The Effects of Model Aromatic Lignin Compounds On Growth and Lipid Accumulation of \u3ci\u3eRhodococcus rhodochrous\u3c/i\u3e

Lignocellulosic biomass is one of the most abundant and renewable organic materials in the world. The lignocellulosic complex is composed of cellulose, hemicellulose, and lignin, which can be pretreated to release sugars that can be utilized for microbial production of valued metabolites. Oleaginous microbes can accumulate over 20% of their cell dry weight as lipids, which are stored as intracellular energy reserves. The characterization of oleaginous bacteria creates opportunities for the development of alternative feedstocks and technologies. Rhodococcus rhodochrous is a bacterium recently determined to be oleaginous when grown in glucose-supplemented media. The purpose of this study was to evaluate model lignin phenolic compounds as substrates for lipid accumulation. Lipid accumulation in R. rhodochrous was evaluated using phenol, 4-hydroxybenzoic acid (HBA) and vanillic acid (VA) as model lignin compounds with and without glucose as a co-substrate. Cell dry weight increased in all treatments, indicating that growth was not impaired in these conditions. However, alterations were observed in the amount of lipids produced. Dry cell weight and lipids were analyzed daily. R. rhodochrous accumulated over 40% of its cell dry weight as lipids when grown in glucose with HBA and VA, but less than 20% when grown in HBA and VA alone. When grown in phenol and glucose, R. rhodochrous accumulated 35% of its dry weight at lipids, but did not accumulate lipids when grown in phenol alone. These data indicate that R. rhodochrous may have the capability to tolerate and utilize lignin-like aromatic compounds for lipid accumulation

A Phase II study of neoadjuvant axitinib for reducing the extent of venous tumour thrombus in clear cell renal cell cancer with venous invasion (NAXIVA).

BACKGROUND: Surgery for renal cell carcinoma (RCC) with venous tumour thrombus (VTT) extension into the renal vein (RV) and/or inferior vena cava (IVC) has high peri-surgical morbidity/mortality. NAXIVA assessed the response of VTT to axitinib, a potent tyrosine kinase inhibitor. METHODS: NAXIVA was a single-arm, multi-centre, Phase 2 study. In total, 20 patients with resectable clear cell RCC and VTT received upto 8 weeks of pre-surgical axitinib. The primary endpoint was percentage of evaluable patients with VTT improvement by Mayo level on MRI. Secondary endpoints were percentage change in surgical approach and VTT length, response rate (RECISTv1.1) and surgical morbidity. RESULTS: In all, 35% (7/20) patients with VTT had a reduction in Mayo level with axitinib: 37.5% (6/16) with IVC VTT and 25% (1/4) with RV-only VTT. No patients had an increase in Mayo level. In total, 75% (15/20) of patients had a reduction in VTT length. Overall, 41.2% (7/17) of patients who underwent surgery had less invasive surgery than originally planned. Non-responders exhibited lower baseline microvessel density (CD31), higher Ki67 and exhausted or regulatory T-cell phenotype. CONCLUSIONS: NAXIVA provides the first Level II evidence that axitinib downstages VTT in a significant proportion of patients leading to reduction in the extent of surgery. CLINICAL TRIAL REGISTRATION: NCT03494816