Pepsin Increases the Proliferation of Vocal Cord Leukoplakia Epithelial Cells by Inducing Autophagy.

OBJECTIVE: To investigate the role of H+ /K+ ATPase in the proliferation of pepsin-induced vocal cord leukoplakia (VCL) cells. STUDY DESIGN: Translation research. SETTING: Affiliated Hospital of University. METHODS: Immunohistochemistry was used to detect pepsin, H+ /K+ ATPase (ATP4A and ATP4B subunits) in VCL cells with varying degrees of dysplasia. After primary cultures of VCL cells had been established, the effects of acidified pepsin on the proliferation, autophagy, and H+ /K+ -ATPase distribution of VCL cells were investigated. RESULTS: The levels of pepsin, ATP4A, and ATP4B were significantly higher in VCL tissue with moderate-to-severe dysplasia than in normal tissue (p < .05); these levels gradually increased according to dysplasia severity. The expression levels of ATP4A and ATP4B were significantly correlated with the amount of pepsin in VCL cells (p < .01). Acidified pepsin enhanced the levels of proliferation and autophagy in human VCL epithelial cells. The cloning- and autophagy-promoting effects of acidified pepsin on VCL cells were partially reversed by pantoprazole; these effects were completely blocked by the autophagy inhibitor chloroquine. Finally, acidified pepsin promoted the colocalization of H+ /K+ -ATPase and lysosomes in VCL cells; it also mediated lysosome acidification. CONCLUSION: Pepsin and H+ /K+ -ATPase may contribute to the progression of VCL. Specifically, acidified pepsin may regulate lysosome acidification by promoting lysosomal localization of H+ /K+ -ATPase.

Epstein-Barr virus-associated leiomyosarcoma of the larynx in an adult patient with human immunodeficiency virus infection: Case report and review of the literature.

We investigated the clinical features, treatment, and prognosis of laryngeal leiomyosarcoma (LLMS) and Epstein-Barr virus-associated (EBV-associated) LMS. We report a case of EBV-associated LLMS in an adult patient with HIV infection. We also conducted a review of the English-language literature on LLMS and EBV-associated leiomyosarcoma. To the best of our knowledge, 62 cases of LLMS and EBV-associated leiomyosarcoma have been reported to date. Of patients with LLS, 18.9% had distant metastases and 17.0% had local recurrence. The overall 5-year survival rate was 64.0%. Distant metastases affected the survival of patients with LLMS (p = 0.04). EBV-positive patients had a low survival rate (p = 0.01). Among patients with EBV-associated LMS, 8.2% had distant metastases and recurrence and the overall 5-year survival rate was 50.0%. EBV-associated LLMS is rare. The EBV infection might be a poor prognostic factor of LLMS.

Angioleiomyoma of the Epiglottis Mimicking Epiglottic Hemangioma: Clinical Experience and Literature Review.

We describe a case of laryngeal angioleiomyoma, discuss its characteristic features and management, and provide a review of the literature, to improve clinical diagnosis and treatment. We report the oldest patient with a laryngeal angioleiomyoma to date and analyze the clinicopathological features reported in the literature. To the best of our knowledge, a total of 36 cases have been described in the English and Chinese medical literature (including our case). The male-to-female ratio was 5:1 and the mean age was 53.89 years. The most common laryngeal site was the supraglottic region (23 cases; 63.89%), followed by the subglottic region (8 cases; 22.22%), and glottis (5 cases; 13.89%). The most common and serious intra- and postoperative complication was massive bleeding. Angioleiomyoma is a benign tumor that rarely occurs in the larynx. Biopsy of this lesion should not be performed; complete surgical resection is the best treatment. Recurrence and malignant transformation are extremely rare.

Effect of Glut-1 and HIF-1α double knockout by CRISPR/CAS9 on radiosensitivity in laryngeal carcinoma via the PI3K/Akt/mTOR pathway.

Hypoxic resistance is the main obstacle to radiotherapy for laryngeal carcinoma. Our previous study indicated that hypoxia-inducible factor 1α (HIF-1α) and glucose transporter 1 (Glut-1) double knockout reduced tumour biological behaviour in laryngeal carcinoma cells. However, their radioresistance mechanism remains unclear. In this study, cell viability was determined by CCK8 assay. Glucose uptake capability was evaluated by measurement of 18 F-fluorodeoxyglucose radioactivity. A tumour xenograft model was established by subcutaneous injection of Tu212 cells. Tumour histopathology was determined by haematoxylin and eosin staining, immunohistochemical staining, and TUNEL assays. Signalling transduction was evaluated by Western blotting. We found that hypoxia induced radioresistance in Tu212 cells accompanied by increased glucose uptake capability and activation of the PI3K/Akt/mTOR pathway. Inhibition of PI3K/Akt/mTOR activity abolished hypoxia-induced radioresistance and glucose absorption. Mechanistic analysis revealed that hypoxia promoted higher expressions of HIF-1α and Glut-1. Moreover, the PI3K/Akt/mTOR pathway was a positive mediator of HIF-1α and/or Glut-1 in the presence of irradiation. HIF-1α and/or Glut-1 knockout significantly reduced cell viability, glucose uptake and PI3K/Akt/mTOR activity, all of which were induced by hypoxia in the presence of irradiation. In vivo analysis showed that knockout of HIF-1α and/or Glut-1 also inhibited tumour growth by promoting cell apoptosis, more robustly compared with the PI3K inhibitor wortmannin, particularly in tumours with knockout of both HIF-1α and Glut-1. HIF-1α and/or Glut-1 knockout also abrogated PI3K/Akt/mTOR signalling transduction in tumour tissues, in a manner similar to wortmannin. HIF-1α and/or Glut-1 knockout facilitated radiosensitivity in laryngeal carcinoma Tu212 cells by regulation of the PI3K/Akt/mTOR pathway.

Epstein-Barr Virus-Positive Langerhans Cell Sarcoma: Is There a Link? A Case Report.

Langerhans cell sarcoma (LCS) is an extremely rare, malignant neoplasm that originates from Langerhans cells (LCs). Fewer than 70 cases have been reported in the English-language literature. LCS typically involves multiple organs, including the skin, lymph nodes, lungs, bone, bone marrow, liver, spleen, and soft tissues. Several etiological factors for LCS have been proposed, including immunosuppression, virus infection, and prior hematological disease. We report a rare case of LCS with Epstein-Barr virus (EBV) infection; bilateral cervical giant cysts were the initial manifestation. To our knowledge, this is the first report of LCS with EBV infection. The case information was complete, and the relevant literature was reviewed to gain insight into LCS. The case raises new questions on the oncogenic character of EBV.

Relationship Between Pepsin Expression and Dysplasia Grade in Patients With Vocal Cord Leukoplakia.

OBJECTIVE: To measure pepsin expression in patients with vocal fold leukoplakia and elucidate its clinical significance. STUDY DESIGN: Retrospective analysis of pathologic archive specimens. SETTING: Affiliated university hospital. SUBJECTS AND METHODS: The study included 45 patients with vocal fold leukoplakia and 19 with vocal fold polyps who underwent surgical treatment between December 2013 and July 2016. Masses were detected on both vocal cords in 5 patients with vocal fold leukoplakia and in 1 patient with vocal fold polyps. Immunohistochemistry was used to assess pepsin expression. In addition, the relationship of pepsin expression level with clinical characteristics of vocal fold leukoplakia was assessed. RESULTS: The rate of pepsin expression was high in the polyp group (75%) and the leukoplakia group (68%); however, the difference between groups was not significant (P > .05). Pepsin expression significantly increased according to grade of dysplasia (mild, 57.1%; moderate, 88.9%; severe, 100.0%; P = .034). Similarly, the percentage of lesions that exhibited strongly positive pepsin expression increased with the grade of dysplasia (mild, 37.1%; moderate, 66.7%; severe, 100.0%; P = .005). The leukoplakia recurrence rate was higher in patients with positive pepsin expression than in patients with negative pepsin expression but without a significant difference (P > .05). CONCLUSION: Our study suggests that pepsin was associated with the grade of dysplasia of vocal cord leukoplakia. Further investigation with appropriate control groups and controlling for other risk factors, such as smoking or alcohol consumption, is needed.

Gastric H+/K+-ATPase Expression in Normal Laryngeal Tissue and Laryngeal Carcinoma.

BACKGROUND: Several studies have suggested that laryngopharyngeal reflux disease (LPRD) or gastroesophageal reflux disease (GERD) is an independent risk factor for laryngeal carcinoma. However, it remains unclear whether either condition affects the level of H+/K+-ATPase expression in laryngeal carcinoma. MATERIALS AND METHODS: Immunohistochemistry, real-time RT-PCR, and Western blotting were used to explore the distributions of proton pump (H+/K+-ATPase) α- and ß-subunits in normal laryngeal tissue and laryngeal carcinoma. RESULTS: Messenger RNAs encoding both the α- and ß-subunits were found in the normal epiglottic, ventricular fold, vocal fold, and arytenoid mucosae, as well as epiglottic cartilage. The distributions and expression levels of H+/K+-ATPase α-subunits in various laryngeal subregions did not significantly differ in IHC, RT-PCR, or Western blotting. However, Western blotting revealed a significant difference between the expression level of the ß-subunit protein in the epiglottic cartilage and the levels in other sites. The expression levels of both subunits were significantly higher in carcinomatous than in paracarcinomatous tissue and normal laryngeal tissue. The mean follow-up duration was 66.2 months (range, 17-162 months). In all, 4 patients died during follow-up, 4 were lost to follow-up, and 22 were alive and free of disease at the end of follow-up. Two patients developed lung metastases and six developed disease recurrences (at 2, 8, 14, 16, 36, and 41 months). The 3- and 5-year overall survival (OS) rates were 93.0% and 77.0%, respectively. Univariate analyses showed that the 5-year OSs were significantly associated with the T, N, and clinical stages but not with age, alcohol use, pathological differentiation, or the expression levels of the α- or ß-subunits (as revealed by IHC, RT-PCR, or Western blotting). However, in multivariate regression analyses, the 5-year OSs were not significantly associated with any clinicopathological factor or the expression levels of either subunit. CONCLUSION: H+/K+-ATPase is expressed in the normal larynx, including in the epiglottic cartilage and the mucosae of the epiglottis, ventricular fold, and arytenoid vocal fold. The expression levels of the H+/K+-ATPase α- and ß-subunits in laryngeal carcinomas were higher than in normal laryngeal tissues.

Collision carcinoma of squamous cell carcinoma and small cell neuroendocrine carcinoma of the larynx: A case report and review of the literature.

BACKGROUND: Collision carcinoma is rare in clinical practice, especially in the head and neck region. In this paper, we report a case of squamous cell carcinoma (SCC) and neuroendocrine carcinoma (NEC) colliding in the larynx and review 12 cases of collision carcinoma in the head and neck to further understand collision carcinoma, including its definition, diagnosis, and treatment. CASE SUMMARY: A 61-year-old man presented with a 1-year history of hoarseness. Contrast-enhanced magnetic resonance imaging of the larynx revealed that the right vocal cord had a nodule-like thickening with obvious enhancement. Laryngoscopy revealed a neoplasm on the right vocal cord, and a malignant tumor was initially considered. A frozen section of right vocal cord was performed under general anesthesia. The pathological result showed a malignant tumor in the right vocal cord. The tumor was excised with a CO2 laser (Vc type). Routine postoperative pathology showed moderately differentiated SCC with small cell NEC in the right vocal cord. No metastatic lymph nodes or distant metastases were found on postoperative positron emission tomography/computed tomography. Because of the coexistence of SCC and NEC, the patient received adjuvant chemotherapy and radiotherapy. The patient was followed for 8 mo, and no recurrence or distant metastasis was found. CONCLUSION: The treatment of collision carcinoma in the head and neck region is uncertain due to the small number of cases.

True hypopharyngeal carcinosarcoma: a case report and literature review.

Objective Carcinosarcoma consists of carcinomatous and sarcomatous tissues and is an aggressive malignant tumor. It is rarely reported in the hypopharynx. Methods A 72-year-old man presented with dysphagia and dyspnea. Laryngoscopy, computed tomography (CT), and 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) showed a neoplasm on the left posterior hypopharyngeal wall. The patient underwent bilateral neck dissection and excision of the hypopharyngeal cancer followed by postoperative radiation therapy. Results Immunohistochemistry revealed carcinomatous cells with membrane positivity for cytokeratin, glucose transporter-1 (GLUT-1), phosphoinositide-3 kinase (PI3K), hypoxia-inducible factor-1α (HIF-1α), and hexokinase-II as well as sarcomatous cells with membrane positivity for smooth muscle actin, GLUT-1, HIF-1α, and PI3K. Histopathology and immunohistochemistry revealed a true carcinosarcoma of the hypopharynx (pT3N0M0, Stage III). Conclusions Thorough immunohistochemistry is required for a correct diagnosis of hypopharyngeal carcinosarcoma. 18F-FDG PET/CT may help to distinguish hypopharyngeal carcinosarcoma from benign tumors.

Cutaneous and Subcutaneous Metastases From Atypical Laryngeal Carcinoids: Case Report and Review of the Literature.

The incidence of cutaneous and subcutaneous metastases from atypical laryngeal carcinoids is approximately 20%. However, the pathogenesis and natural history of, and prognostic factors for, the condition remain poorly understood. We reported a 54-year-old female presented with cutaneous and subcutaneous metastases from atypical laryngeal carcinoid. Laryngoscopy revealed a 0.5 × 1.5-cm reddish mass on the laryngeal surface of the epiglottis. Under general anesthesia, a biopsy sample was obtained via suspension laryngoscopy. Routine pathology revealed atypical laryngeal carcinoid. Immunohistochemical staining of the sections of primary tumor was positive for cytokeratin, chromogranin A, synaptophysin, hypoxia-inducible factor-1α, P53, and CD56. GLUT-1, p-Akt, and PI3K were negative. The Ki-67 index was 15%. Supraglottic laryngectomy and selective right-neck dissection were performed. After 6 months, the patient complained of pain in the right wall of the chest; multiple cutaneous and subcutaneous nodules were evident at that site and in the abdomen. An abdominal nodule was biopsied and pathology revealed that the atypical metastatic carcinoid had metastasized to both cutaneous and subcutaneous areas of the abdomen. Chemotherapy was then prescribed. Currently, the intrathecal drug delivery system remains in place. No local recurrence has been detected. Furthermore, we systematically reviewed clinical manifestations of the disease, pathogenesis, prognostic factors, and treatment. The metastasis rate (cutaneous and subcutaneous) was approximately 12.2%. Thirty patients (62.5%) with cutaneous and subcutaneous metastases exhibited contemporaneous lymph node invasion. The 3-, 5-, and 10-year survival rates were 44.0%, 22.0%, and 13.0%, respectively. The prognosis of patients with atypical laryngeal carcinoids was poor. Relevant prognostic factors included the level of p53, human papilloma virus status, certain hypoxic markers, and distant metastasis. No optimal treatment for such metastases has yet been defined.

Nodular pulmonary amyloidosis and obvious ossification due to primary pulmonary MALT lymphoma with extensive plasmacytic differentiation: Report of a rare case and review of the literature.

Localized (primary) pulmonary amyloidosis associated with pulmonary low-grade B cell lymphoma is rarely occurred. Here we report an unusual case of nodular pulmonary amyloidosis and obvious ossification due to primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma with extensive plasmacytic differentiation in a 59-year-old man; moreover, two bronchial lymph nodes were involved histologically. The patient underwent a left lower lobectomy along with mediastinal lymphadenectomy. He received no adjuvant therapy and the postoperative course was uneventful within the 14 months follow-up period after his initial diagnosis.

Expression and significance of glucose transporter-1, P-glycoprotein, multidrug resistance-associated protein and glutathione S-transferase-π in laryngeal carcinoma.

Increasing glucose transporter-1 (GLUT-1) activity is one of the most important ways to increase the cellular influx of glucose. We previously demonstrated that increased GLUT-1 expression was an independent predictor of survival in patients with laryngeal carcinoma. Thus, GLUT-1 may present a novel therapeutic target in laryngeal carcinoma. In this study, the expression of GLUT-1, P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and glutathione S-transferase-π (GST-π) in laryngeal carcinomas was investigated by immunohistochemistry. Additionally, possible correlations between GLUT-1 and P-gp, MRP1 and GST-π and various clinicopathological parameters were analyzed. In this study, 52.9% (18/34), 58.8% (20/34), 20.6% (7/34) and 58.8% (20/34) of the laryngeal carcinomas were positive for GLUT-1, P-gp, MRP1 and GST-π, respectively. The expression of GLUT-1, P-gp, MRP1 and GST-π was higher in laryngeal carcinoma specimens when compared with laryngeal precancerous lesions (P<0.05). Pearson's correlation analysis showed correlations between GLUT-1 and P-gp (r=0.364; P=0.034), GLUT-1 and MRP1 (r=0.359; P=0.037) and P-gp and GST-π (r=0.426; P=0.012). GLUT-1 expression was found to significantly correlate with tumor-node-metastasis classification (P=0.02) and clinical stage (P=0.037). Furthermore, P-gp was found to significantly correlate with clinical stage (P=0.026). Univariate analysis showed that MRP1 expression was significantly associated with poor survival (c2=5.16; P=0.023). Multivariate analysis revealed that lymph node metastasis (P=0.009) and MRP1 overexpression (P=0.023) were significant predictors of poor survival. In the present study, the expression of GLUT-1, P-gp, MRP1 and GST-π in laryngeal carcinomas was investigated, as well as the correlations between these proteins. P-gp was found to significantly correlate with clinical stage, while MRP1 overexpression was significantly associated with poor survival.

Cell block samples from malignant pleural effusion might be valid alternative samples for anaplastic lymphoma kinase detection in patients with advanced non-small-cell lung cancer.

AIM: To evaluate the clinical value of cell block samples from malignant pleural effusion (MPE) as alternative samples to tumour tissue for anaplastic lymphoma kinase (ALK) detection in patients with advanced non-small-cell lung cancer (NSCLC). METHODS AND RESULTS: Fifty-two matched samples were eligible for analysis. ALK status was detected by Ventana immunohistochemistry (IHC) (with the D5F3 clone), reverse transcription polymerase chain reaction (RT-PCR) and fluorescence in-situ hybridization (FISH) in MPE cell block samples, and by FISH in tumour tissue block samples. In total, ALK FISH results were obtained for 52 tumour tissue samples and 41 MPE cell block samples. Eight cases (15.4%) were ALK-positive in tumour tissue samples by FISH, and among matched MPE cell block samples, five were ALK-positive by FISH, seven were ALK-positive by RT-PCR, and eight were ALK-positive by Ventana IHC. The ALK status concordance rates between tumour tissue and MPE cell block samples were 78.9% by FISH, 98.1% by RT-PCR, and 100% by Ventana IHC. In MPE cell block samples, the sensitivity and specificity of Ventana IHC (100% and 100%) and RT-PCR (87.5% and 100%) were higher than those of FISH (62.5% and 100%). CONCLUSIONS: Malignant pleural effusion cell block samples had a diagnostic performance for ALK detection in advanced NSCLC that was comparable to that of tumour tissue samples. MPE cell block samples might be valid alternative samples for ALK detection when tissue is not available. Ventana IHC could be the most suitable method for ALK detection in MPE cell block samples.

Signet ring cell carcinoma of the ampulla of Vater: Immunophenotype and differentiation.

Signet ring cell carcinoma (SRC) of the ampulla of Vater is extremely rare and the histogenesis remains unknown. In the present study, to investigate the immunohistochemical phenotypes, discuss the histological origin and evaluate the correlation between the immunohistochemical phenotypes and survival of ampullary SRC patients, a retrospective review was conducted. This included all ampullary carcinoma patients treated at The First Affiliated Hospital, College of Medicine, Zhejiang University, and was performed over a five-year period between 2008 and 2012. Eight resected ampullary SRC specimens were examined histopathologically and immunohistochemically, using cytokeratin (CK) and mucin (MUC) immunohistochemical phenotypes. Of all 162 patients with ampullary lesions, eight cases (4.9%) of ampullary SRC were identified. Immunohistochemical analyses of the eight cases revealed the positive expression of CK7 in five, CK19 in seven, CK20 in one, MUC1 in five, MUC2 in three, caudal-related homeobox transcription factor 2 in one, MUC5AC in seven and MUC6 in four of the eight cases, while loss of E-cadherin and ß-catenin was observed in four of the eight cases. According to immunohistochemical classification, ampullary SRC can be classified into four subtypes: Intestinal (I), pancreatobiliary (PB), gastric and mixed types (composed of I mucosa lining and PB epithelium). Patients with the I-type ampullary SRC demonstrated a more favorable prognosis than that of patients with the PB-type ampullary SRC. Additionally, patients with ampullary SRC of I or PB type with gastric differentiation may have a worse prognosis than others. The coexpression of the E-cadherin/ß-catenin complex may also indicate poor prognosis in PB-type ampullary SRC. In conclusion, the clinical five-year follow-up of the patients with pure SRC was more positive than that of those with I-, PB-, gastric- or mixed-type ampullary SRC. The coexpression of the E-cadherin/ß-catenin complex may present a poor prognosis in the PB type of ampullary SRC.

HHV-6-associated acute lymphadenitis in immunocompetent patients: a case report and review of literature.

Human herpesvirus type 6 (HHV-6) has been well described as an agent in immunocompromised hosts, but is a rare cause of acute lymphadenitis in immunocompetent adults. We report an immunocompetent adult with HHV-6-associated acute lymphadenitis. The patient was an elderly man who presented with fever and generalized lymphadenopathy. Microscopically, the lymph node showed diffuse paracortical expansion and scattered large atypical lymphoid cells with large nucleus and eosinophilic nucleoli, resembled immunoblasts. Intranuclear eosinophilic viral inclusions can be found. Immunohistochemical study showed that the large atypical lymphoid cells were positive for CD3 and CD4, but negative for CD8, CD20, CD79a, CD30, ALK, CK, EBV-LMP, and CD56. The antibody against HHV-6 envelope glycoprotein highlighted the viral inclusions which were mostly cytoplasmic with a Golgi distribution. Literatures of HHV-6 associated acute lymphadenitis in immunocompetent patients were reviewed.

Clinical features and hypoxic marker expression of primary sinonasal and laryngeal small-cell neuroendocrine carcinoma: a small case series.

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 follow-up, 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.

Fluorodeoxyglucose uptake in laryngeal carcinoma is associated with the expression of glucose transporter-1 and hypoxia-inducible-factor-1α and the phosphoinositide 3-kinase/protein kinase B pathway.

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.

ABCA1 and ABCG1 expression in the small intestine of type 2 diabetic rats.

OBJECTIVE: Inflammation of the small intestine may occur in type 2 diabetes. This study aimed to investigate whether ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) were altered in chronic inflammation of the small intestine of type 2 diabetic rats. METHODS: Thirty-two male Sprague-Dawley rats were used. Eight rats in the control group were fed with regular chow, and 24 rats were fed a high-fat diet and injected with a single low dose of streptozotocin. All of the control rats and diabetic rats were bred for 10 months. Immunohistochemistry detected ABCA1 and ABCG1 in the small intestine in all the rats. RESULTS: Hematoxylin-eosin staining showed chronic inflammation in the small intestine of the diabetic rats. Immunohistochemistry staining showed that alteration of ABCA1 and ABCG1 was different in the inflammatory and epithelial cells. Quantitative analysis showed that the overall expression of ABCA1 and ABCG1 increased in the diabetic rats compared to the control rats. Both ABCA1 and ABCG1 were enriched in the inflammatory cells of the small intestine in diabetic rats. In the epithelial cells, ABCA1, but not ABCG1, was detected in significantly more diabetic rats than control rats. CONCLUSION: Both ABCA1 and ABCG1 are enriched in chronic inflammation of the small intestine of type 2 diabetic rats. ABCA1, but not ABCG1, is activated in the intestinal epithelial cells of type 2 diabetic rats.

Premelanosome-negative inflammatory angiomyolipoma of liver with expression of cathepsin K and TFE3.

We report the first case of inflammatory variant of hepatic angiomyolipoma (AML) with expression of transcription factor E3 (TFE3) protein but negativity for HMB45 and melan A in a 62-year-old female. Imaging studies revealed a tumor in the left lobe of liver, sized 5.8 cm in maximum diameter. Microscopically, the lesion was composed of large polygonal or epithelioid cells with copious eosinophilic granular cytoplasm. There was a very prominent stromal lymphoplasmacytic infiltrate. Immunohistochemically, the tumor cells showed very strong and diffuse positivity for smooth muscle actin, and cathepsin K, while S-100 protein, keratin, desmin, HMB45 and Melan-A are negative. However, there was multifocal and very convincing nuclear positivity for TFE3, thus confirms the diagnosis.

Upregulation of caveolin-1 and SR-B1 in mice with non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of liver diseases, with markedly increased prevalence. However, its mechanisms are not clear. The present study was undertaken to illustrate the role of caveolin-1 (cav1) and the scavenger receptor class B type 1 (SR-B1) in NAFLD. METHODS: Adult male C57BL/6 mice were fed with a normal diet or high fat and cholesterol (HFC) diet for 14 weeks. The mice were sacrificed to collect plasma and harvest the liver; their plasma lipid concentration was measured. Hepatic cav1 and SR-B1 mRNA and protein expression were determined by real-time quantitative polymerase chain reaction (qPCR) and Western blotting, respectively. In order to study cav1 and SR-B1 distribution and change in hepatocytes, immunohistochemical analysis was performed. RESULTS: HFC diet increased plasma lipids, induced NAFLD and increased the liver/body weight ratio. Compared to the control mice (n=6), the mRNA and protein levels of cav1 and SR-B1 in liver tissue of the NAFLD mice (n=12) increased significantly (cav1 mRNA: 1.536+/-0.226 vs 0.980+/-0.272, P<0.05; protein: 0.643+/-0.240 vs 0.100+/-0.130, P<0.01; SR-B1 mRNA: 1.377+/-0.125 vs 0.956+/-0.151, P<0.01; protein: 2.156+/-0.507 vs 0.211+/-0.211, P<0.01). Furthermore, both cav1 and SR-B1 immunoreactivity increased and their distribution was also changed, mainly in the plasma membrane of hepatocytes, cytoplasm and membrane of lipid droplets and around. CONCLUSION: NAFLD is associated with increased concentration of plasma lipids and upregulation of hepatic cav1 and SR-B1 gene and protein expressions, which indicate that cav1 and SR-B1 might play crucial roles in the pathogenesis of NAFLD.