Reversible Oxidative Addition at Carbon Eichhorn, Antonius F.; Fuchs, Sonja; Flock, Marco ...
Angewandte Chemie International Edition,
August 14, 2017, Letnik:
56, Številka:
34
Journal Article
Recenzirano
The reactivity of N‐heterocyclic carbenes (NHCs) and cyclic alkyl amino carbenes (cAACs) with arylboronate esters is reported. The reaction with NHCs leads to the reversible formation of thermally ...stable Lewis acid/base adducts Ar‐B(OR)2⋅NHC (Add1–Add6). Addition of cAACMe to the catecholboronate esters 4‐R‐C6H4‐Bcat (R=Me, OMe) also afforded the adducts 4‐R‐C6H4Bcat⋅cAACMe (Add7, R=Me and Add8, R=OMe), which react further at room temperature to give the cAACMe ring‐expanded products RER1 and RER2. The boronate esters Ar‐B(OR)2 of pinacol, neopentylglycol, and ethyleneglycol react with cAAC at RT via reversible B−C oxidative addition to the carbene carbon atom to afford cAACMe(B{OR}2)(Ar) (BCA1–BCA6). NMR studies of cAACMe(Bneop)(4‐Me‐C6H4) (BCA4) demonstrate the reversible nature of this oxidative addition process.
Is carbon the better metal? Just like the isolobal complex fragments C2v‐d8‐ML4 or C2v‐d10‐ML2, the carbene cAACMe reacts with selected aryl boronate esters through reversible oxidative addition at room temperature. This reversible, metal‐free B−C bond activation at a carbon center might lead to the development of novel carbon atom based catalysts.
•LCNEC is rare and associated with poor prognosis.•The prognostic implication of the PD1/PD-L1 pathway in LCNEC is unknown.•PD-L1 expression on LCNEC was connected with poorer outcome.•PD-L1 ...exclusively in the tumor microenvironment was associated with better survival.
Large cell neuroendocrine carcinoma of the lung (LCNEC) is associated with an unfavorable prognosis and only few patients are eligible for surgery. In most patients, chemotherapy is recommended alone or in addition to resection. Novel immunotherapies blocking the PD-L1 pathway have been introduced into therapeutic regimens for NSCLC with great success. In order to evaluate a possible efficacy of an anti-PD-L1 therapy, we analyzed the frequency of PD-L1 expression in LCNEC.
We retrospectively reviewed data from 76 patients with LCNEC treated in our institution between 1998 and 2010. The expression of PD-L1 was examined on the tumor cells and the tumor surrounding tissue by immunohistochemistry. An expression of >1% was considered as positive. Statistical analysis was performed to determine significant predictors for survival.
56 of 76 patients with LCNEC were treated with a potentially therapeutic surgical approach. Tumor-specific survival (TSS) of the entire cohort was 29% at five years. 17 patients (22.3%) had PD-L1 positive tumors and 12 of these had no additional PD-L1 expression in the adjacent immune cell infiltrate. Tumor-flanking immune cells were found PD-L1 positive 28 patients; 16 of these had no additional expression on the tumor cells. The most considerable difference in survival was found when comparing patients with isolated PD-L1 expression on tumor cells and PD-L1 negative immune cell infiltrate to their counterpart (positive immune-cell infiltrate and PD-L1 negative tumor cell surface; 5-year TSS: 0% vs. 60%; p < 0.017).
PD-L1 expression in LCNEC was associated with poorer survival whereas PD-L1 expression in the tumor microenvironment seemed to have a beneficial effect. Therapeutic approaches have to be evaluated in future.
•Nodal positive (N1) NSCLC population can be split towards different prognostic subgroups.•Increased nodal burden (pN1b, multiple zone involvement) is associated with significant worsening survival ...in adenocarcinoma.•Future TNM-classifications should consider nodal count and histology as prognostic factors in N1 NSCLC.
Lymph node (LN) metastases predict survival in patients with non-small cell lung cancer (NSCLC) treated with curative surgery. Nevertheless, prognostic differences within the same nodal (N) status have been reported. Consequently, the International Association for the Study of Lung Cancer (IASLC) proposed to stratify patients with limited nodal disease (pN1) from low (pN1a) to high (pN1b) nodal tumor burden. This study aimed to validate the IASLC proposal in a large single-center surgical cohort of patients with pN1 NSCLC.
Data from 317 patients with pN1 NSCLC treated between January 2012 and December 2016, were retrospectively analyzed. Associations between distribution of LN metastases and survival were analyzed for different classification models—toward nodal extension (pN1a: one station involved; pN1b: multiple stations involved) and toward location (pN1 in the hilar LN#10/11 or peripheral zone LN#12-14).
Tumor-specific survival (TSS) in the entire pN1 cohort was 67.1% at five years. Five-year TSS rates for pN1a and pN1b patients were comparable (67.6% vs. 66.5%, p = 0.623). Significant survival differences from pN1a to pN1b were observed only in patients with adenocarcinoma histology and completed adjuvant chemotherapy (5-year TSS: pN1a, 80.4% vs. pN1b, 49.6%; p = 0.005). TSS for LN metastases in the hilar zone/peripheral zone or in both zones was 68.2% and 59.9%, respectively (p = 0.068). In multivariate analysis, adjuvant chemotherapy, squamous cell histology, and nodal disease limited to one zone nodal disease were identified as independent beneficial prognostic factors (p < 0.05).
pN1 in only one region (hilar or lobar) was associated with better outcome than metastatic affection of both regions after surgery and adjuvant therapy. A stratification towards single (pN1a) and multiple (pN1b) N1-metastases was found of prognostic relevance only in adenocarcinoma. Prospective multicenter analysis of prognostic subgroups in N1 NSCLC is required to evaluate its clinical impact for consideration in future TNM classification.
Zusammenfassung
Definition
Intrapulmonale Rundherde stellen in der Regel einen Zufallsbefund im Röntgenbild oder Computertomogramm des Thorax dar. Sie sind definiert als relativ gut abgegrenzte ...Läsionen von bis zu 3 cm Durchmesser, die allseits von Lungengewebe umgeben sind. Die Wahrscheinlichkeit für das Vorliegen eines malignen Tumors steigt mit ihrer Größe. Rundherde ab 1 cm Durchmesser bedürfen der aktiven Abklärung.
Therapie
Zur Behandlung solitärer maligner Tumoren steht für Patienten ohne nennenswert erhöhtes Operations- und Narkoserisiko der chirurgische Eingriff an erster Stelle. Patienten, die aus funktionellen Gründen für einen solchen nicht geeignet sind, können mit Radiofrequenzablation (RFA) oder Einzeitbestrahlung (SBRT) behandelt werden. In diesen Fällen müssen vor Therapiebeginn die Malignität nachgewiesen oder zumindest über einen begrenzten Zeitraum eine Größenzunahme der Läsion dokumentiert worden sein.
Outcome
In Bezug auf die lokale Tumorfreiheit ist die Operation unter den Voraussetzungen einer R0-Resektion den anderen Verfahren überlegen.
Therapeutic options for patients with castration-resistant prostate cancer (CRPC) remain limited. In a multicenter, Phase II study, 65 patients with histologically confirmed CRPC received a ...biomodulatory regimen during the six-month core study. Treatment comprised daily doses of imatinib mesylate, pioglitazone, etoricoxib, treosulfan and dexamethasone. The primary endpoint was prostate-specific antigen (PSA) response. Responders could enter an extension phase until disease progression or intolerable toxicity occurred. Mean PSA was 45.3 ng/mL at baseline, and 77 % of patients had a PSA doubling time <3 months. Of the 61 evaluable patients, 37 patients (60.6 %) responded or had stable disease and 23 of them (37.7 % of 61 patients) were PSA responders. Among the 23 responders mean PSA decreased from 278.9 ± 784.1 ng/mL at baseline to 8.8 ± 11.6 ng/mL at the final visit (week 24). The progression-free survival (PFS) was 467 days in the ITT population. Of the 947 adverse events, 57.6 % were suspected to be drug-related, 13.8 % led to dose adjustment or permanent discontinuation and 40.2 % required concomitant medication. This novel combination approach led to an impressive PSA response rate of 37.7 % in CRPC patients. The good PSA response and PFS rate combined with the manageable toxicity profile suggest an alternative treatment option.
The paper describes the Rossendorf beamline (ROBL) built by the Forschungszentrum Rossendorf at the ESRF. ROBL comprises two different and independently operating experimental stations: a ...radiochemistry laboratory for X‐ray absorption spectroscopy of non‐sealed radioactive samples and a general purpose materials research station for X‐ray diffraction and reflectometry mainly of thin films and interfaces modified by ion beam techniques.
Structural and magnetic properties of Tb implanted ZnO single crystals Zhou, Shengqiang; Potzger, K.; Mücklich, A. ...
Nuclear instruments & methods in physics research. Section B, Beam interactions with materials and atoms,
February 2008, 2008-02-00, 20080201, Letnik:
266, Številka:
4
Journal Article
Recenzirano
ZnO single crystals have been implanted with Tb ions. For an atomic concentration of 1.5%, annealing at 823K leads to an increase of the saturation magnetization per implanted Tb ion up to 1.8μB at ...room temperature. Structural investigations revealed no secondary phase formation, but the out-diffusion of Tb. No significant evidence is found for Tb substituting Zn sites either in the as-implanted or annealed samples. However, indications for the existence of a small amount of Tb nanoclusters however have been found using magnetization versus temperature measurements. The ferromagnetic properties disappear completely upon annealing at 1023K. This behavior is related to the formation of oxide complexes or nanoparticles.
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