The Photometric and Kinematic Structure of Face-On Disk Galaxies. I. Sample Definition, H-alpha Integral Field Spectroscopy, and HI Line-Widths

We present a survey of the photometric and kinematic properties of 39 nearby, nearly face-on disk galaxies. Our approach exploits echelle-resolution integral-field spectroscopy of the H-alpha regions, obtained with DensePak on the WIYN 3.5m telescope Bench Spectrograph. This data is complemented by HI line-profiles observed with the Nancay radio telescope for 25 of these sample galaxies. Twelve additional line-widths are available for sample galaxies from the literature. In this paper, we introduce the goals of this survey, define the sample selection algorithm, and amass the integral field spectroscopic data and HI line-widths. We establish spatially-integrated H-alpha line-widths for the sample. We test the veracity of these spatially-integrated line profiles by convolving narrow-band imaging data with velocity field information for one of the sample galaxies, PGC 38268, and also by comparing to HI line profiles. We find HI and H-alpha line profiles to be similar in width but different in shape, indicating we are observing different spatial distributions of ionized and neutral gas in largely axisymmetric systems with flat outer rotation-curves. We also find vertical velocity dispersions of the ionized disk gas within several disk scale-lengths have a median value of 18 km/s and an 80% range of 12-26 km/s. This is only a factor of ~2 larger than what is observed for neutral atomic and molecular gas. With standard assumptions for intrinsic and thermal broadening for H-alpha, this translates into a factor of three range in turbulent velocities, between 8 and 25 km/s.Comment: 29 pages, 20 figures; accepted for publication in ApJ Supplement Serie

Serum amino acids, biopterin and neopterin during long-term immunotherapy with interferon-alpha in high-risk melanoma patients

Abstract Immunotherapy with interferon-alpha (IFN-a) induces neuropsychiatric side effects, most notably depression. One of the presumed pathophysiological mechanisms is an effect on tryptophan metabolism. As tryptophan is the precursor of serotonin, decreased availability of tryptophan to the central nervous system could result in serotonin deficiency. Tetrahydrobiopterin (BH ) is a cofactor for one of the enzymes synthesizing serotonin. We conducted an exploratory 4 ( ) study into the serum concentrations of large neutral amino acids (AA), biopterin (BIOP) and neopterin (NEOP), of 67 patients with high-risk melanoma, who were either treated with two different doses of IFN-a or were part of an observation-only control group. We found evidence for IFN-a to decrease concentrations of all AA except phenylalanine. The decrease in tryptophan concentration was most prominent and consistent. These changes persisted throughout a year of maintenance treatment. Concentrations of NEOP rose sharply, whereas, those of BIOP did not change. Except for the increase in NEOP and the increase in the ratio between phenylalanine (PHE) and tyrosine (TYR), no support for derangement in BH metabolism was found. The increase in the ratio between PHE and 4 ( ) TYR suggests inhibition of the enzyme phenylalanine hydroxylase. Patients with IFN-a induced anxiety and depression had higher pretreatment concentrations of NEOP. Changes in tryptophan metabolism may play a role in the pathophysiology of the neuropsychiatric side effects of IFN-a, and further research into the predictive potential of NEOP is warranted.

Nitric oxide production and monoamine oxidase activity in cancer patients during interferon-α therapy

Both increased and decreased nitric oxide (NO) synthesis have been reported in patients treated with interferon-α (IFN-α). Animal studies showed that IFN-α administration results in increased levels of biogenic amines, subsequent activation of monoamine oxidases (MAOs), and finally in a change in NO production due to the H2O2 generated by MAOs. We examined the potential relationship between NO production in plasma and MAO-B activity in platelets of 43 cancer patients during 8 weeks of treatment with IFN-α. NO synthesis was quantitated by measuring both the ratio of citrulline and arginine (CIT/ARG-ratio) and total nitrite/nitrate (NOx) levels. Compared to baseline, MAO activity and NOx increased, while the CIT/ARG-ratio decreased. No associations were found between NOx, MAO and CIT/ARG-ratio. Only few associations were observed between changes in the biochemical parameters and changes in psychopathology induced by IFN-α, of which the association between changes in CIT and lassitude was the most consistent. The results suggest that peripheral NO production and MAO activity are unrelated to each other, and that peripheral changes in these biochemical parameters induced by IFN-α are unlikely to contribute to definite psychiatric disturbance

Vemurafenib plus cobimetinib in unresectable stage IIIc or stage IV melanoma

Background: In patients with BRAFV600 mutated unresectable stage IIIc or metastatic melanoma, molecular targeted therapy with combined BRAF/MEK-inhibitor vemurafenib plus cobimetinib has shown a significantly improved progression-free survival and overall survival compared to treatment with vemurafenib alone. Nevertheless, the majority of BRAFV600 mutation-positive melanoma patients will eventually develop resistance to treatment. Molecular imaging with 18F-Fluorodeoxyglucose (18F-FDG) PET has been used to monitor response to vemurafenib in some BRAFV600 mutated metastatic melanoma patients, showing a rapid decline of 18F-FDG uptake within 2 weeks following treatment. Furthermore, preliminary results suggest that metabolic alterations might predict the development of resistance to treatment. 18F-Fluoro-3'-deoxy-3'L-fluorothymidine (18F-FLT), a PET-tracer visualizing proliferation, might be more suitable to predict response or resistance to therapy than 18F-FDG. Methods: This phase II, open-label, multicenter study evaluates whether metabolic response to treatment with vemurafenib plus cobimetinib in the first 7 weeks as assessed by 18F-FDG/18F-FLT PET can predict progression-free survival and whether early changes in 18F-FDG/18F-FLT can be used for early detection of treatment response compared to standard response assessment with RECISTv1.1 ceCT at 7 weeks. Ninety patients with BRAFV600E/K mutated unresectable stage IIIc/IV melanoma will be included. Prior to and during treatment all patients will undergo 18F-FDG PET/CT and in 25 patients additional 18F-FLT PET/CT is performed. Histopathological tumor characterization is assessed in a subset of 40 patients to unravel mechanisms of resistance. Furthermore, in all patients, blood samples are taken for pharmacokinetic analysis of vemurafenib/cobimetinib. Outcomes are correlated with PET/CT-imaging and therapy response.

Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: Final results of EORTC 18991, a randomised phase III trial

info:eu-repo/semantics/publishe

Subcutaneous injection of interleukin 12 induces systemic inflammatory responses in humans: implications for the use of IL-12 as vaccine adjuvant

Interleukin 12 (IL-12) is a cytokine with important regulatory functions bridging innate and adaptive immunity. It has been proposed as an immune adjuvant for vaccination therapy of infectious diseases and malignancies. The inflammatory properties of IL-12 play an important role in the adjuvant effect. We studied the effect of s.c. injections of recombinant human IL-12 (rHuIL-12) in 26 patients with renal cell cancer and demonstrated dose-dependent systemic activation of multiple inflammatory mediator systems in humans. rHuIL-12 at a dose of 0.5 microg/kg induced degranulation of neutrophils with a significant increase in the plasma levels of elastase (p < 0.05) and lactoferrin (p = 0.01) at 24 h. Additionally, rHuIL-12 injection mediated the release of lipid mediators, as demonstrated by a sharp increase in the plasma secretory phospholipase A2 (sPLA2) level (p = 0.003). rHuIL-12, when administered at a dose of 0.1 microg/kg, showed minimal systemic effects. In conclusion, when IL-12 is used as an adjuvant, doses should not exceed 0.1 microg/kg, in order to avoid severe systemic inflammatory response