Clinical trials have not consistently supported the use of induction chemotherapy (IC) for locally advanced head and neck squamous cell cancer. Hypopharynx and base of tongue (BOT) cancer has shown relatively poor survival. We investigated the role of IC in improving outcome over current chemoradiotherapy (CRT) in patients with hypopharynx and BOT cancer. Methods: Treatment-naïve patients with stage III/IV (M0) hypopharynx or BOT cancer were randomly assigned to receive CRT alone (CRT arm: cisplatin 100 mg/m2 on D1 3-weekly, two times plus radiotherapy 68.4 Gy/30 fractions on weekdays) versus two 21-day cycles of IC with TPF (docetaxel & cisplatin 75 mg/m2 on D1, and fluorouracil 75 mg/m2 on D1-4) followed by the same CRT regimen (IC arm). The primary endpoint was progression-free survival (PFS). Results: This study closed early after enrollment of 36 patients (19 in the CRT arm, 17 in the IC arm). After a median follow-up of 47.2 months, there was no significant difference in PFS: the median PFS was 26.8 months for the CRT arm and was not reached for the IC arm (p = 0.13). However, the survival curves were widely separated with a plateau after 3 years, suggesting a potential survival benefit from IC: 3-year PFS rates were 45% and 68%, and 3-year overall survival rates were 56% and 86%, in the CRT and IC arms, respectively. Conclusions: This study failed to demonstrate that induction TPF chemotherapy improves survival in patients with BOT and hypopharynx cancer. However, it suggested a favorable outcome with IC to this population.

BACKGROUND/OBJECTIVES: Anti-inflammatory and antioxidative activities of luteolin and luteolin-7-O-glucoside were compared in galactosamine (GalN)/lipopolysaccharide (LPS)-induced hepatitic ICR mice. MATERIALS/METHODS: Male ICR mice (6 weeks old) were divided into 4 groups: normal control, GalN/LPS, luteolin, and luteolin-7-O-glucoside groups. The latter two groups were administered luteolin or luteolin-7-O-glucoside (50 mg/kg BW) daily by gavage for 3 weeks after which hepatitis was induced by intraperitoneal injection of GalN and LPS (1 g/kg BW and 10 µg/kg BW, respectively). RESULTS: GalN/LPS produced acute hepatic injury by a sharp increase in serum AST, ALT, and TNF-α levels, increases that were ameliorated in the experimental groups. In addition, markedly increased expressions of cyclooxygenase (COX)-2 and its transcription factors, nuclear factor (NF)-κB and activator protein (AP)-1, were also significantly attenuated in the experimental groups. Compared to luteolin-7-O-glucoside, luteolin more potently ameliorated the levels of inflammatory mediators. Phase II enzymes levels and NF-E2 p45-related factor (Nrf)-2 activation that were decreased by GalN/LPS were increased by luteolin and luteolin-7-O-glucoside administration. In addition, compared to luteolin, luteolin-7-O-glucoside acted as a more potent inducer of changes in phase II enzymes. Liver histopathology results were consistent with the mediator and enzyme results. CONCLUSION: Luteolin and luteolin-7-O-glucoside protect against GalN/LPS-induced hepatotoxicity through the regulation of inflammatory mediators and phase II enzymes.
Animals ; Galactosamine ; Hepatitis ; Humans ; Inflammation ; Injections, Intraperitoneal ; Liver ; Luteolin ; Male ; Mice ; Mice, Inbred ICR ; NF-E2-Related Factor 2 ; NF-kappa B ; Prostaglandin-Endoperoxide Synthases ; Transcription Factors

PURPOSE: This study was conducted to evaluate the relationship between epidermal growth factor receptor (EGFR) mutation and clinical outcomes in patients with stage III non-squamous cell lung cancer treated with definitive concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: From January 2008 to December 2013, the medical records of 197 patients with stage III non- squamous non-small cell lung cancer treated with definitive CCRT were analyzed to determine progression-free survival (PFS) and overall survival (OS) according to EGFR mutation status. RESULTS: Among 197 eligible patients, 81 patients were EGFR wild type, 36 patients had an EGFR mutation (exon 19 Del, n=18; L858R, n=9, uncommon [G719X, L868, T790M], n=9), and 80 patients had unknown EGFR status. The median age was 59 years (range, 28 to 80 years) and 136 patients (69.0%) were male. The median follow-up duration was 66.5 months (range, 1.9 to 114.5 months). One hundred sixty-four patients (83.2%) experienced disease progression. Median PFS was 8.9 months for the EGFR mutation group, 11.8 months for EGFR wild type, and 10.5 months for the unknown EGFR group (p=0.013 and p=0.042, respectively). The most common site of metastasis in the EGFR mutant group was the brain. However, there was no significant difference in OS among the three groups (34.6 months for EGFR mutant group vs. 31.9 months for EGFR wild type vs. 22.6 months for EGFR unknown group; p=0.792 and p=0.284). A total of 29 patients (80.6%) with EGFR mutation were treated with EGFR tyrosine kinase inhibitor (gefitinib, n=24; erlotinib, n=3; afatinib, n=2) upon progression. CONCLUSION: EGFR mutation is associatedwith short PFS and the brain is the most common site of distant metastasis in patients with stage III non- squamous cell lung cancer treated with CCRT.
Brain ; Carcinoma, Non-Small-Cell Lung ; Chemoradiotherapy ; Disease Progression ; Disease-Free Survival ; Epithelial Cells ; Erlotinib Hydrochloride ; Follow-Up Studies ; Humans ; Lung Neoplasms ; Lung ; Male ; Medical Records ; Neoplasm Metastasis ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor

OBJECTIVES: The main objectives of this study were to verify the antibacterial activity of two essential oils, lavender and peppermint, against dental caries and to review their synergistic effect when used in combination. Our results provide basic data for the evaluation of the use of these two substances towards the prevention and cure of dental caries. METHODS: The sample solutions of lavender and peppermint oils were prepared in three different concentrations (30%, 50%, and 70% (v/v)) by diluting them with third-distilled water and Tween 20. Streptococcus mutans was selected as the bacterial species for testing. The disk diffusion method was used to measure the antibacterial activity of the sample solutions. For generating growth curves and measuring the number of clusters of the bacterial, the liquid medium-dilution method was used; the absorbance of the medium was measured at 600 nm after 3, 6, 12 and 24 hours. RESULTS: When the antibacterial activity of the oils was tested via the disk diffusion method, the activity improved with increasing concentrations of all the sample solutions of peppermint, lavender, and the blend, but there was no significant difference between them with respect to the type of oil. In the growth curves of S. mutans, growth inhibition was observed after 12 hours. The inhibitory effect of 30% lavender oil on growth was 64.9% and 80.1% after 12 and 24 hours of treatment, respectively whereas that of peppermint oil was 71.3% and 80.1% after 12 and 24 hours of treatment, respectively. The inhibitory effect of the blended oil was 71.9% and 81.0% after 12 and 24 hours of treatment, respectively. CONCLUSIONS: Further research is still required in order to determine the efficacy of lavender and peppermint oils, as well as other essential oils, for wider use in preventing dental caries.
Dental Caries ; Diffusion ; Lavandula ; Mentha piperita ; Methods ; Oils ; Oils, Volatile ; Polysorbates ; Streptococcus mutans ; Streptococcus ; Water

PURPOSE: Papillary thyroid carcinomas (PTCs) frequently involve genetic alterations. The objective of this study was to investigate genetic alterations and further explore the relationships between these genetic alterations and clinicopathological characteristics in a high-recurrence risk (node positive, N1) PTC group. MATERIALS AND METHODS: Tumor tissue blocks were obtained from 240 surgically resected patients with histologically confirmed stage III/IV (pT3/4 or N1) PTCs. We screened gene fusions using NanoString’s nCounter technology and mutational analysis was performed by direct DNA sequencing. Data describing the clinicopathological characteristics and clinical courses were retrospectively collected. RESULTS: Of the 240 PTC patients, 207 (86.3%) had at least one genetic alteration, including BRAF mutation in 190 patients (79.2%), PIK3CA mutation in 25 patients (10.4%), NTRK1/3 fusion in six patients (2.5%), and RET fusion in 24 patients (10.0%). Concomitant presence of more than two genetic alterations was seen in 36 patients (15%). PTCs harboring BRAF mutation were associated with RET wild-type expression (p=0.001). RET fusion genes have been found to occur with significantly higher frequency in N1b stage patients (p=0.003) or groups of patients aged 45 years or older (p=0.031); however, no significant correlation was found between other genetic alterations. There was no trend toward favorable recurrence-free survival or overall survival among patients lacking genetic alterations. CONCLUSION: In the selected high-recurrence risk PTC group, most patients had more than one genetic alteration. However, these known alterations could not entirely account for clinicopathological features of high-recurrence risk PTC.
Gene Fusion ; Humans ; Retrospective Studies ; Sequence Analysis, DNA ; Thyroid Gland* ; Thyroid Neoplasms*

PURPOSE: Oropharyngeal squamous cell carcinoma (OSCC) has been recognized as an immunosuppressive disease. Various mechanisms have been proposed for immune escape, including dysregulation of immune checkpoints such as the PD-1:PD-L1 pathway. We investigated the expression of programmed cell death-ligand 1 (PD-L1) in HPV-negative and HPV-positive OSCC to determine its prevalence and prognostic relevance. MATERIALS AND METHODS: Using immunohistochemistry, 133 cases of OSCC were evaluated for expression of PD-L1. Formalin-fixed paraffin-embedded tumor samples were stained with monoclonal antibody (clone 5H1) to PD-L1. PD-L1 positivity was defined as membrane staining in ≥20% of tumor cells. Correlations between PD-L1 expression and HPV status and survival parameters were analyzed. RESULTS: Of the 133 patients, 68% showed PD-L1 expression, and 67% of patients were positive for p16 expression by immunohistochemistry. No significant difference in PD-L1 expression was observed between HPV(-) and HPV(+) tumors (61% vs. 71%, p=0.274). No significant difference in age, gender, smoking history, location of tumor origin, or stage was observed according to PD-L1 status. With a median follow-up period of 44 months, older age (≥65) (p=0.017) and T3-4 stage (p<0.001) were associated with poor overall survival (OS), whereas PD-L1 expression did not affect OS in univariate and multivariate analysis. CONCLUSION: PD-L1 expression was observed in the majority of OSCC patients regardless of HPV status. Further large prospective studies are required to determine the role of PD-L1 expression as a prognostic or predictive biomarker, and clinical studies of immune checkpoint inhibitors in OCSS are warranted regardless of HPV status.
Carcinoma, Squamous Cell* ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Membranes ; Multivariate Analysis ; Oropharyngeal Neoplasms ; Prevalence ; Prospective Studies ; Smoke ; Smoking ; United Nations

PURPOSE: Dysregulation of adipokines caused by excess adipose tissue has been implicated in the development of obesity-related metabolic diseases. This study evaluated the effects of mugwort (Artemisia princeps Pampanini) ethanol extract on lipid metabolic changes, insulin resistance, adipokine balance, and body fat reduction in obese rats. METHODS: Male Sprague-Dawley rats were fed either a control diet (NC), high-fat diet (HF, 40% kcal from fat), or high-fat diet with 1% mugwort extract (HFM) for 6 weeks. RESULTS: Epididymal and retroperitoneal fat mass increased in the HF group compared with the NC group, and epididymal fat mass was reduced in the HFM group (p < 0.05). No difference was observed in serum levels of total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) among the groups. However, triglyceride (TG), TG/HDL-C ratio, and TC/HDL-C ratio increased in the HF group and significantly decreased in the HFM group. TG and TC levels in the liver were significantly higher in the HF group, whereas these levels were significantly reduced in the HFM group. HF rats had lower insulin sensitivity as indicated by increased homeostasis model assessment of the insulin resistance (HOMA-IR) value. HOMA-IR values significantly decreased in the HFM group. Adiponectin levels were higher in NC rats, and their leptin and PAI-1 levels were lower. Relative balance of adipokines was reversed in the HF group, with lower adiponectin levels but higher leptin and PAI-1 levels. In contrast, the HFM group maintained balance of adiponectin/leptin and adiponectin/PAI-1 levels similar to NC by reducing leptin and PAI-1 levels. CONCLUSION: Overall data indicated that mugwort extract can be effective in alleviating metabolic dislipidemia, insulin resistance, and adipokine dysregulation induced by a high-fat diet.
Adipokines* ; Adiponectin ; Adipose Tissue ; Animals ; Artemisia* ; Cholesterol ; Diet ; Diet, High-Fat ; Ethanol ; Homeostasis ; Humans ; Insulin Resistance ; Intra-Abdominal Fat ; Leptin ; Lipid Metabolism ; Lipoproteins ; Liver ; Male ; Metabolic Diseases ; Plasminogen Activator Inhibitor 1 ; Rats* ; Rats, Sprague-Dawley ; Triglycerides

Tinea incognito (TI) is a dermatophytic infection which has lost its typical clinical appearance because of improper use of steroids or calcineurin inhibitors. The incidence of TI is increasing nowadays. We conducted retrospective review on 283 patients with TI from 25 dermatology training hospitals in Korea from 2002-2010 to investigate the demographical, clinical, and mycological characteristics of TI, and to determine the associated risk factors. More than half (59.3%) patients were previously treated by non-dermatologists or self-treated. The mean duration of TI was 15.0 +/- 25.3 months. The most common clinical manifestations were eczema-like lesion, psoriasis-like, and lupus erythematosus-like lesion. The trunk and face were frequently involved, and 91 patients (32.2%) also had coexisting fungal infections. Among 67 isolated strains, Trichophyton rubrum was the most frequently detected (73.1%). This is the largest study of TI reported to date and the first investigational report concerning TI in Korea. We suggest that doctors should consider TI when a patient has intractable eczema-like lesions accompanied by tinea pedis/unguium. Furthermore, there should be a policy change, which would make over-the-counter high-potency topical steroids less accessible in some countries, including Korea.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Demography ; Eczema/pathology ; Face/pathology ; Female ; Humans ; Lupus Erythematosus, Cutaneous/pathology ; Male ; Middle Aged ; Psoriasis/pathology ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Tinea/*diagnosis/microbiology ; Trichophyton/isolation & purification ; Young Adult

Luteolin is a flavonoid found in abundance in celery, green pepper, and dandelions. Previous studies have shown that luteolin is an anti-inflammatory and anti-oxidative agent. In this study, the anti-inflammatory capacity of luteolin and one of its glycosidic forms, luteolin-7-O-glucoside, were compared and their molecular mechanisms of action were analyzed. In lipopolysaccharide (LPS)-activated RAW 264.7 cells, luteolin more potently inhibited the production of nitric oxide (NO) and prostaglandin E2 as well as the expression of their corresponding enzymes (inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) than luteolin-7-O-glucoside. The molecular mechanisms underlying these effects were investigated to determine whether the inflammatory response was related to the transcription factors, nuclear factor (NF)-kappaB and activator protein (AP)-1, or their upstream signaling molecules, mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase (PI3K). Luteolin attenuated the activation of both transcription factors, NF-kappaB and AP-1, while luteolin-7-O-glucoside only impeded NF-kappaB activation. However, both flavonoids inhibited Akt phosphorylation in a dose-dependent manner. Consequently, luteolin more potently ameliorated LPS-induced inflammation than luteolin-7-O-glucoside, which might be attributed to the differentially activated NF-kappaB/AP-1/PI3K-Akt pathway in RAW 264.7 cells.
Apium graveolens ; Capsicum ; Cyclooxygenase 2 ; Dinoprostone ; Flavones ; Flavonoids ; Glucosides ; Inflammation ; Luteolin* ; Mitogen-Activated Protein Kinases ; NF-kappa B ; Nitric Oxide ; Nitric Oxide Synthase ; Phosphorylation ; Taraxacum ; Transcription Factor AP-1 ; Transcription Factors

We compared the effects of genistein and daidzein on the expression of chemokines, cell adhesion molecules (CAMs), and endothelial nitric oxide synthase (eNOS) in tumor necrosis factor (TNF)-alpha-stimulated human umbilical vascular endothelial cells (HUVECs). TNF-alpha exposure significantly increased expression of monocyte chemoattractant protein (MCP)-1, vascular adhesion molecule (VCAM)-1, and intercellular adhesion molecule-1. Genistein significantly decreased MCP-1 and VCAM-1 production in a dose-dependent manner, whereas CAM expression was not significantly lowered by genistein treatment. However, daidzein slightly decreased MCP-1 production. The effects of genistein and daidzein on MCP-1 secretion coincided with mRNA expression. Pre-treatment with either genistein or daidzein elevated eNOS expression and nitric oxide production disturbed by TNF-alpha exposure. A low concentration of isoflavones significantly inhibited nuclear factor (NF)kappaB activation, whereas a high dose slightly ameliorated these inhibitive effects. These results suggest that genistein had a stronger effect on MCP-1 and eNOS expression than that of daidzein. Additionally, NFkappaB transactivation might be partially related to the down-regulation of these mRNAs in TNF-alpha-stimulated HUVECs.
Cell Adhesion ; Cell Adhesion Molecules ; Chemokines ; Down-Regulation ; Endothelial Cells ; Genistein ; Humans ; Intercellular Adhesion Molecule-1 ; Isoflavones ; Monocytes ; Nitric Oxide ; Nitric Oxide Synthase Type III ; RNA, Messenger ; Transcriptional Activation ; Tumor Necrosis Factor-alpha ; Vascular Cell Adhesion Molecule-1