Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Hitoshi Saito is active.

Publication


Featured researches published by Hitoshi Saito.


American Journal of Rhinology | 2000

Macrolide treatment decreased the size of nasal polyps and IL-8 levels in nasal lavage.

Takechiyo Yamada; Shigeharu Fujieda; Shigehito Mori; Hideyuki Yamamoto; Hitoshi Saito

Recently, epidemiologic and experimental studies have been reported that long-term macrolides are effective for the treatment of chronic airway inflammatory diseases including diffuse panbronchiolitis, chronic rhinosinusitis, and cystic fibrosis (Jaffe A, Francis J, Rosenthal M, et al. Long-term azithromycin may improve lung function in children with cystic fibrosis. Lancet 351:420, 1998), and that macrolides can directly reduce the production of IL-8 by nasal epithelial cells (Suzuki H, Shimomura A, Ikeda K, et al. Inhibitory effect of macrolides on interleukin-8 secretion from cultured human nasal epithelial cells. Laryngoscope 107:1661–1666, 1997). In this study we administered macrolides with 14-membered rings to patients with nasal polyps due to chronic rhinosinusitis for at least 3 months and measured the IL-8 level in nasal lavage from those patients. The IL-8 levels in nasal lavage from patients with nasal polyps were reduced during macrolide treatment. There was significant correlation between decreased IL-8 levels in nasal lavage and the clinical effect of macrolides on the size of the nasal polyps. In the group whose polyps were reduced in size, the IL-8 levels dramatically decreased from 231.2 pg/mL to 44.0 pg/mL (p < 0.05), and were significantly higher before macrolide treatment than those in the group whose polyps showed no change (p < 0.005). This reduction in IL-8 may be an important aspect of the effect of macrolide treatment on nasal polyps in chronic rhinosinusitis.


International Journal of Cancer | 1999

Expression of p27 is associated with Bax expression and spontaneous apoptosis in oral and oropharyngeal carcinoma

Shigeharu Fujieda; Manabu Inuzuka; Nobuyuki Tanaka; Hiroshi Sunaga; Guo-Kang Fan; Toshihisa Ito; Chizuru Sugimoto; Hideaki Tsuzuki; Hitoshi Saito

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 (γ = 0.288, p = 0.028) and with that of cyclin D1‐positive cells (γ = 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. Int. J. Cancer (Pred. Oncol.) 84:315–320, 1999.


International Journal of Cancer | 1999

Inhibition of N-linked glycosylation by tunicamycin enhances sensitivity to cisplatin in human head-and-neck carcinoma cells.

Ichiro Noda; Shigeharu Fujieda; Mizue Seki; Nobuyuki Tanaka; Hiroshi Sunaga; Toshio Ohtsubo; Hideaki Tsuzuki; Guo-Kang Fan; Hitoshi Saito

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 μg/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 μg/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. Int. J. Cancer80:279–284, 1999.


Cancer Letters | 1999

IL-10 expression is associated with the expression of platelet- derived endothelial cell growth factor and prognosis in oral and oropharyngeal carcinoma

Shigeharu Fujieda; Hiroshi Sunaga; Hideaki Tsuzuki; Guo-Kang Fan; Hitoshi Saito

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.


European Archives of Oto-rhino-laryngology | 1986

An experimental study of auditory dysfunction associated with hyperlipoproteinemia

T. Saito; K. Sato; Hitoshi Saito

SummaryWe sought to clarify whether or not hyperlipoproteinemia induces auditory dysfunction. In so doing, we studied the general states and cochlear pathologies of guinea pigs after the administration of a hyperlipid diet for 3 months. Serum biochemistries indicated marked elevations of cholesterol, high density lipoprotein (HDL)-cholesterol and low density lipoprotein (LDL) levels. An increased auditory threshold varying from 10 to 20 dB was observed in 40% of the guinea pigs using auditory brainstem responses. Histochemical study of the inner ear revealed variations in lipid metabolism and partial disorders of the outer hair cells. Electron microscopic observations showed vacuolar and parenchymal protrusions on the surfaces of the stria vascularis and Cortis organ, and vacuolar degeneration was seen around the capillary vessels of the vascular stria. Our data has shown that the auditory dysfunction present in the inner ear was less marked than were the morphological changes seen. Our findings suggest that other factors besides hyperlipoproteinemia are involved in the development of severe auditory damage.


International Journal of Cancer | 1999

Granulocyte‐colony‐stimulating factor enhances invasive potential of human head‐and‐neck‐carcinoma cell lines

Ichiro Noda; Shigeharu Fujieda; Toshio Ohtsubo; Hideaki Tsuzuki; Nobuyuki Tanaka; Hiroshi Sunaga; Hitoshi Saito

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.


European Archives of Oto-rhino-laryngology | 1997

The effect of sodium thiosulfate on ototoxicity and pharmacokinetics after cisplatin treatment in guinea pigs

Takehisa Saito; Z. J. Zhang; Y. Manabe; Toshio Ohtsubo; Hitoshi Saito

The effect of sodium thiosulfate (STS) on the pharmacokinetics and ototoxicity of cisplatin (CDDP) was investigated in guinea pigs. Animals received three intramuscular injections of 7.5 mg/kg CDDP separated by intervals of 5 days with or without STS (1,000 mg/kg) administered intraperitoneally immediately and 1 h after each injection of CDDP or 3 and 6 h later. When administered alone, CDDP caused total outer hair cell (OHC) loss in the basal and second turns of the cochlea. In the group administered CDDP and STS, damage to the OHCs was mild when STS was given concurrently, but was severe when STS was given 3 and 6 h later. Pharmacokinetics measured as free and total platinum (Pt) concentrations in plasma and total Pt concentration in perilymph was not affected after administration of STS with CDDP. These results suggest that an inactive Pt-thiosulfate complex is formed in plasma and is measured as a free Pt component which enters the perilymph via the blood-cochlear barrier. Two possible mechanisms are proposed by which STS reduces ototoxicity: entry of CDDP into target cells such as OHCs and striai marginal cells or binding to intracellular macromolecules of these cells is prevented.


Laryngoscope | 1999

Expression of protein p27 is associated with progression and prognosis in laryngeal cancer

Guo-Kang Fan; Shigeharu Fujieda; Hiroshi Sunaga; Hideaki Tsuzuki; Nobuhisa Ito; Hitoshi Saito

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.


Annals of Otology, Rhinology, and Laryngology | 2000

Morphological and Functional Study of Regenerated Chorda Tympani Nerves in Humans

Yoshiyuki Shibamori; Takehito Yamamoto; Takehisa Saito; Yasuhiro Manabe; Toshio Ohtsubo; Takahiro Yamagishi; Hitoshi Saito

It is still unclear whether the chorda tympani nerves in humans regenerate after being severed during middle ear surgery, although functional studies have demonstrated recovery of taste 1 to 2 years after surgery. To date, 12 cases of regenerated chorda tympani nerves have been found in our series of patients during secondary surgery. The regenerated nerves of 3 cases of the 12 were removed as samples during secondary surgery to detect regenerated myelinated axons. All regenerated nerves were in the submucosal connective tissue layer of the reconstructed eardrum. In the regenerated nerves, myelinated nerve fibers existed in a small fascicle or in connective tissue, but the number of myelinated axons was low compared with that in normal subjects (1,752 ± 78; n = 3), and the distribution was sparse. The total number of regenerated myelinated axons varied from 141 (8.3%) to 979 (55.9%). From a functional study using electrogustometry, incomplete recovery of electrogustation was observed in all 3 cases before secondary surgery, suggesting that chorda tympani nerves actually regenerate in the middle ear and do function.


Cancer Letters | 2000

Conventional tumor markers are prognostic indicators in patients with head and neck squamous cell carcinoma

Yuichi Kimura; Shigeharu Fujieda; Tetsuji Takabayashi; Takeshi Tanaka; Chizuru Sugimoto; Hitoshi Saito

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 (P<0.0001, P<0.001, and P<0.0001). 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 (P<0.0001, 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 H&NSCC (P = 0.0115). The results indicate that IAP, sialic acid and SCC are useful as prognostic factors.

Collaboration


Dive into the Hitoshi Saito's collaboration.

Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Nobuyuki Tanaka

Sapporo Medical University

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Setsuo Takeda

Osaka University of Pharmaceutical Sciences

View shared research outputs
Top Co-Authors

Avatar
Researchain Logo
Decentralizing Knowledge