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Seasonal allergic rhinitis (SAR) caused by Japanese cedar pollen (JCP; ie, sugi-pollinosis) is the most common disease in Japan and has been considered a national affliction. More than one third of all Japanese persons have sugi-pollinosis, and this number has significantly increased in the last 2 decades. In our opinion the reason why sugi-pollinosis became a common disease in the last half century is the increased number of cedar pollens, with global climate change and forest growth caused by the tree-planting program of the Japanese government after World War II playing substantial roles; dust storms containing small particulate matter from China might also contribute to the increased incidence of sugi-pollinosis. To help minimize their symptoms, many Japanese wear facemasks and eyeglasses at all times between February and April to prevent exposure to JCP and aerosol pollutants. Forecasts for JCP levels typically follow the weather forecast in mass media broadcasts, and real-time information regarding JCP levels is also available on the Internet. Because a large amount of JCP is produced over several months, it can induce severe symptoms. Japanese guidelines for allergic rhinitis recommend prophylactic treatment with antihistamines or antileukotrienes before the start of JCP dispersion. Additionally, sublingual immunotherapy will be supported by health insurance in the summer of 2014. However, many patients with sugi-pollinosis do not find satisfactory symptom relief with currently available therapies. Collaboration between scientists and pharmaceutical companies to produce new therapeutics for the control of sugi-pollinosis symptoms is necessary.

The Fas/Fas ligand (FasL) pathway has been shown to be an important cellular pathway mediating apoptosis. In this study we investigated the expression of Fas and FasL and the rate of spontaneous apoptosis in 58 oral and oropharyngeal squamous cell carcinoma (SCC) by using immunohistochemical techniques. There was no correlation between Fas or FasL expression and clinicopathological factors. The expression of Fas in the tumor did not affect spontaneous apoptosis of the tumor cells. However, FasL expression was associated with IL-10 and granulocyte colony-stimulating factor expression in oral and oropharyngeal SCC. These results suggested that the Fas/FasL system is connected with the expression of various factors including cytokines in tumor cells.

It is controversial whether the mucociliary transport system in the nasal mucosa of persons with allergic rhinitis is upregulated after an allergen challenge in vivo. The aim of this study was to assess the effect of a specific allergen challenge on the mucociliary transport system in allergic rhinitis. We used a challenge of house dust mites or a control substance on one side of the nose of 97 volunteers (54 with allergic rhinitis for house dust mites and 43 without allergies). The mucociliary transport system of the ipsilateral or contralateral side of the nose challenged was evaluated using the saccharin clearance time on the right side of the nose. The saccharin clearance time was significantly shortened after an allergen challenge not only on the ipsilateral (right) side of the nose (from 15.0 +/- 11.6 to 10. 9 +/- 9.2 min, mean +/- SD, p = 0.041) but also on the contralateral (left) side of the nose (from 14.7 +/- 10.1 to 8.1 +/- 7.9 min, p = 0.013) in the allergic group. A reduction of the saccharin clearance time was also seen in the allergic group after a control challenge [ipsilateral (right) challenge: from 13.0 +/- 10.0 to 11.6 +/- 10.6 min, contralateral (left) challenge: from 13.5 +/- 9.0 to 10.2 +/- 10.1 min]. There were no reductions of the saccharin clearance time after an allergen or control challenge in the nonallergic groups. These results suggest that a unilateral nasal challenge accelerates the mucociliary transport system bilaterally in the nose of subjects with a hypersensitivity such as allergic rhinitis.

It has been reported that pediatric chronic sinusitis with antrochoanal polyp is difficult to cure because it tends to recur easily even with surgery. Therefore, in order to improve its cure rate, aggressive treatment combining polypectomy, intra-maxillary intubation through the inferior meatus, macrolide administration, etc., was attempted. Thirty-seven sides of pediatric chronic sinusitis with antrochoanal polyp and 44 sides of chronic sinusitis without polyp were evaluated after the same treatments. The mean age of patients was 9.7 years, and the mean intubation period was 20 months. Since subjective improvements in children are questionable, the efficacy was evaluated strictly on the basis of X-ray alone focusing on the maxillary sinus. Twenty-four percent of the group with antrochoanal polyp showed 'excellent' effect, i.e. almost complete resolution of the sinus findings, while 45% of the group without polyp showed 'excellent' effect, with a mean follow-up period of 3 years and 6 months. This difference was significant (P0. 01, chi(2)-test). These results further document the intractableness of chronic sinusitis with choanal polyp in children.

We tested for squamous cell carcinoma-related antigen (SCC), carcinoembryonic antigen (CEA), ferritin, immunosuppressive acid protein (IAP) and sialic acid in the serum from 247 patients with head and neck squamous cell carcinoma prior to therapy. Significant correlations were found between IAP and tumor size, lymph node metastasis, and clinical stage (P0.0001, P0.001, and P0.0001). Also, sialic acid and SCC were also correlated with tumor size, lymph node metastasis, and clinical stage. Moreover IAP, sialic acid and SCC were strongly associated with survival rate (P0.0001, P = 0.0230 and P = 0.0159). A multivariate Cox proportional hazard model demonstrated that being positive for IAP was an independent predictor for patients with HNSCC (P = 0.0115). The results indicate that IAP, sialic acid and SCC are useful as prognostic factors.

Background We previously demonstrated glomerular deposition of Haemophilus parainfluenzae (HP) antigens and the presence of IgA antibody against HP antigens in patients with IgA nephropathy (IgAN). In this report we examine the synthesis of immunoglobulins against HP antigens in tonsillar lymphocytes from patients with IgAN. Methods We used tonsillar lymphocytes isolated from the palatine tonsils of 15 patients with IgAN and 16 patients with chronic tonsillitis but without renal disease. We examined lymphocyte proliferation and production of IgA, IgG, and IgM antibodies against HP antigens by measuring thymidine uptake and concentrations of these antibodies in culture supernatants after lymphocyte incubation with HP antigens by ELISA. Results Lymphocytes from patients with IgAN showed a significantly higher stimulation index (SI) on exposure to HP antigens (thymidine incorporation in tonsillar lymphocytes exposed to HP (c.p.m.)/ thymidine incorporation in unstimulated tonsillar lymphocytes (c.p.m.)) than did controls (P=0. 0015). Lymphocytes from patients with IgAN also showed a significantly higher IgA SI (concentrations of IgA against HP antigens in supernatants from HP-stimulated lymphocytes/IgA against HP antigens in supernatants from unstimulated tonsillar lymphocytes) than did controls (P=0.0004). We found positive correlations between concentrations of IgA and IgG antibodies, between IgA and IgM antibodies, and between IgG and IgM antibodies against HP antigens after HP stimulation. Conclusions Our results suggest that HP antigens stimulate tonsillar T and B lymphocytes in patients with IgAN and that these patients have polyclonal activation of lymphocytes against HP antigens, with isotype switching of antibody production from IgM to IgA.

We investigated the expression of hMSH2, a human mutS homologue from chromosome 2p, in oral and oropharyngeal squamous cell carcinoma (SCC) by an immunohistochemical technique and performed tumor in vitro chemosensitivity testing. In 58 oral and oropharyngeal SCC, the hMSH2 positive score was inversely associated with tumor size, but not with other clinical parameters. Among five anticancer drugs (cisplatin (CDDP), 5-FU, peplomycin, mitomycin C and doxorubicin), only for CDDP was sensitivity to cytotoxicity correlated with the hMSH2 positive score. The susceptibility of hMSH2-positive tumors to CDDP killing was significantly higher than that of hMSH2-negative tumors. Immunohistochemical results regarding hMSH2 are promising in the evaluation of the sensitivity of cancer cells to CDDP cytotoxicity and enable one to select patients for adjuvant chemotherapy for oral and oropharyngeal SCC.

In this study we undertook to provide evidence for local in vivo isotype switching to IgE following nasal challenges. Detection of deleted switch circular DNA (switch circles) by a novel nested polymerase chain reaction-based approach was employed as definitive molecular evidence of Ig isotype switching. Nasal challenge in humans with diesel exhaust particles (DEP) plus ragweed antigen has been shown to enhance local IgE production, stimulate local cytokine production, and markedly increase mucosal IgE antibody to ragweed. Four days after combined intranasal DEP plus ragweed challenge, we detected and characterized clones of deleted switch circular DNA (Sepsilon /Smu) representing switching from mu to epsilon from nasal lavage cells. No switch circular DNA was detected in nasal lavage cells following challenge with DEP alone nor with ragweed allergen alone. These results indicate that the combination of mucosal stimulation with DEP and ragweed allergen is capable of driving in vivo isotype switching to IgE in humans with ragweed allergy. These results are the first direct demonstration of in vivo IgE isotype switching in humans.

We investigated the expression of multidrug resistance-associated protein (MRP) in 115 cases of head and neck squamous cell carcinoma (H&NSCC) by immunohistochemistry and examined the relationship between MRP expression and clinical factors. Thirty-four (30%) of 115 cases of H&NSCC had expression of MRP. The clinical stage was inversely associated with the expression of MRP (P = 0.0090), but not with age, sex, tumor size, metastasis, recurrence, death from disease or overall survival rate for 5 years. In vitro chemosensitivity to five chemotherapeutic agents (cis-diamminedichloroplatinum, 5-fluorouracil, peplomycin, mitomycin C and Adriamycin) was tested by ATP assay and no correlation between the sensitivity of tumor cells to the cytotoxicity of any drug and MRP expression was found. These results suggest that the resistance to anticancer drugs is not dependent only on the expression of MRP in H&NSCC.

Mast cells (MC) play an important role in allergic and non-allergic immune responses. Activation of human MC is modulated by several cell surface inhibitory receptors, including recently identified Allergin-1 expressed on both human and mouse MC. Although Allergin-1 suppresses IgE-mediated, mast cell-dependent anaphylaxis in mice, the expression profile and function of Allergin-1 on human primary MC remains undetermined. Here, we established a seven-color flow cytometry method for assessing expression and function of a very small number of human primary MC. We show that Allergin-1S1, a splicing isoform of Allergin-1, is predominantly expressed on human primary MC in both bronchoalveolar lavage (BAL) fluid and nasal scratching specimens. Moreover, Allergin-1S1 inhibits IgE-mediated activation from human primary MC in BAL fluid. These results indicate that Allergin-1 on human primary MC exhibits similar characteristics as mouse Allergin-1 in the expression profile and function.

Importance The aggressive growth of cholesteatoma in the middle ear involves the angiogenesis of the cholesteatomal perimatrix. However, which transcription factor is involved in this process remains unclear. Objective To identify a transcription factor that supports the aggressive growth of cholesteatoma by controlling the angiogenesis of cholesteatoma in the middle ear milieu. Design We used clinical specimens for the profiling of angiogenic factors and their regulatory transcription factors in cholesteatoma. Human skin keratinocytes and endothelial cells were used for evaluation of the effects of candidate transcription factor on the angiogenic factor regulation and endothelial cell proliferation. Setting University departments of otolaryngology–head and neck surgery. Participants Eight clinical cholesteatomal and 8 control specimens were used for cellular and molecular biologic evaluation. An additional 8 cholesteatomal and 8 aural skin specimens were used for microarray studies. Main Outcome Measures The expression of vascular endothelial growth factor, interleukin 8, and cyclooxygenase 2 as measured by means of immunohistochemistry and molecular biologic methods. Results Human aural cholesteatomal specimens were rich in the expression of angiogenic factors such as vascular endothelial growth factor in the cholesteatomal matrix and perimatrix, accompanied by the transcription factor inhibitor of DNA binding (Id1). We found Id1 to be an essential regulator of vascular endothelial growth factor. In addition, potent angiogenic factors, including interleukin 8 and cyclooxygenase 2, were regulated by Id1 via different molecular mechanisms. Conclusions and Relevance The transcription factor Id1 controls the angiogenesis of cholesteatoma through the regulation of vascular endothelial growth factor, interleukin 8, and cyclooxygenase 2, which are responsible for the angiogenesis of cholesteatoma. Id1 may serve as a good target for the treatment of cholesteatomal progression in the middle ear milieu.

Background Allergic rhinitis (AR) is recognized as a major health problem worldwide. Allergen-specific immunotherapy (SIT) is the only available treatment that can alter the natural course of allergic disease. Recent findings in experimental models of allergic rhinitis suggest that complement 3a and 5a regulate the development of maladaptive Th2 and Th17 immunity. We investigated the changes of C3a, C5a, IL-17a in the serum of patients treated by Sublingual immune therapy (SLIT).

The number of seasonal allergic rhinitis by Japanese cedar pollen (SAR-JCP) patients has been increasing in this decade in Japan. To identify genes that related to SAR-JCP, we analyzed gene expression patterns. Methods We collected samples from February to April, at the time of JCP dispersion. Subjects were SAR-JCP patients (SARJCP group), subjects who had positive specific IgE against JC pollen but no symptoms (Sensitization group) and controls without any allergic symptoms and no elevated IgE to common environmental allergens (control group). Total RNA was extracted from nasal epithelial cells by brushing inferior turbinate and performed microarray analysis with Illumina Human Ref8 BeadChip arrays. Results Microarray analysis revealed that the expressions of 16 genes were significantly altered in nasal epithelial cells during allergen exposure. Among these 16 genes, four genes including ITLN1(intelectin1) were significantly up-regulated during pollen seasons. Experiment using human nasal epithelial cells revealed that intelectin1 expression was induced by IL-4 and IL-13 stimulation. Conclusions The present study identified alteration of genes during natural allergen exposure in patients with SAR-JCP, which may further elucidate the molecular mechanisms underlying SAR

Interleukin-10 (IL-10) has various effects on B cell immunoglobulin (Ig) production. Indirect evidence suggests that IL-10 functions as a switch factor for IgG production. In this study, the switch deleted Ig gene DNA was isolated and characterized, as direct evidence that IL-10 induced isotype switching in human B cells. In addition, 16 chimeric Ig fragments were isolated, representing deleted DNA generated by in vitro isotype switching from mu to gamma in human B cells, following stimulation with IL-10 and anti-CD40 monoclonal antibodies (CD40 mAb). These clones consisted solely of S gamma 1/S mu and S gamma 3/S mu chimeric switch circular DNAs, no S gamma 2/S mu or S gamma 4/S mu switch DNA was observed. In addition, IL-10 alone induced only gamma 1 and gamma 3 germ-line mRNA transcripts, as determined by restriction digestion of the reverse transcription-polymerase chain reaction products. Three modes of mu-gamma 3 isotype switching were detected: (1) direct switching; (2) internal deletion of S mu proceeding mu to gamma 3 switching; and (3) internal deletion of S gamma 3 proceeding mu to gamma 3 switching. These results directly demonstrate that gamma 1 and gamma 3 switching in human B cells is specifically induced by IL-10 in the presence of CD40 mAb.

Background We reported previously that serum levels of IL-33 are significantly increased in patients with allergic rhinitis (AR). However, very little is known about the role of IL-33 for the development of AR. Objective We thought to develop a novel murine model of ragweed pollen–specific AR and examined the pathologic role for ragweed-induced IL-33 in the development of AR manifestation using IL-33–deficient (il33 −/− ) mice. Methods Ragweed-immunized and ragweed-challenged mice were examined for early- and late-phase nasal responses. IL-33 protein expression in the nasal epithelial cells of the AR murine model and patients with AR were assessed by using confocal microscopy. Results After nasal challenge with ragweed pollen, ragweed-immunized wild-type mice manifested early-phase (sneezing) and late-phase (eosinophilic and basophilic accumulation) responses. In contrast, il33 −/− and FceRI −/− mice did not have both early- and late-phase AR responses. IL-33 protein was constitutively expressed in the nucleus of nasal epithelial cells and was promptly released into nasal fluids in response to nasal exposure to ragweed pollen. In human subjects we revealed constitutive expression of IL-33 protein in the nasal epithelial cells of healthy control subjects and downregulated expression of IL-33 protein in inflamed nasal epithelial cells of patients with AR. IL-33–stimulated mast cells and basophils contributed to the early- and late-phase AR manifestation through increasing histamine release and production of chemoattractants for eosinophils/basophils, respectively. Conclusions Ragweed pollen–driven endogenous IL-33 contributed to the development of AR responses. IL-33 might present an important therapeutic target for the prevention of AR.

Papillary thyroid carcinoma (PTC) is one of the most common malignant tumors of the thyroid glands. It tends to grow slowly but is associated with a poor prognosis when metastasis happens. To better understand basic mechanisms of tumor development and identify potential new biomarkers of PTC, we examined protein expression profiling in clinical PTC tissue and matched normal thyroid tissue using fluorescence two-dimensional difference gel electrophoresis (2D-DIGE). To identify the proteins, peptide mass fingerprinting via MALDI-TOF mass spectrometry was carried out. Using these strategies, 85 up-regulated or down-regulated proteins were found in PTC. Imaging software determined 26 proteins to be differentially expressed at the two-fold (or greater) level. Among them, Cathepsin B and Lamin A/C were selected for further analyses. Western blotting and immunohistochemical staining showed a higher expression of these proteins in clinical PTC tissue compared to normal thyroid tissue. We are presently investigating those roles in PTC. Proteomic analysis of PTC using 2D-DIGE and mass spectrometry could provide novel potential biomarkers and insights into global pathophysiologic changes in PTC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1273. doi:1538-7445.AM2012-1273

Atopic dermatitis is a chronic inflammatory skin disease. Multiple genetic and environmental factors are thought to be responsible for susceptibility to AD. In this study, we collected 2,478 DNA samples including 209 AD patients and 729 control subjects from Taiwanese population and 513 AD patients and 1027 control subject from Japanese population for sequencing and genotyping ORAI1. A total of 14 genetic variants including 3 novel single-nucleotide polymorphisms (SNPs) in the ORAI1 gene were identified. Our results indicated that a non-synonymous SNP (rs3741596, Ser218Gly) associated with the susceptibility of AD in the Japanese population but not in the Taiwanese population. However, there is another SNP of ORAI1 (rs3741595) associated with the risk of AD in the Taiwanese population but not in the Japanese population. Taken together, our results indicated that genetic polymorphisms of ORAI1 are very likely to be involved in the susceptibility of AD.

Atopic dermatitis (AD) is a common inflammatory skin disease caused by multiple genetic and environmental factors. AD is characterized by the local infiltration of T helper type 2 (Th2) cells. Recent clinical studies have shown important roles of the Th2 chemokines, CCL22 and CCL17 in the pathogenesis of AD. To investigate whether polymorphisms of the CCL22 gene affect the susceptibility to AD, we conducted association studies and functional studies of the related variants. We first resequenced the CCL22 gene and found a total of 39 SNPs. We selected seven tag SNPs in the CCL22 gene, and conducted association studies using two independent Japanese populations (1(st) population, 916 cases and 1,032 controls; 2(nd) population 1,034 cases and 1,004 controls). After the association results were combined by inverse variance method, we observed a significant association at rs4359426 (meta-analysis, combined P = 9.6×10⁻⁶; OR, 0.74; 95% CI, 0.65-0.85). Functional analysis revealed that the risk allele of rs4359426 contributed to higher expression levels of CCL22 mRNA. We further examined the allelic differences in the binding of nuclear proteins by electrophoretic mobility shift assay. The signal intensity of the DNA-protein complex derived from the G allele of rs223821, which was in absolute LD with rs4359426, was higher than that from the A allele. Although further functional analyses are needed, it is likely that related variants play a role in susceptibility to AD in a gain-of-function manner. Our findings provide a new insight into the etiology and pathogenesis of AD.

Introduction: Hepatocyte growth factor (HGF) is a multifunctional growth factor that acts as mitogen, motogen, and/or morphogen in a variety of cells. MET, a specific receptor tyrosine kinase for HGF, is up-regulated in various tumors including human head and neck squamous cell carcinoma (HNSCC) and its signal transduction induces tumor progression and invasion. However, how HGF affects the expression of downstream functional gene expression has not yet been elucidated in detail. MicroRNAs (miRNAs) are non-coding small RNAs that regulate posttranscriptional gene expression by interfering the translation of target mRNAs. Aberrant expression of miRNA is known to induce various human tumors including HNSCC, but the regulation of miRNA expression is still unknown. In this study, we examined the expression of miRNAs with or without HGF stimulation in human HNSCC cell line HSC3 and the expression of their putative target genes was evaluated. Methods: Human HNSCC cell line HSC3 was cultured with or without HGF for designated periods. Alteration of miRNA expression was examined by miRNA microarray analysis. Validation study of miRNAs showing altered expression was performed by quantitative RT-PCR (qRT-PCR). The expression of putative target mRNAs and their translated proteins were examined by qRT-PCR and western blot analysis, respectively. Results: The expression of several miRNAs including let-7a, miR-16, and miR-205, which are already known as tumor-suppressive miRNAs, was altered after HGF stimulation by miRNA microarray. Among them, we focused on miR-200c and miR-27b which were drastically down-regulated after HGF stimulation, because of their unique target mRNAs involving HGF-mediated functional molecules. The expression of ZEB1, a target mRNA for 200c, was up-regulated 3hr after HGF stimulation and that of E-cadherin, a downstream molecule of ZEB1, was up-regulated 12hr after HGF stimulation. The expression of ST14/matriptase, an activation enzyme of HGF and a target mRNA for miR-27b, was not statistically altered after HGF stimulation, but the protein level was drastically up-regulated 12hr after HGF stimulation. These changes were attenuated in part by the addition of oligo pre-mi27b or pre-miR200c into the culture medium. Conclusion: Our present results suggest that miR-200c down-regulated by HGF might play an important role for epithelial-mesenchymal transition (EMT), through up-regulation of ZEB1 followed by down-regulation of E-cadherin. In addition, it was also suggested that miR-27b down-regulated by HGF might induce auto-activation of HGF in HNSCC. These alterations of miRNA expression by HGF stimulation could be induce the enhanced progressive and invasive characteristics of HNSCC. This is a first report that HGF may directly regulate some miRNAs that affect the expression of HGF-mediated downstream functional molecules. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3972. doi:10.1158/1538-7445.AM2011-3972

Allergic rhinitis is a global health problem that causes major illnesses and disability worldwide. Allergen-specific immunotherapy (SIT) is the only available treatment that can alter the natural course of allergic disease. However, the precise mechanism underlying allergen-SIT is not well understood.The aim of the current study was to identify protein expression signatures reflective of allergen-SIT-more specifically, sublingual immunotherapy (SLIT).Serum was taken twice from patients with seasonal allergic rhinitis caused by Japanese cedar: once before the pollen season and once during the season. A total of 25 patients was randomly categorized into a placebo-treated group and an active-treatment group. Their serum protein profiles were analyzed by 2-dimensional electrophoresis.Sixteen proteins were found to be differentially expressed during the pollen season. Among the differentially expressed proteins, the serum levels of complement C4A, apolipoprotein A-IV (apoA-IV), and transthyretin were significantly increased in SLIT-treated patients but not in placebo-treated patients. Among these proteins, the serum levels of apoA-IV correlated with the clinical symptom-medication scores (r = -0.635; P .05) and with quality of life scores (r = -0.516; P .05) in the case of SLIT-treated patients. The amount of histamine released from the basophils in vitro was greatly reduced after the addition of recombinant apoA-IV in the medium (P .01).Our data will increase the understanding of the mechanism of SLIT and may provide novel insights into the treatment of allergic rhinitis.

The chemosensitivity of various head and neck cancers was investigated with the 5-day rapid thymidine incorporation assay in soft agar culture. The evaluability rate was 56%. Head and neck cancers were sensitive in vitro, in decreasing order, to peplomycin, cisplatin, bleomycin, 5-fluorouracil, mitomycin C, and doxorubicin. Primary tumors and neck metastases exhibited the same sensitivity, with 21% of all specimens tested responding. In vitro chemosensitivities were similar among patients younger than 69 years of age and those older than 70. The predictive accuracy for sensitivity tested prospectively in five cases was 80% and that for resistance in four was 75%.

Objective To identify a strong prognostic biological marker for patients with oral and oropharyngeal squamous cell carcinomas. Design We evaluated the protein expressions of 26 tumor-associated factors, including cytokines and cytokine receptors (granulocyte colony-stimulating factor [G-CSF], interleukin 10 [IL-10], G-CSF receptor [G-CSFR], and IL-12 receptor); angiogenic factors (platelet-derived endothelial cell growth factor [PD-ECGF] and vessel count); cell cycle–related proteins (p27, cyclin D1, and cyclin E); apoptosis-related factors (wild-type p53, Bax, Bcl-2, apoptotic index, Fas, and Fas ligand); oncogene proteins (c-fos and c-Myc); cell-surface proteins (P-glycoprotein, multidrug resistance–associated protein, nm23, and CD40); intracellular proteins (aryl hydrocarbon receptor nuclear translocator, aryl hydrocarbon receptor, and heat shock protein 27); and DNA mismatch-repair genes (protein encoded by human mut L homologue 1 and the human mut S homologue of the chromosome 2p gene) by means of immunohistochemical analysis. Setting Department of Otorhinolaryngology—Head and Neck Surgery, University of Fukui, Fukui, Japan. Patients Fifty-eight patients who underwent surgical resections of oral and oropharyngeal squamous cell carcinomas. Results A low-level PD-ECGF expression, a hypovascular count, or a low-level G-CSFR expression was associated with a favorable clinical outcome using the Kaplan-Meier method. Univariate analysis showed that PD-ECGF expression (odds, 4.19; P = .02), G-CSFR expression (odds, 4.10; P = .01), and vessel count (odds, 2.80; P = .04) had significant hazard rates. When multivariate analysis was performed on 6 factors, including sex, tumor size, lymph node metastasis, PD-ECGF expression, G-CSFR expression, and vessel count, patients with a positive expression of PD-ECGF had the highest relative risk value for death due to the disease (odds, 4.94; P = .01). Also, G-CSFR was an independent prognostic indicator in the model (odds, 3.29; P = .04). No correlations between other factors and prognoses were detected. Conclusion Expression of PD-ECGF was the most effective marker for making prognoses for oral and oropharyngeal squamous cell carcinomas, and G-CSFR expression was the second most effective among 26 tumor-associated factors.

To optimize chemotherapy for head and neck malignant tumors in the elderly we compared patients older than 70 years of age with those younger than 69. Toxic reaction was comparable between the two age groups, except that hematologic and mucosal reactions in the head and neck region were more prevalent in the elderly. However, the response rate and chemosensitivities were similar between the two groups.Our findings indicate that chemotherapy for the elderly should based on a performance status under 3 grade, instead of age, and that anti-cancer drugs not affecting immunological function should be selected.

Background Angiogenesis is one pathogenesis of allergic airway disease. Methods potent angiogenic factor is platelet-derived endothelial cell growth factor (PD-ECGF), also known as thymidine phosphorylase (TP) in the field of cancer-associated research. Vascular endothelial growth factor (VEGF) is another representative angiogenic factor. Both factors were added to the culture system of human peripheral blood mononuclear cells (PBMC) with IL-4 and anti-CD40 monoclonal antibody (mAb). Total IgE levels in the supernatants and signal transduction of stimulated PBMC were evaluated. Results Addition of PD-ECGF enhances in vitro IgE production by PBMC in the presence of IL-4 and anti- CD40 mAb, but VEGF does not enhance IgE production. Although PD-ECGF catalyzes the reversible phosphorolysis of thymidine to 2-deoxy-D-ribose-1-phosphate (2DDR), treatment of 2DDR has no effect on IgE production by human PBMC. Both IL-4 and anti-CD40 mAb induce PD-ECGF by human PBMC. Thymidine phosphorylase inhibitor (TPI), 5-chloro-6-[1- (2-iminopyrrolidinyl) methyl] uracil hydrochloride reduce IgE production via blocking of STAT6- phosphorylation. Conclusions Taken together, these results suggest TP involvement in the enhancement of IgE production and suggest that TPI is a novel strategy against IgE-related allergic disease.