Malnutrition impairs interferon signaling through mTOR and FoxO pathways in patients with chronic hepatitis C.

BACKGROUND & AIMS: Patients with advanced chronic hepatitis C (CH-C) often are malnourished, but the effects of malnutrition on interferon (IFN) signaling and response to treatment have not been determined. We assessed the importance of the nutritional state of the liver on IFN signaling and treatment response. METHODS: We studied data from 168 patients with CH-C who were treated with the combination of pegylated-IFN and ribavirin. Plasma concentrations of amino acids were measured by mass spectrometry. Liver gene expression profiles were obtained from 91 patients. Huh-7 cells were used to evaluate the IFN signaling pathway, mammalian target of rapamycin complex 1 (mTORC1), and forkhead box O (FoxO). Antiviral signaling induced by branched-chain amino acids (BCAAs) was determined using the in vitro hepatitis C virus replication system. RESULTS: Multivariate logistic regression analysis showed that Fischer's ratio was associated significantly with nonresponders, independent of interleukin-28B polymorphisms or the histologic stage of the liver. Fischer's ratio was correlated inversely with the expression of BCAA transaminase 1, and was affected by hepatic mTORC1 signaling. IFN stimulation was impaired substantially in Huh-7 cells grown in medium that was low in amino acid concentration, through repressed mTORC1 signaling, and increased Socs3 expression, which was regulated by Foxo3a. BCAA could restore impaired IFN signaling and inhibit hepatitis C virus replication under conditions of malnutrition. CONCLUSIONS: Malnutrition impaired IFN signaling by inhibiting mTORC1 and activating Socs3 signaling through Foxo3a. Increasing BCAAs to up-regulate IFN signaling might be used as a new therapeutic approach for patients with advanced CH-C.

Effective staining method with iodine for leukoplakia and lesions surrounding squamous cell carcinomas of the tongue assessed by colorimetric analysis.

To determine whether staining with iodine solution provides an efficient criterion for determining the area of resection for the lesions surrounding squamous cell carcinoma (SCC) and leukoplakia of the tongue, we determined the optimum density of iodine solution and staining procedure and analyzed the color of lightly stained lesions (LSLs) in relation to the histopathologic findings. Sixty-five patients with SCC or leukoplakia of the tongue were divided into two groups: lesions stained with 3% Lugol solution and restained with either 5% Lugol solution (n=38) or 10% iodine glycerin (n=27). Among the lesions stained with 5% Lugol solution, significant differences were found in all color values. Color difference values (DeltaE*ab) using 3% and 5% Lugol solutions were significantly different between epithelial hyperplasia/mild epithelial dysplasia and moderate to severe dysplasia (P < 0.05). According to the evaluations of five clinicians in 46 LSLs, a distinctive boundary was most often obtained using 5% Lugol solution. These results suggest that the most effective method for obtaining a clear boundary and distinguishing moderate to severe dysplasia from mild or no epithelial dysplasia according to the measured color value was to stain with 3% followed by 5% Lugol solution.

Dynamic and static light scattering study on the sol-gel transition of resorcinol-formaldehyde aqueous solution.

Structure formation during the sol-gel transition of resorcinol-formaldehyde (RF) solutions was traced by dynamic light scattering (DLS) and static light scattering (SLS) techniques. The decay time spectra obtained by DLS revealed that both the growth rates of colloidal particles formed during the early stage of the sol-gel transition and the time required for the colloidal particles to form a firm network structure could be related to the ratio of catalyst to water (C/W) of the starting RF solution. SLS results indicated that the molecular weight of colloidal particles increased with the progress of the sol-gel transition, the rate of which was also affected by the value of C/W. The mesoporosity of RF aerogels, which were prepared by drying RF hydrogels with supercritical carbon dioxide, was confirmed to depend on the size of colloidal particles estimated from the decay time spectrum collected at the last stage of the sol-gel transition.

Ultrasonography and computed tomography of extracapsular invasion in cervical lymph nodes of squamous cell carcinoma in the oral cavity.

PURPOSE: This study evaluates the efficacy of imaging for diagnosing extracapsular invasion by metastatic cervical lymph nodes. METHODS: The subjects were 47 patients with squamous cell carcinoma of the oral cavity examined by both ultrasonography and computed tomography. All subjects had undergone neck dissection, and histopathologic examination confirmed the presence of one or more metastatic cervical lymph nodes in each of them. RESULTS: Histopathologic examination confirmed extracapsular invasion in 25 of 48 metastatic nodes; in the remaining 23 nodes, the tumor was confined within the capsule. Average short-axis diameters of the lymph nodes of these groups differed significantly (17.4 ± 10.6 and 12.7 ± 4.4 mm, respectively; P = 0.046). The diagnostic sensitivity, specificity, and accuracy of ultrasonography for detecting macroscopic extracapsular invasion were 80%, 74%, and 77%, respectively. The corresponding values for computed tomography were 85%, 83%, and 84%. CONCLUSION: Diagnostic images are effective for the preoperative diagnosis of extracapsular invasion of metastatic cervical nodes of carcinoma of the oral cavity.

Sarcomas of the oral and maxillofacial region: a review of 32 cases in 25 years.

Thirty-two cases of sarcomas involving the oral and maxillofacial region over a period of 25 years were reviewed. The age range was from 5 months to 77 years with a mean age of 42. The male to female ratio was 3:1. The sarcomas were located in the maxilla including the maxillary sinus (n= 13), mandible (n= 13), buccal mucosa (n= 3), temporomandibular fossa (n= 2), and submandibular region (n= 1). Histologically sarcomas were classified as osteosarcoma (n= 9), malignant fibrous histiocytoma (n= 7), rhabdomyosarcoma (n= 5), fibrosarcoma (n= 3), plasmacytoma (n= 2), leiomyosarcoma (n= 2), angiosarcoma (n= 2), liposarcoma (n= 1), and ameloblastic fibrosarcoma (n= 1). Surgical resection was performed in 29 cases. Local recurrence was found in 10 patients and metastasis in 11 patients. Metastases included five regional lymph node metastases and eight distant metastases. The survival of patients with local recurrence or metastasis was poor. Surgery is the most reliable treatment for sarcomas of the oral and maxillofacial region. Adequate excision with safety surgical margin as the initial therapy is important for better survival. The value of radiation therapy and/or chemotherapy is uncertain. The 5-year survival rate of primary cases was 61%.