Immediate Effects of Mindfulness Meditation on the Voice.

OBJECTIVES: The benefits of mindfulness meditation are well documented. This study evaluated the immediate effects of mindfulness meditation (MM) on the voice and voice user. STUDY DESIGN: Prospective experimental study. METHODS: Participants: 19 vocally healthy (VH) individuals, and 26 individuals with common voice disorders (CVD; benign lesions and hyperfunctional muscle tension) deemed stimulable for voice therapy. Exclusionary criteria: prior training or regular meditation practice. Participants recorded speech samples before and after a 11.5-minute prerecorded session of MM. PRIMARY OUTCOMES: phonatory aerodynamics and participants' self-reported experience of voice. SECONDARY OUTCOMES: self-reported anxiety, vocal acoustics, speech breathing patterns, and auditory-perceptual outcomes. Baseline self-reported measures of voice (Voice Handicap Index-10 - VHI-10), breathing (Dyspnea Index - DI), stress (Perceived Stress Scale - PSS), and trait mindfulness (Cognitive and Mindfulness Scale - Revised, CAMS-R, Five Facet Mindfulness Questionnaire - FFMQ) were compared between groups. RESULTS: At baseline, CVD had significantly higher VHI-10 (P< 0.001) and DI (P= 0.0014), and lower trait mindfulness (CAMS-R, P= 0.02). No difference between groups for PSS or FFMQ. Changes postMM: decreased CPP for all-voiced sentences for VH (P= 0.003), decreased mean SPL (P= 0.012) on sustained vowel for VH, increased mean phonatory airflow during sustained vowel for CVD (P = 0.012). VH demonstrated a decrease in CPP on the all-voice sentence, and CVD demonstrated an increase, resulting in a significant between group difference (P= 0.013). Participants reported improvements in voice, emotional and physical states. State anxiety decreased for both groups (= < 0.001). No other objective outcomes reached significance. CONCLUSIONS: After a brief MM, participants experienced improvement in physical, emotional, and cognitive states, and in their perceptions of their voice. Results indicate that a brief, single session of MM may be beneficial for some, but not sufficient to override habitual voice and speech patterns. Given the benefits of MM, future work should evaluate MM in a standard voice therapy protocol.

Acquired Resistance to Antiangiogenic Therapies in Hepatocellular Carcinoma Is Mediated by Yes-Associated Protein 1 Activation and Transient Expansion of Stem-Like Cancer Cells.

Induction of neoangiogenesis is a hallmark feature during disease progression of hepatocellular carcinoma (HCC). Antiangiogenetic compounds represent a mainstay of therapeutic approaches; however, development of chemoresistance is observed in the majority of patients. Recent findings suggest that tumor-initiating cells (TICs) may play a key role in acquisition of resistance, but the exact relevance for HCC in this process remains to be defined. Primary and established hepatoma cell lines were exposed to long-term sorafenib treatment to model acquisition of resistance. Treatment effects on TICs were estimated by sphere-forming capacity in vitro, tumorigenicity in vivo, and flow cytometry. Adaptive molecular changes were assessed by whole transcriptome analyses. Compensatory mechanisms of resistance were identified and directly evaluated. Sustained antiproliferative effect following sorafenib treatment was observed in three of six HCC cell lines and was followed by rapid regrowth, thereby mimicking responses observed in patients. Resistant cells showed induction in sphere forming in vitro and tumor-initiating capacity in vivo as well as increased number of side population and epithelial cell adhesion molecule-positive cells. Conversely, sensitive cell lines showed consistent reduction of TIC properties. Gene sets associated with resistance and poor prognosis, including Hippo/yes-associated protein (YAP), were identified. Western blot and immunohistochemistry confirmed increased levels of YAP. Combined treatment of sorafenib and specific YAP inhibitor consistently revealed synergistic antioncogenic effects in resistant cell lines. Conclusion: Resistance to antiangiogenic therapy might be driven by transient expansion of TICs and activation of compensatory pro-oncogenic signaling pathways, including YAP. Specific targeting of TICs might be an effective therapeutic strategy to overcome resistance in HCC.

Ginkgo biloba induces different gene expression signatures and oncogenic pathways in malignant and non-malignant cells of the liver.

Ginkgo biloba (EGb761) is a widely used botanical drug. Several reports indicate that EGb761 confers preventive as well as anti-tumorigenic properties in a variety of tumors, including hepatocellular carcinoma (HCC). We here evaluate functional effects and molecular alterations induced by EGb761 in hepatoma cells and non-malignant hepatocytes. Hepatoma cell lines, primary human HCC cells and immortalized human hepatocytes (IH) were exposed to various concentrations (0-1000 µg/ml) of EGb761. Apoptosis and proliferation were evaluated after 72h of EGb761 exposure. Response to oxidative stress, tumorigenic properties and molecular changes were further investigated. While anti-oxidant effects were detected in all cell lines, EGb761 promoted anti-proliferative and pro-apoptotic effects mainly in hepatoma cells. Consistently, EGb761 treatment caused a significant reduction in colony and sphere forming ability in hepatoma cells and no mentionable changes in IH. Transcriptomic changes involved oxidative stress response as well as key oncogenic pathways resembling Nrf2- and mTOR signaling pathway. Taken together, EGb761 induces differential effects in non-transformed and cancer cells. While treatment confers protective effects in non-malignant cells, EGb761 significantly impairs tumorigenic properties in cancer cells by affecting key oncogenic pathways. Results provide the rational for clinical testing of EGb761 in preventive and therapeutic strategies in human liver diseases.