PLOD2 is essential to functional activation of integrin β1 for invasion/metastasis in head and neck squamous cell carcinomas.

Identifying the specific functional regulator of integrin family molecules in cancer cells is critical because they are directly involved in tumor invasion and metastasis. Here we report high expression of PLOD2 in oropharyngeal squamous cell carcinomas (SCCs) and its critical role as a stabilizer of integrin β1, enabling integrin β1 to initiate tumor invasion/metastasis. Integrin β1 stabilized by PLOD2-mediated hydroxylation was recruited to the plasma membrane, its functional site, and accelerated tumor cell motility, leading to tumor metastasis in vivo, whereas loss of PLOD2 expression abrogated it. In accordance with molecular analysis, examination of oropharyngeal SCC tissues from patients corroborated PLOD2 expression associated with integrin β1 at the invasive front of tumor nests. PLOD2 is thus implicated as the key regulator of integrin β1 that prominently regulates tumor invasion and metastasis, and it provides important clues engendering novel therapeutics for these intractable cancers

Neural mechanisms of motion sickness

Three kinds of neurotransmitters : histamine, acetylcholine and noradrenaline, play important roles in the neural processes of motion sickness, because antihistamines, scopolamine and amphetamine are effective in preventing motion sickness. Histamine H1-receptors are involved in the development of the symptoms and signs of motion sickness, including emesis. On provocative motion stimuli, a neural mismatch signal activates the histaminergic neuron system in the hypothalamus, and the histaminergic descending impulse stimulates H1-receptors in the emetic center of the brainstem. The histaminergic input to the emetic center through H1-receptors is independent of dopamine D2-receptors in the chemoreceptor trigger zone in the area postrema and serotonin 5HT3-receptors in the visceral afferent, which are also involved in the emetic reflex. Antihistamines block emetic H1-receptors to prevent motion sickness. Scopolamine prevents motion sickness by modifying the neural store to reduce the neural mismatch signal and by facilitating the adaptation/habituation processes. The noradrenergic neuron system in the locus coeruleus is suppressed by the neural mismatch signal. Amphetamine antagonizes mismatch-induced suppression of noradrenergic neural transmission, resulting in preventing motion sickness

The effect of visual-vestibulosomatosensory conflict induced by virtual reality on postural stability in humans

In this study, we examined the effects of sensory inputs of visual-vestibulosomatosensory conflict induced by virtual reality (VR) on subjective dizziness, posture stability and visual dependency on postural control in humans. Eleven healthy young volunteers were immersed in two different VR conditions. In the control condition, subjects walked voluntarily with the background images of interactive computer graphics proportionally synchronized to their walking pace. In the visual-vestibulosomatosensory conflict condition, subjects kept still, but the background images that subjects experienced in the control condition were presented. The scores of both Graybiel’s and Hamilton’s criteria, postural instability and Romberg ratio were measured before and after the two conditions. After immersion in the conflict condition, both subjective dizziness and objective postural instability were significantly increased, and Romberg ratio, an index of the visual dependency on postural control, was slightly decreased. These findings suggest that sensory inputs of visual-vestibulosomatosensory conflict induced by VR induced motion sickness, resulting in subjective dizziness and postural instability. They also suggest that adaptation to the conflict condition decreases the contribution of visual inputs to postural control with re-weighing of vestibulosomatosensory inputs. VR may be used as a rehabilitation tool for dizzy patients by its ability to induce sensory re-weighing of postural control

Chemoradiotherapy with 3-weekly CDDP 80 mg/m2 for head and neck squamous cell carcinoma: 5-year survival data from a phase 2 study

ObjectiveThe global standard for chemoradiation therapy (CCRT) for head and neck squamous cell carcinoma is cisplatin 100 mg/m2 administered once every three weeks, although cisplatin 80 mg/m2 is also widely used as an alternative treatment to reduce adverse events in Japan. We aimed to assess the long-term survival outcomes and late adverse events associated with CCRT with a 3-weekly cisplatin dose of 80 mg/m2.MethodsA phase 2 study on CCRT with a 3-weekly cisplatin dose of 80 mg/m2 was performed in 47 patients between April 2015 and December 2016 at four centers in Japan. Survival outcomes and late adverse events at 5 years after this phase 2 trial were investigated.ResultsThe median follow-up period was 61 months. The 5-year progression-free survival/overall survival of all 47 patients was 66.0%/76.6%, while that of patients with stage III, IV disease (UICC) was 65.6%/71.9%. Seventeen patients (36%) experienced dysphagia as a late adverse event. Univariate and multivariate analyses revealed a significant association between acute mucositis/low body mass index (BMI) during CCRT and late dysphagia.ConclusionThe survival outcomes of CCRT with a 3-weekly cisplatin dose of 80 mg/m2 may be comparable to the previously reported dose of 100 mg/m2. Acute mucositis and low BMI at CCRT were risk factors for late dysphagia, indicating the importance of managing these conditions during CCRT to prevent late adverse events. Caution and care for acute mucositis and swallowing training in patients with low BMI may be important for preventing late-stage dysphagia

Asymptomatic diffuse idiopathic skeletal hyperostosis as a potential risk for severe dysphagia following partial laryngopharyngectomy

Diffuse idiopathic skeletal hyperostosis (DISH) is a common disease in which ossification lesions occur in the bones including the vertebrae. Dysphagia may occur in advanced cases, but there are few cases that require treatment. A 68-year-old man was diagnosed with hypopharyngeal cancer of the left pyriform sinus and asymptomatic DISH on the anterior cervical vertebrae. Due to prior history of radiation, partial laryngopharyngectomy was performed. After surgery, severe dysphagia and aspiration pneumonia occurred, and the patient needed to undergo total laryngectomy. It was determined that dysphagia was due to multiple factors, including insufficient laryngeal elevation and esophageal compression by osteophytes of DISH. Asymptomatic DISH can cause severe dysphagia after partial laryngopharyngectomy. We suggest that evaluation of the swallowing function and surgical options, including laryngeal suspension and cricopharyngeal myotomy should be considered when performing partial laryngopharyngectomy in patients with DISH, even if they demonstrated no difficulties in swallowing before treatment

Endoscopic repair through the medial wall of maxillary sinus for blowout fracture of the inferior orbital wall: a case report

Endoscopic medial maxillectomy (EMM) was originally developed for surgery of maxillary sinus disease. This surgery was recently modified to preserve the inferior turbinate (IT) and the nasolacrimal duct (ND) and is commonly referred to endoscopic modified medial maxillectomy (EMMM). Here we present a case of endoscopic repair for a blowout fracture of the inferior orbital wall via access through the medial wall of the maxillary sinus, thereby preserving IT and ND, similar to EMMM. Two months postoperatively, a diplopia field test, computed tomography, and endoscopic observation were performed. Good recovery of diplopia was obtained, and empty nose syndrome, epiphora, and cheek numbness were not observed. Those complications such as empty nose syndrome, epiphora and cheek numbness can be avoided by the approach presented in this report; therefore, the maxillary medial wall approach, like EMMM, could become a preferred surgical method for blowout fractures of the inferior orbital wall