Epidemiological study of oral allergy syndrome in birch pollen dispersal-free regions.

BACKGROUND: Oral allergy syndrome (OAS) is an immediate allergy caused by a cross-reaction of highly homologous common antigens (pan-allergens) contained in fruits/vegetables and pollen. METHODS: A questionnaire was provided to 6824 outpatient visitors and serum levels of specific IgEs against crude antigens and pan-allergen components were measured to study the relationship between the prevalence of OAS and pollinosis in the Fukui Prefecture where there is almost no dispersal of birch pollen. RESULTS: The prevalence of OAS was 10.8%. The rate of pollinosis complication in the OAS group was 67.4%, and OAS was observed in 16.8% of pollinosis patients. Causative foods in order of frequency were melon, pineapple, kiwi fruit, peach, and apple. A significantly higher number of patients from the OAS group were positive for birch, alder, and timothy grass-specific IgE. The rate of positivity for anti-component IgE corresponding to pollen in OAS group was also significantly higher. Of 34 patients with OAS caused by eating apples, 28 (82.4%) were positive for Mal d1-specific IgE. Of the 52 patients with peach-induced OAS, 41 (78.8%) were positive for Pur p1-specific IgE. The concordance rates between crude antigen-specific IgE and anti-PR-10 component-specific IgE were 87.1% and 93.3% for apple and peach respectively. CONCLUSIONS: In regions where birch pollen is not dispersed, OAS patients have a significant association with the onset of Bet v1-associated allergy. Anti-PR-10 component IgE was useful in diagnosing OAS, and crude antigen-specific IgE was also associated with apple and peach allergies.

Suppression of Poly(rC)-Binding Protein 4 (PCBP4) reduced cisplatin resistance in human maxillary cancer cells.

Cisplatin plays an important role in the therapy for human head and neck cancers. However, cancer cells develop cisplatin resistance, leading to difficulty in treatment and poor prognosis. To analyze cisplatin-resistant mechanisms, a cisplatin-resistant cell line, IMC-3CR, was established from the IMC-3 human maxillary cancer cell line. Flow cytometry revealed that, compared with IMC-3 cells, cisplatin more dominantly induced cell cycle G2/M arrest rather than apoptosis in IMC-3CR cells. That fact suggests that IMC-3CR cells avoid cisplatin-induced apoptosis through induction of G2/M arrest, which allows cancer cells to repair damaged DNA and survive. In the present study, we specifically examined Poly(rC)-Binding Protein 4 (PCBP4), which reportedly induces G2/M arrest. Results showed that suppression of PCBP4 by RNAi reduced cisplatin-induced G2/M arrest and enhanced apoptosis in IMC-3CR cells, resulting in the reduction of cisplatin resistance. In contrast, overexpression of PCBP4 in IMC-3 cells induced G2/M arrest after cisplatin treatment and enhanced cisplatin resistance. We revealed that PCBP4 combined with Cdc25A and suppressed the expression of Cdc25A, resulting in G2/M arrest. PCBP4 plays important roles in the induction of cisplatin resistance in human maxillary cancers. PCBP4 is a novel molecular target for the therapy of head and neck cancers, especially cisplatin-resistant cancers.

Bax-gene transfer enhances apoptosis by steroid treatment in human nasal fibroblasts.

Gene therapy has become a focus not only in the study of cancer but also lifestyle-related diseases. In case of chronic rhinosinusitis with nasal polyps and aspirin-induced asthma, nasal polyps poorly respond to a local administration of steroid. The Bax and Bcl-2 proteins play important roles in the regulation of apoptosis. The treatment of steroid (prednisone) induced apoptosis in the fibroblast. The Bax accelerates apoptosis. Apoptosis is very important in the anti-inflammatory mechanism. In this study, we investigated whether the overexpression of Bax in human fibroblasts influences apoptosis by treatment with a steroid (prednisolone) in vitro. Human nasal fibroblasts were isolated from small pieces of nasal polyp and were transfected with a bax gene-bearing mammalian expression vector. Human nasal fibroblasts were transiently transfected with the expression vector hBaxpcDNA3 (Bax-NF) or native pcDNA3 (Neo-NF). Both transfectants (Bax-NF, Neo-NF) and wild-type-nasal fibroblast (wt-NF) were cultured in conditioning medium and treated with each concentration of prednisolone for 72 h. Prednisolone at a concentration of 10 ng/ml decreased the viability of Bax-NF compared to that of Bax-NF in the absence of prednisolone. The cytotoxicity of prednisolone to Bax-NF was significantly higher than that to Neo-NF or wt-NF (p < 0.01) and the susceptibility of Bax-NF to prednisolone was about 1,000 times that of Neo-NF or wt-NF. We found that the transfer of the exogenous bax gene enhanced the induction of apoptosis by steroid-treatment in human nasal fibroblasts. Therefore, we suggest that exogenous Bax protein expression by gene transfer might be useful for the treatment of nasal polyps. We will further the preclinical study in improving steroids dose and in adopting to transfer bax gene to the nasal polyps by intranasal injection, thus providing a more effective and safer way for the nasal polyps that poorly respond to a local administration of steroids.

Reliability of platelet-derived endothelial cell growth factor as a prognostic factor for oral and oropharyngeal carcinomas.

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 mutL homologue 1 and the human mutS 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.

Combined treatment of cisplatin and overexpression of caspase-activated deoxyribonuclease (CAD) promotes apoptosis in vitro and in vivo.

Recent studies have demonstrated that a caspase-activated deoxyribonuclease (CAD) causes DNA degradation in nuclei after treatment of cells with caspase-3. In this study, we evaluated the effect of CAD overexpression on tumor cells treated with a chemotherapeutic agent in vitro and in vivo. In an in vitro study, we transfected mouse fibroblast L cells with a vector encoding mouse CAD and evaluated the therapeutic potential of CAD gene transfer to L cells treated with cisplatin (CDDP). In an in vivo study, percutaneous transfer of the mouse CAD gene by particle-mediated (gene gun) delivery caused overexpression of CAD in mouse squamous cell carcinoma (SCC). Our results showed that a combined treatment of CDDP and exogenous introduction of the CAD gene into tumor cells in vitro and in vivo arrested tumor growth and induced apoptosis. These results suggest that combined treatment of CDDP and exogenous CAD expression might be a useful strategy for cancer therapy.

PI3K/Akt and apoptosis: size matters.

Recent research has examined Akt and Akt-related serine-threonine kinases in signaling cascades that regulate cell survival and are important in the pathogenesis of degenerative diseases and in cancer. We seek to recapitulate the research that has helped to define the current understanding of the role of the Akt pathway under normal and pathologic conditions, also in view of genetic models of Akt function. In particular, we will evaluate the mechanisms of Akt regulation and the role of Akt substrates in Akt-dependent biologic responses in the decisions of cell death and cell survival. Here, we hope to establish the mechanisms of apoptosis suppression by Akt kinase as a framework for a more general understanding of growth factor-dependent regulation of cell survival.

Influence of platelet-derived endothelial cell growth factor/thymidine phosphorylase on the cell cycle in head and neck squamous cell carcinoma in vitro.

Platelet-derived endothelial cell growth factor (PD-ECGF) was isolated as an endothelial mitogen from platelets and demonstrated to have angiogenic activity and thymidine phosphorylase (TP) activity. It was reported that the overexpression of PD-ECGF occurred with the rapid tumor growth in vivo. In this study, we transfected PD-ECGF into the head and neck squamous cell carcinoma cell line IMC-3 and investigated the property of transfectants in vitro. Highly overexpressed PD-ECGF transfectants rapidly grew compared with parental cells and control vector (CV) transfectants (p<0.05). The expression of cyclin D1 and cyclin E were more enhanced in PD-ECGF transfectants than parental cells and CV transfectants, while the p27kip1 was inhibited in PD-ECGF transfectants. In PD-ECGF transfectants, S and G2/M-phase cells rapidly increased compared with parental cells and CV transfectants. These results showed that the cancer cell line with high expression of PD-ECGF had a rapid cell cycle and consequently facilitated rapid cell growth not only in vivo but also in vitro. Furthermore, the inhibitor of thymidine phosphorylase (TPI) suppressed the cell cycle and rapid cell growth that were acquired by PD-ECGF transfection. Since PD-ECGF was reported to be an independent, poor prognosis factor for head and neck cancer, TPI might be useful for the inhibition of cancer cell growth.