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Apigenin is a natural phyto-oestrogen flavonoid, which exerts various biological effects, including anti-oxidative, anti-inflammatory and anticancer activities. In addition, apigenin has recently been reported to target hypoxic markers; however, there are currently no studies regarding the association between apigenin and glucose transporter-1 (GLUT-1) in adenoid cystic carcinoma (ACC). The present study investigated whether apigenin inhibits the proliferation of ACC cells or suppresses the expression of GLUT-1 in ACC cells. The results of the present study demonstrated that apigenin inhibits ACC-2 cell growth in a dose- and time-dependent manner. Treatment with apigenin also induced apoptosis and G2/M-phase arrest in a dose- and time-dependent manner. Corresponding with the above results, the expression levels of GLUT-1 were significantly decreased following treatment in a dose- and time-dependent manner. These results suggest that the inhibition of ACC-2 cell growth by apigenin may be due to the decreased expression of GLUT-1. [ABSTRACT FROM AUTHOR]

The current study presents a case of extranodal follicular dendritic cell sarcoma (FDCS) of the tonsil and reviews the relevant literature. In the present case, a 59-year-old male presented with a globus sensation in the right pharynx for 6 weeks. On clinical examination, a painless non-ulcerated enlarged right tonsil was identified; the tonsil was covered with a normal mucus membrane. A right tonsillectomy was performed under general anesthesia. The final pathological diagnosis was follicular dendritic cell sarcoma of the right tonsil. Postoperatively, the patient received radiotherapy. The patient remains alive without disease recurrence or metastasis 44 months after tonsillectomy. To the best of our knowledge, only 42 cases of FDCS of the tonsil have been reported to date. Of the 42 cases, 41 patients underwent surgery and one patient refused treatment. A total of 23 (54.7%) received surgery alone. Adjuvant treatment was administered for 18 patients (42.9%). Six patients (14.3%) experienced local recurrences and two patients (4.8%) succumbed to the disease 24 months after treatment. The three-, five-, and eight-year overall survival rates for the entire group were 86.5, 77.8 and 77.8%, respectively. Furthermore, a tumor diameter of ≥4 cm was prognostic upon univariate analysis (Χ² =4.634; P=0.031; excluding incomplete data). Tonsillar FDCS is rare and is associated with high rates of recurrence and metastasis, therefore, adjuvant treatment should be prescribed. [ABSTRACT FROM AUTHOR]

A 67-year-old male presented with a metastatic carcinoma in the right side of the neck from an unknown primary site. 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography showed increased 18F-FDG uptake in the right larynx and right neck lymph nodes. A smooth lesion was identified in the submucosa of the right supraglottic region via a suspension laryngoscopy under general anaesthesia. A biopsy was performed and a frozen section revealed a small-cell (SC) carcinoma. A total laryngectomy and bilateral neck dissection were performed simultaneously, and the pathological results demonstrated a SC neuroendocrine carcinoma. The patient received chemo-radiotherapy postoperatively, however, succumbed due to distant metastasis one year following surgery. [ABSTRACT FROM AUTHOR]

Background Small-cell neuroendocrine carcinoma (SCNEC) of the head and neck is rare. The prognosis of SCNEC in the nasal cavity and larynx is poor. The aim of this study was to investigate the clinicopathological features of nasal and laryngeal SCNEC and to determine the expression of HIF-1α, GLUT-1, PI3K, and p-Akt in SCNEC. Methods Between 2003 and 2012, 10 consecutive patients with histologically demonstrated nasal and laryngeal SCNEC were enrolled. Clinicopathological materials and follow-up data were analyzed retrospectively. Immunohistochemistry was used to detect GLUT-1, HIF-1α, PI3K, and p-Akt expression in paraffin wax-embedded tumor specimens. Results The subjects were eight males and two females with a mean age of 60.8 (range: 53 to 71) years. Tumors were located in the maxillary sinus (n = 3) and larynx (n = 7). At last followup, four patients (40.0%) had local recurrence and five patients (50.0%) had developed distant metastases. Six patients died. The mean overall survival was 19.3 ± 2.1 months. Expression of GLUT-1, HIF-1α, PI3K, and p-Akt was seen in sinonasal and laryngeal SCNEC in 80 (8 out of 10), 50 (5 out of 10), 40 (4 out of 10), and 40% (4 out of 10) of cases, respectively. Expression of GLUT-1, HIF-1α, PI3K, and p-Akt was higher in sinonasal and laryngeal SCNEC than in precancerous lesions. Conclusions Primary sinonasal and laryngeal SCNEC is rare. This paper presents 10 cases of sinonasal and laryngeal SCNEC with more common local recurrence and distant metastasis. HIF-1α, GLUT-1, PI3K, and p-Akt expression was higher in sinonasal and laryngeal SCNEC than in precancerous lesions. [ABSTRACT FROM AUTHOR]

High fluorodeoxyglucose (FDG) uptake by human carcinomas, including head and neck cancers, is associated with a poor prognosis. Glucose transporter-1 (Glut-1) is believed to be an intrinsic marker of hypoxia in malignant tumors. The expression of hypoxia-inducible factor-1α (HIF-1α) and correlated target genes, including Glut-1, is regulated by the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway. However, it remains unclear whether the PI3K/Akt signaling pathway is involved in regulating FDG uptake directly. In the present study, 24 consecutive patients with laryngeal carcinoma were examined pre-operatively and the standardized uptake values (SUV) of the laryngeal carcinomas were determined. Glut-1, HIF-1α, PI3K and phosphorylated-Akt (p-Akt) expression was detected by immunohistochemical staining of paraffin sections from the tumor specimens. Associations among SUVmax, Glut-1, HIF-1α, PI3K and p-Akt protein expression and the other clinical parameters were analyzed. The univariate analyses revealed a significantly shorter survival time along with higher HIF-1α (P=0.018) and PI3K (P=0.008) expression, but the survival time was not significantly correlated with Glut-1 or p-Akt expression. The multivariate analysis demonstrated that higher SUVmax (P=0.043) and PI3K expression (P=0.012) were significantly correlated with a poor survival time. Spearman's rank analysis showed significant correlations between SUVmax and HIF-1α (r=0.577; P=0.003), PI3K (r=1.0; P<0.0001) and p-Akt (r=0.577; P=0.003) expression. PI3K was associated with poorly- and moderately-differentiated laryngeal carcinoma (P=0.012). In conclusion, a high SUVmax indicates a poor prognosis for laryngeal carcinoma. Also, a high SUVmax may be associated with the increased expression of Glut-1, HIF-1α, PI3K and p-Akt. [ABSTRACT FROM AUTHOR]

CD133 is a useful putative marker of cancer stem cells (CSCs) in human laryngeal tumors. Numerous studies have demonstrated that CD133+ CSCs possess higher clonogenicity, invasiveness and tumorigenesis compared with CD133- cells. Recently, interest in the Warburg effect in the microenvironment of CSCs has escalated. The Warburg effect dictates that cancer cells rely on glycolysis rather than oxidative phosphorylation under aerobic conditions. In numerous cancer cells, glucose is used mainly for the glycolytic pathway. Stem cells express high levels of glycolytic enzymes and rely mostly on glycolysis to meet their energy demands. Glucose is transported through cell membranes by glucose transporters (Glut). Studies of Glut-1 expression in CSCs are limited. In the present study, we investigated the proliferation of CD133+ Hep-2 cells and whether Glut-1 is expressed in laryngeal carcinoma CD133+ Hep-2 cells. Real-time reverse transcription-polymerase chain reaction (RT-PCR) demonstrated that the size of the CD133 product was 213 bp. Dissociation curve analysis demonstrated only the expected peaks at 82.1°C for CD133. The mean ▵ Ct of CD133 expression was 10.98. Prior to isolation, the CD133+ fraction was 1.2% by fluorescence-activated cell sorting (FACS) analysis. Following isolation, the CD133+ fraction was increased to 76.1%. Successive tests also demonstrated that cells grew well following isolation. The proliferation of CD133+ and CD133- cells was not different during the first 3 days (P>0.05). From day 4, the proliferation capacity of CD133+ cells in vitro was higher than that of CD133- cells (P<0.05). The mean ▵ Ct of Glut-1 mRNA expression was 1.78 for CD133+ cells and 1.00 for CD133- cells (P<0.05). The mean Glut-1 protein values in CD133+ and CD133- Hep-2 cells relative to β-tubulin were 0.48 ± 0.02 and 0.21 ± 0.03 (μg/μl), respectively (P<0.05). In conclusion, CD133+ cells demonstrated higher proliferation. Glut-1 mRNA and protein levels were higher in CD133+ than in CD133- cells. Our results suggest that Glut-1 is important in the energy supply of laryngeal CD133+ Hep-2 cells and Glut-1 may represent a potential therapeutic target for the inhibition of the proliferation of laryngeal CSCs. [ABSTRACT FROM AUTHOR]