Tenzidek önrendeződése fémfelületeken és hordozókon = Self-organization of surfactants on metal particles and supports

Adszorpciós mikrokalorimetriával jellemeztük tenzidek adszorpcióját (az adszorpciós réteg komplex szerkezetét) nemesfém nanorészecskéken, hidrofil és hidrofób katalizátor hordozókon. Új típusú kolloidkémiai módszereket dolgoztunk ki tenzidekkel stabilizált, méret- és morfológia-kontrollált nemesfém nanorészecskék előállítására réteges szerkezetű hordozók (montmorillonit; hidrotalcit) interlamelláris terében. A katalizátorokat szerkezetérzékeny vizsgálati módszerekkell jellemeztük (XRD, TEM, HR-TEM, IR-Raman és UV-vis spektroszkópia, titrációs- és áramlásos mikrokalorimetria). Az anyagok aktív és szelektív heterogén katalizátoroknak bizonyultak folyadékfázisú hidrogénezési reakciókban; alkinek alkénekké történő átalakításában. Hidrogénszorpciós méréseink szerint a Pd/H béta-hidrid képződés nem befolyásolja e reakciók kötésszelektivitását. Adszorpciós-folyadékkromatográfiás eljárást dolgoztunk ki hordozós átmenetifém katalizátorok diszperzitásának meghatározására. A tenzidek önrendeződésén alapuló ''in-situ'' módszert fejlesztettünk ki átmenetifém és átmenetifém ötvözet nanorészecskék előállítására MCM-41 hordozók mezopórusaiban. A katalizátorok nagy aktivitást és szelektivitást mutattak alkinek alkénekké történő hidrogénezési reakcióiban. | Measurements of the adsorption of surfactants on noble metal nanoparticles and hydrophilic and hydrophobic support materials have been performed by adsorption microcalorimetry. Surfactant-stabilized, size- and morphology-controlled noble metal nanoparticles have been synthesized and deposited in the interlamellar space of layer-structured materials (montmorillonite; hydrotalcite) by novel colloid chemical methods. The heterogeneous catalysts have been characterized by structure-sensitive instrumental methods (XRD, TEM, HR-TEM, IR-Raman and UV-vis spectroscopy, titration- and flow-microcalorimetry). These catalysts proved to be active and selective in the liquid-phase hydrogenations of alkynes to alkenes. Hydrogen sorption measurements indicated that bond-selectivity is not affected by Pd/H beta-hydride formation. A novel adsorption-liquid chromatographic method has been developed for the determination of the dispersion of supported noble metal catalysts. The self-organization of surfactants has been utilized for the ''in-situ'' generation of noble metal and alloyed noble metal nanoparticles in MCM-41 host matrices. These materials proved to be active and selective in the liquid-phase hydrogenations of aklynes to alkenes

Spreading depolarization causes reperfusion failure after cerebral ischemia

Despite successful recanalization, reperfusion failure associated with poor neurological outcomes develops in half of treated stroke patients. We explore here whether spreading depolarization (SD) is a predictor of reperfusion failure. Global forebrain ischemia/reperfusion was induced in male and female C57BL/6 mice (n = 57). SD and cerebral blood flow (CBF) changes were visualized with transcranial intrinsic optical signal and laser speckle contrast imaging. To block SD, MK801 was applied (n = 26). Neurological deficit, circle of Willis (CoW) anatomy and neuronal injury were evaluated 24 hours later. SD emerged after ischemia onset in one or both hemispheres under a perfusion threshold (CBF drop to 21.1 ± 4.6 vs. 33.6 ± 4.4%, SD vs. no SD). The failure of later reperfusion (44.4 ± 12.5%) was invariably linked to previous SD. In contrast, reperfusion was adequate (98.9 ± 7.4%) in hemispheres devoid of SD. Absence of the P1 segment of the posterior cerebral artery in the CoW favored SD occurrence and reperfusion failure. SD occurrence and reperfusion failure were associated with poor neurologic function, and neuronal necrosis 24 hours after ischemia. The inhibition of SD significantly improved reperfusion. SD occurrence during ischemia impairs later reperfusion, prognosticating poor neurological outcomes. The increased likelihood of SD occurrence is predicted by inadequate collaterals

Erythropoietin receptor expression is a potential prognostic factor in human lung adenocarcinoma

Recombinant human erythropoietins (rHuEPOs) are used to treat cancer-related anemia. Recent preclinical studies and clinical trials, however, have raised concerns about the potential tumor-promoting effects of these drugs. Because the clinical significance of erythropoietin receptor (EPOR) signaling in human non-small cell lung cancer (NSCLC) also remains controversial, our aim was to study whether EPO treatment modifies tumor growth and if EPOR expression has an impact on the clinical behavior of this malignancy. A total of 43 patients with stage III-IV adenocarcinoma (ADC) and complete clinicopathological data were included. EPOR expression in human ADC samples and cell lines was measured by quantitative real-time polymerase chain reaction. Effects of exogenous rHuEPOalpha were studied on human lung ADC cell lines in vitro. In vivo growth of human ADC xenografts treated with rHuEPOalpha with or without chemotherapy was also assessed. In vivo tumor and endothelial cell (EC) proliferation was determined by 5-bromo-2'-deoxy-uridine (BrdU) incorporation and immunofluorescent labeling. Although EPOR mRNA was expressed in all of the three investigated ADC cell lines, rHuEPOalpha treatment (either alone or in combination with gemcitabine) did not alter ADC cell proliferation in vitro. However, rHuEPOalpha significantly decreased tumor cell proliferation and growth of human H1975 lung ADC xenografts. At the same time, rHuEPOalpha treatment of H1975 tumors resulted in accelerated tumor endothelial cell proliferation. Moreover, in patients with advanced stage lung ADC, high intratumoral EPOR mRNA levels were associated with significantly increased overall survival. This study reveals high EPOR level as a potential novel positive prognostic marker in human lung ADC

Apelin promotes lymphangiogenesis and lymph node metastasis

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Apelin promotes lymphangiogenesis and lymph node metastasis

Whereas the role of the G-protein-coupled APJ receptor and its ligand, apelin, in angiogenesis has been well documented, the ability of the apelin/APJ system to induce lymphangiogenesis and lymphatic metastasis has been largely unexplored. To this end, we first show that APJ is expressed in lymphatic endothelial cells (LECs) and, moreover, that it responds to apelin by activating the apelinergic signaling cascade. We find that although apelin treatment does not influence the proliferation of LECs in vitro, it enhances their migration, protects them against UV irradiation-induced apoptosis, increases their spheroid numbers in 3D culture, stimulates their in vitro capillary-like tube formation and, furthermore, promotes the invasive growth of lymphatic microvessels in vivo in the matrigel plug assay. We also demonstrate that apelin overexpression in malignant cells is associated with accelerated in vivo tumor growth and with increased intratumoral lymphangiogenesis and lymph node metastasis. These results indicate that apelin induces lymphangiogenesis and, accordingly, plays an important role in lymphatic tumor progression. Our study does not only reveal apelin as a novel lymphangiogenic factor but might also open the door for the development of novel anticancer therapies targeting lymphangiogenesis

Circulating complement component 4d (C4d) correlates with tumor volume, chemotherapeutic response and survival in patients with malignant pleural mesothelioma

Only limited information is available on the role of complement activation in malignant pleural mesothelioma (MPM). Thus, we investigated the circulating and tissue levels of the complement component 4d (C4d) in MPM. Plasma samples from 55 MPM patients, 21 healthy volunteers (HV) and 14 patients with non-malignant pleural diseases (NMPD) were measured by ELISA for C4d levels. Tissue specimens from 32 patients were analyzed by C4d immunohistochemistry. Tumor volumetry was measured in 20 patients. We found no C4d labeling on tumor cells, but on ectopic lymphoid structures within the tumor stroma. Plasma C4d levels did not significantly differ between MPM, HV or NMPD. Late-stage MPM patients had higher plasma C4d levels compared to early-stage (p = 0.079). High circulating C4d was associated with a higher tumor volume (p = 0.047). Plasma C4d levels following induction chemotherapy were significantly higher in patients with stable/progressive disease compared to those with partial/major response (p = 0.005). Strikingly, patients with low C4d levels at diagnosis had a significantly better overall survival, confirmed in a multivariate cox regression model (hazard ratio 0.263, p = 0.01). Our findings suggest that circulating plasma C4d is a promising new prognostic biomarker in patients with MPM and, moreover, helps to select patients for surgery following induction chemotherapy

Ki67 index is an independent prognostic factor in epithelioid but not in non-epithelioid malignant pleural mesothelioma: a multicenter study

BACKGROUND: Estimating the prognosis in malignant pleural mesothelioma (MPM) remains challenging. Thus, the prognostic relevance of Ki67 was studied in MPM. METHODS: Ki67 index was determined in a test cohort of 187 cases from three centres. The percentage of Ki67-positive tumour cells was correlated with clinical variables and overall survival (OS). The prognostic power of Ki67 index was compared with other prognostic factors and re-evaluated in an independent cohort (n=98). RESULTS: Patients with Ki67 higher than median (>15%) had significantly (P<0.001) shorter median OS (7.5 months) than those with low Ki67 (19.1 months). After multivariate survival analyses, Ki67 proved to be-beside histology and treatment-an independent prognostic marker in MPM (hazard ratio (HR): 2.1, P<0.001). Interestingly, Ki67 was prognostic exclusively in epithelioid (P<0.001) but not in non-epithelioid subtype. Furthermore, Ki67 index was significantly lower in post-chemotherapy samples when compared with chemo-naive cases. The prognostic power was comparable to other recently published prognostic factors (CRP, fibrinogen, neutrophil-to-leukocyte ratio (NLR) and nuclear grading score) and was recapitulated in the validation cohort (P=0.048). CONCLUSION: This multicentre study demonstrates that Ki67 is an independent and reproducible prognostic factor in epithelioid but not in non-epithelioid MPM and suggests that induction chemotherapy decreases the proliferative capacity of MPM