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ABSTRACT: Rare sugar d-psicose has cropped up as a non-toxic and effective compound to protect and preserve pancreatic β-islets in the growing type 2 diabetes mellitus (T2DM) rats through the regulation of glucose and fat metabolism. The present study was undertaken to examine the effect of rare sugar d-psicose on the protection of pancreatic β-islets using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a T2DM model. Treated rats were fed with 5% d-psicose or 5% d-glucose supplemented drinking water, and only water in the control for 13weeks. A non-diabetic Long-Evans Tokushima Otsuka (LETO), fed with water served as a counter control of OLETF. d-Psicose significantly attenuated progressive β-islet fibrosis and preserved islets, evaluated by hematoxylin-eosin staining, Masson's trichrome staining and immunostainings of insulin and α-smooth muscle actin (SMA). d-Psicose significantly reduced increase in body weight and abdominal fat deposition. Oral glucose tolerance test (OGTT) showed reduced blood glucose levels suggesting the improvement of insulin resistance. All these data suggests that d-psicose protected and preserved pancreatic β-islets through the maintenance of hyperglycemia and by the prevention of fat accumulation in OLETF rats.
Biochemical and Biophysical Research Communications 08/2012; 425(4):717-23. · 2.48 Impact Factor
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ABSTRACT: Oxidative stress modulates the osteoclast differentiation via redox systems, and thioredoxin 1 (Trx) promotes the osteoclast formation by regulating the activity of transcription factors. The function of Trx is known to be regulated by its binding partner, thioredoxin-interacting protein (TXNIP). We previously reported that the expression of TXNIP gene is strongly induced by a rare sugar D-allose. In this study, we tested the hypothesis that D-allose could inhibit the osteoclast differentiation by regulating the Trx function. We used a murine Raw264 cell line that differentiates to the osteoclast by the receptor activator of nuclear factor-κB ligand (RANKL) treatment. The effect of sugars was evaluated by tartrate-resistant acid phosphatase staining. The expression and localization of TXNIP and Trx protein were examined by Western blotting and immunohistochemisty. The activity of the nuclear factor-κB, nuclear factor of activated T cells, and activator protein 1 transcription factors was measured by the luciferase reporter assay. The addition of D-allose (25 mmol/L) inhibited the osteoclast differentiation down to 9.53% ± 1.27% of a receptor activator of nuclear factor-κB ligand-only treatment. During the osteoclast differentiation, a significant increase of TNXIP was observed by D-allose treatment. The immunohistochemical analysis showed that both Trx and TXNIP existed in the nucleus in preosteoclasts and osteoclasts. Overexpression of TXNIP by plasmid transfection also inhibited the osteoclast formation, indicating the functional importance of TXNIP for the osteoclast differentiation. Transcriptional activity of the activator protein 1, nuclear factor-κB, and nuclear factor of activated T cells, known to be modulated by Trx, were inhibited by D-allose. In conclusion, our data indicate that D-allose is a strong inhibitor of the osteoclast differentiation, and this effect could be caused by TXNIP induction and a resulting inhibition of the Trx function.
Nutrition research (New York, N.Y.) 02/2012; 32(2):116-23. · 1.20 Impact Factor
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Mohammad A Hossain,
Shigeru Kitagaki,
Daisuke Nakano,
Akira Nishiyama,
Yasunobu Funamoto,
Toru Matsunaga,
Ikuko Tsukamoto,
Fuminori Yamaguchi,
Kazuyo Kamitori, Youyi Dong,
Yuko Hirata,
Koji Murao,
Yukiyasu Toyoda,
Masaaki Tokuda
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ABSTRACT: A rare sugar, D-psicose has progressively been evaluated as a unique metabolic regulator of glucose and lipid metabolism, and thus represents a promising compound for the treatment of type 2 diabetes mellitus (T2DM). The present study was undertaken to examine the underlying effector organs of D-psicose in lowering blood glucose and abdominal fat by exploiting a T2DM rat model, Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Rats were fed 5% D-psicose or 5% D-glucose supplemented in drinking water, and only water in the control for 13 weeks and the protective effects were compared. A non-diabetic Long-Evans Tokushima Otsuka (LETO), fed with water served as a counter control of OLETF. After 13 weeks feeding, D-psicose treatment significantly reduced the increase in body weight and abdominal fat mass. Oral glucose tolerance test (OGTT) showed the reduced blood glucose and insulin levels suggesting the improvement of insulin resistance in OLETF rats. Oil-red-O staining elucidated that D-psicose significantly reduced lipid accumulation in the liver. Immunohistochemical analysis showed D-psicose induced glucokinase translocation from nucleus to cytoplasm of the liver which enhances glucokinase activity and subsequent synthesis of glycogen in the liver. D-psicose also protected the pathological change of the β-cells of pancreatic islets. These data demonstrate that D-psicose controls blood glucose levels by reducing lipotoxicity in liver and by preserving pancreatic β-cell function.
Biochemical and Biophysical Research Communications 02/2011; 405(1):7-12. · 2.48 Impact Factor
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ABSTRACT: Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene that controls neural stem cell renewal and differentiation and is a potential target for regeneration in the optic nerve. Here we show that it has a critical pattern of expression in the mammalian developing auditory system. PTEN was expressed in the cochlear-vestibular ganglion at embryonic day 10.5 and then progressively in hair cells as they differentiated from the base to the apex of the cochlea. By postnatal day 7, PTEN was downregulated in hair cells and subsequently in the neurons. This very specific, transient expression pattern suggests that PTEN plays a crucial role in the differentiation of the sensory neurons and hair cells and that it is a potential therapeutic target for hearing regeneration.
Neuroreport 07/2010; 21(10):731-5. · 1.66 Impact Factor
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Yuko Hirata,
Madoka Saito,
Ikuko Tsukamoto,
Fuminori Yamaguchi,
Li Sui,
Kazuyo Kamitori, Youyi Dong,
Eisuke Uehara,
Ryoji Konishi,
Najma Janjua,
Masaaki Tokuda
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ABSTRACT: D-Allose, the C-3 epimer of D-glucose, is one of the rare sugars found in nature. In the present study, we have elucidated for the first time that various leukemia cell lines have different susceptibility to anti-proliferative activity of D-allose, and that this difference is related to the difference in induction of thioredoxin interacting protein (TXNIP) expression. We examined 5 leukemia cell lines (MOLT-4F, IM-9, HL-60, BALL-1 and Daudi), and found that MOLT-4F (T-cell lymphoblastic leukemia) had the highest susceptibility to D-allose, and that Daudi (Burkitt's lymphoma) had the lowest. D-Allose significantly slowed the cell cycle progression without causing apoptosis of MOLT-4F cells. Intracellular TXNIP expression was specifically and markedly enhanced in MOLT-4F cells by D-allose treatment, and subsequent increase of p27(kip1), a cell cycle inhibitor, was observed. On the other hand, D-allose did not increase TXNIP and p27(kip1) levels at all in Daudi cells. These results indicate that D-allose suppresses MOLT-4F cell proliferation possibly by the inhibition of cell cycle progression via induction of TXNIP expression.
Journal of Bioscience and Bioengineering 06/2009; 107(5):562-8. · 1.79 Impact Factor
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ABSTRACT: d-Allose is a novel anti-tumor monosaccharide that causes cell growth inhibition, specifically of the cancer cells, by inducing the tumor suppressor gene thioredoxin interacting protein (TXNIP). The commonly used anti-tumor drug, 5-fluorouracil (5-FU), blocks the cell cycle by inhibiting thymidylate synthase, and is also known to induce TXNIP gene expression. In this study, we examined the synergistic effect of d-allose and 5-FU and the role of TXNIP on cancer cell growth. The treatment of HuH-7 cells with d-allose or 5-FU inhibited the cell growth in a dose-dependent manner (75.2+/-2.7% with 50 mM d-allose and 66.1+/-2.7% with 0.5 mug/ml 5-FU) and d-allose enhanced the anti-tumor effect of 5-FU (55.3+/-1.1 %). TUNEL analysis did not show any evidence of apoptosis with either d-allose or 5-FU treatment. 5-FU suppressed the expression of p27(kip1), p53, and cyclin E, whereas d-allose induced p53 and reduced cyclins D, A, and E. The expression of p27(kip1) remained unchanged by d-allose at transcriptional level, but increased at the protein level suggesting an increase in protein stability by TXNIP. d-Allose and to a lesser extent 5-FU induced TXNIP expression significantly (808.4+/-122.9% and 186.8+/-32.9%, respectively) and the combination of both further enhanced TXNIP expression. As d-allose has no known side effects on normal cells, the combination of d-allose and 5-FU might be a potent candidate for cancer therapy.
Journal of Bioscience and Bioengineering 10/2008; 106(3):248-52. · 1.79 Impact Factor
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ABSTRACT: 'Rare sugars' are defined as monosaccharides that exist in nature but are only present in limited quantities. The development of mass production method of rare sugars revealed some interesting physiological effects of these on animal cells, but the mechanisms have not been well studied. We examined the effect of D-allose on the proliferation of cancer cells and the underlying molecular mechanism of the action. The HuH-7 hepatocellular carcinoma cells were treated with various monosaccharides for 48 h and D-allose was shown to inhibit cell growth by 40% in a dose-dependent manner. D-allose induced G1 cell cycle arrest but not apoptosis. The microarray analysis revealed that D-allose significantly up-regulated thioredoxin interacting protein (TXNIP) gene expression, which is often suppressed in tumor cells and western blot analysis confirmed its increase at protein level. The overexpression of TXNIP also induced G1 cell cycle arrest. Analysis of cell cycle regulatory genes showed p27kip1, a key regulator of G1/S cell cycle transition, to be increased at the protein but not the transcriptional level. Protein interaction between TXNIP and jab1, and p27kip1 and jab1, was observed, suggesting stabilization of p27kip1 protein by the competitive inhibition of jab1-mediated nuclear export of p27kip1 by TXNIP. In addition, increased interaction and nuclear localization of TXNIP and p27kip1 were apparent after D-allose treatment. Our findings surprisingly suggest that D-allose, a simple monosaccharide, may act as a novel anticancer agent via unique TXNIP induction and p27kip1 protein stabilization.
International Journal of Oncology 03/2008; 32(2):377-85. · 2.40 Impact Factor
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ABSTRACT: D-allose, an aldo-hexose, is a rare sugar whose biological functions remain largely unclear. Recently, we demonstrated a novel inhibitory effect of D-allose on production of reactive oxygen species (ROS). Here, we focused on investigating cryoprotective effects of D-allose on cell viability. Mammalian cell lines including OVCAR-3 (human ovarian cancer), HeLa (human cervical cancer), HaCaT (human skin keratinocytes), HDF (human dermal fibroblasts) and NIH3T3 (murine fibroblasts) cells were frozen at -80 degrees C in culture media with various D-allose concentrations. Cells were allowed to recover for 24 h, 1 week or 1 month prior to survival assessment using the trypan blue dye exclusion test, when cell proliferation was evaluated by MTT assay. A beneficial protective role of D-allose on cell survival was found, similar to that of trehalose (disaccharide of glucose), a recognized cryoprotectant. The results suggest that D-allose as a sole additive may provide effective protection for mammalian cells during freezing. Practical studies now need to be performed with D-allose, for example to determine optimal freezing protocols and explore potential for preservation of tissues or organs at non-freezing temperatures.
Cryobiology 11/2007; 55(2):87-92. · 2.06 Impact Factor
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ABSTRACT: We have previously demonstrated the inverse correlation of Jab1 and p27 proteins, as well as prognostic significance in epithelial ovarian carcinomas. In order to investigate Skp2 protein and its correlation with Jab1, p27, and clinical outcome, we evaluated Skp2 expression in a group of epithelial ovarian tumors. Immunohistochemical analysis was performed on 80 cases of ovarian tumors (33 benign and 47 malignant), and 26 of the 80 cases were evaluated by Western blot analysis. Immunofluorescence was carried out in the human ovarian adenocarcinoma cell line OVCAR-3. Skp2 expression was detected in 53.2% of malignant tumors and 18.2% of benign tumors. The positive ratio of Skp2 expression was increased from benign to malignant ovarian tumors (p=0.002). A negative correlation between Skp2 and p27 was found in benign and malignant ovarian tumors (p=0.006 and p<0.0001, respectively). Skp2 expression was significantly associated with high tumor grade (p=0.001), lymph node metastasis (p=0.01), and residual disease (p=0.012). Kaplan-Meier survival analysis showed that Skp2 expression was significantly associated with poor prognosis (p=0.013), and patients with Skp2(+)/Jab1(+)p27(-) expression had the worst prognosis among all phenotypes of Skp2/Jab1/p27 expression (p=0.0007). Our results suggest that Skp2 expression was significantly associated with malignancy, and the Skp2 protein level may be a valuable prognostic factor for epithelial ovarian carcinomas. Furthermore, the combined evaluation of Skp2/Jab1/p27 proteins provides important prognostic information on patients with epithelial ovarian carcinoma.
Oncology Reports 05/2006; 15(4):765-71. · 1.84 Impact Factor
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ABSTRACT: The tumor suppressor PTEN, phosphatase and tensin homolog on chromosome 10, plays an essential role in regulating signaling pathways involved in cell growth and apoptosis and is inactivated in a wide variety of tumors. Survivin, a member of the inhibitor of apoptosis protein family (IAP), is associated with cell proliferation, and overexpressed in common human tumors. Both PTEN and survivin proteins can regulate cell cycle and apoptosis, but their biological effects are adverse. We have previously investigated the role of survivin expression in epithelial ovarian tumors. In this study, we evaluated the alteration and clinical relevance of PTEN expression and further assessed its correlation with survivin expression in epithelial ovarian tumors. Immunohistochemical analysis was performed in 103 cases of ovarian tumors, and 26 of the 103 cases were evaluated by Western blot analysis. PTEN expression was reduced from benign to malignant ovarian tumors (p=0.0003), and an inverse correlation between PTEN and survivin was found in benign, borderline, and malignant tumors (p=0.004, p=0.015 and p=0.0005, respectively). PTEN expression was significantly associated with tumor grade (p=0.001), histological subtype (p=0.037), ascites (p=0.038), and residual disease (p=0.0006). Kaplan-Meier survival analysis showed that the loss of PTEN expression was significantly associated with poor overall survival (p=0.021), and patients with PTEN(-)/survivin(+) expression had the worst prognosis among all phenotypes of PTEN/survivin expression (p=0.039). Our results suggest that the altered PTEN expression and its inverse correlation with survivin may be involved in the development and progression of ovarian tumors, and the combined detection of PTEN and survivin proteins might be more valuable in the evaluation of malignancy and prognosis in epithelial ovarian tumors.
Oncology Reports 05/2006; 15(4):773-8. · 1.84 Impact Factor
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ABSTRACT: Rare sugars are monosaccharides distributed rarely in nature, because of its very limited amount and cost, the biological effect has hardly been studied. Recently, an effective strategy for mass production of rare sugars has been developed. As a result, a wide range of study of rare sugars from the basic to applied research has become possible. For biological application of rare sugars, it is necessary to fundamentally investigate the relationships between rare sugars and living cells in terms of physiology. Therefore, we firstly examined the effect of rare sugars including D-psicose, D-allose, D-altrose and D-talitol on cell proliferation using certain cell lines in vitro. Cell growth was evaluated by MTT assay after 24-, 48- and 72-h treatment. The result shows that D-allose has a significant inhibitory effect on cancer cell proliferation in a dose-dependent manner. Although the exact mechanism remains unclear, this finding represents a novel aspect of the biological profile of D-allose and suggests that D-allose may be an effective adjuvant therapeutic agent against cancer in the future.
International Journal of Oncology 11/2005; 27(4):907-12. · 2.40 Impact Factor
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ABSTRACT: Jun activation domain-binding protein 1 (Jab1) is known as a coactivator of AP1 transcription factor, which contributes to tumor progression by degrading the p27kip1 protein. The purpose of this study is to investigate whether Jab1 expression is correlated with p27kip1 level and cell proliferation, as well as whether Jab1 expression is associated with clinicopathologic variables and prognosis of laryngeal squamous cell carcinoma (LSCC).
Immunohistochemical and/or Western blot analysis was done in HEp-2 cells and 102 cases of LSCCs.
Jab1 expression was negatively associated with p27kip1 expression and was positively associated with cell proliferation both in HEp-2 cells and LSCCs. Jab1 overexpression was detected in 51% LSCCs and was significantly associated with unfavorable clinicopathologic variables. Survival analysis revealed that Jab1 overexpression is significantly associated with short disease-free and overall survival (P = 0.0036 and P = 0.0001, respectively). When Jab1 and p27kip1 are combined, patients with Jab1(+)/p27kip1(-) revealed poor disease-free and overall survival (P= 0.0008 and P < 0.0001, respectively). When Jab1 expression and lymph node status are combined, patients with Jab1(+)/lymph node(+) revealed poorer disease-free andoverall survival than others (P < 0.0001 and P < 0.0001, respectively). Furthermore, patients with the phenotype of Jab1(+)/p27kip1(-)/lymph node(+) revealed the worst disease-free and overall survival (P < 0.0001 and P < 0.0001, respectively). Multivariate analysis revealed that Jab1 protein is an independent prognostic indicator for overall survival.
These findings suggested that Jab1 protein may contribute to the tumor progression and represent a novel prognostic indicator for LSCCs.
Clinical Cancer Research 02/2005; 11(1):259-66. · 7.74 Impact Factor
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Tetsuya Tamura,
Takayuki Nakagawa,
Fukuichiro Iguchi,
Ichiro Tateya,
Tsuyoshi Endo,
Tae-Soo Kim, Youyi Dong,
Tomoko Kita,
Ken Kojima,
Yasushi Naito,
Koichi Omori,
Juichi Ito
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ABSTRACT: This study aimed to examine the possibility of restoration of spiral ganglion neurons, which transmit sound stimulation to the brain, by transplantation of fetal neural stem cells (NSCs) into the modiolus of cochleae. Fetal mouse NSCs expressing green fluorescence were injected into the modiolus of cisplatin-treated cochleae of mice. The temporal bones were collected 14 days after transplantation, and provided histological examination. The cell fate of transplants was determined by immunohistochemistry for a neural or glial cell-marker. Histological analysis 2 weeks after transplantation revealed robust survival of transplant-derived cells in the modiolus of the cochlea. NSCs injected in the basal portion of cochleae migrated as far as the apical end of the modiolus Grafted NSCs expressing a neural cell marker were identified, but the majority of grafted NSCs differentiated into glial cells. These findings suggest the possible use of NSCs in cell therapy for restoration of spiral ganglion neurons. However, further treatments are required to increase the number of NSC-derived neurons in the modiolus to realize functional recovery.
Acta oto-laryngologica. Supplementum 04/2004;
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Fukuichiro Iguchi,
Takayuki Nakagawa,
Ichiro Tateya,
Tsuyoshi Endo,
Tae-Soo Kim, Youyi Dong,
Tomoko Kita,
Ken Kojima,
Yasushi Naito,
Koichi Omori,
Juichi Ito
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ABSTRACT: This study investigated surgical procedures for cell transplantation into the mouse inner ear. Female C57BL/6 mice were used as recipient animals. Fetal mouse neural stem cells expressing green fluorescence were used as donor cells. Two methods, an injection of transplants from the lateral semicircular canal (LSCC) and from the cochlear lateral wall (CLW), were examined. Two weeks after transplantation, the distribution of transplant-derived cells in the cochlea was examined. Effects on auditory function were assessed by measurement of auditory brain stem responses (ABRs). Cochleae receiving cell transplantation from the LSCC exhibited robust survival of transplant-derived cells mainly in the scala vestibuli and scala tympani. Transplantation from the LSCC caused elevation of ABR thresholds by less than 10 dB SPL. However, transplantation from the CLW resulted in considerable hearing loss, even though transplant-derived cells settled in the scala media. These findings demonstrate that an approach from the LSCC can be utilized for cell transplantation into the perilymph without causing apparent auditory disorder, while an approach from the CLW delivers cells to the endolymph but appears to cause auditory dysfunction.
Acta oto-laryngologica. Supplementum 04/2004;
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Shinji Takebayashi,
Takayuki Nakagawa,
Ken Kojima,
Tae-Soo Kim,
Tomoko Kita, Youyi Dong,
Tsuyoshi Endo,
Fukuichiro Iguchi,
Yasushi Naito,
Koichi Omori,
Juichi Ito
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ABSTRACT: This study investigated the role of beta-catenin in the development of mouse auditory epithelia. Inner ears obtained from embryonic and newborn mice were used. Expression of beta-catenin was examined together with the expression of Ki-67, a marker for proliferating cells, or myosin VIIa, a marker for differentiated hair cells. In the early phase of development, intense expression of beta-catenin was found in auditory epithelia in which a number of Ki-67-positive cells were identified. Together with a decrease in proliferating cells, the intensity and area of beta-catenin expression were reduced. In addition, during differentiation and maturation of hair cells, the area of beta-catenin expression was further limited. These findings suggest that patterns of expression of beta-catenin are closely linked with the status of auditory epithelia development.
Acta oto-laryngologica. Supplementum 04/2004;
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ABSTRACT: The survival of the spiral ganglion (SG) is a critical issue in preservation of hearing. Research on topics related to this issue requires a mouse experimental model because such a model has advantages including use of genetic information and knockout or "knockin" mice. Thus, the aim of the study was to establish a mouse model for induction of apoptosis of SG neurons with a definite time course.
Laboratory study using experimental animals.
C57BL/6 mice were used as experimental animals and were subjected to direct application of cisplatin into the inner ear. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay and immunostaining for Neurofilament 200-kD (NF) and peripherin were used for analysis of SG degeneration. In addition, generation of peroxynitrite in affected spiral ganglions was examined by immunostaining for nitrotyrosine. Cellular location of activated caspase-9 and cytochrome-c in dying SG neurons were examined for analysis of cell death pathway.
The TUNEL assay and immunohistochemical analysis for NF and peripherin indicated that type I neurons in spiral ganglions were deleted through the apoptotic pathway over time. Spiral ganglion neurons treated with cisplatin exhibited expression of nitrotyrosine, indicating induction of peroxynitrite by cisplatin. In dying SG neurons, expression of activated caspase-9 and translocation of cytochrome-c from mitochondria to cytoplasm were observed, indicating the mitochondrial pathway of apoptosis.
The predictable fashion of induction of apoptosis in SG neurons over a well-defined time course in the model in the study will aid studies of the molecular mechanism of cell death and elucidation of a strategy for prevention of SG degeneration.
The Laryngoscope 07/2003; 113(6):994-9. · 1.75 Impact Factor
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ABSTRACT: The F-box protein, Skp2 positively regulates the G1-S transition by controlling the stability of several G1 regulators, including p27. To evaluate the role of Skp2 in the mammalian developing auditory systems, the expression of Skp2 was examined together with the expression of p27 in auditory systems. Our data show expression of Skp2 in auditory epithelia and neurons at an early stage of development. During differentiation processes, the onset of p27 expression was observed together with the down-regulation of Skp2 expression, in auditory epithelia. In contrast, an alteration of expression of p27 and Skp2 in the greater epithelial ridge and spiral ganglion appeared after differentiation of hair cells. These findings suggest that Skp2 plays a crucial role in development of mammalian auditory systems.
Neuroreport 05/2003; 14(5):759-61. · 1.66 Impact Factor
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ABSTRACT: The aim of this study was to examine roles of p27, a cyclin-dependent kinase inhibitor, in cochleae of adult mice. Expression of p27 was found in cochlear supporting cells and spiral ganglion neurons of normal mice. Cisplatin treatment caused progressive degeneration of cochlear supporting cells and spiral ganglion neurons, and numbers of p27-positive cells in these cells decreased. This indicates a close relationship between p27 and cell death in cochleae. However, the relationships between decrease in number of p27-positive cells and that of survival cells differed according to type of cell. For Deiters' cells, there was apparent decrease in number of p27-positive cells, although no decrease in cell numbers. The present findings indicate that p27 plays roles in degeneration of cochleae according to cell type.
Neuroscience Letters 01/2003; 334(3):173-6. · 2.11 Impact Factor
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ABSTRACT: Survivin is a new member of the inhibitors of apoptosis proteins (IAP) family, selectively overexpressed in common human cancers but not in normal adult tissues, and associated with aggressiveness of the disease and unfavorable outcomes. Recent study also found that survivin expression is associated with cell proliferation. In order to gain insight into the role of survivin in ovarian tumors, we investigated the expression of survivin in a group of epithelial ovarian tumors, and examined the relationship of its expression with cell proliferation and clinical outcome. Immunohistochemical analysis was performed in 103 cases of epithelial ovarian tumors. Twenty-six of the 103 cases were evaluated by Western blot analysis. The results showed that survivin overexpression was detected in 21.2% (7 of 33) of benign tumors, 47.8% (11 of 23) of borderline tumors, and 51.1% (24 of 47) of ovarian carcinomas. The positive ratio was significantly higher in malignant or borderline tumors than in benign tumors, and the overexpression of survivin was significantly correlated with the size of residual disease. A positive correlation between survivin expression and proliferative activity of tumor cell measured by PCNA index was found. Kaplan-Meier analysis demonstrated that the patients with survivin overexpression have a short overall survival. These findings suggest that survivin overexpression may play a pivotal role in the progression of ovarian tumors and may provide an important prognostic implication for epithelial ovarian carcinomas.
International Journal of Oncology 09/2002; 21(2):315-20. · 2.40 Impact Factor
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ABSTRACT: Cyclin B1 is a key molecule for G2/M phase transition during the cell cycle and is overexpressed in various human tumors. However, the expression status of cyclin B1 in laryngeal squamous cell carcinoma (LSCC) and its clinical significance remain unknown. We used immunohistochemical studies to examine the expression of cyclin B1 in 102 patients with LSCC. The results showed that cyclin B1 overexpression was observed in 40 cases (39.2%) of LSCCs and was significantly correlated with the tumor site (P=0.031), tumor size (P<0.0001), and advanced stage (P=0.003). In addition, cyclin B1 overexpression was associated with patients' overall survival, but not with disease-free survival using Kaplan-Meier analysis. On multivariate analysis, cyclin B1 expression was not recognized as an independent prognostic factor. These findings indicate that cyclin B1 overexpression may be associated with the malignant biological behavior of LSCC.
Cancer Letters 04/2002; 177(1):13-9. · 4.24 Impact Factor
