SOCS1 Gene Therapy for Head and Neck Cancers: An Experimental Study.

BACKGROUND/AIM: Head and neck squamous cell carcinoma (HNSCC) is a fatal and debilitating disease, which is characterized by steady, poor survival rates despite advances in treatment. Suppressor of cytokine signaling (SOCS) 1 is up-regulated following cytokine-induced Janus kinase - signal transducer and activator of transcription (JAK-STAT) pathway activation, and inhibitors of cytokine signaling play roles in regulating cell growth and differentiation. We investigated the therapeutic potential of SOCS1 for HNSCC. MATERIALS AND METHODS: We used cell lines of oropharyngeal and tongue cancers (Detroit-562 and SCC-9, respectively) and a recombinant adenovirus vector expressing SOCS1 (AdSOCS1). RESULTS: AdSOCS1-induced SOCS1 overexpression significantly decreased cell proliferation through G2M phase cell cycle arrest and apoptosis. AdSOCS1 inhibited cell growth more strongly in SCC-9 cells than in Detroit-562 cells. JAK inhibitor I induced cell cycle arrest at the G0/G1 and GfM phases in Detroit-562 and SCC-9 cells, respectively. AdSOCS1 also decreased the activity of phosph-STAT3 (pSTAT3) and phosphop44/42 mitogen-activated protein kinase (p-p44/42 MAPK), as well as the expression of the anti-apoptotic protein B-cell lymphoma-extra large (Bcl-xL). JAK inhibitor I decreased the expression of pSTAT3, but not p-p44/42 or Bcl-xL. The MAPK/extracellular signal-regulated kinase (MEK) inhibitor, U0126, decreased the expression of Bcl-xL in SCC-9 cells, but not in Detroit-562 cells. AdSOCS1 treatment inhibited tumor growth in mouse xenograft models. CONCLUSION: Overexpression of SOCS1 has a potent antitumor effect on HNSCC, suggesting the potential for clinical use. The varying effectiveness among cancer cells by over expression of SOCS1 may contribute to efficacy of SOCS 1 gene therapy for clinical use.

Changes during medical treatments before adenotonsillectomy in children with obstructive sleep apnea.

OBJECTIVES: The severity of pediatric obstructive sleep apnea (OSA) can vary from mild to very severe (AHI ≥ 30 events/h) with the seasons. The efficacy of medical treatment has been investigated in cases of mild and moderate pediatric OSA, but not in severe cases thoroughly. METHODS: Our prospective cohort study involved 205 children who visited our outpatient clinic between December 2014 and May 2020. We performed home sleep tests after the initial visit, and then polysomnography after optimizing the control of rhinitis, sinusitis, adenoid hypertrophy, and tonsillitis by using medical treatments. RESULTS: The respective proportions of patients who improved to obstructive AHI (O-AHI) < 1/h or who proceeded to surgery were 43.4% and 62.3% in mild cases; 43.3% and 52.2% in moderate cases; 30.2% and 68.4% in severe cases; and 0.0% and 100% in very severe cases. Additionally, nadir SaO2 improved significantly between before and after medical treatment in both O-AHI < 1/h and O-AHI ≥ 1/h patients (respectively p < 0.0001, p = 0.0009). The lowest nadir SaO2 before medical treatment was 74% in patients in whom O-AHI was normalized after medical treatments. CONCLUSION: Medical treatment instituted before a surgical decision is made can provide substantial benefits and avoid unnecessary surgery if there is time for such treatments. In contrast, it may be difficult to normalize the O-AHI in pediatric patients with very severe OSA or a nadir SaO2 of less than 74% by medical treatment.

Laryngeal malignant peripheral nerve sheath tumor mixed with high- and low-grade malignancies.

Malignant peripheral nerve sheath tumors (MPNSTs), as defined by immunohistochemical evaluation, are identified along a spectrum ranging from atypical neurofibroma to high-grade MPNST because these tumors are similar in terms of cell shape and tissue components on hematoxylin-eosin (HE) staining. The patient was a 57-year-old male referred to our hospital, with a recurrent red tumor at the anterior commissure of the larynx and submucosal swelling of the right vocal fold. A surgical specimen from a right horizontal partial laryngectomy was evaluated immunohistochemically. A high-grade MPNST lesion was included in the submucosal white tumor, whereas a low-grade MPNST lesion was encountered around the high-grade MPNST lesion. This tumor may involve different malignancies even when it is small. Although intra-tumor heterogeneity in cancers has been reported recently, careful immunohistochemical examination can be important and beneficial for eradicating the tumor while preserving vocal function.

Apnea hypopnea indices categorized by REM/NREM sleep and sleep positions in 100 children with adenotonsillectomy for obstructive sleep apnea disease.

OBJECTIVES: In pediatric obstructive sleep apnea (OSA), the relationship between rapid eye movement sleep and upper airway collapse, and between sleep position and airway dimensions are well known. However, the interrelations between these factors and the obstructive apnea hypopnea index (O-AHI) have not been thoroughly investigated. METHODS: A retrospective study including 100 children who underwent adenotonsillectomy between March 2010 and July 2017. Total O-AHI was divided into four subcategories by sleep stage and position. RESULTS: Preoperatively 14 of 47 mild cases of OSA (1 ≤ total O-AHI) and 17 of 18 moderate (5 ≤ total O-AHI) had time showing severe apnea (10 ≤ subcategorized O-AHI). Twenty-two of 24 severe cases (10 ≤ total O-AHI) exhibited very severe apnea (30 ≤ subcategorized O-AHI). All 11 very severe cases (30 ≤ total O-AHI) experienced more than 50 apnea events per hour in at least one of the O-AHI subcategories. After surgery, 23 of 70 cases classified as completely resolved (total O-AHI < 1) still had mild apnea in the O-AHI subcategories, and six of 13 cases who continued to experience apnea events had moderate-to-severe apnea. Seventeen cases worsened in the O-AHI subcategories, and total O-AHI deteriorated in two cases of the 17. The amount of REM sleep and use of the supine position increased significantly postoperatively in the quartile groups with the lowest baseline values (p < 0.0001). CONCLUSIONS: When an unexpected AHI value is encountered, the O-AHI subcategories may be informative regarding the indications for surgery and evaluating the efficacy thereof.