Clinical outcome and patterns of recurrence of head and neck squamous cell carcinoma with a limited field of postoperative radiotherapy.

BACKGROUND: Postoperative radiotherapy is the standard treatment for head and neck squamous cell carcinoma having high-risk features in surgical specimens. However, its severe toxicity can be a significant problem. This study was undertaken to evaluate the efficacy of our limited-field postoperative radiotherapy with the aim of reducing morbidity by minimizing the radiation field. METHODS: Between 2000 and 2009, 154 patients with head and neck squamous cell carcinoma received limited-field postoperative radiotherapy. The reason for postoperative radiotherapy was close/positive margins in 33 patients and extracapsular extension in 91. The median radiation dose was 50 Gy (30-66.4). The radiation field covered the tumor bed without lymph node regions for close/positive margins and only involved sites of the neck region were irradiated for multiple nodes or extracapsular extension. RESULTS: With a median follow-up of 43 months for surviving patients, the 3-year overall survival and progression-free survival rates were 53.7 and 42.1%, respectively. The 3-year rates of progression-free survival of the group having major risks (i.e. close/positive margins and/or extracapsular extension) and the group with other risks were 34.7 and 62.8%, respectively (P < 0.01). Thirty-one local recurrences (20%), of which 22 were located out-of-field, and 44 regional recurrences (29%), of which 16 were located out-of-field, developed. Late toxicity of grade 3 or greater developed in only six patients (3.8%). CONCLUSIONS: Although the toxicities associated with limited-field postoperative radiotherapy could be kept to lower levels, the locoregional control rate did not seem to be sufficient. We should arrange the radiation field depending on risk factors.

Peach leaf contains multiflorin a as a potent inhibitor of glucose absorption in the small intestine in mice.

Peach leaf extract has anti-hyperglycemic effects on the postprandial blood glucose level in glucose-loaded mice. In our previous study, the mechanism of action was considered to be the inhibition of glucose absorption in the small intestine. To elucidate the active principle in peach leaf, purification of the active compound and a structure determination were performed. With the use of bioassay-guided fractionation using glucose-loaded mice, the acetylated kaempferol glycoside multiflorin A (MFA), a potent inhibitor of glucose absorption from the intestine, was isolated from the MeOH extract of leaf of the edible peach Prunus persica. The structure was identified by HPLC using thiazolizine derivatives and by an analysis of its spectral data. The inhibitory effect of MFA against glucose absorption was demonstrated in the dose dependent manner in mice. However, as the deacetylated analog of MFA, multiflorin B did not show the activity at the in vivo, the activity of MFA was suggested to depend on the acetyl group on the sugar moiety. This is the first report of anti-hyperglycemic activity of MFA in peach leaf extract. MFA may be useful in functional foods or medicines for preventing the postprandial absorption of glucose in hyperglycemia.

Green tea polyphenol EGCG induces lipid-raft clustering and apoptotic cell death by activating protein kinase Cδ and acid sphingomyelinase through a 67 kDa laminin receptor in multiple myeloma cells.

EGCG [(-)-epigallocatechin-3-O-gallate], the major polyphenol of green tea, has cancer chemopreventive and chemotherapeutic activities. EGCG selectively inhibits cell growth and induces apoptosis in cancer cells without adversely affecting normal cells; however, the underlying molecular mechanism in vivo is unclear. In the present study, we show that EGCG-induced apoptotic activity is attributed to a lipid-raft clustering mediated through 67LR (67 kDa laminin receptor) that is significantly elevated in MM (multiple myeloma) cells relative to normal peripheral blood mononuclear cells, and that aSMase (acid sphingomyelinase) is critical for the lipid-raft clustering and the apoptotic cell death induced by EGCG. We also found that EGCG induces aSMase translocation to the plasma membrane and PKCδ (protein kinase Cδ) phosphorylation at Ser664, which was necessary for aSMase/ceramide signalling via 67LR. Additionally, orally administered EGCG activated PKCδ and aSMase in a murine MM xenograft model. These results elucidate a novel cell-death pathway triggered by EGCG for the specific killing of MM cells.

Mode of action of the immunostimulatory effect of collagen from jellyfish.

We have previously demonstrated that collagen from jellyfish simulated immunoglobulin and cytokine production by human-human hybridoma line HB4C5 cells and by human peripheral blood lymphocytes (hPBL). The mode of action of the collagen as an immunostimulatory factor was investigated. The expression levels of immunoglobulin mRNAs in HB4C5 cells, and those of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and transforming growth factor (TGF)-beta in hPBL were up-regulated by jellyfish collagen. In addition, this collagen activated IgM production by transcription-suppressed HB4C5 cells that had been treated with actinomycin D. This collagen also enhanced IgM production by translation-suppressed HB4C5 cells that had been treated with sodium fluoride, but was ineffective in accelerating IgM production by HB4C5 cells treated with cycloheximide. Moreover, the intracellular IgM level in HB4C5 cells treated with the post-translation inhibitor, monensin, was increased by this collagen. These results suggest that collagen from jellyfish stimulated not only the transcription activity, but also the translation activity for enhanced immunoglobulin and cytokine production.

Long-term beneficial effects of lung volume reduction surgery on quality of life in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation, which results in exertional dyspnea and physical disability. Subsequently, those cause a difficulty in performing routine activities of daily living and affect their health-related quality of life (HRQOL). Lung volume reduction surgery (LVRS) has been reported to be an effective treatment for selected patients with advanced COPD to improve pulmonary function, lung mechanics, exercise tolerance, and dyspnea. However, the long-term effects of LVRS on HRQOL have not been fully investigated. Therefore the effects of LVRS on generic and disease-specific HRQOL were assessed in patients with COPD following LVRS for 36 months. Nineteen patients (65.1 +/- 7.0 [mean +/- S.D.] years old) who underwent pulmonary rehabilitation plus LVRS (LVRS group), and 8 patients (67.2 +/- 5.8 years old) who did pulmonary rehabilitation but not LVRS (Medical group) were studied. In both groups, optimal medication was given throughout this period. Generic HRQOL and disease-specific HRQOL were evaluated before rehabilitation, and 3, 12, 24, and 36 months after LVRS. Following LVRS, the generic HRQOL was significantly improved and the disease-specific HRQOL was maintained up to 36 months. In Medical group, disease-specific HRQOL rapidly deteriorated. In conclusion, the long-term effects of LVRS on HRQOL in COPD patients were maintained up to 36 months compared with Medical group. Both generic and disease-specific HRQOL changed differently, suggesting the importance of both assessments especially in long-term follow up.

Immunostimulation effect of jellyfish collagen.

Certain edible large jellyfishes belonging to the order Rhizostomeae are consumed in large quantities in China and Japan. The exumbrella part of the edible jellyfish Stomolophus nomurai was cut and soaked in dilute hydrochloric acid solution (pH 3.0) for 12 h, and heated at 121 degrees C for 20 min. The immunostimulation effects of the jellyfish extract were examined. The jellyfish extract enhanced IgM production of human hybridoma HB4C5 cells 34-fold. IgM and IgG production of human peripheral blood lymphocytes (PBL) were also accelerated, 2.8- and 1.4-fold respectively. Moreover, production of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha by human PBL was stimulated 100- and 17-fold respectively. Collagenase treatment inactivated the immunostimulation activity of the jellyfish extract. In addition, purified collagen from bovine Achilles' tendon accelerated IgM production of hybridoma cells. These facts mean that collagen has an immunostimulation effect, and that the active substance in jellyfish extract is collagen.

Influences of genetic and environmental factors on the concentration of the allergen Cry j 1 in sugi (Cryptomeria japonica) pollen.

Pollen from sugi (Japanese cedar, Cryptomeria japonica D. Don), a forest tree species that is widely grown in Japan, causes serious allergic disease. The major allergens from sugi pollen, Cry j 1 and Cry j 2, have been isolated and characterized. It has been reported that Cry j 1 concentration in pollen varies considerably among trees. If Cry j 1 concentration is genetically controlled, the planting of trees with low Cry j 1 concentrations would reduce pollinosis. We investigated genetic and environmental effects on Cry j 1 concentration in eight clones growing at four sites. Concentrations of Cry j 1 in pollen were measured with a monoclonal antibody-based Enzyme Linked Immunosorbent Assay (ELISA). The Cry j 1 concentrations differed significantly among clones and sites, but the site x clone interaction was not significant, suggesting that the Cry j 1 concentration is controlled primarily by genetic factors. We examined correlations between Cry j 1 concentration and temperature and precipitation from July through February. Temperature was not significantly related to Cry j 1 concentration, whereas cumulative precipitation during the 8 months and mean daily precipitation in September showed significant negative correlations with Cry j 1 concentration.

Human lens epithelial cell damage and stimulation of their secretion of chemical mediators by benzalkonium chloride rather than latanoprost and timolol.

OBJECTIVE: To investigate the effects of latanoprost, timolol maleate, and benzalkonium chloride on cell damage and induction of the secretion of chemical mediators of stress and wound healing by human lens epithelial cells in culture. METHODS: Cells from a human lens epithelial cell line (SRA01/04) were cultured in Dulbecco minimum essential medium supplemented with 5% fetal bovine serum. The amounts of latanoprost (50 micro g/mL), timolol maleate (5 mg/mL), or benzalkonium chloride (200 micro g/mL) used in eyedrops, and x10 to x1000 dilutions thereof, were added to the medium. After 7 days' culture, cell morphological changes were assessed using phase-contrast microscopy, and cell-free culture supernatants were collected for prostaglandin E2 (PGE2), interleukin 1alpha (IL-1alpha), and interleukin 6 (IL-6) iodine I 125 radioimmunoassay, enzyme-linked immunosorbent assay, and chemiluminescent enzyme immunoassay, respectively. RESULTS: All cells that were cultured with the concentrations of latanoprost, timolol, or benzalkonium chloride used in eyedrops detached from the culture dish and died within 3 days. At a x10 dilution of latanoprost or timolol or a x100 dilution of benzalkonium chloride, no proliferation or elongation of the cells was observed. Secretions of PGE2, IL-1alpha, and IL-6 at x10 dilutions of latanoprost or timolol were 3 to 77 times higher than in controls, whereas they were 190 to 305 times higher at a x180 dilution of benzalkonium chloride. The amounts of these soluble mediators in culture supernatants depended on the dose of latanoprost, timolol, or benzalkonium chloride added. CONCLUSION: Our results indicate that benzalkonium chloride, used as the preservative in eyedrops containing latanoprost or timolol, is the agent most damaging to lens epithelial cells and most strongly stimulates the expression of soluble chemical mediators in these cells.