Cancer Res. 2009 Aug 25; Wang Y, Ma X, Yan S, Shen S, Zhu H, Gu Y, Wang H, Qin G, Yu QConstitutive activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway occurs frequently in cancer cells and contributes to oncogenesis. Among the members of STAT family, STAT3 plays a pivotal role in the development and progression of human tumors. The STAT3-mediated signaling pathway has been recognized as a promising anticancer target. Here, we show that 17-Hydroxy-jolkinolide B (HJB), a diterpenoid from the Chinese medicinal herb Euphorbia fischeriana Steud, strongly inhibits interleukin (IL)-6-induced as well as constitutive STAT3 activation. Furthermore, we show that HJB directly targets the JAK family kinases, JAK1, JAK2, and TYK2, by inducing dimerization of the JAKs via cross-linking. Addition of DTT or glutathione prevents the JAK cross-linking and blocks the inhibitory effects of HJB on IL-6-induced STAT3 activation, suggesting that HJB may react with cystein residues of JAKs to form covalent bonds that inactivate JAKs. Liquid chromatography/mass spectrometry analysis confirmed that each HJB reacted with two thiols. The effect of HJB on the JAK/STAT3 pathway is specific as HJB has no effect on platelet-derived growth factor, epidermal growth factor, or insulin-like growth factor I signaling pathways. Finally, we show that HJB inhibits growth and induces apoptosis of tumor cells, particularly those tumor cells with constitutively activated STAT3. We propose that the natural compound HJB is a promising anticancer drug candidate as a potent STAT3 signaling inhibitor. [Cancer Res 2009;69(18):OF1-9].

Mov Disord. 2009 Aug 24; Kompoliti K, Fan W, Leurgans SThe aim of this study was to describe the use of complementary and alternative medicine (CAM) in patients with Tourette syndrome (TS) and explore associations with CAM use. In recent years CAM use has increased, but rates of CAM use in TS patients are not reported. Consecutive TS patients or their parent(s), seen in an academic movement disorder center, completed a questionnaire regarding their use of CAM. One hundred TS patients or parents completed the questionnaire, mean age 21.5 +/- 13.5, 76 males, 87 Caucasians. Sixty four patients had used at least one CAM modality. CAM treatments used were prayer (28), vitamins (21), massage (19), dietary supplements (15), chiropractic manipulations (12), meditation (10), diet alterations (nine), yoga (nine), acupuncture (eight), hypnosis (seven), homeopathy (six), and EEG biofeedback (six). Fifty six percent of patients using CAM reported some improvement. Users paid out of pocket for 47% of treatments pursued, and 19% of these payers received partial reimbursement by third party payer. Users and non-users did not differ in age, gender, race, income, educational level, general health, tic severity, medication use for TS, current satisfaction from medications or experience of side effects from medications. CAM use was associated with the presence of affective disorder (P = 0.004), but not with either ADHD or OCD. Among CAM users, 80% initiated CAM without informing their doctor. CAM is commonly used in children and adults with TS, and often without the neurologist's knowledge. Physicians should inquire about CAM to understand the spectrum of interventions that patients with TS use. (c) 2009 Movement Disorder Society.