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Biomedical subjects

N Takeichi

Publications and source records attributed to N Takeichi.

At least 55 records · Page 3Linked to original sources
PubMed1996

Enhancing effects of epidermal growth factor on human squamous cell carcinoma motility and matrix degradation but not growth.

In order to ascertain the effects of epidermal growth factor (EGF) on human cancer invasion abilities, three cell lines of human oral squamous cell carcinoma were studied using a phagokinetic track assay and zymography. EGF (1-100 ng/ml) was found to inhibit the growth but enhance the random motility of all three cell lines in a concentration-dependent fashion. Exposure to EGF, dose-dependently, led to an increased production of urokinase-type plasminogen activator and M(r) 92 kD matrix metalloproteinase by the same cells. These results strongly suggest that EGF may promote human squamous cell carcinoma invasion and metastasis.

Carcinoma, Squamous Cell↗
PubMed1996

[Outcome of hypopharyngeal cancer].

An analysis of 41 patients with hypopharyngeal cancer treated between April 1985 and March 1996 is presented. Our guidelines for the treatment of hypopharyngeal cancer are a combination of chemotherapy, radiotherapy and surgery. The schedule of combination therapy is as follows: chemotherapy first, preoperative radiotherapy second, and surgery last. The surgery for hypopharyngeal cancer is pharyngolaryngoesophagectomy with radical neck dissection. In many cases free jejunum transplantation was used for reconstruction. The mean age of the patients was 64.8 years, and there were 39 men and 2 women. There were 33 cases of pyriform sinus type, 4 cases of postcricoid type, 3 cases of retropharyngeal type, and 1 case of unclassified type. Histopathologically, there were 40 cases of squamous cell carcinoma and 1 case of anaplastic carcinoma. Five-year total survival rates were 23.0% and 5-year survival rates at each tumor stage were 0% (T-1), 19.9% (T-2), 32.4% (T-3), 0% (T-4). There were no statistically significant differences between tumor stages. Five-year survival rates for each nodal stage were 14.1% (N-0), 54.5% (N-1), 0% (N-2), 0% (N-3). The survival rate for stage N-1 was significantly better (p < 0.05) than that for stage N-2. Five-year survival rates for all stages were 0% (I), 0% (II), 46.3% (III), 0% (IV). The survival rate for stage III was significantly better (p < 0.05) than that for stage IV. Twenty-five patients were operated on with or without chemotherapy and radiotherapy and, 16 patients received nonsurgical treatment. The 5-year cause-specific survival rate for patients who underwent surgery was 57.7% and for patients who underwent nonsurgical treatment was 0%. The survival rate for the radical treatment group was significantly better (p < 0.05) than that for the nonradical treatment group. The 5-year cause-specific survival rate for patients who underwent radical radiotherapy was 0%. That for patients who were treated by chemotherapy was 51.4% and for patients who were not so treated was 20.1%. The results of this study suggest several significant conclusions: 1, Stage is not a good predictor of outcome in hypopharyngeal cancer. 2, Patients undergoing surgery with or without chemotherapy and radiotherapy as the primary treatment enjoyed improved survival. 3, Radical radiotherapy provided poor prognosis. We think that chemotherapy provided some survival benefit.

Adult↗
PubMed1996

[Clinical study of laryngeal cancer].

An analysis of 74 patients with laryngeal cancer treated between February 1985 and July 1995 is presented. Their mean age was 64 years, and the male to female ratio was 14:1. There were 48 cases of the glottic type, 21 cases of the supraglottic type, 2 cases of the subglottic type, and 3 cases of the transglottic type. Histopathologically, there were 72 cases of squamous cell carcinoma and 2 cases of mucoepidermoid carcinoma. Cervical lymph node metastasis was detected in 12 cases (16%). The incidence of cervical lymph node metastasis in supraglottic carcinoma was significantly higher (p < 0.01) than that in glottic carcinoma. There were 12 cases of second primary cancers. The location of the lesions was as follows: lung, 4; esophagus, 2; stomach, 2; prostate, 2; liver, 1; and gingiva, 1. Radical radiotherapy was performed in 52 cases; the local control rate was 98%, and the recurrence rate was 20%. Combined radiotherapy and total laryngectomy or laryngectomy alone was performed in 23 cases, and the recurrence rate was 23%. The recurrence rate for glottic carcinoma after initial therapy was 13%, supraglottic carcinoma 38%, subglottic carcinoma 100% and transglottic carcinoma 33%. Five-year total survival and cause-specific survival rate were 69% and 82%, respectively. Five-year cause-specific survival rates according to subsite were 95% for glottic carcinoma, 69% for supraglottic carcinoma, 0% for subglottic carcinoma, and 50% for transglottic carcinoma. The survival rate in glottic carcinoma was significantly better (p < 0.05) than in supraglottic carcinoma. These results led us to establish the following guidelines for the treatment of laryngeal cancer: for T1 or T2 cases of the glottic type, radiotherapy is recommended first; for T3 or T4 cases of the glottic type, total laryngectomy after radiation therapy is recommended; for T1 or T2N0 cases of the supraglottic type, radiotherapy is recommended first; for T2N(+) or T3 or T4 cases of the supraglottic type, total laryngectomy after radiation therapy is recommended. If cervical lymph node metastasis is presently, neck dissection is necessary.

Adult↗
PubMed1996

Surgical Method for Implanted Tinnitus Suppressor.

A surgical method of fully internal tinnitus suppressor is presented. The surgical approach for the placement of the electrode is very simple and causes less injury to the cochlea. This surgical approach is quite similar to the exploratory tympanotomy. The unit is located at the seat which is drilled in the mastoid bone just behind the external ear canal. The stimulating electrode is introduced to the middle ear beneath the skin of the ear canal on the posterior bony wall. The tip of the electrode located on the promontory is secured by the fascia The primary coil is contained in the Behind-the-Ear case.

Journal Article↗
PubMed1996

Improved Selective Attention and Word Perception in Tinnitus Patients Treated with Electrical Stimulation.

Grammatically correct but nonsense twenty 4-segment sentences mixed with multiple talk recorded on CD were delivered to ears tested in 47 tinnitus patients at a comfortable level via a headphone. The signal-to-noise ratios were 0dB, 5dB and 10dBSPL. Patients were requested to repeat what they heard before and after electrical treatment. A sinusoidal wave of 10kHz at the intensity of about 200mA was delivered to ears for 30 minutes by using a plate electrode for ECG at the tragus or a stimulating Pt-Ir electrode on the middle ear. Alternatively, 0.5mA DC was delivered to patients using a iontophoretic instrument. Improved word perception under noises was observed in most patients with tinnitus relief following electrical stimulation of the ear, demonstrating that electrical stimulation improved auditory selective attention. There may be a relationship between tinnitus relief and improved selective attention. It may be electrical stimulation of the ears that produced improved selective attention, inducing tinnitus relief and improved word perception according to our previous reports.

Journal Article↗
PubMed1996

Feasibility of using decades-old archival tissues in molecular oncology/epidemiology.

Archival tissues are a bountiful resource for various studies. Polymerase chain reaction permits the use of such tissues for molecular biological analyses of disease causation. However, a comprehensive study using a large number of decades-old samples (20 or more years) for molecular oncology/epidemiology has never been shown to be feasible. We have relied upon the unique tumor registry of atomic bomb survivors to show that such studies are possible using 275 hepatocellular carcinoma and 41 skin cancer cases. We used 23 relatively recent thyroid papillary carcinoma cases from persons living in the vicinity of the Chernobyl nuclear reactor accident for comparison. Degradation of DNA is severe in autopsy hepatocellular carcinoma samples but can be compensated for by decreasing the polymerase chain reaction product size. Increasing the amount of DNA that is used by a factor of 8 improved amplification efficiency from approximately 60 to 80%. Age of the samples was not as great a problem as was the source of procurement. The extracted DNA can be used for all types of assays that require polymerase chain reaction amplification, such as restriction fragment length polymorphism, single-strand conformation polymorphism, and direct sequencing.

Base Sequence↗
PubMed1995

Enhanced effect of epidermal growth factor on pulmonary metastasis and in vitro invasion of rat mammary carcinoma cells.

We examined the effects of epidermal growth factor (EGF) on metastatic and in vitro invasive capacity of weakly malignant ER-1 cells derived from a rat mammary carcinoma cell line, c-SST-2. EGF enhanced the metastatic capacity and in vitro invasiveness to reconstituted basement membrane, Matrigel, of ER-1 cells in a dose-dependent fashion. EGF-stimulated invasiveness was inhibited by anti-EGF antibody, which is able to neutralize the binding of EGF to EGF receptor, in the invasion assay system. EGF stimulated chemotactic migration toward fibronectin, laminin or newborn rat fibroblast-conditioned medium which was used as a chemoattractant in the in vitro invasion assay, but showed neither adhesion to Matrigel nor production of gelatinase and plasminogen activators. These results suggested that the increased metastatic and invasive capacity of ER-1 cells by EGF might be due to the increase in cell motility.

Animals↗
PubMed1995

Magnetic resonance imaging of Long-Evans cinnamon rats as a new model of hepatocellular carcinoma.

RATIONALE AND OBJECTIVES: Following hereditary hepatitis, Long-Evans Cinnamon (LEC) rats spontaneously develop hepatocellular carcinomas (HCC) histopathologically similar to human well-differentiated HCC. We demonstrated that LEC rats are an appropriate model of evaluating magnetic resonance (MR) imaging of well-differentiated liver tumors. METHODS: Six 23-25-month-old LEC rats were studied using liver MR imaging and histologic observation. RESULTS: Signal intensity of HCCs without cystic areas was normal or slightly high on T1-weighted images and slightly high on T2-weighted images. Histopathologically, most tumors resembled human highly or well-differentiated HCCs. CONCLUSION: The LEC rat is a good model of investigating MR imaging of well-differentiated HCC.

Animals↗
PubMed1995

Differing distribution of hepatocyte growth factor-positive cells in the liver of LEC rats with acute hepatitis, chronic hepatitis and hepatoma.

Using anti-rat hepatocyte growth factor (HGF) antibody, we investigated the distribution of HGF-positive cells in the liver tissues of LEC rats at various phases of liver diseases. During the phase of fulminant hepatitis, HGF-positive cells increased remarkably, and many of them were localized at the portal triads; these cells were identified from their shape as non-epithelial cells. A reduced number of HGF-positive cells was observed during the phase of chronic hepatitis, while no HGF-positive cells were seen in the tissue of cholangiofibrosis. During the phase of carcinoma, staining revealed that both the hepatocellular carcinoma cells and the non-epithelial cells in cancerous liver tissue were HGF-positive. These results suggest that, in LEC rats, HGF may play an important role in the regeneration of hepatocytes as well as in the development of hepatocellular carcinoma.

Acute Disease↗
PubMed1995

A possible role of 92 kDa type IV collagenase in the extramedullary tumor formation in leukemia.

Production of metalloproteinases such as collagenases has been reported to be involved in the metastasis of cancer cells. Granulocytic sarcoma in extramedullary sites can be formed by similar steps to other cancers. In this study, we have examined the secretion of type IV collagenases and a tissue inhibitor of metalloproteinase-1 (TIMP-1) in several human leukemia cell lines, including a granulocytic sarcoma-derived cell line established from a patient with granulocytic sarcomas in dermal tissues. We have also examined the invasive capacity of these leukemia cell lines into reconstituted basement membrane, Matrigel, which was used for in vitro invasion assay. Among the human leukemia cell lines used in this study, only the granulocytic sarcoma cell line was found to secrete type IV collagenase constitutively. Other myeloid leukemia cell lines such as HL-60 and U-937 produced type IV collagenase only after treatment with 12-O-tetradecanoylphorbol-13-acetate. All the cell lines secreted similar amounts of the tissue inhibitor of metalloproteinases. In vitro invasion assay revealed that the granulocytic sarcoma cell line showed higher invasive capacity than the other cell lines. These results suggest that the secretion of 92 kDa type IV collagenase plays a role in the leukemia cells' invasion of extramedullary tissues.

Collagenases↗
PubMed1994

Enhanced synthesis of metallothionein as a possible cause of abnormal copper accumulation in LEC rats.

Long-Evans rats with a cinnamon-like coat color (LEC) is an inbred strain accumulating copper (Cu) in the liver abnormally and showing spontaneous hepatitis and hepatoma. The present study was intended to clarify how Cu accumulates in the LEC rat liver. For this purpose, the distribution profiles of Cu and zinc (Zn) and the inducibility of metallothionein (MT) synthesis were examined in the liver between Cu-loaded Long Evans agouti (LEA, the original strain of LEC) rats and were compared with those in control LEC rats. LEA rats (female, five weeks old) were injected subcutaneously with CuCl2 daily at a dose of 3 mg Cu/kg body weight for 2, 4, 6, and 9 days. The concentration of Cu (124 micrograms/g) accumulated in the LEA rat liver after four injections was comparable to that in control LEC rats. Only 20% of Cu in the liver of LEA rats was recovered in the supernatant fraction in the form of MT, while Cu in the LEC rat liver (113 micrograms/g) was recovered mostly in the supernatant fraction, and was bound to MT. Although the increased concentration of Cu in the LEA rat liver was further elevated after additional injections of Cu, the amount of MT did not increase further. The MT mRNA content in the LEA rat liver remained lower than that of LEC rats even after further injections of Cu. Therefore, the present results suggest that LEC rats can accumulate Cu at a high concentration in the liver because of their extremely high inducibility of MT.

Animals↗
PubMed1994

A role for oxygen radicals in rat monocytic leukemia cell differentiation under stimulation with platelet-activating factor.

Combined stimulation, by superoxide ions generated by the xanthine-xanthine oxidase reaction, and platelet-activating factor (PAF), induced cell differentiation of rat monocytic leukemia cells (c-WRT-LR) to macrophage-like mature cells. Monitoring of cytochrome c reduction revealed that PAF stimulation induced the release of superoxide ions from c-WRT-LR. To further investigate the effect of superoxide ions in the autocrine or paracrine mechanism in cell differentiation, molecular species of the oxygen radicals under PAF stimulation were examined using the EPR spin trap, 5,5'-dimethyl-1-pyrroline N-oxide (DMPO). PAF and/or phorbol myristate acetate caused the formation of EPR spectra, a combination of DMPO/.OOH and DMPO/.OH. Since both spectra were diminished in the presence of superoxide dismutase, it was concluded that DMPO/.OH was derived from superoxide ions. Mannitol and catalase suppressed cell differentiation induced by combined stimulation with PAF and oxygen radicals generated by the xanthine-xanthine oxidase reaction. Taken together, these results suggest that hydroxyl radicals generated by Fenton reaction from H2O2 may be involved in the mechanism of cell differentiation in rat monocytic leukemia cells.

Animals↗
PubMed1994

Decreased expression of liver glutathione peroxidase in Long-Evans cinnamon mutant rats predisposed to hepatitis and hepatoma.

The Long-Evans Cinnamon rat is a mutant strain that contracts hereditary hepatitis and, eventually, spontaneous hepatoma. Recently, abnormal copper accumulations in Long-Evans Cinnamon rat livers were shown to be genetically linked to the development of hepatitis. Because reduced glutathione and glutathione-related enzymes are known to play important roles in cellular resistance to transition metal toxicity, we determined the levels of reduced glutathione and glutathione-related enzymes in seven different tissues of Long-Evans Cinnamon and control Long-Evans Agouti rats. Of the enzymes examined, only hepatic glutathione peroxidase was markedly decreased in Long-Evans Cinnamon rats. Glutathione peroxidase content in the liver of Long-Evans Cinnamon rats was 39%, 53% and 58% of the control values at 9 (normal stage), 19 (acute hepatitis stage) and 27 (chronic hepatitis stage) wk of age, respectively. Northern-blot analysis revealed that messenger RNA levels of glutathione peroxidase in the livers of Long-Evans Cinnamon rats were about 40% of the control levels. The activity of glutathione S-transferase was slightly decreased in the livers of Long-Evans Cinnamon rats. These data suggest that the liver of the Long-Evans Cinnamon rat is poorly protected against active oxygen species, the production of which is enhanced in the presence of excess copper. Glutathione-reductase activity in the livers of Long-Evans Cinnamon rats increased to 166% and 148% of the control levels at 19 and 27 wk of age, respectively. No significant changes were observed in the activity of gamma-glutamylcysteine synthetase or in the content of total reduced glutathione in the liver of the Long-Evans Cinnamon rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Establishment of a retrodifferentiated cell line from a single differentiated rat myelomonocytic leukemia cell: possible roles of retrodifferentiation in relapses of leukemia after differentiation-inducing therapy.

In order to demonstrate possible roles of retrodifferentiation in relapses after differentiation therapies, we have established a retrodifferentiated cell line (RD-1) from a single rat myelomonocytic leukemia cell which differentiated into a macrophage-like cell by treatment with lipopolysaccharide (LPS). The established RD-1 cells showed microscopic features slightly maturer than their parent cells. The RD-1 cells had the ability to differentiate into macrophage-like cells by treatment with fewer doses of LPS than those for parent cells. All rats inoculated with the parent cells (more than 10(2)/rat) died within 50 days. Rats inoculated with 10(4) RD-1 cells survived for more than 120 days, whereas two out of four rats inoculated with 10(5) cells and all the rats inoculated with 5 x 10(5) cells died of leukemia. These results suggest that RD-1 cells are retrodifferentiated cells from a single rat myelomonocytic leukemia cell which differentiated into a macrophage-like cell; they have similar phenotypes and lower tumorigenicity than the parent cells and they also suggest that the appearance of retrodifferentiated leukemia cells may be responsible for relapse after differentiation therapy for leukemia in some cases.

Animals↗
PubMed1994

Involvement of oxygen radicals in the differentiation of rat myelomonocytic leukemia cells in vitro and in vivo.

We have found that LPS induces the differentiation of an LPS-resistant subline (LR) of rat myelomonocytic leukemia cell line, c-WRT-7, in vivo, which are resistant to the differentiation inducing effects of LPS in vitro. Furthermore, we have found that the differentiation of LR cells induced by LPS is inhibited by superoxide dismutase, which is one of radical scavengers. Accordingly, we have examined the differentiation inducing effects of xanthine oxidase, a potential source of oxygen radicals, on LR cells in vitro and in vivo. Xanthine oxidase induced the differentiation of LR cells into macrophage-like cells in vitro; and superoxide dismutase inhibited the differentiation of LR cells induced by xanthine oxidase both in vitro and in vivo. These results suggest that oxygen radicals are involved in the differentiation inducing effects of LPS.

Animals↗
PubMed1994

Enhancement of in vitro prostaglandin E2 production by mouse fibrosarcoma cells after co-culture with various anti-tumour effector cells.

We have previously reported that an increase in the production of immunosuppressive prostaglandin E2 by a QR tumour (QR-32) is accompanied by progressive growth of the tumour in syngeneic C57BL/6 mice. In order to determine what kinds of cell and factor(s) enable QR-32 cells to promote PGE2 production, we investigated the amounts of PGE2 in the supernatant of QR-32 cells by co-culturing them with various anti-tumour effector cells. Significantly high levels of PGE2 production were observed when the QR-32 cells were co-cultured with lymphokine-activated killer (LAK) cells, natural killer (NK) cells, polymorphonuclear (PMN) leucocytes and streptococcal preparation (OK432)-activated or resident peritoneal macrophages (activated and resident macrophages). On the other hand, PGE2 production was not increased when QR-32 cells were co-cultured with cytotoxic T lymphocytes (CTLs) specific to QR-32 cells. The high levels of PGE2 production were partially or totally inhibited by the presence of radical scavengers such as superoxide dismutase (SOD), catalase and mannitol, although the cytotoxicity of LAK cells was not. We also exposed QR-32 cells to human recombinant cytokines and the growth factors which are produced when anti-tumour effector cells come in contact with tumour cells. Significant PGE2 production by QR-32 cells was observed when the cells were treated with interferon alpha (IFN-alpha), tumour necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) (all P < 0.001). These results suggest that oxygen radicals produced by anti-tumour effector cells and inflammatory cytokines provoke QR-32 cells to produce large amounts of immunosuppressive PGE2.

Animals↗