Multi Scale Curriculum CNN for Context-Aware Breast MRI Malignancy Classification

Classification of malignancy for breast cancer and other cancer types is usually tackled as an object detection problem: Individual lesions are first localized and then classified with respect to malignancy. However, the drawback of this approach is that abstract features incorporating several lesions and areas that are not labelled as a lesion but contain global medically relevant information are thus disregarded: especially for dynamic contrast-enhanced breast MRI, criteria such as background parenchymal enhancement and location within the breast are important for diagnosis and cannot be captured by object detection approaches properly. In this work, we propose a 3D CNN and a multi scale curriculum learning strategy to classify malignancy globally based on an MRI of the whole breast. Thus, the global context of the whole breast rather than individual lesions is taken into account. Our proposed approach does not rely on lesion segmentations, which renders the annotation of training data much more effective than in current object detection approaches. Achieving an AUROC of 0.89, we compare the performance of our approach to Mask R-CNN and Retina U-Net as well as a radiologist. Our performance is on par with approaches that, in contrast to our method, rely on pixelwise segmentations of lesions.Comment: Accepted to MICCAI 201

Combinatorial Effect of Non-Steroidal Anti-inflammatory Drugs and NF-κB Inhibitors in Ovarian Cancer Therapy

Several epidemiological studies have correlated the use of non-steroidal anti-inflammatory drugs (NSAID) with reduced risk of ovarian cancer, the most lethal gynecological cancer, diagnosed usually in late stages of the disease. We have previously established that the pro-apoptotic cytokine melanoma differentiation associated gene-7/Interleukin-24 (mda-7/IL-24) is a crucial mediator of NSAID-induced apoptosis in prostate, breast, renal and stomach cancer cells. In this report we evaluated various structurally different NSAIDs for their efficacies to induce apoptosis and mda-7/IL-24 expression in ovarian cancer cells. While several NSAIDs induced apoptosis, Sulindac Sulfide and Diclofenac most potently induced apoptosis and reduced tumor growth. A combination of these agents results in a synergistic effect. Furthermore, mda-7/IL-24 induction by NSAIDs is essential for programmed cell death, since inhibition of mda-7/IL-24 by small interfering RNA abrogates apoptosis. mda-7/IL-24 activation leads to upregulation of growth arrest and DNA damage inducible (GADD) 45 α and γ and JNK activation. The NF-κB family of transcription factors has been implicated in ovarian cancer development. We previously established NF-κB/IκB signaling as an essential step for cell survival in cancer cells and hypothesized that targeting NF-κB could potentiate NSAID-mediated apoptosis induction in ovarian cancer cells. Indeed, combining NSAID treatment with NF-κB inhibitors led to enhanced apoptosis induction. Our results indicate that inhibition of NF-κB in combination with activation of mda-7/IL-24 expression may lead to a new combinatorial therapy for ovarian cancer

Dealumination of mordenite zeolite and its catalytic performance evaluation in m-xylene isomerization reaction

Mordenite zeolite with Si/Al = 18 was successfully synthesized by the hydrothermal method. This zeolite was modified by partially dealuminated in HNO3 at 70 °C. Our analysis showed that the surface area of modified mordenite was increased more than that of the mordenite zeolite. Acid leaching removes impurities and aluminium from the zeolite network, improving Si/Al ratio of the framework and increasing the external surface area of the zeolite.The catalytic performances of these synthesized catalysts were investigated for meta-xylene isomerization reaction in a fixed bed reactor. The performances were then benchmarked with the performance of SAPO-11, a commercially available catalyst.The results showed that p-xylene/o-xylene ratio over the catalysts was found to be in the order: dealuminated mordenite > mordenite > SAPO-11, however dealuminated mordenite and SAPO-11 gave higher m-xylene conversion than that of the mordenite

Efficacy and safety of sunitinib in patients with well-differentiated pancreatic neuroendocrine tumours

BACKGROUND: In a phase III study, sunitinib led to a significant increase in progression-free survival (PFS) versus placebo in patients with pancreatic neuroendocrine tumours (panNETs). This study was a post-marketing commitment to support the phase III data. METHODS: In this ongoing, open-label, phase IV trial (NCT01525550), patients with progressive, advanced unresectable/metastatic, well-differentiated panNETs received continuous sunitinib 37.5 mg once daily. Eligibility criteria were similar to those of the phase III study. The primary endpoint was investigator-assessed PFS per Response Evaluation Criteria in Solid Tumours v1.0 (RECIST). Other endpoints included PFS per Choi criteria, overall survival (OS), objective response rate (ORR), and adverse events (AEs). RESULTS: Sixty-one treatment-naive and 45 previously treated patients received sunitinib. By March 19, 2016, 82 (77%) patients had discontinued treatment, mainly due to disease progression. Median treatment duration was 11.7 months. Investigator-assessed median PFS per RECIST (95% confidence interval [CI]) was 13.2 months (10.9-16.7): 13.2 (7.4-16.8) and 13.0 (9.2-20.4) in treatment-naive and previously treated patients, respectively. ORR (95% CI) per RECIST was 24.5% (16.7-33.8) in the total population: 21.3% (11.9-33.7) in treatment-naive and 28.9% (16.4-44.3) in previously treated patients. Median OS, although not yet mature, was 37.8 months (95% CI, 33.0-not estimable). The most common treatment-related AEs were neutropenia (53.8%), diarrhoea (46.2%), and leukopenia (43.4%). CONCLUSIONS: This phase IV trial confirms sunitinib as an efficacious and safe treatment option in patients with advanced/metastatic, well-differentiated, unresectable panNETs, and supports the phase III study outcomes. AEs were consistent with the known safety profile of sunitinib