Biotransformation of the UV-Filter Sulisobenzone: Challenges for the Identification of Transformation Products

The UV-filter substance Sulisobenzone (BP-4) is widely employed in sunscreens and other personal care products. In the current study, its behavior during biological wastewater treatment was investigated. In contact with activated sludge BP-4 was degraded in aerobic batch experiments forming at least nine transformation products (TPs). The mass balance in the batch experiments was closed, as measurements with LC-UV underlined that the quantity of the TPs was comparable to the BP-4 quantity transformed. The chemical structures of the nine TPs could be proposed based on accurate mass measurements by high resolution mass spectrometry (LTQ-Orbitrap-MS), several fragmentation experiments up to MS⁶ and synthesis of one TP. NMR analyses of the main TP confirmed its proposed chemical structure. At the beginning of the biotransformation of BP-4, a benzhydrol analogue was formed due to the reduction of the keto moiety. Further reactions (e.g., oxidation, demethylation, decarboxylation) led to the formation of extremely polar TPs. A biodegradation pathway was proposed based on the TP structures identified and the sequence of the TP formation. The isolated TPs exhibited higher toxic effects on <i>Vibrio fischeri</i> than BP-4. The results contribute to a better general understanding and prediction of the biotransformation of aromatic sulfonic acids in WWTPs

Loss or Inhibition of Stromal-Derived PlGF Prolongs Survival of Mice with Imatinib-Resistant Bcr-Abl1(+) Leukemia (vol 19, pg 740, 2011)

status: publishe

Loss or inhibition of stromal-derived PlGF prolongs survival of mice with imatinib-resistant Bcr-Abl1⁺leukemia

Imatinib has revolutionized the treatment of Bcr-Abl1&lt;sup&gt;+&lt;/sup&gt; chronic myeloid leukemia (CML), but, in most patients, some leukemia cells persist despite continued therapy, while others become resistant. Here, we report that PlGF levels are elevated in CML and that PlGF produced by bone marrow stromal cells (BMSCs) aggravates disease severity. CML cells foster a soil for their own growth by inducing BMSCs to upregulate PlGF, which not only stimulates BM angiogenesis, but also promotes CML proliferation and metabolism, in part independently of Bcr-Abl1 signaling. Anti-PlGF treatment prolongs survival of imatinib-sensitive and -resistant CML mice and adds to the anti-CML activity of imatinib. These results may warrant further investigation of the therapeutic potential of PlGF inhibition for (imatinib-resistant) CML