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Background: tinnitus is a symptom with no specific cause known to date, and there are no associated pharmacogenomics of hearing disorders and no FDA-approved drugs for tinnitus treatment. The effectiveness of drug treatments is not reproducible on idiopathic patients and inexistent in refractory patients. Personalized treatments for these patients are a great clinical need. Our study investigated the outcome of potential alternative and complementary treatment modalities for idiopathic and refractory tinnitus patients. Methods: we were the first to evaluate the tinnitus handicap inventory (THI) score changes over the course of treatment up to 15 days after complete cessation of treatment for novel transmeatal low-level laser therapy (LLLT) modalities using light alone, as well as LLLT combined with vacuum therapy (VT), ultrasound (US), Ginkgo biloba (GB) and flunarizine dihydrochloride (FD), while also comparing all treatment outcomes with laser puncture (LP), FD alone and GB alone. Results: a positive treatment outcome (superior to a placebo effect) was achieved by using either LP or transmeatal LLLT, whereas short-term antagonistic effects of VT, US, GB and FD when combined with LLLT. For transmeatal LLLT, an improvement in the treatment outcome was observed by increasing the irradiation time from 6 min to 15 min (with 100-mW of applied laser power at 660 nm). Finally, a lasting therapeutic effect higher than the placebo was observed at 15 days after treatment upon combining LLLT with VT, GB or by using FD alone, by using the transmeatal LLLT alone or by using LP. Conclusions: LP and Transmeatal LLLT can be promising alternative treatments for idiopathic and refractory tinnitus patients. Future studies should investigate the long-term effects of LLLT in tinnitus patients, as well as the dosimetry and wavelength of transmeatal LLLT. Full article

Glioblastoma (GBM) is the most prevalent and malignant type of primary brain cancer. The rapid invasion and dissemination of tumor cells into the surrounding normal brain is a major driver of tumor recurrence, and long-term survival of GBM patients is extremely rare. Actin-rich cell membrane protrusions known as invadopodia can facilitate the highly invasive properties of GBM cells. Ion channels have been proposed to contribute to a pro-invasive phenotype in cancer cells and may also be involved in the invadopodia activity of GBM cells. GBM cell cytotoxicity screening of several ion channel drugs identified three drugs with potent cell killing efficacy: flunarizine dihydrochloride, econazole nitrate, and quinine hydrochloride dihydrate. These drugs demonstrated a reduction in GBM cell invadopodia activity and matrix metalloproteinase-2 (MMP-2) secretion. Importantly, the treatment of GBM cells with these drugs led to a significant reduction in radiation/temozolomide-induced invadopodia activity. The dual cytotoxic and anti-invasive efficacy of these agents merits further research into targeting ion channels to reduce GBM malignancy, with a potential for future clinical translation in combination with the standard therapy. Full article