PIP4K2B Protein Regulation by NSD1 in HPV-Negative Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) ranks among the most prevalent global cancers. Despite advancements in treatments, the five-year survival rate remains at approximately 66%. The histone methyltransferase NSD1, known for its role in catalyzing histone H3 lysine 36 di-methylation (H3K36me2), emerges as a potential oncogenic factor in HNSCC. Our study, employing Reverse Phase Protein Array (RPPA) analysis and subsequent validation, reveals that PIP4K2B is a key downstream target of NSD1. Notably, PIP4K2B depletion in HNSCC induces downregulation of the mTOR pathway, resulting in diminished cell growth in vitro. Our investigation highlights a direct, positive regulatory role of NSD1 on PIP4K2B gene transcription through an H3K36me2-dependent mechanism. Importantly, the impact of PIP4K2B appears to be context-dependent, with overexpression rescuing cell growth in laryngeal HNSCC cells but not in tongue/hypopharynx cells. In conclusion, our findings implicate PIP4K2B as a novel NSD1-dependent protein in HNSCC, suggesting its potential significance for laryngeal cancer cell survival. This insight contributes to our understanding of the molecular landscape in HNSCC and establishes PIP4KB as a promising target for drug development.

Surgical anatomy of the lingual lymph nodes: systematic literature analysis and proposition for topographic classification.

PURPOSE: Metastatic involvement of the lingual lymph nodes (LLNs) in oral cavity squamous cell cancer (SCC) has recently been proven to significantly reduce locoregional control and survival. Despite recent refinements in the detection of these lesions, the understanding of the LLN topographic anatomy among clinicians is limited. A proposition of a topographic division on LLN based on a comprehensive literature search and synthesis may be helpful in this condition. METHODS: A literature search and election based on contemporary PRISMA guidelines was performed for sources on LLN anatomy with special attention on their subdivision. RESULTS: Four topographic LLN subgroups were defined: median-between genioglossal and geniohyoid muscles; intermediate parahyoid-medial to the hyoglossal muscle, at the greater cornu of the hyoid bone; lateral sublingual (paraglandular) LLNs-at the sublingual salivary gland; lateral submandibular (paraglandular) LLNs -lateral to the hyoglossal muscle, at the deep surface of the submandibular salivary gland. CONCLUSION: The development and implementation of a unified anatomical topographic classification of LLN subgroups may be among the important conditions for improving the detection and treatment of LLN lesions.

The Carpentier-Edwards Classic and Physio Annuloplasty Rings in Repair of Degenerative Mitral Valve Disease: A Retrospective Study.

BACKGROUND: Physio ring (SR) is considered an improved version of the Classic rigid ring (RR). Today, SR is more widely used in mitral valve (MV) repair. We sought to compare the long-term outcomes of repair with RR and SR in degenerative mitral valve disease. METHODS: In a computerized registry of our institution, 306 patients had MV repair with either RR (139 patients) or SR (167 patients) ring between 2005 and 2015. Fifteen of them had concomitant tricuspid valve repair. Ninety-two (30.1%) had Barlow's disease and 214 (69.9%) had fibroelastic deficiency. The patients had similar demographic and echocardiographic characteristics. RESULTS: There were 4 (1.3%) operative mortalities. Mean follow-up time was 107.4 ± 13.2 months. Left ventricular end diastolic and end systolic diameters significantly improved in both groups but not between groups. Survival at 10 years was 84.6% (93.1% in RR and 91.5% in SR; p = 0.177) and 10-year freedom from recurrent MR ≥ 2+ was 74.5% (88.2% in RR and 86.3% in SR; p = 0.110). Reoperations for repair failure were 8 in RR and 6 in SR. By Cox regression analysis, Barlow's disease and preoperative MR = 4+ were predictors of repair failure. Old age (≥70 years), NYHA functional class IV and pulmonary artery systolic pressure (≥40 mmHg) were predictors of poor survival by univariate analysis. CONCLUSION: Long-term outcomes of repair for degenerative MV disease with the Classic and Physio rings are comparable. We also reiterate the importance of large size annuloplasty rings for Barlow's disease to avoid the incidence left ventricular outflow obstruction.