Biomedical subjects

I Noda

Publications and source records attributed to I Noda.

At least 19 recordsLinked to original sources

PubMed2001

Granulocyte colony-stimulating factor (G-CSF)-mediated signaling regulates type IV collagenase activity in head and neck cancer cells.

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 through its binding to the specific receptor (G-CSFR) on the cells. The type IV collagenase [matrix metalloproteinase 2 (MMP-2)] is known to play a main role in the process of invasion and metastasis, but its regulation, for example, in expression or in activation, is not clearly understood. In this study, we investigated the role of G-CSF in the regulation of tumor cell invasion and the synthesis of MMP-2. G-CSFs producing the head and neck carcinoma cell line T3M-1 cells with metastatic ability and no G-CSF receptor (G-CSFR) expression were transfected with G-CSFR expression vector. In vitro treatment of G-CSFR-transfectant T3M-1 cells with recombinant G-CSF (rG-CSF) significantly augmented their invasive potential in a reconstituted basement membrane (Matrigel) system compared with that of parental cells. Moreover, MMP-2 activity of G-CSFR-transfectant T3M-1 cells was enhanced by the stimulation with rG-CSF, as assessed by gelatin zymography. These results identify G-CSF as a regulator of MMP-2 and cellular invasion.

Carcinoma, Squamous Cell↗

PubMed2001

Expression of p-glycoprotein is associated with that of multidrug resistance protein 1 (MRP1) in the vestibular labyrinth and endolymphatic sac of the guinea pig.

Expression of p-glycoprotein (p-gp) and multidrug resistance protein 1 (MRP1) was detected in the vestibular labyrinth and endolymphatic sac (ES) of the guinea pig by immunohistochemical staining using anti-p-gp monoclonal antibody (mAb) C219 and anti-MRP mAb MRPr1. P-gp was detected in capillary endothelial cells of the crista ampullaris, utricle, saccule and ES. MRP1 was detected in the epithelial lining of the crista ampullaris, utricle, saccule, and epithelial cells of the ES. Since p-gp and MRP1 act as extrusion pumps, they may coordinate with each other in vestibular organs and ES and play an important role in the blood-labyrinth barrier.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2001

Expression of multidrug resistance protein 1 (MRP1) in the rat cochlea with special reference to the blood-inner ear barrier.

Expression of multidrug resistance protein 1 (MRP1) was detected in the rat cochlea by RT-PCR and immunohistochemistry using anti-MRP monoclonal antibody MRPr1. Use of primers specific for rat mrp1 gene resulted in the amplification of an expected 394 bp fragment prepared from brain and cochlear tissues. Immunohistochemically, MRP was found in the choroid plexus, stria vascularis, spiral ligament, spiral prominence and cochlear nerve in the modiolus. From these results, it was suggested that MRP in the rat cochlea might function as an extrusion pump and play an important role in the blood-inner ear barrier.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2001

Homozygous disruption of the mdrla P-glycoprotein gene affects blood-nerve barrier function in mice administered with neurotoxic drugs.

We investigated the expression and function of mdr1a p-glycoprotein in peripheral nerves, including the VIIth and VIIIth nerves, using mdr1a p-glycoprotein gene knockout mice [mdr1a(-/-) mice] and wild-type mdr1a(+/+) mice. P-glycoprotein expression in capillary endothelial cells of the peripheral nerve tissues was detected by immunohistochemical and RT-PCR analyses in mdr1a(+/+) mice but not in mdr1a(-/-) mice. Pharmacokinetic analyses indicated that, compared to mdr1a(+/+) mice, mdr1a(-/-) mice showed a significantly higher accumulation of p-glycoprotein substrate drugs such as vinblastine and doxorubicin, which are neurotoxic. Tissue concentrations of vinblastine and doxorubicin were lower in the order of the brain, peripheral nerves and most other organs. However, increased accumulation was not detected after administering another neurotoxic drug, cisplatin, indicating that p-glycoprotein is selective at extruding drugs. These data indicate that mdr1a p-glycoprotein, which acts as an efflux pump, might play an important role in the blood-nerve barrier to prevent side effects induced by neurotoxic p-glycoprotein substrate drugs. The participation of p-glycoprotein in the blood-nerve barrier is considered to represent a new functional mechanism of this barrier.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2001

Doxorubicin ototoxicity is induced in mice by combination treatment with cyclosporin A.

Although doxorubicin [adriamycin (ADM)] ototoxicity has not been detected to date, it has been reported that neurotoxicity in the central nervous system was induced by chemotherapy with ADM in patients receiving chronic cyclosporin A (CsA) treatment. ADM ototoxicity may be induced by combination therapy with CsA because extrusion of ADM from the inner ear by p-glycoprotein (p-gp), which acts as an extrusion pump and is expressed on the surface of endothelial cells of capillary blood vessels, might be inhibited by CsA. resulting in significant accumulation of ADM in the inner ear. ADM (10 mg/kg) was administered to FVB mice either with or without CsA (200 mg/kg). Auditory brainstem responses (ABRs) were recorded before and after treatment. ABR changes were not observed in mice treated with either ADM or CsA alone. Threshold elevation, elongation of wave I-V latencies and interpeak latencies of waves I-II, I-III, I-IV and I-V were detected in mice treated with ADM in combination with CsA. These changes reached their peak values 3 weeks after treatment, and then recovered to pre-treatment levels. In normal mice, ADM is extruded by p-gp from the inner ear and auditory pathway, thus preventing hearing disorder. However, ADM ototoxicity was induced by combination therapy with CsA, indicating that CsA has an inhibitory action on p-gp function in the auditory pathway, including the inner ear. After organ transplantation, therefore, clinical administration of ADM in combination with CsA should be performed with caution.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

Long-term follow-up results of electrogustometry and subjective taste disorder after middle ear surgery.

OBJECTIVES: The present study compares the long-term follow-up results of electrogustometry with patient reports of taste dysfunction after middle ear surgery. STUDY DESIGN: Retrospective review of 371 patients who underwent middle ear surgery. METHODS: Patients were divided into the following groups depending on the degree of manipulation or surgical damage to the chorda tympani nerves: the no-touch group (group 1 [n = 109]); the touch group (group 2 [n = 149]); and the severed nerve group (group 3 [n = 113]). Electrogustometry was periodically performed over the course of several years. RESULTS: The incidences of postoperative subjective taste disorder in groups 1, 2, and 3 were 2.8%, 25.5%, and 38.9%, respectively. Although the subjective taste disorder usually recovered within 1 to 2 years after surgery in all groups, it persisted for more than 2 years in 2.7% of the touch group and 5.3% of the severed nerve group. Concerning postoperative electrogustometric results, in the no-touch group, 8.3% of patients showed threshold elevation on electrogustometry, but the elevated thresholds completely recovered in all cases. In the touch group, 45% of patients exhibited elevated electrogustometric thresholds on their first postoperative test, including 32.9% who subsequently had complete electrogustometric recovery, 10.1% who subsequently had incomplete recovery, and 2% who failed to recover during the follow-up period. In the severed nerve group, none of the patients was responsive to the electrical stimulus on the first postoperative test, including 8.8% of patients who subsequently exhibited complete electrogustometric recovery, 32.7% who later had incomplete electrogustometric recovery, and 58.4% who never recovered any electrogustometric responsiveness. Nerve repair in the severed nerve group produced better recovery, as measured electrically. CONCLUSIONS: The incidence of postoperative subjective taste disorder was low, although inconsistent with the high incidence of threshold elevation on electrogustometry, especially in the severed nerve group. Preservation or repair of the chorda tympani nerve is recommended in order to maintain or recover gustatory function.

Adult↗

PubMed2001

Recent outcome of tympanoplasty in the elderly.

OBJECTIVE: To investigate the outcome of tympanoplasty in the elderly (patients older than 60 years) compared with younger patients. PATIENTS AND STUDY DESIGN: Retrospective review of 87 (28.3%) older patients among a total of 307 patients with chronic otitis media with or without cholesteatoma who were surgically treated at a university hospital by the senior author. Follow-up was systematically provided at the same institution. INTERVENTIONS: Surgery included tympanoplasty with mastoidectomy performed as the primary procedure in 358 ears. Tympanoplasty was performed with canal-wall-up or canal-wall-down with canal wall reconstruction, ossiculoplasty with autologous or homologous ossicle interposition or columella. Mean follow-up was 30 months (range, 12-70 months). MAIN OUTCOME MEASURES: Pre- and postoperative air- and bone-conduction thresholds were calculated as an average of three speech frequencies (0.5, 1, and 2 kHz). Analysis was subsequently carried out on the postoperative air-bone gap, hearing gain, and postoperative problems such as elevation of the bone-conduction threshold, delayed epithelialization, and reperforation of the eardrum. Statistical analysis was performed by chi-square or Student's t-test. A p value less than 0.05 was considered significant. RESULTS: Compared with results from younger patients, there was no particular disadvantage in postoperative hearing results and complications in the elderly, although preoperative bone-conduction thresholds were gradually worsened with age. CONCLUSIONS: There is no contraindication for tympanoplasty in older patients if their physical status is the same or better than what is normal for their chronological age.

Adolescent↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1997

P-glycoprotein expression in capillary endothelial cells of the 7th and 8th nerves of guinea pig in relation to blood-nerve barrier sites.

Expression of P-glycoprotein (P-gp) was detected by immunohistochemical staining and Western blot analysis in the peripheral nerves (7th and 8th nerves) of the guinea pig using anti-P-gp monoclonal antibody C219. P-gp was detected in the capillary endothelial cells of these nerves. Immunoreactivity in these nerves was similar to that in the brain. Besides these nerves, positive staining was observed in the sciatic nerve, although immunoreactivity was somewhat lower than that of the 7th and 8th nerves. The present investigation suggested that P-gp in the endothelial cells of the peripheral nerves might play a very important role as a part of the blood-nerve barrier function, since P-ag acts as an extension pump in these cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1997

Hydroxyapatite-coating on titanium arc sprayed titanium implants.

We developed a new titanium spray technique using an inert gas shielded arc spray (titanium arc spray). Hydroxyapatite (HA)-coating can be applied to the implant without any surface pore obstruction after the rough surface is made by this technique. Scanning electron microscopy (SEM) of various porous implant surfaces after HA-coating revealed that the bead and fiber metal-coated implants had either a pore obstruction or an uneven HA-coating. On the other hand, the titanium arc sprayed implant demonstrated an even HA-coating all the way to the bottom of the surface pore. In the first set of animal experiments (Exp. 1), the interfacial shear strength to bone of four kinds of cylindrical Ti-6A1-4V (Ti) implants were compared using a canine transcortical push-out model 4 and 12 weeks after implantation. The implant surfaces were roughened by titanium arc spray (group A-C) and sand blasting (group D) to four different degrees (roughness average, Ra = group A: 56.1, B: 44.9, C: 28.3, D: 3.7 microns). The interfacial shear strength increased in a surface roughness-dependent manner at both time periods. However, the roughest implants (group A) showed some failed regions in the sprayed layers after pushout test. In the second set of animal experiments (Exp. 2), four kinds of Ti implants; HA-coated smooth Ti (sHA) with Ra of 3.4 microns, bead-coated Ti (Beads), titanium arc sprayed Ti (Ti-spray) with Ra of 38.1 microns and HA-coated Ti-spray (HA + Ti-spray) with Ra of 28.3 microns were compared using the same model as that in Exp. 1. The interfacial shear strength of HA + Ti-spray was significantly greater than that of sHA and Beads at both time periods, and that of Ti-spray at 4 weeks. Although a histological examination revealed that HA-coating enhanced bone ingrowth, sHA showed the lowest shear strength at both time periods. SEM after pushout test showed that sHA consistently demonstrated some regional failure at the HA-implant substrate interface. HA + Ti-spray had many failed regions either at the HA-bone interface or within the bone tissue rather than at the HA-implant substrate interface. These results suggested that the HA-coated smooth surfaced implants had a mechanical weakness at the HA-substrate interface. Therefore, HA should be coated on the rough surfaced implants to avoid a detachment of the HA-coating layer from the substrate and thus obtain a mechanical anchoring strength to bone. HA-coating on this new type of surface morphology may thus lead to a solution to the problems of conventional HA-coated and porous-coated implants.

Alloys↗

PubMed1996

Prevention of persistent ear drum perforation after long-term ventilation tube treatment for otitis media with effusion in children.

The effect of tape patch technique using Steri-Strip tape in combination with freshening of the perforation edge after removal of long-term ventilation tubes for preventing permanent ear drum perforation was evaluated. The longer the tubes remained in place, the higher the incidence of persistent perforation after tube removal. The perforation rate after Goode T-tube treatment was 4.0% in the spontaneous extrusion group and 14.3% in the intentional removal group. In the ears treated by tape patch application, none of the perforations persisted after removal of the Goode T-tube. After removal or extrusion of Paparella Type II tube, perforations did not close in 13.2% of the group without tape patch application. When a tape patch was applied, only one perforation (3.3%) did not close. From these results, tape patch technique in combinations with freshening of the perforation edge at the time of tube removal was useful to promote healing and prevent persistent ear drum perforation.

Chi-Square Distribution↗

PubMed1996

Effects of sequence and temperature of hyperthermia and peplomycin on human pharyngeal carcinoma KB cells in vitro.

To maximize the interactive effect, we examined the time sequence of high (above 43 degrees C) or low (below 43 degrees C)-hyperthermia and peplomycin (PEP)(0.5 microgram/ml). Simultaneous or post-hyperthermic PEP treatment at 44 degrees C resulted in a slight synergistic effect with thermoenhancement ratios (TER) of 1.30 or 1.34, respectively. However, at 42 degrees C, maximal interaction was obtained (TER = 10.19) when KB cells were simultaneously heated with PEP. Furthermore, pre-treatment at 44 degrees C for 25 min or 42 degrees C for 4 h enhanced PEP cytotoxicity more than that of post-treatment at 44 degrees C for 25 min or 42 degrees C for 4 h, respectively. However, chemoenhancement ratios (CER) of pre-treatment at 44 degrees C for 25 min and at 42 degrees C for 4 h were 19.1 and 3.5, respectively, although the isothermic dose decreased the cell count to 60% in both cases. These results indicated that simultaneous or post-hyperthermic PEP treatment with high-hyperthermia, and simultaneous PEP treatment with low-hyperthermia, are the most effective means of PEP thermochemotherapy with hyperthermia.

Cell Survival↗

PubMed1995

Heat shock enhances the susceptibility of tumor cells to lysis by lymphokine-activated killer cells.

OBJECTIVE: To determine whether heat-treated thyroid cancer cells augment the susceptibility of target cells to lysis by autologous lymphokine-activated killer cells. DESIGN: Peripheral blood lymphocytes from patients with thyroid cancer were incubated with recombinant interleukin 2 (100 U/mL) for 7 days, and thyroid cancer cells obtained from surgical specimens were heated at 44 degrees C for 20 minutes and incubated at 37 degrees C for 18 hours before performing the radioactive chromium Cr 51 release assay. RESULTS: The susceptibility of heat-treated thyroid cancer cells to lysis by autologous and allogeneic lymphokine-activated killer cells was significantly greater than that of untreated tumor cells. The mechanism of enhanced susceptibility was unclear. However, the effect depended on de novo protein synthesis, because inhibition of RNA synthesis by dactinomycin completely abolished the heat-enhanced susceptibility of tumor cells. CONCLUSION: Immunotherapy combined with hyperthermia may be useful in management of thyroid cancer.

Adenocarcinoma, Papillary↗

PubMed1995

Synthesis of high-molecular-weight poly([R]-(-)-3-hydroxybutyrate) in transgenic Arabidopsis thaliana plant cells.

High-molecular-weight poly([R]-(-)-3-hydroxybutyrate) (PHB), a biodegradable thermoplastic, was produced from a suspension culture of transgenic Arabidopsis thaliana plant cells expressing two genes from the bacterium Alcaligenes eutrophus involved in the synthesis of PHB. The molecular structure of the plant-produced polymer was analysed by gas chromatography, mass spectrometry, proton nuclear magnetic resonance spectroscopy, infra-red spectroscopy, spectropolarimetry, differential scanning calorimetry, X-ray diffraction and size exclusion chromatography. The results indicate that the polymer from transgenic plants appears to have a chemical structure identical to that of PHB produced by bacteria. However, the molecular weight distribution of the plant-produced PHB was much broader than that of typical bacterial PHB.

Alcaligenes↗

PubMed1994

Swainsonine augments the cytotoxicity of human lymphokine-activated killer cells against autologous thyroid cancer cells.

OBJECTIVE: Swainsonine (SW), an inhibitor of mammalian Golgi alpha-mannosidase II, blocks the processing of high mannose to complex type oligosaccharides. In this study, the effect of SW on the cytotoxicity of lymphokine-activated killer (LAK) cells against autologous thyroid cancer was investigated. DESIGN: Peripheral blood lymphocytes from patients with thyroid cancer were incubated with recombinant interleukin 2 (100 U/mL) and 0.5 mg/L of SW for 7 days, and thyroid cancer cells obtained from surgical specimens were pretreated with SW (0.5 mg/L) for 18 hours. The cytotoxicity of SW-treated LAK cells against tumor cells tested in a standard 4-hour radioactive chromium Cr 51 release assay. RESULTS: The cytotoxicity of SW-treated LAK cells against autologous thyroid cancer cells was found to be significantly greater than that of standard LAK cells incubated with interleukin 2 alone. The N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester esterase activity of LAK cells, this activity being a cytotoxic factor that is necessary for the lethal hit stage, was also increased by SW treatment. Further, thyroid cancer cells incubated with SW, as compared with nontreated tumor cells, showed much higher susceptibility to LAK killing. CONCLUSIONS: Our results suggest that SW might have potential immunomodulatory properties in the treatment of thyroid cancer.

Adenocarcinoma, Papillary↗