PRKCA Overexpression Is Frequent in Young Oral Tongue Squamous Cell Carcinoma Patients and Is Associated with Poor Prognosis.

Oral tongue squamous cell carcinomas (OTSCCs) have an increasing incidence in young patients, and many have an aggressive course of disease. The objective of this study was to identify candidate prognostic protein markers associated with early-onset OTSCC. We performed an exploratory screening for differential protein expression in younger (≤45 years) versus older (>45 years) OTSCC patients in The Cancer Genome Atlas (TCGA) cohort (n = 97). Expression of candidate markers was then validated in an independent Austrian OTSCC patient group (n = 34) by immunohistochemistry. Kaplan-Meier survival estimates were computed, and genomic and mRNA enrichment in silico analyses were performed. Overexpression of protein kinase C alpha (PRKCA) was significantly more frequent among young patients of both the TCGA (p = 0.0001) and the Austrian cohort (p = 0.02), associated with a negative anamnesis for alcohol consumption (p = 0.009) and tobacco smoking (p = 0.02) and poorer overall survival (univariate p = 0.02, multivariate p< 0.01). Within the young subgroup, both overall and disease-free survival were significantly decreased in patients with PRKCA overexpression (both p < 0.001). TCGA mRNA enrichment analysis revealed 332 mRNAs with significant differential expression in PRKCA-upregulated versus PRKCA-downregulated OTSCC (all FDR ≤ 0.01). Our findings suggest that PRKCA overexpression may be a hallmark of a novel molecular subtype of early-onset alcohol- and tobacco-negative high-risk OTSCC. Further analysis of the molecular PRKCA interactome may decipher the underlying mechanisms of carcinogenesis and clinicopathological behavior of PRKCA-overexpressing OTSCC.

HS-173, a selective PI3K inhibitor, induces cell death in head and neck squamous cell carcinoma cell lines.

BACKGROUND: The selective PI3K (Phosphatidylinositol 3-kinase) inhibitor HS-173 has anticancer activity in non-small cell lung cancer and pancreatic cancer cells. Of all head and neck squamous cell carcinomas (HNSCC) 20% harbor specific mutations in the genome. The aim of this study was to investigate the effect of HS-173 on HNSCC cell lines. METHODS: The cell lines SCC25, CAL27 and FaDu were incubated with HS-173. Its antiproliferative effect was determined using the CCK­8 cell proliferation assay. Combined incubation with cisplatin was performed and combination index analysis was conducted. To investigate its effect on radiotherapy, cells were irradiated with 2, 4, 6 and 8 Gy, respectively. Synergistic effects of radiation and HS-173 were measured by proliferation assays and clonogenic survival. RESULTS: The use of HS-173 induced significant reduction of cell proliferation across all cell lines. Most interestingly, it showed a synergistic effect with cisplatin treatment. Clonogenic survival revealed a radiosensitizing effect in CAL27 and FaDu cells. The HS-173 caused significant induction of apoptosis in SCC25 and FaDu cells. CONCLUSION: The selective PI3K inhibitor HS-173 is a potent chemosensitizing and also radiosensitizing drug in treatment of HNSCC cell lines and could be an effective treatment in PI3K-mutated HNSCC.

Early effects of cigarette smoke extract on human oral keratinocytes and carcinogenesis in head and neck squamous cell carcinoma.

BACKGROUND: Cigarette smoking is a major risk factor for head and neck squamous cell carcinoma. Still, the effect of cigarette smoke on the molecular level is unclear. The aim of the present study was to investigate the early effects of cigarette smoke on carcinogenesis of head and neck squamous cell carcinoma. METHODS: Human oral keratinocytes were exposed for 1 week to standardized cigarette smoke extract, and subsequently RT-quantitative PCR array was performed. Protein expression of dysregulated genes was determined by immunohistochemistry in tissue samples of oral squamous cell carcinoma, oral leukoplakia, and tonsil mucosa. RESULTS: RT-PCR revealed upregulation of ITGA-2 and MMP-1, whereas TEK receptor tyrosine kinase was downregulated in human oral keratinocytes. ITGA-2 and MMP-1 were significantly overexpressed in tissue samples of oral squamous cell carcinoma in comparison to normal mucosa (P <.01 in all experiments). CONCLUSION: Upregulation of ITGA-2 and MMP-1 induced by cigarette smoke contributes significantly to oral carcinogenesis.

Computed tomography accelerates staging in patients with Merkel cell carcinoma.

PURPOSE: No imaging algorithms for diagnostic imaging in patients suffering from Merkel cell carcinoma (MCC) have been established so far and thus staging work-up is challenging. Long presentation-to-treatment intervals determine further treatment course and, consequently, have an impact on clinical outcome in patients with MCC. METHODS: In this retrospective study, diagnostic imaging of 37 MCC patients was analyzed. CT, ultrasound, and PET/PET-CT imaging for primary staging work-up with time frames from patients´ initial presentation and imaging until completion of tumor staging were analyzed. RESULTS: Tumor staging could be completed earlier when (1) less examinations (35 vs. 42 days) were carried out or (2) computed tomography was used as the initial imaging modality (28 vs. 35 days). Furthermore, CT imaging, when used as the initial imaging study, was linked to less follow-up imaging (3 vs. 6). CONCLUSION: Computed tomography as the first-staging imaging technique in MCC patients leads to less follow-up studies and fastest completion of tumor staging.

6-shogaol induces apoptosis and enhances radiosensitivity in head and neck squamous cell carcinoma cell lines.

Ginger (Zingiber officinale Roscoe) is used for a wide array of conditions in traditional medicine in Asia, but little is known about the effect on head and neck cancer. In this study, the effect of two major pharmacologically active compounds of ginger, 6-gingerol and 6-shogaol, were studied on head and neck cancer cell lines. Furthermore, experiments in combination with established treatment methods for head and neck cancer were performed. Proliferation assays showed a dose-dependent reduction of cell viability. Flow cytometry analysis revealed the induction of apoptosis. Western blot analysis indicated that the antiapoptotic protein survivin was suppressed after treatment. Although a combination of 6-shogaol with cisplatin exhibited no synergistic effect, the combination with irradiation showed a synergistic reduction of clonogenic survival. In conclusion, ginger compounds have many noteworthy effects on head and neck cancer cell lines. In particular, the enhancement of radiosensitivity is remarkable.

The effect of tonsillotomy on chronic recurrent tonsillitis in children.

OBJECTIVES: The objective of this study is to determine whether partial tonsillectomy (tonsillotomy) impacts the occurrence of acute or recurrent tonsillitis in children. METHODS: One hundred and eighty patients (1-14 years) were retrospectively surveyed by a questionnaire or by data analysis of a regional database. Subjects who suffered from severe systemic diseases or immunodeficiency syndromes were excluded. Episodes of acute tonsillitis before and after surgery, rate of antibiotic treatment, postoperative hemorrhage, and re-operation were obtained. RESULTS: Fifty-one patients suffered from preoperative tonsillitis. The rate of reinfection was 9.8%. The frequency of tonsillitis was significantly reduced in children after tonsillotomy (p < .001). Further, tonsillotomy led to a significant reduction of antibiotic treatment (p < .001). The rate of definitive tonsillectomy was 1.1% and thus effectiveness was very high. About 1.7% of all children suffered from postoperative bleeding, of which one (0.6%) required surgical revision. None of the bleedings was life threatening. CONCLUSIONS: Tonsillotomy is beneficial for patients with recurrent tonsillitis and carries less risk of postoperative complications than tonsillectomy.