A phase 1b/2 study evaluating efficacy and safety of MP0250, a designed ankyrin repeat protein (DARPin) simultaneously targeting vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), in combination with bortezomib and dexamethasone, in patients with relapsed or refractory multiple myeloma.

MP0250 is a designed ankyrin repeat protein that specifically inhibits both vascular endothelial growth factor A (VEGF-A) and hepatocyte growth factor (HGF), aiming at potentiating cancer therapy by disrupting the tumour microenvironment. Encouraging results from a phase 1 trial of MP0250 in patients with solid tumours prompted further investigation in multiple myeloma (MM) as both MP0250 targets are reported to be drivers of MM pathogenesis. In this open-label, single-arm phase 1b/2 study (NCT03136653) in patients with proteasome inhibitor- and/or immunomodulatory drug-relapsed or refractory MM, MP0250 was administered every 3 weeks with standard bortezomib/dexamethasone regimen.

Single early palliative care intervention added to usual oncology care for patients with advanced cancer: A randomized controlled trial (SENS Trial).

Background: International oncology societies recommend early palliative care. Specific models to integrate early palliative care efficiently into clinical practice are debated. The authors designed a study to look at the quantitative and qualitative outcomes of an early palliative care intervention in oncological care to decrease stress and improve quality of life.

ESMO / ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2016.

The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) are publishing a new edition of the ESMO/ASCO Global Curriculum (GC) thanks to contribution of 64 ESMO-appointed and 32 ASCO-appointed authors. First published in 2004 and updated in 2010, the GC edition 2016 answers to the need for updated recommendations for the training of physicians in medical oncology by defining the standard to be fulfilled to qualify as medical oncologists. At times of internationalisation of healthcare and increased mobility of patients and physicians, the GC aims to provide state-of-the-art cancer care to all patients wherever they live.

MicroRNA-106a targets autophagy and enhances sensitivity of lung cancer cells to Src inhibitors.

Objectives: Src tyrosine kinase inhibitors (TKIs) significantly inhibit cell migration and invasion in lung cancer cell lines with minor cytotoxic effects. In clinical trials, however, they show modest activity in combination with chemotherapeutic agents. Possible resistance mechanisms include the induction of cytoprotective autophagy upon Src inhibition.

Amelioration of bauxite residue sand by intermittent additions of nitrogen fertiliser and leaching fractions: The effect on growth of kikuyu grass and fate of applied nutrients.

Bauxite residue, a waste product of aluminium processing operations is characterised by high pH, salinity and exchangeable sodium which hinders sustainable plant growth. The aim of this study was to investigate the uptake form, optimum application rate and timing of nitrogen fertiliser to improve bauxite residue characteristics for plant growth. Kikuyu grass was grown in plastic columns filled with residue sand/carbonated residue mud mixture (20:1) previously amended with gypsum, phosphoric acid and basal nutrients.

The RNA binding proteins RBM38 and DND1 are repressed in AML and have a novel function in APL differentiation.

The RNA binding proteins RBM binding motif protein 38 (RBM38) and DEAD END 1 (DND1) selectively stabilize mRNAs by attenuating RNAse activity or protecting them from micro(mi)RNA-mediated cleavage. Furthermore, both proteins can efficiently stabilize the mRNA of the cell cycle inhibitor p21(CIP1). Since acute myeloid leukemia (AML) differentiation requires cell cycle arrest and RBM38 as well as DND1 have antiproliferative functions, we hypothesized that decreased RBM38 and DND1 expression may contribute to the differentiation block seen in this disease.

Low DICER1 expression is associated with attenuated neutrophil differentiation and autophagy of NB4 APL cells.

Successful myeloid differentiation depends on the expression of a series of miRNAs. Thus, it is hardly surprising that miRNAs are globally repressed in AML, a disease mainly characterized by a block in cellular myeloid differentiation. Studies investigating the mechanisms for low miRNA expression in AML has mostly focused on altered transcriptional regulation or deletions, whereas defective miRNA processing has received less attention.

Linking the SUMO protease SENP5 to neutrophil differentiation of AML cells.

In an mRNA profiling screen performed to unveil novel mechanisms of leukemogenesis, we found that the sentrin-specific protease 5 (SENP5) was significantly repressed in clinical acute myeloid leukemia when compared to healthy neutrophil samples. SENP5 is an enzyme that targets and cleaves small ubiquitin-like modifier (SUMO) residues from SUMOylated proteins. Further investigation with AML neutrophil differentiation cell models showed increased SENP5 expression upon induction of differentiation; in contrast, knocking down SENP5 resulted in significantly attenuated neutrophil differentiation.

[Today's cancer medicine: less could often be more].

Modern oncology has much to offer, and the prognosis of cancer patients has undoubtedly improved over the last few decades. Nevertheless, medical and economic toxicities of modern cancer medicine demand that our many tools are viewed with a critical eye. Screening mammography and PSA screening for the detection of early breast, or prostate cancer, resp.

Induction of the autophagy-associated gene MAP1S via PU.1 supports APL differentiation.

The PU.1 transcription factor is essential for myeloid development. We investigated if the microtubule-associated protein 1S (MAP1S) is a novel PU.

CEBPA-dependent HK3 and KLF5 expression in primary AML and during AML differentiation.

The basic leucine zipper transcription factor CCAAT/enhancer binding protein alpha (CEBPA) codes for a critical regulator during neutrophil differentiation. Aberrant expression or function of this protein contributes to the development of acute myeloid leukemia (AML). In this study, we identified two novel unrelated CEBPA target genes, the glycolytic enzyme hexokinase 3 (HK3) and the krüppel-like factor 5 (KLF5) transcription factor, by comparing gene profiles in two cohorts of CEBPA wild-type and mutant AML patients.

Crizotinib inhibits migration and expression of ID1 in MET-positive lung cancer cells: implications for MET targeting in oncology.

Aims: ID1 is an important component of the MET-SRC signaling pathway, which is a regulator of cell migration and invasion. We hypothesized that the ALK/MET inhibitor crizotinib inhibits migration via MET-SRC-ID1, rather than ALK.

Materials & Methods: We used ALK fusion-positive and -negative lung cancer cell lines; crizotinib, PHA-665752, and saracatinib, and stable transfection with shMET.

Spontaneous vegetation encroachment upon bauxite residue (red mud) as an indicator and facilitator of in situ remediation processes.

The spontaneous colonization of a bauxite residue (alumina refining tailings) deposit by local vegetation in Linden, Guyana, over 30 years, indicates that natural weathering processes can ameliorate tailings to the extent that it can support vegetation. Samples were collected from vegetated and unvegetated areas to investigate the relationships between bauxite residue properties and vegetation cover. Compared to unvegetated areas, bauxite residue in vegetated areas had lower pH (mean pH 7.

The tumor suppressor gene DAPK2 is induced by the myeloid transcription factors PU.1 and C/EBPα during granulocytic differentiation but repressed by PML-RARα in APL.

DAPK2 is a proapoptotic protein that is mostly expressed in the hematopoietic tissue. A detailed DAPK2 expression analysis in two large AML patient cohorts revealed particularly low DAPK2 mRNA levels in APL. DAPK2 levels were restored in APL patients undergoing ATRA therapy.

Inhibition of GATE-16 attenuates ATRA-induced neutrophil differentiation of APL cells and interferes with autophagosome formation.

Autophagy is an intracellular bulk degradation process involved in cell survival upon stress induction, but also with a newly identified function in myeloid differentiation. The autophagy-related (ATG)8 protein family, including the GABARAP and LC3 subfamilies, is crucial for autophagosome biogenesis. In order to evaluate the significance of the GABARAPs in the pathogenesis of acute myeloid leukemia (AML), we compared their expression in primary AML patient samples, CD34(+) progenitor cells and in granulocytes from healthy donors.

Protective autophagy is involved in resistance towards MET inhibitors in human gastric adenocarcinoma cells.

MET, also known as hepatocyte growth factor receptor (HGFR), is a receptor tyrosine kinase with an important role, both in normal cellular function as well as in oncogenesis. In many cancer types, abnormal activation of MET is related to poor prognosis and various strategies to inhibit its function, including small molecule inhibitors, are currently in preclinical and clinical evaluation. Autophagy, a self-digesting recycling mechanism with cytoprotective functions, is induced by cellular stress.

BIRC6 (APOLLON) is down-regulated in acute myeloid leukemia and its knockdown attenuates neutrophil differentiation.

Background: Inhibitors of apoptosis (IAPs) were intensively investigated in the context of cancer where they promote tumor growth and chemoresistence. Overexpression of the IAP BIRC6 is associated with unfavorable clinical features and negatively impacts relapse-free survival in childhood acute myeloid leukemia (AML). Currently, BIRC6 levels in adult primary AML have not been compared to the expression in normal myeloid cells.

Inhibition of damage-regulated autophagy modulator-1 (DRAM-1) impairs neutrophil differentiation of NB4 APL cells.

The damage-regulator autophagy modulator 1 (DRAM-1) is a lysosomal protein that positively regulates autophagy in a p53-dependent manner. We aimed at analyzing the role of DRAM-1 in granulocytic differentiation of APL cells. We observed a significant increase of DRAM-1 expression during all-trans retinoic acid (ATRA)-induced neutrophil differentiation of NB4 APL cells but not in ATRA-resistant NB4-R2 cells.

MicroRNA-381 represses ID1 and is deregulated in lung adenocarcinoma.

Introduction: MicroRNAs are small, noncoding RNAs that suppress gene expression by binding to the 3' untranslated region (UTR) and thereby repress translation or decrease messenger RNA stability. Inhibitor of differentiation 1 (ID1) is a putative stem-cell gene involved in invasion and angiogenesis. We previously showed that ID1 is regulated by Src kinases, overexpressed in human lung adenocarcinoma, and targeted by Src-dependent microRNAs.

PU.1 is linking the glycolytic enzyme HK3 in neutrophil differentiation and survival of APL cells.

The transcription factor PU.1 is a master regulator of myeloid differentiation and function. On the other hand, only scarce information is available on PU.