NANTEN 12CO (J=1-0) observations around the star WR 55

Context: A complete study of the molecular and ionized gas in the environs of the nebula RCW 78 around WR 55 is presented. Aims: The aim of this work is to investigate the spatial distribution, physical characteristics, and kinematical properties of the molecular gas linked to the galactic nebula RCW 78 to achieve a better understanding of its interaction with the star and with the ionized gas. Methods: This study was based on 12CO(1-0) fully sampled observations of a region of ~0.45{\deg} in size around the star WR 55 and the nebula RCW 78 obtained with the 4-m NANTEN telescope, radio continuum archival data at 1.4 and 4.85 GHz, obtained from SGPS and PMNRAO Southern Radio Survey, respectively, and available infrared MIPSGAL images at 24 microns. Results: A molecular gas component in the velocity range from ~ -58 to -45 km s-1, compatible with the velocity of the ionized gas, was found to be associated with the optical nebula. Adopting a distance of ~ 5 kpc, the mass of this molecular component is about 3.4 x 10^4 Msun. The analysis of the molecular data revealed the presence of a velocity gradient, in agreement with the Halpha line. New radiocontinuum flux density determinations confirm the thermal nature of RCW 78. This indicates that the ionized gas in RCW 78 arises from photoionization of the molecular gas component in the velocity range from -58 km s-1 to -45 km s-1. A molecular concentration at a velocity of -56.1 km s-1 (identified as C1) is very likely associated with the star HD 117797 and with a collection of candidate YSOs, lying at a distance of 3.9 kpc, while the rest of the molecular gas at velocities between -56 and -46 km s-1 constitute an incomplete ring-like structure which expands around WR 55 at a velocity of about ~ 5 km s-1. Mechanical energy and time requirements indicate that WR 55 is very capable of sustaining the expansion of the nebula.Comment: 14 pages, 10 figures.Accepted for publication in A&

The embedded clusters DBS 77, 78, 102, and 160-161 and their link with the interstellar medium

Aims. We report a study of the global properties of some embedded clusters placed in the fourth quadrant of the Milky Way to clarify some issues related with their location into the Galaxy and their stellar formation processes. Methods. We performed BVI photometric observations in the region of DBS 77, 78, 102, 160, and 161 clusters and infrared spectroscopy in DBS 77 region. They were complemented with JHK data from VVV survey combined with 2MASS catalogue, and used mid-infrared information from GLIMPSE catalogue. We also searched for HI data from SGPS and PMN radio surveys, and previous spectroscopic stellar classification. The spectroscopic and photometric information allowed us to estimate the spectral classification of the brightest stars of each studied region. On the other hand, we used the radio data to investigate the interstellar material parameters and the continuum sources probably associated with the respective stellar components. Results. We estimated the basic physical parameters of the clusters (reddening, distance, age, and initial mass function). We searched for HII regions located near to the studied clusters and we analyzed the possible link between them. In the particular case of DBS 160-161 clusters, we identified the HI bubble B332.5-0.1-42 located around them. We found that the mechanical energy injected to the interstellar medium by the more massive stars of this couple of clusters was enough to generate the bubble.Comment: 15 pages, 14 figures, 6 tables, accepted for publication in A&

A radio continuum survey of the southern sky at 1420 MHz. Observations and data reduction

We describe the equipment, observational method and reduction procedure of an absolutely calibrated radio continuum survey of the South Celestial Hemisphere at a frequency of 1420 MHz. These observations cover the area 0h < R.A. < 24h for declinations less than -10 degree. The sensitivity is about 50 mK T_B (full beam brightness) and the angular resolution (HPBW) is 35.4', which matches the existing northern sky survey at the same frequency.Comment: 9 pages with 9 figures, A&A, in pres

Unknown Primary Melanoma: Worldwide Survey on Clinical Management

Background: How to deal with melanoma of unknown primary (MUP) origin is a debated topic in the literature. Objective: We performed a worldwide survey to inquire what clinical and investigational workup is performed as well as the physicians' perception of this disease. Methods: A questionnaire was sent via mail to clinicians involved in melanoma care from December 2015 to April 2016 using the International Dermoscopy Society website. Results: 119 physicians from 47 different countries answered the questionnaire. The most reported examination was skin examination followed by CT and/or PET scans. All the participants declared asking about previous excisions of skin lesions with 81% of them asking for a histopathological slide review of previous biopsies. Half of the participants checked for a possible vitiligo phenomenon that may explain regression of the primary lesion. BRAF, cKIT, and GNAQ mutations were screened by 32% of participants. The majority of participants (76%) applied the same treatment protocols for MUP as patients with known primary melanomas of the same AJCC stage. Conclusion: Strong heterogeneity was found between physicians dealing with MUP. Thus, a consensus document should be strongly encouraged

Enhancement of electroporation facilitated immunogene therapy via T-reg depletion

Regulatory T cells (T-regs) can negatively impact tumor antigen-specific immune responses after infiltration into tumor tissue. However, depletion of T-regs can facilitate enhanced anti-tumor responses, thus augmenting the potential for immunotherapies. Here we focus on treating a highly aggressive form of cancer using a murine melanoma model with a poor prognosis. We utilize a combination of T-reg depletion and immunotherapy plasmid DNA delivered into the B16F10 melanoma tumor model via electroporation. Plasmids encoding murine granulocyte macrophage colony-stimulating factor and human B71 were transfected with electroporation into the tumor and transient elimination of T-regs was achieved with CD25-depleting antibodies (PC61). The combinational treatment effectively depleted T-regs compared to the untreated tumor and significantly reduced lung metastases. The combination treatment was not effective in increasing the survival, but only effective in suppression of metastases. These results indicate the potential for combining T-reg depletion with immunotherapy-based gene electrotransfer to decrease systemic metastasis and potentially enhance survival

GS100-02-41: a new large HI shell in the outer part of the Galaxy

Massive stars have a profound effect on the surrounding interstellar medium. They ionize and heat the neutral gas, and due to their strong winds, they swept the gas up forming large HI shells. In this way, they generate a dense shell where the physical conditions for the formation of new stars are given. The aim of this study is to analyze the origin and evolution of the large HI shell GS100-02-41 and its role in triggering star forming processes.To characterize the shell and its environs, we carry out a multi-wavelength study. We analyze he HI 21 cm line, the radio continuum, and infrared emission distributions. The analysis of the HI data shows an expanding shell structure centred at (l, b) = (100.6 deg, -2.04 deg) in the velocity range from -29 to -51.7 km/s. We infer for GS100-02-41, a kinematical distance of 2.8 +/- 0.6 kpc. Several massive stars belonging to Cep OB1 are located in projection within the large HI, shell boundaries. The analysis of the radio continuum and infrared data reveal that there is no continuum counterpart of the HI shell. On the other hand, three slightly extended radio continuum sources are observed in projection onto the dense HI shell. From their flux density determinations we infer that they are thermal in nature. An analysis of the HI emission distribution in the environs of these sources shows, for each of them, a region of low emissivity having a good morphological correlation with the ionized gas in a velocity range similar to the one where GS100-02-41 is detected. The origin of GS100-02-41 could have been mainly due to the action of the Cep OB1 massive stars located inside the HI shell. The obtained age difference between the HI shell and the HII regions, together with their relative location, led us to conclude that the ionizing stars could have been created as a consequence of the shell evolution.Comment: Accepted for publication in A&

Efficacy, Safety, and Quality of Life (Qol) Data from the Eortc 18071 Phase III Trial of Ipilimumab (Ipi) Versus Placebo After Complete Resection of Stage III Melanoma

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Efficacy and safety of nilotinib in patients with KIT-mutated metastatic or inoperable melanoma: final results from the global, single-arm, phase II TEAM trial

Background: The single-arm, phase II Tasigna Efficacy in Advanced Melanoma (TEAM) trial evaluated the KIT-selective tyrosine kinase inhibitor nilotinib in patients with KIT-mutated advanced melanoma without prior KIT inhibitor treatment. Patients and methods: Forty-two patients with KIT-mutated advanced melanoma were enrolled and treated with nilotinib 400mg twice daily. TEAM originally included a comparator arm of dacarbazine (DTIC)-treated patients;the design was amended to a single-arm trial due to an observed low number of KIT-mutated melanomas. Thirteen patients were randomized to DTIC before the protocol amendment removing this study arm. The primary endpoint was objective response rate (ORR), determined according to Response Evaluation Criteria In Solid Tumors. Results: ORR was 26.2% (n = 11/42;95% CI, 13.9%-42.0%), sufficient to reject the null hypothesis (ORR <= 10%). All observed responses were partial responses (PRs;median response duration, 7.1 months). Twenty patients (47.6%) had stable disease and 10 (23.8%) had progressive disease;1 (2.4%) response was unknown. Ten of the 11 responding patients had exon 11 mutations, four with an L576P mutation. The median progression-free survival and overall survival were 4.2 and 18.0 months, respectively. Three of the 13 patients on DTIC achieved a PR, and another patient had a PR following switch to nilotinib. Conclusion: Nilotinib activity in patients with advanced KIT-mutated melanoma was similar to historical data from imatinib-treated patients. DTIC treatment showed potential activity, although the low patient number limits interpretation. Similar to previously reported results with imatinib, nilotinib showed greater activity among patients with an exon 11 mutation, including L576P, suggesting that nilotinib may be an effective treatment option for patients with specific KIT mutations

Prospective assessment of a gene signature potentially predictive of clinical benefit in metastatic melanoma patients following MAGE-A3 immunotherapeutic (PREDICT)

Background: Genomic profiling of tumor tissue may aid in identifying predictive or prognostic gene signatures (GS) in some cancers. Retrospective gene expression profiling of melanoma and non-small-cell lung cancer led to the characterization of a GS associated with clinical benefit, including improved overall survival (OS), following immunization with the MAGE-A3 immunotherapeutic. The goal of the present study was to prospectively evaluate the predictive value of the previously characterized GS. Patients and methods: An open-label prospective phase II trial ('PREDICT') in patients with MAGE-A3-positive unresectable stage IIIB-C/IV-M1a melanoma. Results: Of 123 subjects who received the MAGE-A3 immunotherapeutic, 71 (58.7%) displayed the predictive GS (GS +). The 1-year OS rate was 83.1%/83.3% in the GS+/GS- populations. The rate of progression-free survival at 12 months was 5.8%/4.1% in GS+/GS- patients. The median time-to-treatment failure was 2.7/2.4 months (GS+/GS-). There was one complete response (GS-) and two partial responses (GS+). The MAGE-A3 immunotherapeutic was similarly immunogenic in both populations and had a clinically acceptable safety profile. Conclusion: Treatment of patients with MAGE-A3-positive unresectable stage IIIB-C/IV-M1a melanoma with the MAGE-A3 immunotherapeutic demonstrated an overall 1-year OS rate of 83.5%. GS- and GS+ patients had similar 1-year OS rates, indicating that in this study, GS was not predictive of outcome. Unexpectedly, the objective response rate was lower in this study than in other studies carried out in the same setting with the MAGE-A3 immunotherapeutic. Investigation of a GS to predict clinical benefit to adjuvant MAGE-A3 immunotherapeutic treatment is ongoing in another melanoma study. This study is registered at www.clinicatrials.gov NCT00942162