Purpose: Aim of the present study was to investigate the sensitivity of high resolution ultrasound (HRU), standard contrast-enhanced ultrasound (CEUS) and CEUS using a novel vascular endothelial growth factor receptor 2 (VEGFR2)-targeted contrast agent for the detection of hepatic metastases in a mouse model of colorectal cancer using clinical standard technology. Materials and Methods: The human colon cancer cell line HT29, transfected with luciferase cDNA for in vivo bioluminescence monitoring, was injected intrasplenically into CB17.SCID mice. Mice were monitored weekly by bioluminescence and after 2 and 4.5 weeks by HRU and CEUS. Contrast media (untargeted BR1, targeted BR55) was applied and digital cine loops from the arterial phase (15 - 45 sec), portal venous phase (50 - 120 s) and late phases (3 - 5 min, 1hour) of the whole liver were analyzed. Data were correlated with postmortem histopathology. Results: Without contrast enhancement, lesions > 4 mm were reliably detected. After use of untargeted CEUS, lesions > 2 mm were reliably detected and enhanced rim vascularization and late-phase wash-out was shown. With BR55, lesions > 0.8 mm were reliably detected with excellent documentation of vascularization. A persistent contrast enhancement was seen > 30 min after injection. Contrast-enhancement patterns with BR55 significantly correlated with CD31 (R2 = 0.74) and VEGFR2-immunohistochemistry (R2 = 0.66). Conclusion: Detection of metastases by HRU and CEUS was earlier and more accurate than monitoring via bioluminescence. In vivo monitoring of hepatic micrometastases can thus be performed without prior modification of cancer cells using standard technology.
© Georg Thieme Verlag KG Stuttgart · New York.

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On April 27, 2016 Swedish Orphan Biovitrum AB (publ) (Sobi(TM)) reported its 2015 Annual Report, themed "A new chapter of our story" (Press release, Swedish Orphan Biovitrum, APR 27, 2016, View Source;Media/News/RSS/?RSS=View Source [SID:1234511482]). The integrated report summarises the business as well as financial highlights for 2015, and gives a deeper insight into the company’s strategic agenda and its patient-centric innovation model.

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The 2015 Annual Report is available both in print and as an interactive online version, in responsive design to enable viewing on all mobile devices. New features in the online version include pdf and excel downloads of the report and the financial results as well as video comments from CEO Geoffrey McDonough and stakeholders.

CEO and President Geoffrey McDonough wrote in his letter to the shareholders, "We believe that the culture of pioneering in the service of patients with rare diseases requires a small, agile, and human scale organisation that can stay responsive to the changing landscape of patient needs, science and society. We began our transition five years ago and over this period Sobi’s market capitalisation has increased more than sevenfold."

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To read the digital version of the report please follow this link.
To read or download the annual report in Swedish, please follow this link.
To read or download the annual report in English, please follow this link.
To order a printed copy, please send an email to [email protected].

Elotuzumab is a first in class humanized IgG1 monoclonal antibody for the treatment of multiple myeloma (MM). Elotuzumab targets the glycoprotein signaling lymphocyte activation molecule family 7 (SLAMF7, also described as CS1 or CRACC) which is expressed on the surface of myeloma cells and a subset of immune cells, including natural killer cells. A soluble version of SLAMF7 (sSLAMF7) has also been reported in MM patients but has not been evaluated as a potential biomarker following therapeutic intervention. In order to measure serum levels of sSLAMF7, two immunoassays were developed to monitor changes in circulating sSLAMF7 before and after elotuzumab treatment. Free (drug-unbound) and total (drug-bound and unbound) electrochemiluminescence (ECL) ELISA assays were developed and validated following a fit for purpose (FFP) methodology. Both assays met analytical acceptance criteria for precision, drug interference, dilution linearity, spike recovery, parallelism, and stability. Both exhibited the range and sensitivity necessary to measure clinical samples with an LLOQ of 51.2 pg/mL and ULOQs of 160 (free) and 800 ng/mL (total). Previously described assays were unable to detect sSLAMF7 in healthy individuals. However, due to the increased sensitivity of these new assays, low but measurable sSLAMF7 levels were detected in all normal healthy sera evaluated and were significantly elevated in MM patients. Cohort statistics revealed a significant increase of circulating sSLAMF7 in MM patients versus normal controls and both significant decreases in free and increases in total levels of protein post-elotuzumab treatment.

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On April 27, 2016 Varian Medical Systems (NYSE: VAR), reported that its 3D volumetric imaging technology is now being used at a California proton therapy center to enhance the precision and quality of its treatments for cancer patients (Press release, Varian Medical Systems, APR 27, 2016, View Source [SID:1234511483]). The treatments with image-guided intensity modulated proton therapy (IMPT) are being delivered on Varian’s ProBeam system at Scripps Proton Therapy Center in San Diego.

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3D volumetric image-guided IMPT is enabled by Varian’s cone beam computed tomography (CBCT) technology and supports adaptive treatment planning and delivery wherein clinicians can revise plans based on what they see in images during the course of treatment. Volumetric imaging is particularly important for proton radiosurgery, an ultra-precise form of treatment. ProBeam cone beam imaging is based on the same leading technology used in Varian’s radiation oncology systems including the TrueBeam platform.

The unique combination of 3D volumetric imaging with controlled pencil beam scanning makes it possible to conform dose to the size, shape and location of the tumor while potentially reducing side effects. With proton therapy, the risk of damage to healthy tissues and potential side effects are reduced because proton beams can be controlled so that they deposit their energy within the tumor site rather than passing all the way through the patient.

"Volumetric imaging is enormously beneficial, because IMPT is very sensitive to anatomic changes," said Dr. Lei Dong, chief of Medical Physics, Scripps Proton Therapy Center. "For the optimum treatment we need to know of any changes, not only to the target, but also the anatomy outside of the target. The cone beam imaging on the Varian ProBeam System is excellent and stays true to the same high quality that I’ve seen on their photon systems."

"This is an important milestone for Varian where we are bringing the most advanced 3D imaging capability to the ProBeam system for proton therapy patients," said Dr. Moataz Karmalawy, general manager of Varian’s Particle Therapy division. "This should enable clinicians to deliver proton radiosurgery that will allow precise treatments for cancer patients to be completed in fewer sessions. It should be a win for everybody."

For more information on Varian’s proton therapy solutions, visit View Source

The HIV-1-envelope (Env) trimer is covered by a glycan shield of ∼90 N-linked oligosaccharides, which comprises roughly half its mass and is a key component of HIV evasion from humoral immunity. To understand how antibodies can overcome the barriers imposed by the glycan shield, we crystallized fully glycosylated Env trimers from clades A, B, and G, visualizing the shield at 3.4-3.7 Å resolution. These structures reveal the HIV-1-glycan shield to comprise a network of interlocking oligosaccharides, substantially ordered by glycan crowding, that encase the protein component of Env and enable HIV-1 to avoid most antibody-mediated neutralization. The revealed features delineate a taxonomy of N-linked glycan-glycan interactions. Crowded and dispersed glycans are differently ordered, conserved, processed, and recognized by antibody. The structures, along with glycan-array binding and molecular dynamics, reveal a diversity in oligosaccharide affinity and a requirement for accommodating glycans among known broadly neutralizing antibodies that target the glycan-shielded trimer.
Copyright © 2016 Elsevier Inc. All rights reserved.

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