 yr and baseline patient risk (derived from the multivariable analysis).Results and limitations
Overall, 243 patients (48%) underwent aRT, and 267 (52%) underwent initial observation. Within the latter group, 141 patients experienced PSA relapse and received esRT. Median follow-up after RP was 94 mo (interquartile range [IQR]: 53–126) and 92 mo (IQR: 70–136), respectively (p = 0.2). MFS (92% vs 91%; p = 0.9) and OS (89% vs 92%; p = 0.9) at 8 yr after surgery were not significantly different between the two groups. These results were confirmed in multivariable analysis, in which observation followed by esRT was not associated with a significantly higher risk of distant metastasis (hazard ratio [HR]: 1.35; p = 0.4) and overall mortality (HR: 1.39; p = 0.4) compared with aRT. Using the nonparametric curve fitting method, a comparable proportion of MFS and OS at 8 yr among groups was observed regardless of pathologic cancer features (p = 0.9 and p = 0.7, respectively). Limitations consisted of the retrospective nature of the study and the relatively small size of the patient population.Conclusions
At long-term follow-up, no significant differences between aRT and esRT were observed for MFS and OS. Our study, although based on retrospective data, suggests that esRT does not compromise cancer control and potentially reduces overtreatment associated with aRT.Patient summary
At long-term follow-up, no significant differences in terms of distant metastasis and mortality were observed between immediate postoperative adjuvant radiation therapy (aRT) and initial observation followed by early salvage radiation therapy (esRT) in case of prostate-specific antigen relapse. Our study suggests that esRT does not compromise cancer control and potentially reduces overtreatment associated with aRT. 相似文献998.
Roukens Robin Lauster Frank Bara Maria Eifert Bernd Willemsen Dietrich Randall Thomas Herzog Jürgen Wendt Constanze Schmidt-Wilcke Tobias Knecht Stefan 《Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz》2017,60(10):1075-1082
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Die Zahl von Patienten mit multiresistenten Erregern (MRE) in Rehabilitationseinrichtungen nimmt zu. Der dadurch steigende... 相似文献
999.
1000.