Neoadjuvant chemoradiation and pancreaticoduodenectomy for initially locally advanced head pancreatic adenocarcinoma

International audienceThe most accepted treatment for locally advanced pancreatic adenocarcinoma (LAPA) is chemoradiotherapy (CRT). We sought to determine the benefit of pancreaticoduodenectomy (PD) in patients with LAPA initially treated by neoadjuvant CRT

A BARF1-specific mAb as a new immunotherapeutic tool for the management of EBV-related tumors.

The use of monoclonal antibodies (mAb) for the diagnosis and treatment of malignancies is acquiring an increasing clinical importance, thanks to their specificity, efficacy and relative easiness of use. However, in the context of Epstein-Barr virus (EBV)-related malignancies, only cancers of B-cell origin can benefit from therapeutic mAb targeting specific B-cell lineage antigens. To overcome this limitation, we generated a new mAb specific for BARF1, an EBV-encoded protein with transforming and immune-modulating properties. BARF1 is expressed as a latent protein in nasopharyngeal (NPC) and gastric carcinoma (GC), and also in neoplastic B cells mainly upon lytic cycle induction, thus representing a potential target for all EBV-related malignancies. Considering that BARF1 is largely but not exclusively secreted, the BARF1 mAb was selected on the basis of its ability to bind a domain of the protein retained at the cell surface of tumor cells. In vitro, the newly generated mAb recognized the target molecule in its native conformation, and was highly effective in mediating both ADCC and CDC against BARF1-positive tumor cells. In vivo, biodistribution analysis in mice engrafted with BARF1-positive and -negative tumor cells confirmed its high specificity for the target. More importantly, the mAb disclosed a relevant antitumor potential in preclinical models of NPC and lymphoma, as evaluated in terms of both reduction of tumor masses and long-term survival. Taken together, these data not only confirm BARF1 as a promising target for immunotherapeutic interventions, but also pave the way for a successful translation of this new mAb to the clinical use

Phase I/II study of verteporfin photodynamic therapy in locally advanced pancreatic cancer

Background:Patients with pancreatic cancer have a poor prognosis apart from the few suitable for surgery. Photodynamic therapy (PDT) produces localised tissue necrosis but previous studies using the photosensitiser meso-tetrahydroxyphenylchlorin (mTHPC) caused prolonged skin photosensitivity. This study assessed a shorter acting photosensitiser, verteporfin.Methods: Fifteen inoperable patients with locally advanced cancers were sensitised with 0.4 mg kg-1 verteporfin. After 60-90 min, laser light (690 nm) was delivered via single (13 patients) or multiple (2 patients) fibres positioned percutaneously under computed tomography (CT) guidance, the light dose escalating (initially 5 J, doubling after each three patients) until 12 mm of necrosis was achieved consistently.Results:In all, 12 mm lesions were seen consistently at 40 J, but with considerable variation in necrosis volume (mean volume 3.5 cm 3 at 40 J). Minor, self-limiting extrapancreatic effects were seen in multifibre patients. No adverse interactions were seen in patients given chemotherapy or radiotherapy before or after PDT. After PDT, one patient underwent an R0 Whipple's pancreaticoduodenectomy.Conclusions:Verteporfin PDT-induced tumour necrosis in locally advanced pancreatic cancer is feasible and safe. It can be delivered with a much shorter drug light interval and with less photosensitivity than with older compounds. © 2014 Cancer Research UK

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Engineering phase competition between stripe order and superconductivity in La1.88_{1.88}Sr0.12_{0.12}CuO4_4

Unconventional superconductivity often couples to other electronic orders in a cooperative or competing fashion. Identifying external stimuli that tune between these two limits is of fundamental interest. Here, we show that strain perpendicular to the copper-oxide planes couples directly to the competing interaction between charge stripe order and superconductivity in La$_{1.88}$Sr$_{0.12}$CuO$_{4}$ (LSCO). Compressive c-axis pressure amplifies stripe order within the superconducting state, while having no impact on the normal state. By contrast, strain dramatically diminishes the magnetic field enhancement of stripe order in the superconducting state. These results suggest that c-axis strain acts as tuning parameter of the competing interaction between charge stripe order and superconductivity. This interpretation implies a uniaxial pressure-induced ground state in which the competition between charge order and superconductivity is reduced

Exploring the link between star and planet formation with Ariel

The goal of the Ariel space mission is to observe a large and diversified population of transiting planets around a range of host star types to collect information on their atmospheric composition. The planetary bulk and atmospheric compositions bear the marks of the way the planets formed: Ariel’s observations will therefore provide an unprecedented wealth of data to advance our understanding of planet formation in our Galaxy. A number of environmental and evolutionary factors, however, can affect the final atmospheric composition. Here we provide a concise overview of which factors and effects of the star and planet formation processes can shape the atmospheric compositions that will be observed by Ariel, and highlight how Ariel’s characteristics make this mission optimally suited to address this very complex problem

A study of lymph node ratio in stage IV colorectal cancer

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: The finding of metastasis in colorectal cancer, stage IV disease, has a major impact on prognosis and treatment strategy. Known important factors include the extent of the metastasis and the patients ' performance status. The lymph node factors are of known importance in earlier cancer stages but less described in metastatic disease. The aim of the study was to evaluate lymph node status and ratio as prognostic markers in stage IV colorectal cancer. Methods: The study was retrospective and assessing all patients operated, with bowel resection, for an initial stage IV colorectal cancer during 1999–2003 (n = 136). Basic demographic data as well as given treatment was assessed. The Lymph node ratio (LNR), the quota between the number of lymph node metastasis and assessed lymph nodes, was calculated. LNR groups were created by ratio thirds, 3 equally sized groups. The analysis was made by LNR group and by eligibility for chemotherapy with cancer specific survival as outcome parameter. Results: The median survival (CSS) for the entire group was 431 days with great variability. For the patients eligible for chemotherapy it ranged from 791 days in LNR-group 1 to 433 days for th

CACNA1E Variants Affect Beta Cell Function in Patients with Newly Diagnosed Type 2 Diabetes. The Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 3

Background: Genetic variability of the major subunit (CACNA1E) of the voltage-dependent Ca 2+ channel Ca V2.3 is associated to risk of type 2 diabetes, insulin resistance and impaired insulin secretion in nondiabetic subjects. The aim of the study was to test whether CACNA1E common variability affects beta cell function and/or insulin sensitivity in patients with newly diagnosed type 2 diabetes. Methodology/Principal Findings: In 595 GAD-negative, drug naïve patients (mean6SD; age: 58.5610.2 yrs; BMI: 29.965 kg/m 2, HbA1c: 7.061.3) with newly diagnosed type 2 diabetes we: 1. genotyped 10 tag SNPs in CACNA1E region reportedly covering,93 % of CACNA1E common variability: rs558994, rs679931, rs2184945, rs10797728, rs3905011, rs12071300, rs175338, rs3753737, rs2253388 and rs4652679; 2. assessed clinical phenotypes, insulin sensitivity by the euglycemic insulin clamp and beta cell function by state-of-art modelling of glucose/C-peptide curves during OGTT. Five CACNA1E tag SNPs (rs10797728, rs175338, rs2184945, rs3905011 and rs4652679) were associated with specific aspects of beta cell function (p,0.0520.01). Both major alleles of rs2184945 and rs3905011 were each (p,0.01 and p,0.005, respectively) associated to reduced proportional control with a demonstrable additive effect (p,0.005). In contrast, only the major allele of rs2253388 was related weakly to more severe insulin resistance (p,0.05). Conclusions/Significance: In patients with newly diagnosed type 2 diabetes CACNA1E common variability is strongl

Field induced bound state condensation and spin nematic phase in SrCu2 BO3 2 revealed by neutron scattering up to 25.9 T

In quantum magnetic materials, ordered phases induced by an applied magnetic field can be described as the Bose Einstein condensation BEC of magnon excitations. In the strongly frustrated system SrCu2 BO3 2, no clear magnon BEC could be observed, pointing to an alternative mechanism, but the high fields required to probe this physics have remained a barrier to detailed investigation. Here we exploit the first purpose built high field neutron scattering facility to measure the spin excitations of SrCu2 BO3 2 up to 25.9 T and use cylinder matrix product states MPS calculations to reproduce the experimental spectra with high accuracy. Multiple unconventional features point to a condensation of S amp; 8201; amp; 8201;2 bound states into a spin nematic phase, including the gradients of the one magnon branches and the persistence of a one magnon spin gap. This gap reflects a direct analogy with superconductivity, suggesting that the spin nematic phase in SrCu2 BO3 2 is best understood as a condensate of bosonic Cooper pair