This phase 2 study evaluated the efficacy and safety of inotuzumab ozogamicin (InO) in patients with indolent B-cell non-Hodgkin lymphoma (NHL) refractory to rituximab alone, rituximab plus chemotherapy or anti-CD20 radioimmunotherapy. Patients received InO 1·8 mg/m(2) intravenously on a 28-d cycle for a planned 4-8 cycles. The initial InO dose and schedule could be adjusted for tolerability and patients were allowed to receive 2 additional cycles (up to 8 total) after achieving a complete response (CR). The primary endpoint was overall response. Eighty-one patients were enrolled, among whom 48 (59%) received ≥3 InO cycles and 13 (16%) completed the treatment phase. The overall response rate was 67% (CR, 31%). Median (95% confidence interval) progression-free survival was 12·7 (8·9-26·9) months; median overall survival was not reached. Haematological adverse events (AEs) were common, particularly thrombocytopenia (74%) and neutropenia (56%). These were also the most common AEs leading to treatment discontinuation (37% and 11%, respectively); 58% of patients reported AEs leading to treatment discontinuation. InO demonstrated robust activity in these heavily pretreated patients, although treatment duration was limited by haematological toxicities. Additional studies may determine dosing regimens that allow for reduced toxicity.
© 2016 John Wiley & Sons Ltd.

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[(18)F]BF4 (-), the first (18)F-labelled PET imaging agent for the sodium/iodide symporter (NIS), was produced by isotopic exchange yielding a product with limited specific activity (SA, ca. 1 GBq/μmol) posing a risk of sub-optimal target-to-background ratios (TBR) in PET images due to saturation of NIS in vivo. We sought to quantify this risk and to develop a method of production of [(18)F]BF4 (-) with higher SA.
A new radiosynthesis of [(18)F]BF4 (-) was developed, involving reaction of [(18)F]F(-) with boron trifluoride diethyl etherate under anhydrous conditions, guided by (11)B and (19)F NMR studies of equilibria involving BF4 (-) and BF3. The SA of the product was determined by ion chromatography. The IC50 of [(19)F]BF4 (-) as an inhibitor of [(18)F]BF4 (-) uptake was determined in vitro using HCT116-C19 human colon cancer cells expressing the human form of NIS (hNIS). The influence of [(19)F]BF4 (-) dose on biodistribution in vivo was evaluated in normal mice by nanoPET imaging and ex vivo tissue counting.
An IC50 of 4.8 μΜ was found in vitro indicating a significant risk of in vivo NIS saturation at SA achieved by the isotopic exchange labelling method. In vivo thyroid and salivary gland uptake decreased significantly with [(19)F]BF4 (-) doses above ca. 10 μg/kg. The new radiosynthesis gave high radiochemical purity (>99 %) and moderate yield (15 %) and improved SA (>5 GBq/μmol) from a starting activity of only 1.5 GBq.
[(18)F]BF4 (-) produced at previously reported levels of SA (1 GBq/μmol) can lead to reduced uptake in NIS-expressing tissues in mice. This is much less likely in humans. The synthetic approach described provides an alternative for production of [(18)F]BF4 (-) at higher SA with sufficient yield and without need for unusually high starting activity of [(18)F]fluoride, removing the risk of NIS saturation in vivo even in mice.
ISRCTN75827286 .

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The Cell Index Database, (CELLX) (View Source) provides a computational framework for integrating expression, copy number variation, mutation, compound activity, and meta data from cancer cells. CELLX provides the computational biologist a quick way to perform routine analyses as well as the means to rapidly integrate data for offline analysis. Data is accessible through a web interface which utilizes R to generate plots and perform clustering, correlations, and statistical tests for associations within and between data types for ~20,000 samples from TCGA, CCLE, Sanger, GSK, GEO, GTEx, and other public sources. We show how CELLX supports precision oncology through indications discovery, biomarker evaluation, and cell line screening analysis.

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Tumor initiating cells (TICs), responsible for tumor initiation, and cancer stem cells (CSCs), responsible for tumor expansion and propagation, are often resistant to chemotherapeutic agents. To find therapeutic targets against sarcoma initiating and propagating cells we used models of myxoid liposarcoma (MLS) and undifferentiated pleomorphic sarcoma (UPS) developed from human mesenchymal stromal/stem cells (hMSCs), which constitute the most likely cell-of-origin for sarcoma. We found that SP1-mediated transcription was among the most significantly altered signaling. To inhibit SP1 activity, we used EC-8042, a mithramycin (MTM) analog (mithralog) with enhanced anti-tumor activity and highly improved safety. EC-8042 inhibited the growth of TIC cultures, induced cell cycle arrest and apoptosis and upregulated the adipogenic factor CEBPα. SP1 knockdown was able to mimic the anti-proliferative effects induced by EC-8042. Importantly, EC-8042 was not recognized as a substrate by several ABC efflux pumps involved in drug resistance, and, opposite to the chemotherapeutic drug doxorubicin, repressed the expression of many genes responsible for the TIC/CSC phenotype, including SOX2, C-MYC, NOTCH1 and NFκB1. Accordingly, EC-8042, but not doxorubicin, efficiently reduced the survival of CSC-enriched tumorsphere sarcoma cultures. In vivo, EC-8042 induced a profound inhibition of tumor growth associated to a strong reduction of the mitotic index and the induction of adipogenic differentiation and senescence. Finally, EC-8042 reduced the ability of tumor cells to reinitiate tumor growth. These data suggest that EC-8042 could constitute an effective treatment against both TIC and CSC subpopulations in sarcoma.

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X-ray field to image receptor active area alignment is usually tested in mammographic QC. In digital breast tomosynthesis (dBT), the source moves during the acquisition, generating a displacement of the X-ray beam edges relative to the detector, in or out of the detector active area. To minimise unnecessary radiation while maximising the useful field of view, a solution consisting in adjusting the collimation with the source rotation was implemented on the GE SenoClaire dBT system. This solution is described and tested using three different methods based on: (1) images from the detector, (2) a non-screen film and (3) a semi-conductor tool providing the X-ray intensity profile. Method 1 demonstrated a maximum positioning error of 0.3 mm. Method 2 was found non-applicable; Method 3 provided measurements within 1.5 mm. Dynamic collimation enables maintaining an X-ray field to detector congruence comparable with 2D. Measuring the position of the X-ray field edges using a dedicated tool makes routine QC possible.
© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

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