[Chemokine, cytokine, and adhesion molecule dynamics in the nasal washings of patients with nasal polyps].
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Adult↗
Biomedical subjects
S Fujieda
Publications and source records attributed to S Fujieda.
Apoptosis-promoting gene (bax) transfer potentiates sensitivity of squamous cell carcinoma to cisplatin in vitro and in vivo.
Modulation of apoptosis may potentiate the sensitivity of tumor cells to chemotherapeutic agents, thus improving the clinical outcome of cancer treatment. Bax, an apoptosis-promoting member of the bcl-2 family, may be a key factor influencing the chemosensitivity of tumor cells, however, its involvement in cellular sensitivity to anti-cancer drugs remains uncertain in squamous cell carcinoma (SCC). To investigate the role of bax gene expression in modulating cisplatin (CDDP)-induced apoptosis in vitro, an established CDDP-resistant human head and neck SCC (IMC-3 cell line) was transfected with bax gene-bearing mammalian expression vector. Overexpression of the bax gene in CDDP-resistant IMC-3 cells elevated the CDDP susceptibility of tumor cells to a level similar to that of the parental IMC-3 cells. In an in vivo study, percutaneous transfer of apoptosis-promoting bax gene by particle-mediated (gene gun) delivery caused overexpression of Bax in SCC, which was confirmed by immunohistochemical staining, and inhibited the growth of mouse CDDP-resistant SCC. Furthermore, combination therapy with bax gene transfer and subcutaneous administration of CDDP at 3-day intervals markedly inhibited the growth of mouse SCC. Thus, overexpression of bax in SCC by a gene gun system appears to be a rational approach to improving the efficacy of chemotherapy and treatment outcome. We suggest that exogenous bax expression may have therapeutic applications for enhancing chemotherapy in SCC.
Animals↗
Expression of p27 is associated with Bax expression and spontaneous apoptosis in oral and oropharyngeal carcinoma.
p27Kip1, a cyclin-dependent kinase inhibitor, is a negative regulator of the cell cycle, and apoptosis is a genetically encoded program of cell death. To clarify the relationship between the cell cycle and apoptosis, we investigated expression of p27, cyclin D1 and apoptosis-related proteins (p53, Bax, Bcl-2 and c-Myc) in 60 cases of oral and oropharyngeal squamous-cell carcinoma (SCC) using an immuno-histochemical approach, and evaluated spontaneous apoptosis in vivo. Our most notable finding was that spontaneous apoptosis in the p27-positive group was significantly higher than that in the p27-negative group (p = 0.028). In addition, the percentage of p27-positive cells was clearly correlated with that of Bax-positive cells (gamma = 0.288, p = 0.028) and with that of cyclin D1-positive cells (gamma = 0.416, p = 0.002). Expression of p27 was inversely associated with the clinical stage of total tumor progression (p = 0.027). However, no correlation was found between p27 expression and the following parameters: gender, tumor size, lymph node metastasis, overall survival and disease-free survival. Our results give evidence that the action of the cell-cycle regulator p27 is closely linked with apoptosis in clinical samples from patients and indicate that over-expression of p27 might induce apoptosis in cancer cells through elevation of Bax expression, thereby acting on tumor progression.
Adult↗
Decreased expression of Bax is correlated with poor prognosis in oral and oropharyngeal carcinoma.
We investigated the expression of apoptosis-related factors, p53, Bax, Bcl-2, and spontaneous apoptosis in 57 cases of oral and oropharyngeal squamous cell carcinoma (SCC) by immunochemical staining and ApopTag kit. Positive expression of Bax was inversely associated with advanced tumor stage (P = 0.0225), lymph node metastasis (P = 0.0225), clinical stage (P = 0.0083) and poor prognosis (P = 0.0478). Positive expression of p53 was related to poor prognosis (P = 0.0445) and was associated with negative expression of Bax (P = 0.0439). The apoptosis index did not correlate with clinical outcome. These results suggest that abnormality of Bax expression plays an important role in tumor progression in oral and oropharyngeal SCC.
Apoptosis↗
Staining of interleukin-10 predicts clinical outcome in patients with nasopharyngeal carcinoma.
BACKGROUND: Interleukin-10 (IL-10) has been implicated as an important modulator of lymphoid cells, and its sequence is homologous to an open reading frame in the Epstein-Barr virus (EBV) genome. Nasopharyngeal carcinoma (NPC) is a representative tumor related to EBV infection. METHODS: The authors investigated the expression of IL-10 in 21 primary NPCs by using an immunohistochemical approach to examine its prognostic significance. RESULTS: IL-10 staining was positive in 12 of 21 primary NPCs (57%). There was no association between IL-10 expression and gender, tumor size, the occurrence of lymph node metastases, clinical stage, or recurrence. However, there was a significant difference in overall survival between the negative expression and positive expression of IL-10 (P = 0.0348). Although 87.5% of the IL-10 negative group survived for 5 years, only 15.6% of IL-10 positive patients survived for that length of time by the Kaplan-Meier method. IL-10 expression was significant as an independent prognostic indicator of overall survival by multivariate analysis using the Cox proportional hazards model (odds ratio, 26.64; P = 0.0019). CONCLUSIONS: The results imply that expression of IL-10 is a prognostic factor in patients with NPC and may prove valuable in selecting patients with NPC who are candidates for aggressive therapy.
Adult↗
IL-10 expression is associated with the expression of platelet-derived endothelial cell growth factor and prognosis in oral and oropharyngeal carcinoma.
We investigated the expression of IL-10 in oral and oropharyngeal squamous cell carcinoma (SCC) specimens by an immunohistochemical technique. Of 58 SCC, 13 (22%) and 35 (60%) cases showed intense and moderate positive staining of IL-10, respectively. There was no association between the staining of IL-10 and clinicopathological features. However, the patients with intense staining of IL-10 had a significantly lower overall survival rate than those with moderate or negative staining of IL-10 (P = 0.019). In addition, the patients with intense staining of IL-10 had the highest score of platelet-derived endothelial cell growth factor (PD-ECGF), which is established as a poor prognostic indicator (P = 0.0105). These results suggested that IL-10 contributes to the clinical outcome of oral and oropharyngeal SCC.
Carcinoma, Squamous Cell↗
Inhibition of N-linked glycosylation by tunicamycin enhances sensitivity to cisplatin in human head-and-neck carcinoma cells.
Tunicamycin (TM), a naturally occurring antibiotic, blocks the first step in the biosynthesis of N-linked oligosaccharides in cells. In this study, we investigated whether changes in N-linked glycosylation affect the sensitivity of head-and-neck carcinoma cell lines to cis-diaminedichloroplatinum(II) (cisplatin) in vitro and in vivo. In vitro treatment of the IMC-3 and KB cell lines with TM significantly decreased the 50% inhibitory concentration (IC50) of cisplatin, as determined by the MTT assay (24.15 to 10.97 microg/ml, p < 0.05). In addition, TM significantly decreased the IC50 of cisplatin against established cisplatin-resistant IMC-3/CR cells (>100 to 14.4 microg/ml, p < 0.05) to levels similar to those against parental IMC-3 cells. TM treatment decreased the number of Con A- and L-PHA-binding sites on the surface of tumor cells but had no effect on the intracellular platinum concentration. Induction of apoptosis in vitro by TM plus cisplatin in combination was increased compared with that by cisplatin alone. Furthermore, in vivo administration of TM plus cisplatin in combination significantly inhibited local tumor growth in the cisplatin-resistant in vivo C3H/He mouse model as compared with the control group (p < 0.05) and increased in vivo apoptosis of tumor cells. Our results suggest that the manipulation of glycosylation by TM in tumor cells might be a useful therapeutic strategy for successful chemotherapy using cisplatin against head-and-neck cancer.
Animals↗
Granulocyte-colony-stimulating factor enhances invasive potential of human head-and-neck-carcinoma cell lines.
Granulocyte-colony-stimulating factor (G-CSF), a hematopoietic cytokine, regulates the proliferation and differentiation of granulocytic progenitor cells and functionally activated mature neutrophils. G-CSF also affects nonhematopoietic tumor cells by the binding of G-CSF to its specific receptor (G-CSFR) on the cells. In this study, we investigated the effect of G-CSF on the invasive potential of head-and-neck carcinoma cells, and explored the intracellular events initiated by the binding of G-CSF in tumor cells. In vitro treatment of head-and-neck-carcinoma cell lines, IMC-2, IMC-3, KB, Ca9-22, SCCKN and SCCTF, with recombinant G-CSF (rG-CSF) significantly augmented their invasive potential in dose- and time-dependent manners. Among these cancer cells, IMC-2, IMC-3, KB and Ca9-22 cells produced little G-CSF, while large amounts of G-CSF were produced by SCCKN and SCCTF cell lines. Anti-G-CSF antibody (Ab) abrogated the rG-CSF-enhanced invasiveness to the control level of that in untreated cancer cell lines. Immunocytochemical staining and Western blotting using anti-G-CSFR monoclonal antibody (MAb) revealed the expression of G-CSFR on head-and-neck-cancer cell lines exhibiting the enhancement of invasive activity by rG-CSF. IMC-2 cells, having the highest invasive ability among the cell lines used, showed augmentation of G-CSFR expression on stimulation with rG-CSF. Furthermore, stimulation of IMC-2 cells with rG-CSF induced rapid activation of tyrosine-phosphorylated JAK1, suggesting that the G-CSF signal may be transduced into the cells through G-CSFR. Moreover, the gelatinolytic activity of IMC-2 cells was enhanced by stimulation of rG-CSF, and the enhanced invasiveness was inhibited on addition of the tissue inhibitors of metalloproteinases (TIMPs). These results suggest that exogenous rG-CSF may increase the risk of metastasis and/or local recurrence in patients with G-CSFR-positive head-and-neck squamous-cell carcinoma, via an invasive mechanism.
Antibodies, Monoclonal↗
Nonequilibrium / nonlinear chemical oscillation in the virtual absence of gravity.
The Belousov-Zhabotinsky (BZ) reactions were used as typical examples of a nonlinear system far from equilibrium in connection with biological evolution. The virtual absence of gravity in the present work was given from the free-fall facility of Japan Microgravity Center (JAMIC) in Hokkaido. The reaction solution of BZ reaction was composed of bromate in sulfuric acid, 1,4-cyclohexanedione and ferroin to visualize the time development of patterns of chemical oscillations in the reaction-diffusion system. It is a bubble-free constitution in the aging of the reaction. Therefore, the setup constructed to collect image data via CCD cameras was simplified. The operation sequences of necessary devices were comprised of simple solid state relays which were started by a command from the operation room of JAMIC. The propagation profile of chemical patterns under microgravity of 10(-5) g was collected as image data for 9.8 s, and processed by a software of STM-STS2. In the aqueous solutions, propagation velocity of chemical patterns under microgravity was decreased to 80.9 % of that under normal gravity, owing to suppression of convection. On the other hand, in gel matrix, gravity did not influence the propagation velocity.
Bromates↗
Epidemiological research into nasopharyngeal carcinoma in the Chubu region of Japan.
Although patient death due to nasopharyngeal carcinoma (NPC) is increasing, few epidemiological analyses of NPC in Japan have been conducted since Sawaki's report in 1979. To determine the current incidence of NPC in Japan we examined NPC case in the Chubu area from 1986 to 1995. The leaders and reporting representatives of all otorhinolaryngological groups in the area were asked for their support of this epidemiological research. A total of 607 cases (445 male and 162 female NPC patients) were analyzed epidemiologically, histologically, serologically and clinically in this study. The incidence of NPC gradually increased with age. The mean age of the patients was 54.1 years. The age-standardized annual incidence in the Chubu region was 0.28 per 10(5) persons per year. The incidence in prefectures bordering Japan Sea (0.36) was significantly higher than that of prefectures facing the Pacific Ocean (0.21, P<0.05). On the basis of World Health Organization (WHO) histological criteria, 12%) of the cases were classified as WHO I, 54% as WHO II and 34% as WHO III. As for tumor origin, in 58% of the cases it originated posterosuperiorly, in 32% laterally and in 1% inferiorly. Tumor staging showed 4% to belong to stage I, 9% to stage II, 15% to stage III and 72% to stage IV. The positive rates of serum titers of the antibodies to Epstein Barr virus
Adolescent↗
Submucous turbinectomy decreases not only nasal stiffness but also sneezing and rhinorrhea in patients with perennial allergic rhinitis.
BACKGROUND: Turbinate surgery, in which mucous epithelium is resected, has often been used for patients with perennial allergic rhinitis, since the mucous epithelium is the principal site for immunoglobulin (Ig)E-mediated allergic reactions and chronic inflammation. OBJECTIVE: To assess the effect of submucous turbinectomy on allergic rhinitis. METHODS: Sixty patients with severe perennial allergic rhinitis underwent submucous turbinectomy and were followed-up for 1 year. Nasal symptoms were evaluated with a standard symptom score. Rhinometry was used to evaluate nasal congestion, and nasal provocation tests in vivo were performed to evaluate allergic reactions. In 16 cases, biopsies from the nose were also available for immunohistochemical analysis. These examinations were performed before and after submucous turbinectomy. RESULTS: The mean total nasal symptom score (7.2 +/- 1.7, mean +/- SD before surgery) was significantly reduced after surgery (1.2 +/- 1.4, P < 0.0001), and the effect of the surgery on nasal symptoms continued for at least 12 months (1.9 +/- 1.8, P < 0.0001). Submucous turbinectomy reduced both nasal discharge and sneezing, as well as nasal stiffness. Histopathological examination following surgery revealed that the lamina propria was occupied by fibrous tissues, and that the number of vessels, nasal glands, eosinophils and infiltrating IgE+ cells decreased in the turbinate. There were no significant differences in the levels of either house dust mite-specific or non-specific IgE in the serum between before and after surgery. CONCLUSION: Submucous turbinectomy preserving the ciliary epithelium is a powerful strategy for improving nasal symptoms induced by allergic reaction via the reduction in the number of allergy-related cells in the nose.
Adult↗
Free peroneal skin flap for oropharyngeal reconstruction.
The thicknesses of three dermal flaps, platysma, forearm, and fibula, which are often used for oropharyngeal reconstruction, were measured in 21 subjects using 15 MHz Doppler ultrasonography. The mean (SD) thicknesses were 2.2 (0.3), 3.1 (0.5), and 3.8 (0.6) mm, respectively. The free peroneal skin flap from the leg was used in 14 patients with head and neck cancer. These flaps were successfully transplanted in 13 of 14 patients (93%) with no problems at the donor site. This flap offers many advantages, including its distance from the head and neck, its cosmetic superiority to a forearm flap, it allows two flaps with two cutaneous branches, it is possible to close the donor site primarily without a skin graft, and it has thin subcutaneous tissue. We found that the free peroneal skin flap is particularly useful for oropharyngeal reconstruction.
Adult↗
Expression of protein p27 is associated with progression and prognosis in laryngeal cancer.
OBJECTIVE: A cyclin-dependent kinase inhibitor, p27kip1, is recognized as a negative regulator of the cell cycle. To clarify whether immunohistochemical detection of p27 might provide prognostic information, we investigated the expression of p27 in laryngeal squamous cell carcinoma (SCC). STUDY DESIGN: A retrospective study of patients was performed in 109 cases of laryngeal SCC. In addition, we investigated the expression of p53 and granulocyte colony-stimulating factor receptor (GCSF-R) to examine the prognostic significance of them in the same samples. METHODS: Immunohistochemical staining by specific monoclonal antibodies was performed using the avidin-biotin-peroxidase complex technique. RESULTS: Advanced tumor size and clinical stage and the occurrence of lymph node metastasis were associated with the absence of p27 expression, but not correlated with p53 expression and GCSF-R expression. The overall 5-year survival rate in the p27-positive group was significantly higher than that in the p27-negative group. In the Cox proportional hazard model, p27 was demonstrated to be the most powerful prognostic factor among gender, tumor size, lymph node metastasis, stage of disease, and p53 and GCSF-R expression. CONCLUSIONS: We concluded that assessment of p27 expression is useful as a prognostic factor for laryngeal SCC and of value in selecting patients with laryngeal SCC for aggressive therapy.
Adult↗
DNA from Mycobacterium bovis bacillus Calmette-Guérin (MY-1) inhibits immunoglobulin E production by human lymphocytes.
A DNA fraction purified from Mycobacterium bovis bacillus Calmette-Guérin (BCG) and designated MY-1 induced interferon (IFN)-gamma production by human peripheral blood mononuclear cells (PBMC). IFN-gamma is well known as a downregulator of IgE production. In this study we investigated whether MY-1 regulates IgE production by human PBMC in vitro. MY-1 inhibited IgE production in PBMC taken from normal donors and stimulated with interleukin (IL)-4 plus monoclonal anti-CD40 antibody, without affecting production of IgA. MY-1 enhanced production of IFN-gamma and IL-12 by PBMC. Inhibition by MY-1 of IgE production was mediated by both IFN-gamma and IL-12, since the MY-1-induced suppression was blocked by the addition of monoclonal anti-IFN-gamma antibody, monoclonal anti-IL-12 antibody or a monoclonal antibody (mAb) directed at the IL-12 receptor. MY-1 inhibited the induction of epsilon germ-line transcript by IL-4. Additionally, MY-1 inhibited spontaneous in vitro production of IgE by PBMC from atopic donors in the absence of IL-4 plus anti-CD40 mAb. These results suggest that exposure to MY-1 may be a novel strategy for the treatment of IgE-related allergic disease.
Antibodies, Monoclonal↗
[Bacterial infection and production of immunoglobulin in the tonsil].
Immunoglobulin (Ig) isotype switching is the process whereby B cells initially expressing IgM and/or IgD on their surface switch to other Ig heavy-chain loci. We demonstrated that TGF-beta, IL-10 and VIP in the presence of CD40 mAb, can induce isotype switching for IgA in human tonsillar B cells by the generation of switch circular DNA (S alpha/S mu), the induction of alpha germ-line transcripts and a significant amount of IgA production. IgA is the predominant immunoglobulin effector molecule of mucosal immunity that functions as the first line of specific immunologic defense against many microbial pathogens. However, IgA causes IgA nephropathy. We investigated here, whether tonsillar mononuclear cells from patients with IgA nephropathy produce HP-specific IgA and/or IgA-related cytokines by stimulation with components of HP outer membranes (OMHP). HP-specific IgA was predominately induced by tonsillar mononuclear cells of IgA nephropathy, compared to those from chronic tonsillitis. Production of IL-10 and TGF-beta was enhanced by stimulation with OMHP in tonsillar mononuclear cells from IgA nephropathy. These results suggested that local infection of HP and HP-specific IgA induction in the tonsil are associated with pathogens in IgA nephropathy.
Bacterial Infections↗
Expression of hMSH2 correlates with in vitro chemosensitivity to CDDP cytotoxicity in oral and oropharyngeal carcinoma.
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.
Adult↗
Expression of multidrug resistance-associated protein (MRP) in head and neck squamous cell carcinoma.
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.
ATP-Binding Cassette Transporters↗
Expression of granulocyte colony-stimulating factor receptor correlates with prognosis in oral and mesopharyngeal carcinoma.
Granulocyte colony-stimulating factor receptors (G-CSFRs) have been observed on the surface of not only hematopoietic cells but also several cancer cells. The stimulation of G-CSF has been demonstrated to induce proliferation and activation of G-CSFR-positive cells. In this study, we investigated the expression of G-CSFR on the surface of tumor cells and G-CSF production in oral and mesopharyngeal squamous cell carcinoma (SCC) by an immunohistochemical approach. Of 58 oral and mesopharyngeal SCCs, 31 cases (53.4%) and 36 cases (62.1%) were positive for G-CSFR and G-CSF, respectively. There was no association between G-CSFR expression and G-CSF staining. In the group positive for G-CSFR expression, relapse was significantly more likely after primary treatment (P = 0.0069), whereas there was no association between G-CSFR expression and age, sex, tumor size, lymph node metastasis, and clinical stage. Also, the G-CSFR-positive groups had a significantly lower disease-free and overall survival rate than the G-CSFR-negative groups (P = 0.0172 and 0.0188, respectively). However, none of the clinical markers correlated significantly with G-CSF staining, nor did the status of G-CSF production influence the overall survival. The results imply that assessment of G-CSFR may prove valuable in selecting patients with oral and mesopharyngeal SCC for aggressive therapy.
Aged↗