Methylation of phenol over high-silica beta zeolite: effect of zeolite acidity and crystal size on catalyst behaviour

A systematic investigation was carried out to elucidate several aspects of the gas/solid methylation of phenol over high Si/Al ratio beta-structured zeolite in protonated form, characterised by various techniques, including XRD, SEM, BET, ICP, FTIR, TGA, microcalorimetry, and modeling by ab initio calculations. Data on the characteristics and the kinetic and mechanistic features of the catalytic reaction, as well as on catalyst deactivation, show that these zeolites, besides being very active for the present reaction, lead to cresols and anisole as primary products. As catalyst deactivation proceeds, the selectivity to cresols and anisole increases substantially, accompanied by a rapid decrease in selectivity to polyalkylated species. Medium- to low-strength silanols are the main contributors to catalyst surface acidity. High-strength Lewis acid sites either are virtually absent (especially when metal cations partially substitute for protons) or play a role essentially in catalyst deactivation. Stacking faults in the zeolite framework, generated by the intergrowth of at least two beta polymorphs, lead to an increased concentration of silanol-based Br\uf8nsted acid sites. Deactivation is due to the interaction of phenol and oxygenated products with the silanol-based acid sites and of methanol only with the strong acid sites of both Lewis and Br\uf8nsted nature. Self-oligomerisation\u2013cyclisation of methanol to olefins and aromatics, followed by further alkylation to aromatic C atoms, contributes to catalyst deactivation. At any conversion level and at any temperature, the anisole/cresol ratio is systematically lower for the larger-crystal size zeolite, because the secondary transformations of anisole to cresols by both intramolecular rearrangement and intermolecular alkylation of phenol is favoured by the longer residence time of anisole within the zeolite pores

Weekly platinum chemotherapy for recurrent ovarian cancer

British Journal of Cancer (2002) 86, 2–4. DOI: 10.1038/sj/bjc/6600062 www.bjcancer.co

Chemotherapy in advanced ovarian cancer: four systematic meta-analyses of individual patient data from 37 randomized trials. Advanced Ovarian Cancer Trialists' Group.

The purpose of this systematic study was to provide an up to date and reliable quantitative summary of the relative benefits of various types of chemotherapy (non-platinum vs platinum, single-agent vs combination and carboplatin vs cisplatin) in the treatment of advanced ovarian cancer. Also, to investigate whether well-defined patient subgroups benefit more or less from cisplatin- or carboplatin-based therapy. Meta-analyses were based on updated individual patient data from all available randomized controlled trials (published and unpublished), including 37 trials, 5667 patients and 4664 deaths. The results suggest that platinum-based chemotherapy is better than non-platinum therapy, show a trend in favour of platinum combinations over single-agent platinum, and suggest that cisplatin and carboplatin are equally effective. There is no good evidence that cisplatin is more or less effective than carboplatin in any particular subgroup of patients

Exosomal Expression of CXCR4 Targets Cardioprotective Vesicles to Myocardial Infarction and Improves Outcome after Systemic Administration.

Cell therapy has been evaluated to enhance heart function after injury. Delivered cells mostly act via paracrine mechanisms, including secreted growth factors, cytokines, and vesicles, such as exosomes (Exo). Intramyocardial injection of cardiac-resident progenitor cells (CPC)-derived Exo reduced scarring and improved cardiac function after myocardial infarction in rats. Here, we explore a clinically relevant approach to enhance the homing process to cardiomyocytes (CM), which is crucial for therapeutic efficacy upon systemic delivery of Exo. By overexpressing exosomal CXCR4, we increased the efficacy of plasmatic injection of cardioprotective Exo-CPC by increasing their bioavailability to ischemic hearts. Intravenous injection of Exo <sup>CXCR4</sup> significantly reduced infarct size and improved left ventricle ejection fraction at 4 weeks compared to Exo <sup>CTRL</sup> (p < 0.01). Hemodynamic measurements showed that Exo <sup>CXCR4</sup> improved dp/dt min, as compared to Exo <sup>CTRL</sup> and PBS group. In vitro, Exo <sup>CXCR4</sup> was more bioactive than Exo <sup>CTRL</sup> in preventing CM death. This in vitro effect was independent from SDF-1α, as shown by using AMD3100 as specific CXCR4 antagonist. We showed, for the first time, that systemic administration of Exo derived from CXCR4-overexpressing CPC improves heart function in a rat model of ischemia reperfusion injury These data represent a substantial step toward clinical application of Exo-based therapeutics in cardiovascular disease

EARLY METABOLIC RESPONSE IN FOLLICULAR LYMPHOMA: A SUBSET ANALYSIS OF THE FOLL12 TRIAL BY THE FONDAZIONE ITALIANA LINFOMI (FIL)

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The neutrophil to lymphocyte ratio (NLR) and the presence of large nodal mass are independent predictors of early response: A subanalysis of the prospective phase II PET-2-adapted HD0607 trial

Background: The neutrophil to lymphocyte ratio (NLR) and the lymphocyte to monocyte ratio (LMR) can reflect both the myeloid dysfunction and T-cell immune suppression and have prognostic significance. Methods: In 771 newly diagnosed advanced-stage Hodgkin Lymphoma (HL) patients we evaluated the baseline values of NLR and LMR as predictors of clinical outcome. According to the multicenter prospective phase II GITIL-HD0607 trial, all patients received two ABVD courses and if PET-2 negative received four additional ABVD cycles while if PET-2-positive patients were randomized to either BEACOPP escalated (Be) plus BEACOPP baseline (Bb) (4 + 4 courses) or Be + Bb (4 + 4) and Rituximab. PET scans were centrally reviewed by an expert panel by Blinded Independent Central Review. Results: Higher NLR and lower LMR were associated with a PET-2 positivity and failure to achieve long-term disease control, respectively. By univariate and multivariate analysis, large nodal mass (>7 cm), IPS ≥ 3, NLR > 6 were strong independent predictors of early PET-2 response after ABVD. Only NLR > 6 and IPS ≥ 3 were strong independent predictors of outcome at diagnosis; however, when PET-2 status was added, only PET-2-positive status and IPS ≥ 3 were independent predictors of PFS. Focusing on PET-2-negative patients, those with NLR > 6 had an inferior 3-year PFS compared to patients with NLR ≤ 6 (84% vs 89% months, P =.03). Conclusion: In advanced-stage HL patients treated with a PET-2-driven strategy, IPS ≥ 3 and NLR > 6 are independent predictors of outcome at diagnosis while the presence of large nodal mass, IPS ≥ 3, and NLR > 6 at diagnosis are independent predictors of early ABVD response

Influenza vaccination induces NK-cell-mediated type-II IFN response that regulates humoral immunity in an IL-6-dependent manner

The role of natural killer (NK) cells in the immune response against vaccines is not fully understood. Here, we examine the function of infiltrated NK cells in the initiation of the inflammatory response triggered by inactivated influenza virus vaccine in the draining lymph node (LN). We observed that, following vaccination, NK cells are recruited to the interfollicular and medullary areas of the LN and become activated by type I interferons (IFNs) produced by LN macrophages. The activation of NK cells leads to their early production of IFNγ, which in turn regulates the recruitment of IL-6+ CD11b+ dendritic cells. Finally, we demonstrate that the interleukin-6 (IL-6)-mediated inflammation is important for the development of an effective humoral response against influenza virus in the draining LN