Explore the vast range of titles available.

Among patients with smoldering multiple myeloma at high risk for progression, progression-free survival at 5 years was 63.1% with daratumumab monotherapy, as compared with 40.8% with active monitoring.

Mutant KRAS is a major driver of oncogenesis in a multitude of cancers but remains a challenging target for classical small molecule drugs, motivating the exploration of alternative approaches. Here, we show that aggregation-prone regions (APRs) in the primary sequence of the oncoprotein constitute intrinsic vulnerabilities that can be exploited to misfold KRAS into protein aggregates. Conveniently, this propensity that is present in wild-type KRAS is increased in the common oncogenic mutations at positions 12 and 13. We show that synthetic peptides (Pept-ins™) derived from two distinct KRAS APRs could induce the misfolding and subsequent loss of function of oncogenic KRAS, both of recombinantly produced protein in solution, during cell-free translation and in cancer cells. The Pept-ins exerted antiproliferative activity against a range of mutant KRAS cell lines and abrogated tumor growth in a syngeneic lung adenocarcinoma mouse model driven by mutant KRAS G12V. These findings provide proof-of-concept that the intrinsic misfolding propensity of the KRAS oncoprotein can be exploited to cause its functional inactivation.

Since 2003, the pig industry in Flanders (Belgium) is obliged to process a portion of the nutrient overproduction. In general, pig manure processing occurs as follows: i) separation into liquid and solid fractions, ii) conversion of the solid fraction to an exportable product (e.g. composting) and iii) reduction of nutrient contents in the liquid fraction before discharge into surface water or spreading on arable land. The aim of this study was to evaluate the potential of constructed wetlands (CWs) planted with Phragmites australis to reduce nitrogen (N), phosphorus (P) and chemical oxygen demand (COD) in the liquid fraction to levels below discharge criteria. In addition, the removal efficiency of heavy metals (Cu, Zn) present at elevated levels in the liquid fraction was evaluated. A greenhouse experiment was conducted with subsurface flow (SSF) reed beds (2 × 0.125 × 0.11 m) filled with sand, loam, clayey sand or expanded clay (argex). The liquid manure load was set at 1 mm per day. Removal efficiencies varied between 64-75% for COD, 73-83% for N and 71-92% for P, depending on the matrix material used. However, effluent levels still remained significantly above the Flemish legal discharge criteria of 2 mgl^sup -1^, 15 mgl^sup -1^ and 125 mgl^sup -1^ for P, N and COD respectively.[PUBLICATION ABSTRACT]

The removal of Co, Ni, Cu and Zn from synthetic industrial wastewater was studied in subsurface flow constructed wetland microcosms filled with gravel or a gravel/straw mixture. Half of the microcosms were planted with Phragmites australis and half were left unplanted. All microcosms received low-strength wastewater (1 mg L−1 of Co, Ni, and Zn, 0.5 mg L−1 Cu, 2,000 mg L−1 SO4) during seven 14-day incubation batches. The pore water was regularly monitored at two depths for heavy metals, sulphate, organic carbon and redox potential. Sorption properties of gravel and straw were assessed in a separate experiment. A second series of seven incubation batches with high-strength wastewater (10 mg L−1 of each metal, 2,000 mg L−1 SO4) was then applied to saturate the substrate. Glucose was added to the gravel microcosms together with the high-strength wastewater. Sorption processes were responsible for metal removal during start-up, with the highest removal efficiencies in the gravel microcosms. The lower initial efficiencies in the gravel/straw microcosms were presumably caused by the decomposition of straw. However, after establishment of anaerobic conditions (Eh∼−200 mV), precipitation as metal sulphides provided an additional removal pathway in the gravel/straw microcosms. The addition of glucose to gravel microcosms enhanced sulphate reduction and metal removal, although Phragmites australis negatively affected these processes in the top-layer of all microcosms.

Abstract Protein aggregation is an underappreciated mechanism that may contribute to the loss- and oncogenic-gain-of-function of mutant tumor suppressors such as p53 and axin. In the present study, we describe amyloid-like aggregation behaviour of the second most frequently mutated tumor suppressor in human cancer, PTEN. In silico analysis revealed a particularly high aggregation vulnerability for this protein, which was corroborated by in vitro aggregation assays. In cultured tumor cells, we found that under stress conditions, PTEN readily undergoes amyloid-like aggregation as a result of mutation. However, we also show that severe dysregulation of protein homeostasis may lead to aggregation of wild-type PTEN. These observations were supported by a small survey of patient-derived uterine tumor tissues, which found that more than 25% of tumors analyzed displayed wild-type PTEN aggregation. Finally, in an exploratory clinical study we found that PTEN aggregation status was correlated with a decline in clinical outcome. Our findings establish that the tumor suppressor PTEN is highly aggregation-prone and our work suggests that protein aggregation might be an underestimated but prevalent component of cancer cell biology. Competing Interest Statement The authors have declared no competing interest.