Separation of bacteria with imprinted polymeric films

Separation of compounds out of complex mixtures is a key issue that has been solved for small molecules by chromatography. However, general methods for the separation of large bio-particles, such as cells, are still challenging. We demonstrate integration of imprinted polymeric films (IPF) into a microfluidic chip, which preferentially capture cells matching an imprint template, and separate strains of cyanobacteria with 80–90% efficiency, despite a minimal difference in morphology and fluorescence, demonstrating its general nature. It is currently thought that the imprinting process, conducted while the polymer cures, transfers chemical information of the cell’s external structure to the substrate. Capture specificity and separation can be further enhanced by orienting the imprints parallel to the flow vector and tuning the pH to a lower range

FDG uptake is a surrogate marker for defining the optimal biological dose of the mTOR inhibitor everolimus in vivo

This study aimed to test whether [18F]fluoro-D-glucose (FDG) uptake of tumours measured by positron emission tomography (PET) can be used as surrogate marker to define the optimal biological dose (OBD) of mTOR inhibitors in vivo. Everolimus at 0.05, 0.5, 5 and 15 mg kg−1 per day was administered to gastric cancer xenograft-bearing mice for 23 days and FDG uptake of tumours was measured using PET from day 1 to day 8. To provide standard comparators for FDG uptake, tumour volume, S6 protein phosphorylation, Ki-67 staining and everolimus blood levels were evaluated. Everolimus blood levels increased in a dose-dependent manner but antitumour activity of everolimus reached a plateau at doses ⩾5 mg kg−1 per day (tumour volume treated vs control (T/C): 51% for 5 mg kg−1 per day and 57% for 15 mg kg−1 per day). Correspondingly, doses ⩾5 mg kg−1 per day led to a significant reduction in FDG uptake of tumours. Dose escalation above 5 mg kg−1 per day did not reduce FDG uptake any further (FDG uptake T/C: 49% for 5 mg kg−1 per day and 52% for 15 mg kg−1 per day). Differences in S6 protein phosphorylation and Ki-67 index reflected tumour volume and changes in FDG uptake but did not reach statistical significance. In conclusion, FDG uptake might serve as a surrogate marker for dose finding studies for mTOR inhibitors in (pre)clinical trials

Deep sequencing of gastric carcinoma reveals somatic mutations relevant to personalized medicine

<p>Abstract</p> <p>Background</p> <p>Globally, gastric cancer is the second most common cause of cancer-related death, with the majority of the health burden borne by economically less-developed countries.</p> <p>Methods</p> <p>Here, we report a genetic characterization of 50 gastric adenocarcinoma samples, using affymetrix SNP arrays and Illumina mRNA expression arrays as well as Illumina sequencing of the coding regions of 384 genes belonging to various pathways known to be altered in other cancers.</p> <p>Results</p> <p>Genetic alterations were observed in the WNT, Hedgehog, cell cycle, DNA damage and epithelial-to-mesenchymal-transition pathways.</p> <p>Conclusions</p> <p>The data suggests targeted therapies approved or in clinical development for gastric carcinoma would be of benefit to ~22% of the patients studied. In addition, the novel mutations detected here, are likely to influence clinical response and suggest new targets for drug discovery.</p

Pre-treatment and extraction techniques for recovery of added value compounds from wastes throughout the agri-food chain

The enormous quantity of food wastes discarded annually force to look for alternatives for this interesting feedstock. Thus, food bio-waste valorisation is one of the imperatives of the nowadays society. This review is the most comprehensive overview of currently existing technologies and processes in this field. It tackles classical and innovative physical, physico-chemical and chemical methods of food waste pre-treatment and extraction for recovery of added value compounds and detection by modern technologies and are an outcome of the COST Action EUBIS, TD1203 Food Waste Valorisation for Sustainable Chemicals, Materials and Fuels

Targeted Therapy Recommendations for Therapy Refractory Solid Tumors—Data from the Real-World Precision Medicine Platform MONDTI

Advanced therapy-refractory solid tumors bear a dismal prognosis and constitute a major challenge in offering effective treatment strategies. In this real-world retrospective analysis of our precision medicine platform MONDTI, we describe the molecular profile of 554 patients diagnosed with 17 different types of advanced solid tumors after failure of all standard treatment options. In 304 cases (54.9% of all patients), a molecular-driven targeted therapy approach could be recommended, with a recommendation rate above 50% in 12 tumor entities. The three highest rates for therapy recommendation per tumor classification were observed in urologic malignancies (90.0%), mesothelioma (78.6%), and male reproductive cancers (71.4%). Tumor type (p = 0.46), expression of p-mTOR (p = 0.011), expression of EGFR (p = 0.046), and expression of PD-L1 (p = 0.023) had a significant impact on the targeted therapy recommendation rate. Therapy recommendations were significantly more often issued for men (p = 0.015) due to gender-specific differences in the molecular profiles of patients with head and neck cancer and malignant mesothelioma. This analysis demonstrates that precision medicine was feasible and provided the basis for molecular-driven therapy recommendations in patients with advanced therapy refractory solid tumors

The terrestrial and freshwater invertebrate biodiversity of the archipelagoes of the Barents Sea; Svalbard, Franz Josef Land and Novaya Zemlya

Arctic terrestrial ecosystems are generally considered to be species poor, fragile and often isolated. Nonetheless, their intricate complexity, especially that of the invertebrate component, is beginning to emerge. Attention has become focused on the Arctic both due to the importance of this rapidly changing region for the Earth and also the inherent interest of an extreme and unique environment. The three archipelagoes considered here, Svalbard, Franz Josef Land and Novaya Zemlya, delineate the Barents Sea to the west, north and east. This is a region of convergence for Palearctic and Nearctic faunas re-colonising the Arctic following the retreat of the ice after the Last Glacial Maximum (LGM). Despite the harsh Arctic environment and the short period since deglaciation, the archipelagoes of the Barents Sea are inhabited by diverse invertebrate communities. But there is an obvious imbalance in our knowledge of many taxa of each archipelago, and in our knowledge of many taxa. Research effort in Svalbard is increasing rapidly while there are still few reports, particularly in the western literature, from Franz Josef Land and Novaya Zemlya. Nevertheless, there appears to be a surprising degree of dissimilarity between the invertebrate faunas, possibly reflecting colonization history. We provide a baseline synthesis of the terrestrial and freshwater invertebrate fauna of the Barents Sea archipelagoes, highlight the taxa present, the characteristic elements of fauna and the complexity of their biogeography. In doing so, we provide a background from which to assess responses to environmental change for a region under increasing international attention from scientific, industrial and political communities as well as non-governmental organizations and the general public

ESMO OpenCancer Horizons / Interim analysis of a real-world precision medicine platform for molecular profiling of metastatic or advanced cancers: MONDTI

Background: High-throughput genomic profiling of tumour specimens facilitates the identification of individual actionable mutations which could be used for individualised targeted therapy. This approach is becoming increasingly more common in the clinic; however, the interpretation of results from molecular profiling tests and efficient guiding of molecular therapies to patients with advanced cancer offer a significant challenge to the oncology community. Experimental design: MONDTI is a precision medicine platform for molecular characterisation of metastatic solid tumours to identify actionable genomic alterations. From 2013 to 2016, comprehensive molecular profiles derived from real-time biopsy specimens and archived tumour tissue samples of 295 patients were performed. Results and treatment suggestions were discussed within multidisciplinary tumour board meetings. Results: The mutational profile was obtained from 293 (99%) patients and a complete immunohistochemical (IHC) and cytogenetic profile was obtained in 181 (61%) and 188 (64%) patients. The most frequent cancer types were colorectal cancer (12%), non-Hodgkins lymphomas (9.8%) and head and neck cancers (7.8%). The most commonly detected mutations were TP53 (39%), KRAS (19%) and PIK3CA (9.5%), whereas 1 mutation were identified in 217 (74%) samples. Regarding the results for IHC testing, samples were positive for phospho-mammalian target of rapamycin (phospho-mTOR) (71%), epidermal growth factor receptor (EGFR) (68%), mesenchymal epithelial transition (MET) (56%) and/or platelet-derived growth factor alpha (PDGFR)-expression (48%). Of the 288 tumour samples with one or more genetic alteration detected, 160 (55.6%) targeted therapy recommendations through 67 multidisciplinary tumour board meetings were made; in 69 (24%) cases, an individual treatment concept was initiated. Conclusions: The results reveal that the open concept for all solid tumours characterised for molecular profile and immunotherapy could not only match individualised treatment concepts at a high rate but also underscores the challenges encountered when offering molecularly matched therapies to a patient population with an advanced stage cancer.(VLID)489854

Oncotarget / Results of the extended analysis for cancer treatment (EXACT) trial: a prospective translational study evaluating individualized treatment regimens in oncology

Background: The concept of personalized medicine defines a promising approach in cancer care. High-throughput genomic profiling of tumor specimens allows the identification of actionable mutations that potentially lead to tailored treatment for individuals benefit. The aim of this study was to prove efficacy of a personalized treatment option in solid tumor patients after failure of standard treatment concepts. Results: Final analysis demonstrates that 34 patients (62%) had a longer PFS upon experimental treatment (PFS1) when compared to previous therapy (PFS0); PFS ratio > 1.0 (p = 0.002). The median PFS under targeted therapy based on molecular profiling (PFS1) was 112 days (quartiles 66/201) and PFS0 = 61 days (quartiles 51/92; p = 0.002). Of the 55 patients, 31 (56%) showed disease control (DCR), consisting of 2 (4%) patients which achieved a complete remission, 14 (25%) patients with a partial remission and 15 (27%) patients who had a stabilization of disease. Median OS from start of experimental therapy was 348 days (quartiles 177/664). Conclusion: The prospective trial EXACT suggests that treatment based on real-time molecular tumor profiling leads to superior clinical benefit. Materials and Methods: In this prospective clinical phase II trial, 55 cancer patients, after failure of standard treatment options, aimed to achieve a longer progression-free survival on the experimental treatment based on the individuals molecular profile (PFS1) when compared to the last treatment given before (PFS0). The personalized medicine approach was conceived to be clinical beneficial for patients who show a PFS ratio (PFS 1/PFS0) of > 1.0.(VLID)491062