Nicotine promotes lymph node metastasis and cetuximab resistance in head and neck squamous cell carcinoma.

Epidermal growth factor (EGF) is overexpressed in many cancers and is associated with worse prognosis. EGF binds to its cell surface receptor (EGFR), which induces EGFR phosphorylation. Phosphorylated EGFR (p‑EGFR) is translocated into the nucleus, which increases cancer cell activity. Nicotine, which is one of the main components of tobacco, is absorbed through pulmonary alveoli and mucosal epithelia in the head and neck region by smoking and moves into the blood. Nicotine in blood binds to nicotinic acetylcholine receptor (nAChR) in the central nervous system and serves a crucial role in tobacco addiction. Although nAChR localization is thought to be limited in the nervous system, nAChR is present in a wide variety of non‑neuronal cells, including cancer cells. Recent studies suggest that nicotine contributes to the metastasis and resistance to anti‑cancer drugs of various cancer cells. However, it remains unknown whether head and neck squamous cell carcinoma (HNSCC) cells can utilize nicotine‑nAChR signaling to metastasize and acquire resistance to anti‑cancer drugs, even though the mucosal epithelia of the head and neck region are the primary sites of exposure to tobacco smoke. To the best of our knowledge, the present study is the first to demonstrate the role of nicotine in metastasis and anti‑EGFR‑therapy resistance of HNSCC. The present findings demonstrated that nicotine increased proliferation, migration, invasion, p‑EGFR nuclear translocation and protein kinase B (Akt) phosphorylation in HNSCC cells. It was also demonstrated that nicotine restored cetuximab‑inhibited proliferation, migration and invasion of HNSCC cells. Finally, an in vivo experiment revealed that nicotine increased lymph node metastasis of xenografted tumors, whereas an nAChR inhibitor suppressed lymph node metastasis and p‑EGFR nuclear localization of xenografted tumors. Taken together, these results demonstrated that nicotine induced nuclear accumulation of p‑EGFR, and activation of Akt signaling. These signaling pathways elevated the activities of HNSCC cells, causing lymph node metastasis and serving a role in cetuximab resistance

Reliability and validity of the Japanese version of the ADL-focused Occupation-based Neurobehavioural Evaluation (A-ONE J): Applying Rasch analysis methods.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadThe rating scale structure might be improved by collapsing two categories twice (from five categories to three categories). Unidimensionality of the items was obtained for 20 items. Targeting was acceptable, and separation reliability for item calibrations was high and acceptable for people.Conclusion/limitations: This study provides important information regarding the possibilities for revising the ordinal A-ONE J FI Scale, converting it into a unidimensional scale. Further study with increased and more diverse sample is needed.Japanese Association of Occupational Therapist

Optical conductivity of Yb1-xLuxB12 : Energy gap and mid-infrared peak in diluted Kondo semiconductors

We have measured the optical conductivity σ(ω) of Yb1-xLuxB12 (0≤x≤1), where the system evolves from a Kondo semiconductor at x=0 to a nonmagnetic metal at x=1. For x=0, σ(ω) exhibits a clear energy gap with an onset at ∼20 meV and a shoulder at 38 meV. As x increases, the gap is rapidly filled in from the bottom, while the shoulder remains at ∼40 meV up to x=1/2. These results suggest that Lu substitution into YbB12 produces an in-gap band, but the characteristic energy for the gap remains unchanged in a wide range of x. Spectral evolutions of a characteristic mid-infrared peak, which results from Yb 4f-derived states near the Fermi level, suggest a strong coupling of Yb 4f electrons with conduction electrons