The use of a standardized Chinese herbal formula in patients with advanced lung cancer: a feasibility study.

OBJECTIVE: Increasing numbers of cancer patients are using Chinese herbs (CHs). However, differences among prior studies make it difficult to draw firm conclusions about the clinical usefulness of any specific CH formula. The primary objective of this study was to establish the acceptability of taking a standardized CH formula for patients with advanced lung cancer. The secondary objective was to identify any toxicities attributable to this CH formula and to measure changes in quality of life. METHODS: A single-arm, prospective study of a 6-week intervention with a selected CH formula in 15 patients with stage 4 nonsmall-cell lung cancer (NSCLC, Seventh American Joint Committee on Cancer TNM staging system). RESULTS: Patients with advanced lung cancer were interested in using the CH formula. Completion (93%) and adherence (98%) levels were very high and most patients perceived the CH treatment as easy to take and were willing to take the CHs used in the study again if it was available. About half of the patients reported adverse events, all of which were mild (Grade 1 or 2) and only a small minority (8%) were potentially related to CHs. No biochemical or hematological evidence of toxicity was observed. Overall, there were improvement in quality of life, and reduced feelings of tiredness and sleepiness. CONCLUSION: This study provides preliminary evidence that short-term use of a carefully selected and prepared CH formula in patients with stage 4 NSCLC is acceptable and safe.

Knockout of USP19 Deubiquitinating Enzyme Prevents Muscle Wasting by Modulating Insulin and Glucocorticoid Signaling.

Muscle atrophy arises because of many chronic illnesses, as well as from prolonged glucocorticoid treatment and nutrient deprivation. We previously demonstrated that the USP19 deubiquitinating enzyme plays an important role in chronic glucocorticoid- and denervation-induced muscle wasting. However, the mechanisms by which USP19 exerts its effects remain unknown. To explore this further, we fasted mice for 48 hours to try to identify early differences in the response of wild-type and USP19 knockout (KO) mice that could yield insights into the mechanisms of USP19 action. USP19 KO mice manifested less myofiber atrophy in response to fasting due to increased rates of protein synthesis. Insulin signaling was enhanced in the KO mice, as revealed by lower circulating insulin levels, increased insulin-stimulated glucose disposal and phosphorylation of Akt and S6K in muscle, and improved overall glucose tolerance. Glucocorticoid signaling, which is essential in many conditions of atrophy, was decreased in KO muscle, as revealed by decreased expression of glucocorticoid receptor (GR) target genes upon both fasting and glucocorticoid treatment. This decreased GR signaling was associated with lower GR protein levels in the USP19 KO muscle. Restoring the GR levels in USP19-deficient muscle was sufficient to abolish the protection from myofiber atrophy. Expression of GR target genes also correlated with that of USP19 in human muscle samples. Thus, USP19 modulates GR levels and in so doing may modulate both insulin and glucocorticoid signaling, two critical pathways that control protein turnover in muscle and overall glucose homeostasis.